Background of the Invention Allylic oxidation is of significant interest to organic chemists practicing in a variety of fields from agricultural products to pharmaceuticals. Allylic oxidation reactions have traditionally been performed with chromium reagents, such as chromium trioxide and sodium/potassium dichromate. While generally effective, such reactions usually require a large excess of the reagent under harsh conditions (e. g. , a large volume of aqueous acetic acid, anhydrous acetic acid (Fieser's Reagent) or concentrated or dilute sulfuric acid).

Chromium trioxide pyridine complex allows the oxidation to be carried out at ambient temperature, but requires the use of a large excess of the reagent (-20 equiv. ) and is highly hygroscopic, making the reagent unattractive for large scale production.

Pyridinium chlorochromate (PCC) and pyridinium dichromate have become ubiquitous for chromate-based oxidations as they are generally effective and can be prepared by a procedure significantly less hazardous than that required to prepare the chromium trioxide-pyridine complex. However, these reagents also tend to require a large excess (-20 equiv.) of the reagent. The use of tert-butyl hydroperoxide in combination with a chromium reagent affords allylic oxidation under relatively mild processing conditions, but often requires the use of an undesirable organic solvent, such as benzene. A further drawback associated with the aforementioned procedures is the incomplete nature of the conversion, requiring the implementation of expensive techniques, such as chromatography, to remove unreacted starting material and obtain a product of sufficient purity.

Marwah and coworkers have described a cost effective procedure for allylic oxidation of organic compounds utilizing sodium periodate or periodic acid and aqueous tert-butyl hydroperoxide. See U. S. Pat. No. 5, 869,709. In addition, Marwah has described a

method for effecting the oxidation of an allylic compound having at least two allylic hydrogen atoms on the same carbon atom. This process is carried out using the combination of a metal hypochlorite and an alkyl hydroperoxide in a mixture of suitable conventional organic solvent (s) and/or water at a temperature of between about-5 °C to +25 °C. See U. S. patent 6,274, 746. The method is attractive because it offers an eco-friendly, cost-effective procedure based on green chemistry for the allylic oxidation of organic compounds.

Callahan has disclosed that olefins, such as propylene, can be oxidized at the allylic position to unsaturated aldehydes and carboxylic acids, such as acrolein and acrylic acid, by contacting the olefin with molecular oxygen in the presence of a trifluoroalkyl sulfonate or phosphonate catalyst. The catalyst for these transformations is prepared by reaction of vanadyl oxide with trifluoromethyl sulfonate. See U. S. patent 4,309, 310. The acrolein and acrylic acid products obtained from this reaction are valuable commodities in textile manufacture.

Other common oxidants are potassium permanganate, manganese dioxide, ruthenium compounds, selenium dioxide, copper and its compounds. Catalytic oxidation using oxygen or air is known in which metal compounds and N-hydroxy cyclic imides have been used as catalysts. However, most of these procedures are not environmentally friendly, and typically suffer from one or more additional drawbacks, such as unsatisfactory yields, use of large excess of the oxidant (s), harsh reaction conditions, use of toxic chemicals, difficulty in scaling up, generation of copious amount of toxic waste, and use of expensive reagents. Therefore, they are not industrially feasible processes for bulk production.

Advances have also been made in identifying catalytic allylic oxidation systems that form branched alcohols or acetates a to monosubstituted olefins; however, these are limited by low conversions and/or lack of substrate generality due to poor functional group tolerance. SeO2/t-BuOOH : Umbreit, M. A.; Sharpless, K. B. J. Am. Clieni. Soc. 1977, 99, 5526. Cu (I)/t-butyl perbenzoate : Andrus, M. B.; Lashley, J. C. Tetrahedron, 2002, 58, 845.

Accordingly, the need exists for a mild allylic oxidation procedure that produces products in high overall yield and high regioselectivity.

Summary of the Itzvention The present invention generally relates to a method of preparing allylic carboxylate compounds comprising the step of contacting a compound comprising an allylic hydrogen atom with a carboxylic acid in the presence of palladium, a sulfoxide compound, and an oxidant. In certain embodiments, the carboxylic acid is an alkyl or aryl carboxylic acid. In a preferred embodiment, the carboxylic acid is acetic acid. In a preferred embodiment, the compound comprising an allylic hydrogen atom is a monosubstituted olefin. In a preferred embodiment, the palladium is palladium acetate. In a preferred embodiment, the sulfoxide compound is dimethyl sulfoxide, phenyl vinyl sulfoxide or 1, 2-bis (benzylsulfinyl) ethane.

In certain embodiments, the oxidant is benzoquinone, benzoquinone/Mn02, or benzoquinone/Cu (OAc) 2/02. In a preferred embodiment, the oxidant is benzoquinone.

Another aspect of the present invention generally relates to sulfoxide compounds that are useful as catalysts to effect C-H oxidation. In a preferred embodiment, the sulfoxide compound comprises 1, 2-bis (benzylsulfinyl) ethane or phenyl vinyl sulfoxide and palladium. Another aspect of the present invention relates to a catalytic method for the direct C-H oxidation of monosubstituted olefins to prepare linear (E) -allylic acetates in high regio-and stereoselectivities. In addition, the method of the instant invention can be used to prepare branched allylic carboxylates with high yield and regioselectivity. Moreover, the method of the instant invention can be used to oxidize a-olefins to branched allylic esters.

Remarkably, the allylic oxidation method of the invention is compatible with a wide range of functionality, such as amides, carbamates, carbonates, esters, and ethers.

Brief Descriptio) t of Figures Figure 1 depicts the effect of DMSO and bis-sulfoxide ligation on Pd (II) catalyzed oxidations of terminal olefins. yields determined by GC for an average of 2-3 runs from reactions carried out on a 0.2 mmol scale. Yields are corrected for response factor variations. bMajor linear allylic acetate product observed (E: Z selectivity, Figure 10).

'Major vinyl acetate product observed.

Figure 2 depicts a 4A MS screen using 10 mol% Pd (OAc) 2.

Figure 3 depicts a 4A MS screen using 10 mol% Pd (TFA) 2.

Figure 4 depicts a solvent screen (solvent: AcOH = 1: 1) at 40 °C using 10 mol% Pd (OAc) 2, and BQ (2 eq).

Figure 5 depicts a solvent screen (solvent: AcOH = 1: 1) at 40 °C using 10 mol% catalyst 1, and BQ (2 eq).

Figure 6 depicts an oxidant screen at 40 °C using 10 mol% Pd (OAc) 2, 4A MS, and DMSO: AcOH (1 : 1).

Figure 7 depicts a benzoquinone equivalents screen at 40 °C using 10 mol% Pd (OAc) 2, 4A MS, and DMSO: AcOH (1: 1).

Figure 8 depicts a reaction screen of various DMSO: AcOH ratios at 40 °C using 10 mol% Pd (OAc) 2, 4A MS, and BQ (2eq).

Figure 9 depicts a reaction temperature screen using 10 mol% Pd (OAc) 2, BQ (2, eq), 4A MS, and DMSO : AcOH (1: 1).

Figure 10 depicts allylic oxidation of terminal olefins to (E)-allylic acetates. aAll data reported ( [L : B], [E : Z] ratios, yields) based on an average of two runs. Minor peaks consistent with diene byproducts were detected by IH NMR analysis of the crude. blo mol% Pd (TFA) 2. ratio based on GC analysis of crude. Not corrected for small response factor variations. dRatio based on 1H NMR analysis of crude. eIsolated yields after chromatography from reactions carried out on a 1.0 mmol scale (0.17 M).

Figure 11 depicts the optimization if reaction conditions for the allylci oxidation of a-olefins to branched allylic esters. Yields were determined by GC analysis for an average of 3 runs from reacitons carried out on a 0.2 or 0.4 mmol scale. Yields are corrected for response factor variations. BQ = benzoquinone ; BQ (Me) = 2-methylbenzoquinone; BQ (Me) 2 = 2, 6-dimethylbenzoquinone ; DQ = 2,3, 5, 6-tetramethylbezoquinone.

Figure 12 depicts allylic oxidation of terminal olefins to branched allylic acetates.

All data reported is based on average of 3-4 runs. The branched : linear ratios are based on IH NMR analysis of the crude isolated products. Isolated yields were measured after chromatography from reactions carried out on a 1.0 mmol scale.

Figure 13 depicts examples of macrolactonization by the instant invention to form 12-, 14-and 16-membered rings.

Figure 14 depicts a solvent screen with phenyl vinyl sulfoxide 2 and Pd (OAc) 2.

Figure 15 depicts an acetic acid equivalents screen with phenyl vinyl sulfoxide 2 and Pd (OAc) 2.

Figure 16 depicts an oxidant screen phenyl vinyl sulfoxide 2, Pd (OAc) 2 and (a) 52 eq. AcOH or (b) 4 eq. AcOH.

Figure 17 depicts a quninone oxidant screen with phenyl vinyl sulfoxide 2, Pd (OAc) 2, and 4 eq. AcOH.

Figure 18 depicts isomerization studies with phenyl vinyl sulfoxide 2 and Pd (OAc) 2.

Detailed Description of tize Invention The development of selective methodologies for the oxidation of saturated C-H bonds would enable the direct installation of functionality into preassembled hydrocarbon frameworks, thereby providing alternatives to methods that rely upon C-C bond-forming reactions between pre-oxidized fragments. A method for the selective oxidation of monosubstituted olefins to yield versatile, a-functionalized olefins would be highly useful.

Well-known, mild allylic oxidation methods using palladium (II) salts in acetic acid (AcOH) are available for transforming internal olefins into regioisomeric mixtures of allylic acetates. Pd (II) allylic acetoxylation: (a) Hansson, S.; Heumann, A. ; Rein, T.; Akermark, B.

J. Org Chem. 1990, 55, 975. (b) Heumann, A.; Reglier, M.; Waegell, B. Angew. Chem. Int.

Ed. Engl. 1982, 21, 366. (c) Heumann, A.; Akermark, B. Angew. Chem. Int. Ed. Engl. 1984, 23,453. (d) McMurry, J. E.; Kocovsky, P. Tetrahedron Lett. 1984, 25, 4187. (e) Akermark, B.; Larsson, E. M.; Oslob, J. D. J. Org. Chez. 1994, 59, 5729. (f) Macsari, I. ; Szabo, K. J.

Tetrahedron Lett. 1998, 39, 6345. These reactions are thought to proceed via substitution of s-allyl intermediates generated through allylic C-H cleavage. Grennberg, H.; Backvall, <BR> <BR> <BR> <BR> J. -E. Chem. Eur. J. 1998, 4, 1083. (b) Wolfe, S.; Campbell, P. G. C. J. Am. Chem. Soc. 1971, 93, 1497,1499. For reasons that are not clear, under these same conditions monosubstituted olefins predominantly undergo Wacker oxidation (Markovnikov oxypalladation/ß-hydride elimination) to yield mixtures of vinyl acetates and methyl ketone. Kitching, W.; Rappoport, Z.; Winstein, S.; Young, W. G. J. Am. Chem. Soc. 1966, 88, 2054. Notably, highly electrophilic Pd (II) salts with non-nucleophilic counterions must

be used to generate stoichiometrically s-allylpalladium complexes from monosubstituted olefins. Trost, B. M.; Metzner, P. J. J. Am. Chem. Soc. 1980, 102, 3572. Wacker C-H oxidation DMSO oxidation Pd (II) X2 ORg Pd (ll) X2 catalyst R OAc catalyst R (1) . au. BQ +. catalystl Acon Phs % Ph < Pd (OAc) 2 catalyst 1 Remarkably, we have discovered that addition of a sulfoxide (e. g., DMSO) to the Pd (OAc) 2/benzoquinone (BQ) /AcOH catalyst system results in a general C-H oxidation method for converting monosubstituted olefins to linear (E)-allylic acetates with high regio- and stereoselectivities and in preparatively useful yields. This report is the first of a sulfoxide significantly altering both the reaction pathway selectivity and regioselectivity in a Pd (II) -catalyzed oxidation. For Pd (II)/DMSO/O2 : alcohol oxidation: Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am. Chem. Soc. 2002, 124, 766. annulation : Larock, R. C.; Hightower, T. R.; J. Org. Chez. 1993, 58, 5298.1, 4-diacetoxylation: Grennberg, H.; Gogoll, A.; Backvall, J.-E. J. Org. Chem. 1991, 56, 5808. We believe these effects result from sulfoxide ligation to palladium. In support of this explanation, we have also demonstrated that a bis-sulfoxide Pd (II) acetate complex 1 is an effective allylic oxidation catalyst for monosubstituted olefins in the absence of DMSO. Moreover, use of sulfoxide 1 results in a reversal of regioselectivity, favoring formation of branched allylic acetates. 1 (10 mol %) OAc TBDPSO'w BQ (2 eq). TBDPSO'" (2) CHZCI2 : AcOH (1 : 1) 40°C, 72h 65/yield, [L : B] = 1 : 6 H OAc above m 01-1l)- zu 69 % yield, [L : B] = 1 : 5 In the process of investigating the catalytic Pd (OAc) 2/BQ/AcOH-mediated oxidation of 1-decene, we discovered that addition of DMSO significantly shifts the product distribution from predominant formation of mixtures of vinyl acetates and methyl ketone to favor formation of linear (E)-allylic acetate ( [E : Z] = 12: 1, Figure 1). A similar

observation in a stoichiometric Pd (OAc) 2 system was observed by Kitching, W. and coworkers in J. Am. Chem. Soc. 1966, 88, 2054. We considered that this effect may be due to stabilization of a charged intermediate in the catalytic cycle for C-H oxidation by the highly polar DMSO solvent. However, when we evaluated the reaction in a diverse range of dielectric media (e. g., CH3CN, dioxane, CH2Cl2, benzene), we observed no correlation between the polarity of the added solvent and its ability to promote the C-H oxidation pathway (Figure 4).

To explore the potential role of the sulfoxide as a ligand in promoting the palladium (II) catalyzed C-H oxidation pathway, we formed bis-sulfoxide palladium (II) acetate complex 1 via routine metal complexation with 1, 2-bis-phenylmethanesulfinyl-ethane in CH2Cl2 at 40°C. S-Pd coordination mode is tentatively assigned based on other Pd (II) bis- sulfoxide complexes and Pd (II) DMSO complexes: Bennett, M. J. ; Cotton, F. A.; Weaver, D. L. Nature. 1966, 212, 286 and Pettinari, C.; Pellei, M.; Cavicchio, G. Crucianelli, M.; Panzeri, W.; Colapietro, M.; Cassetta, A. Organometallics 1999, 18, 555. In the absence of DMSO, complex 1 was found to be an effective catalyst for allylic C-H oxidation in a variety of standard solvents (CH2Cl2, dioxane, THF, Et2O, DME, benzene, toluene-Figure 5), leading to formation of < 1% of the undesired Wacker oxidation products (Figure 1).

Moreover, a reversal in regioselectivity was observed with 1 for a variety of substrates to give the branched allylic acetates as the major products with good selectivities and yields (e. g. , eq 2 and 3). It is remarkable that the regioselectivities reported in entries 4 and 8 (Figure 10) and equations 2 and 3 represent a turnover from 31: 1 to 1: 6 and 13: 1 to 1: 5 (respectively). These results demonstrate for the first time that sulfoxide ligation of Pd (II) salts can selectively promote C-H oxidation versus Wacker oxidation chemistry and control the regioselectivity in the C-H oxidation products. Further studies will probe the effects of steric and electronic tuning of the C2-symmetric bis-sulfoxide compound framework on the reactivity and selectivity of the C-H oxidation reaction and on its amenability to asymmetric catalysis.

Because (E)-allylic acetates and their respective alcohols are valuable synthetic intermediates, we explored the generality and synthetic utility of the DMSO-promoted C-H oxidation reaction (Figure 10). Evaluation of reaction parameters (Figures 2-9) indicated that the reaction conditions Pd (OAc) 2 (10 mol%)/BQ (2eq)/4A MS/DMSO: AcOH (1 : 1, v/v) at 40°C are presently optimal. Palladium (II) trifluoroacetate [Pd (TFA) 2] gave similar results in the presence of 4A MS and, in general, the addition of 4A MS increased formation of

linear (E)-allylic acetate (Figures 2 and 3). Reaction times were determined by balancing considerations of maximizing yields while maintaining high linear : branched ([L : B]) ratios (the latter decreased over the course of the reaction for the majority of substrates examined). For example, entry 3, Figure 10: 24h, [L: B] = 34 : 1; 72h, [L: B] = 11 : 1.

Submission of regioisomerically pure (E) -acetic acid dec-2-enyl ester to the reaction conditions resulted in the same trend, consistent with a background Pd- (II) catalyzed allylic acetate isomerization pathway: Henry, P. M. J. Ant. Chem. Soc. 1972, 94, 5200 and Overman, L. E.; Knoll, F. M. Tetrahedron Lett. 1979, 4, 321. Notably, these conditions are operationally simple and tolerant of a wide range of functionality. Benzyl and silyl ether-, ketal-, ester-, carbamate-and amide-functionalized monosubstituted olefins underwent direct oxidation with excellent regio-and stereoselectivities to generate the corresponding linear (E)-allylic acetates in preparatively useful yields (Figure 10). The high selectivity, functional group compatibility and directness of this method makes it a powerful alternative to C-C bond forming procedures that require multistep routes for accessing the majority of products in Figure 10. For a standard HWE-based 5-6 step synthetic route towards (E)- allylic acetates see Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1980, 102, 4743.

Cross-metathesis has been used to directly synthesize entry 10 in 51% yield: Chatterjee, A. K.; Choi, T. -L. ; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360 The observed high trans selectivities and detection of diene byproducts is consistent with a mechanism involving a s-allylpalladium intermediate. Trost, B. M.; Metzner, P. J. J.

Am. Chem. Soc. 1980, 102, 3572. We envision that sulfoxide ligation supports formation of electrophilic Pd (II) species which may be needed to effect C-H cleavage and/or activate a -allyl intermediate toward nucleophilic attack. Neutral, strongly coordinating Pd (II) ligands (e. g. , DMSO, PPh3) have been used to activate stoichiometric n-allyl chloride complexes towards alkylation. See Collins, D. J.; Jackson, W. R.; Timms, R. N. Tetrahedron Lett. 1976,495 ; Trost, B. M.; Fullerton, T. J. J. Am. Chem. Soc. 1973, 95, 292; and Trost, B. M. Acc. Chem. Res. 1980, 13, 385. Investigation of the reaction mechanism and studies toward an understanding of the role of sulfoxide ligation on selectivity are in progress.

A catalytic method for the direct C-H oxidation of monosubstituted olefins to linear (E)-allylic acetates in high regio-and stereoselectivities and preparatively useful yields is described. Sulfoxide ligation to Pd (II) salts is shown to selectively promote C-H oxidation versus Wacker oxidation chemistry and control the regioselectivity in the C-H oxidation products. The method using benzoquinone as the stoichiometric oxidant and 10 mol%

Pd (OAc) 2 or Pd (02CCF3) 2 as the catalyst in a DMSO/AcOH (1 : 1) solution was found to be compatible with a wide range of functionality (e. g. , amides, carbamates, carbonates, esters, and ethers). Addition of DMSO was found to be critical for promoting the C-H oxidation pathway, with AcOH alone, or in combination with a diverse range of dielectric media, leading to mixtures favoring Wacker-type oxidation products. To explore the role of DMSO as a ligand, a bis-sulfoxide Pd (OAc) 2 complex 1 was formed and found to be an effective C-H oxidation catalyst in the absence of DMSO. Moreover, catalyst 1 effects a reversal of regioselectivity favoring formation of branched allylic acetates. Step 1 Step 2 GHcleavage Fundionalization O O Ph 2 F R l ° R' , (10moi%)- BQ 1 . (4) R> pd mol/) ( ; , g (l (10moM) 5743% 57-83%, [B : [j=a94 : 6 In the process of investigating our catalytic bis-sulfoxide promoted Pd (OAc) 2/BQ/AcOH allylic oxidation system (described above) it was found that 1,2- bis (phenylsulfinyl) ethane (see Example 7) partially decomposes under the reaction conditions (< 5% by 1H NMR) to its corresponding vinyl sulfoxide 2 (Figure 11). We tested 2 and undetected sulfenic acid byproducts for their ability to promote the reaction alone and in catalytically relevant combinations. In addition, it was determined that 10 mol% commercially available phenyl vinyl sulfoxide 2 alone with 10 mol% Pd (OAc) 2 was able to effectively promote the allylic oxidation in a wide variety of standard solvents (for example: dioxane, CH2Cl2, THF, benzene, CHC13) with yields and regioselectivities comperable to 1, 2-bis (phenylsulfinyl) ethane and with no detectable decomposition under the reaction conditions (Figure 11). For examples of Pd (II)/DMSO/02 oxidations see: (a) Grennberg, H.; Gogoll, A.; Backvall, J. -E. J. Org. Chein. 1991, 56, 5808. (b) Larock, R. C.; Hightower, T. R.; Hasvold, L. A.; Peterson, K. P. J. Org. Chez. 1996, 61, 3584. (c) Steinhoff, B. A.; Fix, S. R.; Stahl, S. S. J. Am. Client. Soc. 2002, 124, 766. For examples of Pd (II) /DMSO arene C-H functionalization see: Zhou, C.; Larock, R. C. J. Am. Chers. Soc.

2004, 126, 2302.

It was further determined that lowering the stoichiometry of acetic acid from 52 to 4 equivalents results in significant improvements in regioselectivities without compromising yields or lengthening reaction times (Figure 11). Significantly, at 4 eq. AcOH a background Pd (II) -mediated allylic isomerization is suppressed in the presence of a-olefin. See Overman, L. E.; Knoll, F. M. Tetrahedron Lett. 1979, 4, 321. This discovery facilitated the exploration of heavier carboxylic acid substrates which were found to be effective a-olefin coupling partners at synthetically relevant 1.5 eq. stoichiometries furnishing branched esters in good yields and excellent regioselectivities.

0 5 Ph BufNCI x mol% Pd (CI)/2 Pd (OAc) 2 x= I eq., 64% 1% lk-"Cs H 17 x. ; (5) CDC 3 40°C x= 10 mol°/A AcOH CeHj' 40JC A + C8H174 eq. eq. x = 10 mol%, 50%, [29 : 1] Mechanistic studies were carried out to establish the fundamental steps of the catalytic cycle. When mixtures of 1-undecene with stoichiometric or catalytic Pd (OAc) 2/ phenyl vinyl sulfoxide 2 (1: 1 ratio) were heated to 40 °C in CDC13 and monitored by'H NMR, 7c-allylpalladium acetate complex A was observed as the major product (ca.-60% stoichiometric/catalytic), and its structure was confirmed by independent synthesis (eq 5, below). Chloride anion metathesis furnished the s-allylpalladium chloride complex in 64% isolated yield from the stoichiometric reaction. In the absence of phenyl vinyl sulfoxide 2 under identical conditions only olefin oxidation products (i. e. vinyl acetates, methyl ketone) were observed; this respresents the first report of conditions in which Pd (II) with nucleophilic counterions is able to efficiently effect formation of a s-allylpalladium complexes from a-olefins. For related reactions see (a) Trost, B. M.; Metzner, P. J. J. Am.

Chem. Soc. 1980, 102, 3572 ; (b) Robinson, S. D.; Shaw, B. L. J. Organomet. Chem. 1965,3, 367; and (c) Brown, R. G.; Chaudhari, R. V.; Davidson, J. M. J. Chem. Soc. Dalton Trans.

1977,176.

Addition of acetic acid and benzoquinone to in situ generated solutions of A results in formation of the branched allylic acetate product with similar overall reaction times, yields, and regioselectivities as those observed under analogous catalytic reaction conditions (eq 5 above). Significantly, formation of complex A is not reversible as evidenced by no exchange with l-benzyloxy-4-pentene (10 eq) in the presence of AcOH (40 eq) and 2 (1 eq w/respect to Pd) after 48h at 40 °C in dioxane. Therefore, reaction by a pathway separate from one involving a Pd-n-allyl intermediate is unlikely.

Addition of AcOH alone to stoichiometric in situ generated complex A results in trace amounts of product (8%, GC) with no regioselectivity (1: 1); whereas addition of BQ

alone results in similar branched allylic acetate yields and regioselectivities to those of the stoichiometric control reaction (56% GC yield, 11: 1; control 62%, 9: 1). This data suggests that BQ's role in this reaction is not simply just that of an oxidant. In support of this, no significant product formation was observed under catalytic reaction conditions with other standard Pd (0)/Pd (II) oxidants such as Cu (OAc) 2 and duroquinone and a significant decrease in yield and regioselectivity was observed as the steric hinderance of the BQ is increased (Figure 11).

In order to examine the role of vinyl sulfoxide 2 on the functionalization step, its effect on the regioselectivity and yield of product formation using independently synthesized complex A under conditions that mock the reaction of a Pd-s-allyl intermediate during one catalytic reaction cycle was examined. It was found that the regioselectivities and yields of product formation with BQ alone are identical to those of BQ/vinyl sulfoxide 2 and to those observed under catalytic reaction conditions. This data strongly suggests that BQ is acting alone as a ligand for a Pd-W-allyl intermediate to promote and control the regioselectivity of functionalization. Scheme 1. Ph S O b Pd (OAc) 2 vs = DHQ (vs) Pd (OAc) 2 2 eq AcOH 7 R (vs) Pd (OAc) I BQ (vs) T vs I (BQ) Pd (L) il L = BQ or OAc Based on this data, a serial ligand catalysis mechanism for the allylic oxidation reaction in which phenyl vinyl sulfoxide 2 and BQ interact separately and reversibly with Pd to promote the C-H cleavage and carboxylate functionalization steps (respectively) of the catalytic cycle is proposed (Scheme 1, above). It is postulated that phenyl vinyl sulfoxide 2 associates with Pd (OAc) 2 to generate a monomeric Pd species that binds to o- olefins and effects electrophilic allylic C-H cleavage to form a Pd-n-allyl intermediate I. It is of interest to note that no binding of 2 with Pd (OAc) 2 was detected by 1H NMR or IR, suggesting that binding is reversible and that the equilibrium strongly favors Pd (OAc) 2. In

the absence of BQ, Pd-s-allyl intermediate I dimerizes to give complex A. Although catalysis via vinyl sulfoxide 2 (10 mol%) /complex A (10 mol% Pd) proceeds with similar overall reaction times, yields and regioselectivities as those observed under standard catalytic reaction conditions, the initial rate of product formation is slower suggesting that complex A does not lie precisely within the catalytic cycle. 9 Moreover, complex A is not observed by 1H NMR under catalytic reaction conditions signifying that it is not a resting state intermediate. Under the reaction conditions, I binds BQ to form intermediate 11 that is activated towards nucleophilic carboxylate functionalization. Treatment of complex A with BQ generates intermediate II, as evidenced by formation of product with the same yields and regioslectivities as those obtained under catalytic reaction conditions. We believe the role of BQ in activation may be that of a s-acid promoting the reductive functionalization step from either a neutral or cationic Pd-s-allyl species. Note that s-Acids have been demonstrated to promote reductive elimination in Ni (acac) 2 catalyzed cross-coupling reactions in Giovannina, R.; Knochel, P. J. Am. Chem. Soc. 1998, 120, 11186. In addition benzoquinone has been shown to be a ligand for Pd (II) in Backvall, J. -E. ; Bystrom, S. E.; Nordberg, R. E. J. Org. C1le7n. 1984,49, 4619 and Grennberg, H.; Gogoll, A.; Backvall, J.- E. J. Org. Chenu. 1991, 56, 5808. The differential trans-effects between the BQ and carboxylate coordinating functionalities may result in an electronic dissymetry of the Pd-7v- allyl intermediate that accounts for the observed preference for carboxylate functionalization at the internal carbon. See von Matt, P.; Pfaltz, A. Angew. Chem. Int. Ed.

Engt. 1993, 32, 566. Finally, standard BQ-mediated oxidation of Pd (0) to Pd (II) completes the catalytic cycle.

Experiments that probe the scope of the a-olefin and carboxylic acid components are summarized in Figure 12 and in the Exemplification. The high functional group compatibility of this method is seen in the range of functionality tolerated on the a-olefin substrate. Incorporation of benzylic, acidic, and basic functionality is possible without a loss in efficiency or regiocontrol. Significantly, with di-olefin substrates, chemoseleclectivity is observed for the a-olefin. Considerable variation in the steric and electronic demand of the carboxylic acid component is also well-tolerated, with the best results obtained using electron deficient benzoic acids.

In summary, one embodiment of this invention describes a new, highly regio-and chemoselective Pd-catalyzed reaction for the conversion of allylic C-H bonds of a-olefins

to esters. Evidence is provided that supports a novel serial ligand catalysis mechanism for this reaction where two different ligands interact separately and reversibly with Pd during different steps of the cycle to promote catalysis.

A further embodiment of this invention is its use intramolecularly to form macrolactones, as shown in Figure 13 and Example 6. In a prefered embodiment this method may be used to form 12-, 14-and 16-membered macrolactones.

Palladium Catalyst In preferred embodiments, the transition metal catalyst complex is provided in the reaction mixture in a catalytic amount. In certain embodiments, that amount is in the range of 0.0001 to 30 mol%, and preferably 0.05 to 20 mol%, and most preferably 5-15 mol%, with respect to the limiting reagent, which may be the alkene oxidation substrate, depending upon which reagent is in stoichiometric excess.

The reaction can be catalyzed by a palladium catalyst in which the palladium may be provided in the form of, for illustrative purposes only, Pd/C, PdCl2, Pd (OAc) 2, Pd (02CCF3) 2, (CH3CN) 2PdCl2, Pd [P (C6H5) 3] 4, and polymer supported Pd (0). In the instance where the molecular formula of the catalyst complex includes more than one metal, the amount of the catalyst complex used in the reaction may be adjusted accordingly.

By way of example, Pd2 (dba) 3 has two metal centers; and thus the molar amount of Pd2 (dba) 3 used in the reaction may be halved without sacrificing catalytic activity. Suitable soluble palladium complexes include, but are not limited to, tris (dibenzylideneacetone) dipalladium [Pd2 (dba) 3], bis (dibenzylideneacetone) palladium [Pd (dba) 2] and palladium acetate.

The catalyst can be provided in the reaction mixture as metal-ligand complex comprising a bound supporting ligand, that is, a metal-supporting ligand complex. The ligand, if chiral can be provided as a racemic mixture or a purified stereoisomer. The ligand may be a cheating ligand, such as by way of example only, alkyl and aryl derivatives of sulfoxides, phosphines, bisphosphines, amines, diamines, imines, arsines, and hybrids thereof, including hybrids of phosphines with amines. Weakly or non- nucleophilic stabilizing ions are preferred to avoid undesired side reactions involving the counter ion. The catalyst complex may include additional ligands as required to obtain a

stable complex. Moreover, the ligand can be added to the reaction mixture in the form of a metal complex, or added as a separate reagent relative to the addition of the metal.

The supporting ligand may be added to the reaction solution as a separate compound or it may be complexed to the metal center to form a metal-supporting ligand complex prior to its introduction into the reaction solution. Supporting ligands are compounds added to the reaction solution which are capable of binding to the catalytic metal center. In some preferred embodiments, the supporting ligand is a chelating ligand. In addition, the ligand may be a mixture of enantiomers, a single enantiomer, or meso. Examples of ligands that are potentially useful in the present invention are described in Khiar, N. et al. J. Org. Chem.

2002, 67, 345; Pettinari, C. et al. Organometallics 1999, 18, 555; and Evans, D. R. et al.

Organometallics 2002, 21, 893. Although not bound by any theory of operation, it is hypothesized that the supporting ligands suppress unwanted side reactions as well as enhance the rate and efficiency of the desired processes. Additionally, they typically prevent precipitation of the catalytic transition metal. In certain instances, the ligand may be chiral.

Reaction Conditions The reactions of the present invention may be performed under a wide range of conditions, though it will be understood that the solvents and temperature ranges recited herein are not limitative and only correspond to a preferred mode of the process of the invention.

In general, it will be desirable that reactions are run using mild conditions which will not adversely affect the reactants, the catalyst, or the product. For example, the reaction temperature influences the speed of the reaction, as well as the stability of the reactants and catalyst. The reactions will usually be run at temperatures in the range of 0°C to 300°C, more preferably in the range 10°C to 150°C, and even more preferably in the range 25°C to 60°C. The oxidant should optimally have a standard reduction potential in the range of about 0.1 V to about 1.7 V. In certain instances, the oxidant may preferrably have a standard reduction potential in the range of about 0.3 V to about 1.3 V. The allylic oxidation of the present invention has been shown to work in the presence of MnO2 which has a standard reduction potential of 1.23 V. (MnO2 (s) + 4H+ + 2e--> Mn2+ + 2H20, E°= +1.23 V; See Skoog, D. A.; Holler, F. J.; Neiman, T. A.; Principles of Instrumental Analysis,

5th Ed.; Saunders College Publishing: Philadelphia, 1998.) The reaction of the invention works well using benzoquinone as the oxidant (E° = 0.7 V). Hence, in a more preferred embodiment, the oxidant has a standard reduction potential in the range of about 0.6 V to about 0. 8 V.

In general, the subject reactions are carried out in a liquid reaction medium. The reactions may be run without addition of solvent. Alternatively, the reactions may be run in an inert solvent, preferably one in which the reaction ingredients, including the catalyst, are substantially soluble. Suitable solvents include ethers such as diethyl ether, 1,2- dimethoxyethane, diglyme, t-butyl methyl ether, tetrahydrofuran, dioxane and the like; halogenated solvents such as chloroform, dichloromethane, dichloroethane, chlorobenzene, and the like; aliphatic or aromatic hydrocarbon solvents such as benzene, xylene, toluene, hexane, pentane and the like; esters and ketones such as ethyl acetate, acetone, and 2- butanone; polar aprotic solvents such as acetonitrile, dimethylformamide and the like; polar protic solvents such as acetic acid and the like; or combinations of two or more solvents.

The invention also contemplates reaction in a biphasic mixture of solvents, in an emulsion or suspension, or reaction in a lipid vesicle or bilayer. In certain embodiments, it may be preferred to perform the catalyzed reactions in the solid phase with one of the reactants anchored to a solid support.

The reaction processes of the present invention can be conducted in continuous, semi-continuous or batch fashion and may involve a liquid recycle operation as desired.

The processes of this invention are preferably conducted in batch fashion. Likewise, the manner or order of addition of the reaction ingredients, catalyst and solvent are also not generally critical to the success of the reaction, and may be accomplished in any conventional fashion.

The reaction can be conducted in a single reaction zone or in a plurality of reaction zones, in series or in parallel or it may be conducted batchwise or continuously in an elongated tubular zone or series of such zones. The materials of construction employed should be inert to the starting materials during the reaction and the fabrication of the equipment should be able to withstand the reaction temperatures and pressures. Means to introduce and/or adjust the quantity of starting materials or ingredients introduced batchwise or continuously into the reaction zone during the course of the reaction can be conveniently utilized in the processes especially to maintain the desired molar ratio of the

starting materials. The reaction steps may be effected by the incremental addition of one of the starting materials to the other. Also, the reaction steps can be combined by the joint addition of the starting materials to the metal catalyst. When complete conversion is not desired or not obtainable, the starting materials can be separated from the product and then recycled back into the reaction zone.

The processes may be conducted in either glass lined, stainless steel or similar type reaction equipment. The reaction zone may be fitted with one or more internal and/or external heat exchanger (s) in order to control undue temperature fluctuations, or to prevent any possible"runaway"reaction temperatures. Furthermore, one or more of the reactants can be immobilized or incorporated into a polymer or other insoluble matrix.

Definitioras For convenience, certain terms employed in the specification, examples, and appended claims are collected here.

The term"heteroatom"is art-recognized and refers to an atom of any element other than carbon or hydrogen. Illustrative heteroatoms include boron, nitrogen, oxygen, phosphorus, sulfur and selenium.

The term"alkyl"is art-recognized, and includes saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In certain embodiments, a straight chain or branched chain alkyl has about 30 or fewer carbon atoms in its backbone (e. g., Cl-C30 for straight chain, C3-C30 for branched chain), and alternatively, about 20 or fewer. Likewise, cycloalkyls have from about 3 to about 10 carbon atoms in their ring structure, and alternatively about 5,6 or 7 carbons in the ring structure.

Unless the number of carbons is otherwise specified,"lower alkyl"refers to an alkyl group, as defined above, but having from one to about ten carbons, alternatively from one to about six carbon atoms in its backbone structure. Likewise,"lower alkenyl"and"lower alkynyl"have similar chain lengths.

The term"aralkyl"is art-recognized and refers to an alkyl group substituted with an aryl group (e. g. , an aromatic or heteroaromatic group).

The terms"alkenyl"and"alkynyl"are art-recognized and refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

The terms"allyl"and"allylic"refer to the position on a carbon-carbon double- bond-containing organic compound that is located adjacent to the carbon-carbon double bond. For example, C 1 is the allylic position on the partial structure shown below. In addition, the R-group attached to Cl would be refered to as an allylic group. In instances where R = H, the hydrogen atom at Cl would be referred to as an allylic hydrogen atom.

Analogous substitutions can be made to alkenyl and alkynyl groups to produce, for example, aminoalkenyls, aminoalkynyls, amidoalkenyls, amidoalkynyls, iminoalkenyls, iminoalkynyls, thioalkenyls, thioalkynyls, carbonyl-substituted alkenyls or alkynyls.

The term"aryl"is art-recognized and refers to 5-, 6-and 7-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, naphthalene, anthracene, pyrene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. Those aryl groups having heteroatoms in the ring structure may also be referred to as"aryl heterocycles"or"heteroaromatics. "The aromatic ring may be substituted at one or more ring positions with such substituents as described above, for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties,- CF3,-CN, or the like. The term"aryl"also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are"fused rings") wherein at least one of the rings is aromatic, e. g. , the other cyclic rings may be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls.

The terms ortho, meta and para are art-recognized and refer to 1,2-, 1, 3- and 1,4- disubstituted benzenes, respectively. For example, the names 1,2-dimethylbenzene and ortho-dimethylbenzene are synonymous.

The terms"heterocyclyl", "heteroaryl", or"heterocyclic group"are art-recognized and refer to 3-to about 10-membered ring structures, alternatively 3-to about 7-membered rings, whose ring structures include one to four heteroatoms. Heterocycles may also be polycycles. Heterocyclyl groups include, for example, thiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxanthene, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine, piperazine, morpholine, lactones, lactams such as azetidinones and pyrrolidinones, sultams, sultones, and the like.

The heterocyclic ring may be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety,-CF3,-CN, or the like.

The terms"polycyclyl"or"polycyclic group"are art-recognized and refer to two or more rings (e. g. , cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) in which two or more carbons are common to two adjoining rings, e. g. , the rings are"fused rings". Rings that are joined through non-adjacent atoms are termed"bridged"rings. Each of the rings of the polycycle may be substituted with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety,-CF3,-CN, or the like.

The term"carbocycle"is art-recognized and refers to an aromatic or non-aromatic ring in which each atom of the ring is carbon.

The term"nitro"is art-recognized and refers to-NO2 ; the term"halogen"is art- recognized and refers to-F,-Cl,-Br or-I ; the term"sulfhydryl"is art-recognized and refers to-SH; the term"hydroxyl"means-OH; and the term"sulfonyl"is art-recognized and refers to-SO2."Halide"designates the corresponding anion of the halogens, and "pseudohalide"has the definition set forth on 560 of"Advanced Inorganic Chemistry"by Cotton and Wilkinson.

The terms"amine"and"amino."are art-recognized and refer to both unsubstituted and substituted amines, e. g. , a moiety that may be represented by the general formulas:

wherein R50, R51 and R52 each independently represent a hydrogen, an alkyl, an alkenyl,- (CH2) m-R61, or R50 and R51, taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure ; R61 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and m is zero or an integer in the range of 1 to 8. In other embodiments, R50 and R51 (and optionally R52) each independently represent a hydrogen, an alkyl, an alkenyl, or-(CH2) m-R61. Thus, the term "alkylamine"includes an amine group, as defined above, having a substituted or unsubstituted alkyl attached thereto, i. e. , at least one of R50 and R51 is an alkyl group.

The term"acylamino"is art-recognized and refers'to a moiety that may be represented by the general formula: wherein R50 is as defined above, and R54 represents a hydrogen, an alkyl, an alkenyl or- (CH2) m-R61, where m and R61 are as defined above.

The term"amido"is art recognized as an amino-substituted carbonyl and includes a moiety that may be represented by the general formula: wherein R50 and R51 are as defined above. Certain embodiments of the amide in the present invention will not include imides which may be unstable.

The term"alkylthio"refers to an alkyl group, as defined above, having a sulfur radical attached thereto. In certain embodiments, the"alkylthio"moiety is represented by one of-S-alkyl,-S-alkenyl,-S-alkynyl, and-S- (CH2) m-R61, wherein m and R61 are defined above. Representative alkylthio groups include methylthio, ethyl thio, and the like.

The term"carboxyl"is art recognized and includes such moieties as may be represented by the general formulas: wherein X50 is a bond or represents an oxygen or a sulfur, and R55 and R56 represents a hydrogen, an alkyl, an alkenyl,- (CH2) m-R61or a pharmaceutically acceptable salt, R56 represents a hydrogen, an alkyl, an alkenyl or- (CH2) m-R61, where m and R61 are defined above. Where X50 is an oxygen and R55 or R56 is not hydrogen, the formula represents an "ester". Where X50 is an oxygen, and R55 is as defined above, the moiety is referred to herein as a carboxyl group, and particularly when R55 is a hydrogen, the formula represents a"carboxylic acid". Where X50 is an oxygen, and R56 is hydrogen, the formula represents a"formate". In general, where the oxygen atom of the above formula is replaced by sulfur, the formula represents a"thiolcarbonyl"group. Where X50 is a sulfur and R55 or R56 is not hydrogen, the formula represents a"thiolester."Where X50 is a sulfur and R55 is <BR> <BR> <BR> <BR> hydrogen, the formula represents a"thiolcarboxylic acid. "Where X50 is a sulfur and R56 is hydrogen, the formula represents a"thiolformate."On the other hand, where X50 is a bond, and R55 is not hydrogen, the above formula represents a"ketone"group. Where X50 is a bond, and R55 is hydrogen, the above formula represents an"aldehyde"group.

The term"carbamoyl"refers to-O (C=O) NRR', where R and R'are independently H, aliphatic groups, aryl groups or heteroaryl groups.

The term"oxo"refers to a carbonyl oxygen (=O).

The terms"oxime"and"oxime ether"are art-recognized and refer to moieties that may be represented by the general formula :

wherein R75 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or-(CH2) m-R61.

The moiety is an"oxime"when R is H; and it is an"oxime ether"when R is alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or- (CH2) m-R61.

The terms"alkoxyl"or"alkoxy"are art-recognized and refer to an alkyl group, as defined above, having an oxygen radical attached thereto. Representative alkoxyl groups include methoxy, ethoxy, propyloxy, tert-butoxy and the like. An"ether"is two hydrocarbons covalently linked by an oxygen. Accordingly, the substituent of an alkyl that renders that alkyl an ether is or resembles an alkoxyl, such as may be represented by one of - O-alkyl,-O-alkenyl,-O-alkynyl,,-O- (CH2) m-R61, where m and R61 are described above.

The term"sulfonate"is art recognized and refers to a moiety that may be represented by the general formula:

in which R57 is an electron pair, hydrogen, alkyl, cycloalkyl, or aryl.

The term"sulfate"is art recognized and includes a moiety that may be represented by the general formula :

in which R57 is as defined above.

The term"sulfonamido"is art recognized and includes a moiety that may be represented by the general formula : in which R50 and R56 are as defined above.

The term"sulfamoyl"is art-recognized and refers to a moiety that may be represented by the general formula:

in which R50 and R51 are as defined above.

The term"sulfonyl"is art-recognized and refers to a moiety that may be represented by the general formula: in which R58 is one of the following: hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl.

The term"sulfoxido"is art-recognized and refers to a moiety that may be represented by the general formula: in which R58 is defined above.

The term"phosphoryl"is art-recognized and may in general be represented by the formula: wherein Q50 represents S or O, and R59 represents hydrogen, a lower alkyl or an aryl.

When used to substitute, e. g. , an alkyl, the phosphoryl group of the phosphorylalkyl may be represented by the general formulas:

wherein Q50 and R59, each independently, are defined above, and Q51 represents O, S or N. When Q50 is S, the phosphoryl moiety is a"phosphorothioate".

The term"phosphoramidite"is art-recognized and may be represented in the general formulas : wherein Q51, R50, R51 and R59 are as defined above.

The term"phosphonamidite"is art-recognized and may be represented in the general formulas : wherein Q51, R50, R51 and R59 are as defined above, and R60 represents a lower alkyl or an aryl.

Analogous substitutions may be made to alkenyl and alkynyl groups to produce, for example, aminoalkenyls, aminoalkynyls, amidoalkenyls, amidoalkynyls, iminoalkenyls, iminoalkynyls, thioalkenyls, thioalkynyls, carbonyl-substituted alkenyls or alkynyls.

The definition of each expression, e. g., alkyl, m, n, and the like, when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.

The term"selenoalkyl"is art-recognized and refers to an alkyl group having a substituted seleno group attached thereto. Exemplary"selenoethers"which may be substituted on the alkyl are selected from one of-Se-alkyl,-Se-alkenyl,-Se-alkynyl, and- Se-(CH2) m-R61, m and R61 being defined above.

The terms triflyl, tosyl, mesyl, and nonaflyl are art-recognized and refer to trifluoromethanesulfonyl, p-toluenesulfonyl, methanesulfonyl, and nonafluorobutanesulfonyl groups, respectively. The terms triflate, tosylate, mesylate, and nonaflate are art-recognized and refer to trifluoromethanesulfonate ester, p-toluenesulfonate ester, methanesulfonate ester, and nonafluorobutanesulfonate ester functional groups and molecules that contain said groups, respectively.

The abbreviations Me, Et, Ph, Tf, Nf, Ts, and Ms represent methyl, ethyl, phenyl, trifluoromethanesulfonyl, nonafluorobutanesulfonyl, p-toluenesulfonyl and methanesulfonyl, respectively. A more comprehensive list of the abbreviations utilized by organic chemists of ordinary skill in the art appears in the first issue of each volume of the Journal of Organic Chemistry ; this list is typically presented in a table entitled Standard List of Abbreviations.

Certain compounds contained in compositions of the present invention may exist in particular geometric or stereoisomeric forms. In addition, polymers of the present invention may also be optically active. The present invention contemplates all such compounds, including cis-and trans-isomers, R-and S-enantiomers, diastereomers, (D) -isomers, (L)- isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention. Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group. All such isomers, as well as mixtures thereof, are intended to be included in this invention.

If, for instance, a particular enantiomer of compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral

auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.

It will be understood that"substitution"or"substituted with"includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e. g. , which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction.

The term"substituted"is also contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described herein above. The permissible substituents may be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This invention is not intended to be limited in any manner by the permissible substituents of organic compounds.

The phrase"protecting group"as used herein means temporary substituents which protect a potentially reactive functional group from undesired chemical transformations.

Examples of such protecting groups include esters of carboxylic acids, silyl ethers of alcohols, and acetals and ketals of aldehydes and ketones, respectively. The field of protecting group chemistry has been reviewed (Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Syratlzesis, 2nd ed.; Wiley: New York, 1991). Protected forms of the inventive compounds are included within the scope of this invention.

Contemplated equivalents of the compounds described above include compounds which otherwise correspond thereto, and which have the same general properties thereof (e. g., functioning as ligands or catalysts), wherein one or more simple variations of

substituents are made which do not adversely affect the efficacy of the compound. In general, the compounds of the present invention may be prepared by the methods illustrated in the general reaction schemes as, for example, described below, or by modifications thereof, using readily available starting materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variants which are in themselves known, but are not mentioned here.

For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover.

Methods of the Invention One aspect of the present invention relates to a method of preparing an allylic carboxylate, comprising the step of : contacting a compound comprising an allylic hydrogen atom with a carboxylic acid in the presence of a Group 10 transition metal, a sulfoxide compound, and an oxidant that has a reduction potential in the range of about 0.1 V to about 1.7 V; wherein the stereochemical configuration at any stereocenter of said sulfoxide compound is R, S, or a mixture of these configurations.

In certain embodiments, the present invention relates to the aforementioned method, wherein said Group 10 transition metal is palladium.

In certain embodiments, the present invention relates to the aforementioned method, wherein said Group 10 transition metal is PdCl2, Pd (OAc) 2, Pd (O2CCF3) 2, (CH3CN) 2PdC12, (CH3CN) 2PdCl2/Ag (OTf) 2, (CH3CN) 2PdCl2/Ag (SbF6), Pd [P (C6Hs) 3] 4, Pd2 (dba) 3, or polymer supported Pd (0).

In certain embodiments, the present invention relates to the aforementioned method, wherein said Group 10 transition metal is Pd (OAc) 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said Group 10 transition metal is Pd (OAc) 2, and said Pd (OAc) 2 is present in 5-15 mol%.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant that has reduction potential in the range of about 0.3 V to about 1.3 V.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant that has reduction potential in the range of about 0.6 V to about 0. 8 V.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is selected from the group consisting of benzoquinone, benzoquinone/MnO2, benzoquinone/Cu (OAc) 2/O2, Cu (OAc) 2, Cu (OAc) 2/O2, and 02.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is benzoquinone, benzoquinone/MnO2, or benzoquinone/Cu (OAc) 2/02.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is benzoquinone.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R8 represents independently for each occurrence alkyl,-C (R6) 3, alkenyl, alkynyl, aryl, or aralkyl ; R7 represents independently for each occurrence H or alkyl ; R6 represents independently for each occurrence H, alkyl, alkenyl, alkynyl, aryl, or aralkyl ; and m is 2,3, 4,5, or 6.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R6 represents independently for each occurrence H, alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R6 represents independently for each occurrence H or alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is dimethylsulfoxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R3 is alkyl,-C (R6) 3, alkenyl, alkynyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R8 is aryl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R8 is phenyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R represents independently for each occurrence H or alkyl ; Rg represents independently for each occurrence alkyl, aryl, or aralkyl ; and m is 2,3, 4,5, or 6.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R7 represents independently for each occurrence H; R8 represents independently for each occurrence aralkyl ; and m is 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sulfoxide compound is wherein R7 represents independently for each occurrence H; R8 represents independently for each occurrence benzyl; and m is 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2, said sulfoxide compound is dimethylsulfoxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2, said sulfoxide compound is wherein R3 is phenyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2, said sulfoxide compound is wherein R7 represents independently for each occurrence H; W represents independently for each occurrence benzyl; and m is 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said carboxylic acid has the formula R9C02H, wherein R9 is alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said carboxylic acid has the formula R9CO2H, wherein R9 is alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said carboxylic acid has the formula R9CO2H, wherein R9 is methyl, ethyl, propyl, butyl, pentyl, or hexyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1:

1 wherein Rl represents H, hydroxyl, amino, halide, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, aralklyamino, nitro, sulfhydryl, alkylthio, acylthio, carboxamide, carboxyl, phosphate, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, alkylsulfonyloxy, arylsulfonyloxy,-C (O) alkyl, -C (O) H,-C02R5,-C (O) N (R5) 2,- OC (O) N (Rs) 2, or-CN; R represents H, hydroxyl, amino, halide, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, aralklyamino, nitro, sulfhydryl, alkylthio, acylthio, carboxamide, carboxyl, phosphate, silyl, thioalkyl, alkylsulfonyl,

arylsulfonyl, alkylsulfonyloxy, arylsulfonyloxy,-C (O) alkyl,-C (O) H,-C02R5,-C (O) N (R5) 2, -OC (O) N (Rs) 2, or-CN; or any two geminal occurrences of R2 taken together form a carbon-oxygen double bond; or two occurrences of R2 are joined by a covalent bond; R3 represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; R4 represents independently for each occurrence alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; R represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; and n is 0 to 15.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and RI represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, -C (O) alkyl,-C02R5,-C (O) N (Rs) 2, or-OC (O) N (Rs) 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-C02R5,-C (O) N (Rs) 2, or-OC (O) N (Rs) 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R2 represents independently for each occurrence represents H, alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and represents independently for each occurrence represents H or alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and represents independently for each occurrence H or alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and represents independently for each occurrence alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and represents independently for each occurrence alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R4 represents independently for each occurrence methyl, ethyl, propyl, or butyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R4 represents independently for each occurrence methyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and n is 1, 2,3, 4,5, 6,7, 8,9, or 10.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R' represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-C02R5,-C (O) N (Rs) 2, or-OC (O) N (Rs) 2; R represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl; represents independently for each occurrence alkyl; and n is 1,2, 3,4, 5,6, or 7.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2Rs,-C (O) N (Rs) 2, or-OC (O) N (Rs) 2; W represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl; R4 represents independently for each occurrence alkyl; n is 1,2, 3,4, 5,6, or 7; said oxidant has a standard reduction potential in the range of about 0.6 V to 0.8 V; and said Group 10 transition metal is palladium.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2Rs,-C (O) N (R5) 2, or-OC (O) N (Rs) 2 ; R2 represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl ; n is 1,2, 3,4, 5,6, or 7; said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2; and said sulfoxide compound is dimethylsulfoxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2RS,-C (O) N (Rs) 2, or-OC (O) N (Rs) 2 ; W represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl ; n is 1, 2,3, 4,5, 6, or 7; said oxidant is benzoquinone ; said Group 10 transition metal is Pd (OAc) 2 ; said sulfoxide compound is dimethylsulfoxide; and said carboxylic acid is acetic acid.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R' represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2Rs,-C (O) N (Rs) 2, or-OC (O) N (R5) 2 ; R represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl ; n is 1,2, 3,4, 5,6, or 7; said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2, and said sulfoxide compound is phenyl vinyl sulfoxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein said compound comprising an allylic hydrogen atom has the formula 1, and R' represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-C02R5,-C (O) N (R5) 2, or-OC (O) N (Rs) 2; R represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ;

R4 represents independently for each occurrence alkyl ; n is 1,2, 3,4, 5,6, or 7; said oxidant is benzoquinone, said Group 10 transition metal is Pd (OAc) 2, said sulfoxide compound is phenyl vinyl sulfoxide ; and said carboxylic acid is acetic acid In certain embodiments, the present invention relates to the aforementioned method, wherein said method further comprises the step of adding 4 A molecular sieves.

In certain embodiments, the present invention relates to the aforementioned method, wherein the reaction temperature is about 10 to about 100 °C.

In certain embodiments, the present invention relates to the aforementioned method, wherein the reaction temperature is about 25 to about 60 °C.

In certain embodiments, the present invention relates to the aforementioned method, wherein said allylic carboxylate is prepared in greater than about 40% yield.

In certain embodiments, the present invention relates to the aforementioned method, wherein said allylic carboxylate is prepared in greater than about 60% yield.

In certain embodiments, the present invention relates to the aforementioned method, wherein said allylic carboxylate has the formula 2 or 3: 2 3 wherein Rl represents H, hydroxyl, amino, halide, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, aralklyamino, nitro, sulfhydryl, alkylthio, acylthio, carboxamide, carboxyl, phosphate, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, alkylsulfonyloxy, arylsulfonyloxy,-C (O) alkyl, -C (O) H,-CO2Rs,-C (O) N (R5) 2, - OC (O) N (Rs) 2, or-CN; R2 represents independently for each occurrence H, hydroxyl, amino, halide, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, aralklyamino, nitro, sulfhydryl, alkylthio, acylthio, carboxamide, carboxyl, phosphate, silyl, tliioalkyl, alkylsulfonyl, arylsulfonyl, alkylsulfonyloxy, arylsulfonyloxy,-C (O) alkyl, - C (O) H,-C02R5,-C (O) N (R5) 2,-OC (O) N (R5) 2, or-CN; or any two geminal occurrences of R taken together form a carbon-oxygen double bond; or two occurrences of R2 are joined

by a covalent bond; R3 represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; R4 represents independently for each occurrence alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl ; R9 is alkyl, aryl, or aralkyl ; and n is 0 to 15.

In certain embodiments, the present invention relates to the aforementioned method, wherein Rl represents independently for each occurrence H, alkyl, cycloalkyl, heteroalkyl, aryl, aralkyl, heteroaryl, alkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, alkylamino, arylamino, acylamino, -C (O) alkyl,-C02R5,-C (O) N (R5) 2, or-OC (O) N (Rs) 2.

In certain embodiments, the present invention relates to the aforementioned method, wherein R represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2Rs,-C (O) N (R5) 2, or- OC (O) N (R5) 2- In certain embodiments, the present invention relates to the aforementioned method, wherein W represents independently for each occurrence represents H, alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein W represents independently for each occurrence represents H or alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R3 represents independently for each occurrence H or alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R4 represents independently for each occurrence alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R4 represents independently for each occurrence alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R4 represents independently for each occurrence methyl, ethyl, propyl, or butyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R4 represents independently for each occurrence methyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R9 is alkyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein R9 is methyl, ethyl, propyl, butyl, pentyl, or hexyl.

In certain embodiments, the present invention relates to the aforementioned method, wherein n is 1,2, 3,4, 5,6, 7,8, 9, or 10.

In certain embodiments, the present invention relates to the aforementioned method, wherein Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-C02RS,-C (O) N (Rs) 2, or- OC (O) N (Rs) 2; R2 represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl; R9 is alkyl ; and n is 1,2, 3,4, 5,6, or 7.

In certain embodiments, the present invention relates to the aforementioned method, wherein Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-C02R5,-C (O) N (Rs) 2, or- OC (O) N (Rs) 2 ; R represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl; R ? is alkyl; n is 1,2, 3,4, 5,6, or 7; said oxidant has a standard reduction potential in the range of about 0.6 V to 0.8 V, and said Group 10 transition metal is palladium.

In certain embodiments, the present invention relates to the aforementioned method, wherein Rl represents independently for each occurrence alkyl, cycloalkyl, arylalkoxyl, aryloxy, arylalkyloxyl, acyloxy, silyloxy, acylamino,-CO2Rs,-C (O) N (R5) 2, or- OC (O) N (Rs) 2 ; R2 represents independently for each occurrence represents H, alkyl, cycloalkyl, heteroalkyl, aryl, or aralkyl ; R3 represents independently for each occurrence H, alkyl, aryl, or aralkyl ; R4 represents independently for each occurrence alkyl; R9 is methyl; n is 1, 2,3, 4,5, 6, or 7; said oxidant is benzoquinone; said Group 10 transition metal is Pd (OAc) 2; and said sulfoxide compound is dimethylsulfoxide or phenyl vinyl sulfoxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein an allylic carboxylate of formula 2 and an allylic carboxylate of formula 3 are prepared.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 2 to the allylic carboxylate of formula 3 is greater than about 99: 1.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 2 to the allylic carboxylate of formula 3 is greater than about 95: 5.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 2 to the allylic carboxylate of formula 3 is greater than about 90: 10.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 2 to the allylic carboxylate of formula 3 is greater than about 80 : 20.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 2 to the allylic carboxylate of formula 3 is greater than about 70: 30.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 3 to the allylic carboxylate of formula 2 is greater than about 99: 1.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 3 to the allylic carboxylate of formula 2 is greater than about 95: 5.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 3 to the allylic carboxylate of formula 2 is greater than about 90: 10.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 3 to the allylic carboxylate of formula 2 is greater than about 80: 20.

In certain embodiments, the present invention relates to the aforementioned method, wherein the ratio of the allylic carboxylate of formula 3 to the allylic carboxylate of formula 2 is greater than about 70: 30.

Compounds of the Invention One aspect of the present invention relates to the compound of formula 4:

wherein M is a Group 10 transition metal; Rl represents independently for each occurrence H, alkyl, aryl, heteroaryl, or aralkyl ; R represents independently for each occurrence alkyl, aryl, heteroaryl, or aralkyl ; n is 2,3, 4,5, or 6; and the stereochemical configuration at any stereocenter of a compound represented by 2 is R, S, or a mixture of these configurations.

In certain embodiments, the present invention relates to the aforementioned compound, wherein R'represents independently for each occurrence H or alkyl.

In certain embodiments, the present invention relates to the aforementioned compound, wherein R2 represents independently for each occurrence alkyl, aryl, or aralkyl.

In certain embodiments, the present invention relates to the aforementioned compound, wherein n is 2 or 3.

In certain embodiments, the present invention relates to the aforementioned compound, wherein Rl represents independently for each occurrence H; R represents independently for each occurrence aralkyl ; and n is 2.

In certain embodiments, the present invention relates to the aforementioned compound, wherein RI represents independently for each occurrence H; R8 represents independently for each occurrence benzyl; and n is 2.

In certain embodiments, the present invention relates to the aforementioned compound, wherein M is palladium.

In certain embodiments, the present invention relates to the aforementioned compound, wherein M is PdCl2, Pd (OAc) 2, Pd (02CCF3) 2, (CHsCPdCb, (CH3CN) 2PdCl2/Ag (OTf) 2, (CH3CN) 2PdCl2/Ag (SbF6), Pd [P (C6Hs) 3] 4, Pd2 (dba) 3, or polymer supported Pd (0).

In certain embodiments, the present invention relates to the aforementioned compound, wherein M is PdCl2, Pd (OAc) 2, or Pd (O2CCF3) 2.

In certain embodiments, the present invention relates to the aforementioned compound, wherein M is Pd (OAc) 2.

In certain embodiments, the present invention relates to the aforementioned compound, wherein Rl represents independently for each occurrence H; W represents independently for each occurrence benzyl; n is 2; and M is Pd (OAc) 2.

Exemplification The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention.

Example 1 General Information: Unless stated otherwise, reactions were conducted with stirring in 2 mL (0.2 mmol reactions) or 40 mL (1.0 mmol reactions) VWRbrand borosilicate glass vials with red PTFE-faced silicone lined plastic screw caps or teflon-lined solid caps (respectively) under an air atmosphere. Vials were used as received (no cleansing or drying was done prior to reaction). All commercially obtained reagents (Sigma-Aldrich Chemical Company, unless stated otherwise) were used as received: anhydrous (Sure/Seal) DMSO; 4A (powered, <5 micron) activated molecular sieves; 1,4-benzoquinone ; glacial acetic acid (Mallinckrodt Chemicals); Pd (OAc) 2 (Strem Chemicals); Pd (O2CCF3) 2 (Strem Chemicals).

Both palladium sources were stored in a glove box under a nitrogen atmosphere. Pd (OAc) 2 was weighed in the air whereas Pd (O2CCF3) 2 [Pd (TFA) 2] was weighed in the glove box.

Solvents tetrahydrofuran (THF), diethyl ether (Et20), ethylene glycol dimethyl ether (DME), methylene chloride (CH2Cl2), toluene, benzene were purified prior to use by passage through a bed of activated alumina (Glass Contour, Laguna Beach, California).

Acetonitrile (CH3CN) was distilled from CaH2. Gas chromatographic (GC) analyses were performed on Agilent Technologies 6890N Series instrument equipped with FID detectors using a HP-5 (5%-Phenyl) -methylpolysiloxane column (30 m, 0.32 mm, 0.25 llm). GC yields reported relative to an internal standard (nitrobenzene) and corrected for response factor variations. Unless otherwise noted, linear to branched allylic acetate ratios [L: B]

were determined by GC analysis of the crude and were not corrected for small response factor variations. Retention times for the branched isomers were determined by independent synthesis using catalyst 1 (see general procedure for catalyst 1, equations 2 and 3) which gave the branched as the major products for substrates constituting entries 3-9 in Table 1 or as mixtures for entry 1 and 10 ( [L : B] = 4: 1, [L: B] = 2: 1, respectively). Thin- layer chromatography (TLC) was conducted with E. Merck silica gel 60 F254 precoated plates (0.25 mm) and visualized with W and potassium permanganate staining. Reaction progression was monitored by both GC and TLC analysis. Flash column chromatography was performed as described by Still et al. using EM reagent silica gel 60 (230-400 mesh).

Still, W. C.; Kahn, M.; Mitra, A. J. Org Chem. 1978, 43, 2923. lu NMR spectra were recorded on a Varian Mercury-400 (400 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 7.26 ppm). Data reported as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, app = apparent; coupling constant (s) in Hz; integration. Ratios of E to Z isomers were determined by 1H NMR analysis of the crude upon workup and are based on integration of the allylic hydrogens of the acetoxy-bearing carbon of the two isomers. Assignments of all isomers were confirmed by gCOSY experiments. Proton-decoupled 13C NMR spectra were recorded on a Varian Mercury-400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 77.0 ppm). IR spectra were recorded as thin films on NaCl plates on a Matterson FTIR 3000 and are reported in frequency of absorption (cm-1). High resolution mass spectra were obtained at the Harvard University Mass Spectrometry Laboratory.

Elemental analysis was conducted at Desert Analytics, Tucson, Arizona.

Synthesis of Catalyst 1: A t. NaOEt (2 eq), 1. NaOEt (2 eq), O O Ph pd (OAc) 2 (1 eq) ph o o ph HS SH 0. s s-LL , S S---.- 2. benzyl bromide AcOH CHZCIZ, 40°C g2 eq), 97% Pd (OA) 2 benzene su/ 1, 2-bis (benzylthio) ethane (See Lucas, R. C.; Liu, S.; Newlands, M. J.; Gabe, E. Can. J.

Clzem. 1990, 68, 1357): A flame-dried 500 mL round bottom flask was charged

sequentially with a stir bar, NaOEt (2.94 g, 43.2 mmol), and EtOH (105 mL) under a N2 atmosphere. 1,2-ethanedithiol (1.8 mL, 21.4 mmol) was added dropwise via syringe to the NaOEt solution and the mixture was allowed to stir for 20 min. A solution of benzyl bromide (5 mL, 42.0 mmol) in benzene (63 mL) was added dropwise via cannula. The reaction was allowed to stir overnight. Solvents were removed under house vacuum (-25 torr) with mild heating (40°C). The residue was diluted with CHC13 (400 mL) and washed with brine (150 mL). The brine was extracted three times with CHC13 (3 x 150 mL). The organic layers were combined, dried over MgS04, filtered and concentrated in vacuo to give a yellow oil. The yellow oil was suspended in EtOH (40 mL) and allowed to sit at 0°C for-Ih. A white solid crashed out and was washed with EtOH until the supernatant was clear (3 x 30 mL). The solid was dried under high vacuum for 7 h to give 1,2- bis (benzylthio) ethane in 80% yield (4.7 g, 17.1 mmol). 1H NMR (400 MHz, CDC13) 8 7.28 (m, 10H), 3.69 (s, 4H), 2. 58 (s, 4H); 13C NMR (100 MHz, CDC13) 8 138.1, 128.8, 128.5, 127.0, 36.2, 30.9. HRMS (E) m/z calc'd for [Cl6Hl8S2] + : 274.0850, found 274.0842.

1, 2-bis (benzylsulfmyl) ethane (See Bell, E. V.; Bennett, G. M. J. Chem. Soc. 1928, 3189 and Gasparrini, F. ; Giovannoli, M.; Misiti, D.; Natile, G.; Palmieri, G.

Tetrahedro7z 1984, 40, 165): A 100 mL round bottom flask was charged with a stir bar, 2.5 g (9.1 mmol) of 1, 2-bis (benzylthio) ethane, and 22 mL of glacial acetic acid. The mixture was allowed to stir at room temperature until it became homogeneous at which time it was cooled to 0°C and H202 (50 wt% solution, 1.05 mL, 18.22 mmol) was added dropwise. The reaction was allowed to come to room temperature and was stirred overnight. The acetic acid was removed with mild heating (50°C) under high vacuum and the white solid was washed with EtOH until the washings were clear (3 x 40 mL). The white solid was dried under high vacuum overnight to give 2.71 g (8.84 mmol) of 1,2- bis (benzylsulfinyl) ethane in 97% yield.'H NMR (400 MHz, CDC13) 8 7.36 (m, 5H), 7.27 (m, 5H), 4.03 (app dq, J= 3.6, 13.2 Hz, 4H), 3.03 (m, 2H), 2.87 (m, 2H); 13C NMR (100 MHz, CDC13) 6 130.1, 129.1, 128.9, 128.8, 128.7, 128.69, 58.9, 58.5, 43.5, 42.7 ; IR (film, cm'') : 2959,2913, 1454,1024, 768,698 ; HRMS (EI) m/zoal'dfor [Cl6HlsO2S2] + : 306.0748, found 306. 0751.

Catalyst 1: A flame dried 250 mL flask was charged with 1.5 g (4.89 mmol) of 1,2- bis (benzylsulfinyl) ethane, 70 mL of CH2C12, and 1. 1 g (4.89 mmol) of Pd (OAc) 2. The mixture was stirred at reflux under a nitrogen atmosphere for 22h. During this time the reaction was observed to turn from a heterogeneous orange brown mixture to a homogeneous, dark red solution. The solution was concentrated in vacuo and dried over a N2 stream for 12 h to give a dark red solid that was used without further purification. IR (film, cm-1) : 3032,1736, 1555,1495, 1454,1413, 1231,1070, 1045,1030, 766,698.

MS (ESI) m/z 413 ([M- (OAc) 2 + H] +, center of isotope cluster); Anal. Calcd for [C2oH2406PdS2] (%) : C, 45.24 ; H, 4.56 ; Pd, 20.04 ; S, 12. 08. Found (%): C, 45.61 ; H, 4.53 ; Pd, 20.63 ; S, 12.81.

Example 2 General procedure for Figures 1-9: Vials (2 mL, borosilicate) were sequentially charged with the following solids: Pd (OAc) 2 (4.5 mg, 0.02 mmol, 10 mol%) or Pd (TFA) 2 (6.6 mg, 0.02 mmol, 10 mol%) or catalyst 1 (10.6 mg, 0.02 mmol, 10 mol%), benzoquinone (43.2 mg, 0.4 mmol, 2 eq), and 4A MS (43 mg). Separate vials (2 mL, borosilicate) were sequentially charged with the following liquids: 1-decene (28 mg, 38, uL, 0.2 mmol, 1 eq), nitrobenzene (9.9 mg, 8 ; j. L, 0. 08 mmol, 40 mol%), 1.2 mL AcOH or 0.6 mL DMSO/0.6 mL AcOH or 0.6 mL solvent/0.6 mL AcOH. Aliquots were taken from the liquid vials (- 50 gel filtered with Et20 through a short pipette plug of silica) to determine GC initial ratios of 1-decene to the nitrobenzene internal standard. The liquids were transferred via pipette into the appropriate solids vials, charged with a stir bar, capped and allowed to heat at 40°C with stirring. Aliquots were taken (as above) at t= 24h, t= 48h (shown) and t= 72h to determine GC yields. Each product was independently synthesized via known methods (L: Horner-Wadsworth-Emmons olefination of octyl aldehyde followed by reduction and acetylation, B : vinyl magnesium bromide alkylation of octyl aldehyde followed by acetylation, va: 2-decanone, isopropenyl acetate, p-toluenesulfonic acid See Dauben, W. G.; Wolf, R. E. J. Org Clieiii. 1970, 35, 2361, mk: Aldrich). Response factors relative to decene were determined for each product. Note: Figure 5 done on half the scale indicated above (i. e. 1-decene : 14.0 mg, 19 jjL, 0.1 mmol, etc.).

Example 3 General procedure for Figure 10: A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol, 10 mol%) or Pd (TFA) 2 (33. 2 mg, 0.1 mmol, 10 mol%), benzoquinone (217 mg, 2.0 mmol, 2 eq), and 4A MS (217 mg). In cases (entries 2,4, 5) where Pd (TFA) 2 was used, Pd (OAc) 2 gave slightly lower yields and/or [L: B] selectivities. To the solids vial was sequentially added the following : DMSO (3 mL), olefin substrate (1.0 mmol, 1 eq), AcOH (3 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C. Aliquots were taken (-50 ; nL filtered through a silica plug with Et2O) at t= 24 h, 48 h, and 72 h to determine linear: branched ratios [L: B]. For the majority of substrates examined (entries 3-9), the general trend observed was that of a slight decrease in [L: B] ratios over the course of the reaction (see below). The reaction was quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H20 (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil. A crude IH NMR was taken to determine [E : Z] ratios. Purification of the crude by flash chromatography afforded the linear E-allylic acetates as the major products with trace amounts of the linear Z-allylic acetates and the branched acetates. All data reported in Figure 10 are based on an average of 2 runs.

Terminal olefin substrates: The following terminal olefin substrates used were obtained from commercial sources: l-decene (entry 3) ; allylbenzene (entry 10); ethyl 4-pentenoate (entry 2, Lancaster Synthesis). The remainder of the substrates were prepared via previously reported literature routes: 2-allylcyclohexanone ethylene ketal (entry 1) See Brust, D. P.; Tarbell, D. S. J. Org Chem. 1966, 31, 1251; 5- (tert-butyldiphenylsiloxy)- l-pentene (entry 4) See Nemoto, H.; Shiraki, M.; Fukumoto. J. Org. Chenu. 1996, 61, 1347; 1-benzyloxy-4-pentene (entry 5) See Lowik, D. W. P. M.; Liskamp, R. M. J. Eur. J.

Org. Chez. 2000,1219 ; 2-hydroxy-benzoic acid hex-5-enyl ester (entry 6/7) See Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608 ; phenyl-carbamic acid hex-5-enyl ester (entry 8) See Breit, B.; Seiche, W. J. Am. Chem. Soc. 2003, 125, 6608; and N, N diethyl-6-heptenamide (entry 9) See Musa, O. M.; Choi, S. -Y. ; Horner, J. H.; Newcomb, M. J. Org Chem. 1998,63, 786.

Entry 1: 72 h. run 1,2 : [L: B] = >99: 1, [E : Z] = >20: 1 (branched or Z isomers were not observed by GC or'H NMR). Purification by flash chromatography (10% EtOAc/hexanes eluent) provided pure linear (E)-allylic acetate (run 1: 119 mg, 0.49 mmol, 49% yield; run 2: 120.5 mg, 0.5 mmol, 50% yield; average yield: 50%).'H NMR (400 MHz, CDC13) 8 5.80 (dd, J = 15. 6,7. 6 Hz, 1H), 5.61 (dt, J = 15. 6,6. 0 Hz, 1H), 4.52 (d, J = 6. 8 Hz, 2H), 3.90 (m, 4H), 2.31 (m, 1H), 2.05 (s, 3H), 1.78-1. 2 (m, 8H); 13C NMR (100 MHz, CDC13) 5170. 9,135. 2,125. 1,109. 9,65. 3,65. 1,64. 9, 48. 2,35. 2,30. 0,24. 3,23. 8, 21.0 ; IR (film, cm-1) : 2936, 2884, 2864,1740, 1447,1233 ; HRMS (EI) m/z calc'd for [Cl3H20041+ : 240.1362, found 240. 1369.

Entry 2: 48 h. run 1,2 : [L: B] = >20 1, [E : Z] = 13 : 1. Both ratios determined by 1H NMR.

Purification by flash chromatography (15% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 102.4 mg, 0.55 mmol, 55%; run 2: 96.8 mg, 0.52 mmol, 52%; average yield: 54%). After column : [L: B] = >20: 1; [E : Z] = 16: 1. 1H NMR (400 MHz, CDCl3) # 5.88 (dt, J= 15. 6,6. 8 Hz, 1H), 5.70 (dt, J= 15. 6, 6. 4 Hz, 1H), 4.55 (dd, J = 6. 4,1. 2 Hz, 2H), 4.14 (q, J = 7.2 Hz, 3H), 3.09 (dd, J= 6.8, 0.8 Hz, 2H), 2.06 (s, 3H), 1.26 (t, J=7. 2Hz, 3H); 13C NMR (100 MHz, CDC13) # 171. 2,170. 7,127. 8,127. 1,64. 4,60. 8,37. 6,20. 9,14. 1; IR (film, cm-1) : 2984, 2943,2911, 1740,1447, 1383,1367, 1233,1175 ; HRMS (EI) m/zzalc'dfor [CgHl404] + : 186.0892, found 186. 0898.

Entry 3: 48 h. run 1: [L: B] = 24 : 1, [E: Z] = 12: 1; run 2 : [L: B] = 24 : 1, [E: Z] = 11 : 1 ; average: [L: B] = 24 : 1, [E: Z] 12 : 1 (24 h, [L: B] = 40: 1). Purification by flash chromatography (3% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 108 mg, 0.54 mmol; 54%; run 2: 101 mg, 0.51 mmol, 51% ; average yield : 52%). After column : [L: B] = 22 : 1, [E : Z] = 13 : 1.'H NMR (400 MHz, CDC13) 8 5.77 (dt, J= 15. 2,6. 8 Hz, 1H), 5. 56 (dt, J = 15. 6,6. 8 Hz, 1H), 4. 50 (d, J= 6. 4 Hz, 2H), 2.06 (s, 3H), 1.4-1. 2 (m, 12H), 0.87 (t, J = 6.8 Hz, 3H) ; 13C NMR (100 MHz, CDC13) 8 170.9, 136.8, 123.6, 65.3, 32.2, 31. 8, 29.1, 28.8, 22.6, 21.0, 14.1 ; IR (film, cm-1) : 3021,2957, 2928,2857, 1744,1460, 1231. HRMS (EI) m/zcalc'dfor [C12H22O2]+ : 198.1620, found 198.1623.

Entry 4: 72 h. run 1: [L: B] = 33: 1, [E : Z] = 10: 1; run 2 : [L: B] = 28: 1, [E : Z] = 11 : 1; average: [L: B] = 31 : 1, [E:Z] = 11 : 1 (24h, [L: B] =71 : 1,48h, [L: B] = 43 : 1). Purification by flash chromatography (3% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 191.2 mg, 0.50 mmol, 50 %; run 2: 191.4, 0.50 mmol, 50%; average yield : 50%). After column : [L: B] = 87 : 1, [E:Z] = 12:1. 1H NMR (400 MHz, CDC13) # 7. 66 (m, 4H), 7.40 (m, 6H), 5.77 (dt, J= 14, 6.8 Hz, 1H), 5.61 (dt, J= 14,6. 4 Hz, 1H), 4.5 (d, J = 6.4 Hz, 2H), 3.7 (t, J=6. 4Hz, 2H), 2.31 (brq, J = 5.6 Hz, 2H), 2.05 (s, 3H), 1.04 (s, 9H) ; 13C NMR (100 MHz, CDCl3) # 170. 8,135. 6,133. 8, 132.8, 129.6, 127.6, 125. 8, 65.1, 63.1, 35.6, 26.8, 21.0, 19.2 ; IR (film, cm-1) : 3071, 3050,2999, 2957,2932, 2893,2859, 1742,1472, 1427,1111, 1231; HRMS (CI, NH3) m/z calc'd for C23H34NO3Si [M+NH4] + : 400. 2308, found 400.2306.

Entry 5 48h. runl : [L: B] = 31 : 1, [E:Z] = 11 : 1, run2 : [L: B] =31 : 1, [E:Z] = 10 : 1; average: [L: B] = 31 : 1, [E:Z] = 11 : 1 (24h, [L: B] = 52 : 1). Purification by flash chromatography (5% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 133.0 mg, 0.57 mmol, 57%; run 2 : 133.2 mg, 0.57 mmol, 57%; average yield : 57%). After column : [L: B] = 41 : 1; [E:Z] = 12 : 1. IHNMR (400 MHz, CDC13) 8 7.37-7. 26 (m, 5H), 5.8 (dt, J= 15. 2,6. 8Hz, 1H), 5.66 (dt, J= 15. 6, 6.4 Hz, 1H), 4.52 (d, J=4. 8 Hz, 2H), 4.51 (s, 2H), 3.52 (t, J = 6. 4 Hz, 2H), 2. 39 (brq, J=6. 4Hz, 2H), 2.06 (s, 3H); 13C NMR (100 MHz, CDCl3) # 170.8, 138. 3,132. 5, 128.4, 127.64, 127.58, 125.8, 72.9, 69.3, 65.0, 32.7, 21.0 ; IR (film, cm-1) : 3088, 3063,3030, 2936,2859, 2793,1740, 1454,1364, 1233; HRMS (CI, NH3) m/z calc'd forCl4H22NO3 [M+NH4] + : 252.1600, found 252. 1593.

Entry 6 : 72 h. run 1, 2: [L: B] = 14 : 1, [E:Z] = 11 : 1 (24h, [L: B] = 39 : 1, 48h, [L: B] = 20: 1). Purification by flash chromatography (5% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 172.0 mg, 0.62 mmol, 62%; run2 : 166. 0 mg, 0. 60 mmol, 60%; average yield : 61%). After column : [L: B] = 14 : 1, [E:Z] = 12 : 1. 1H NMR (400 MHz, CDCl3) # 10. 8 (s, 1H), 7.83 (dd, J = 8. 4,1. 6 Hz, 1H), 7.46 (ddd, J= 8.6, 7.2, 2.0 Hz, 1H), 6.98 (dd, J= 8.4, 0. 8 Hz, 1H), 6.88 (ddd, J = 8. 2,8. 0,1. 2 Hz, 1H), 5.8 (dt, J= 15. 2,6. 8Hz, 1H), 5.64 (dt, J = 15. 2,6. 4 Hz, 1H), 4.52 (dd, J = 6. 2,0. 8 Hz, 2H), 4.36 (t, J= 6.4 Hz, 2H), 2.24 (bq, J= 7. 6 Hz, 2H),

2.06 (s, 3H), 1.90 (m, 2H); 13C NMR (100 MHz, CDCl3) # 170.8, 170.1, 161.7, 135. 7, 134.4, 129.8, 125.1, 124. 9,119. 1,117. 6,112. 5,64. 9,64. 6,28. 6,27. 7,21. 0; IR (film, cm-1) : 3187,3156, 2953,1740, 1674,1615, 1485,1302, 1250. HRMS (EI) m/z calc'd for [C15H18O5] +: 278.1154, found 278. 1152.

Entry 7 : 72 h. run 1 : [L: B] =16 : 1, [E:Z] = 12 : 1 ; run 2 : [L: B] =17 : 1, [E:Z] = 13 : 1 ; average: [L: B] = 17 : 1, [E : Z] 13 : 1 (24h, [L: B] = 40 : 1,48h, [L: B] = 22 : 1). Purification by flash chromatography (15% EtOAc/hexanes eluent) provided the desired linear (E)- allylic acetate as the major product (run 1 : 160.2 mg, 0.55 mmol, 55%; run 2: 162.9 mg, 0.56 mmol, 56%; average yield: 56%). After column : [L: B] = 18 : 1, [E : Z] = 13 : 1. 1H NMR (400 MHz, CDCl3) # 7. 78 (dd, J= 8. 0,2. 0 Hz, 1H), 7.46 (ddd, J= 8. 4,7. 6,1. 6 Hz, 1H), 6.97 (m, 2H), 5.80 (dt, J= 15. 6,6. 8 Hz, 1H), 5.63 (dt, J= 15. 2,6. 4 Hz, 1H), 4.51 (dd, J= 6. 4,0. 8 Hz, 2H), 4.30 (t, J= 6. 4 Hz, 2H), 3.9 (s, 3H), 2.23 (q, J = 8. 0 Hz, 2H), 2.05 (s, 3H), 1.85 (m, 2H) ; 13C NMR (400 MHz, CDCl3) # 170. 8,166. 2, 159.1, 134.9, 133.4, 131.5, 124.7, 120.2, 120.1, 112.0, 65.0, 64.0, 55.9, 28.7, 27.9, 21.0 ; IR (film, cm-1) : 3079,3003, 2949,2841, 1736 (br), 1601,1493, 1302,1250 ; HRMS (EI) m/z calc'd for [Cl6H20Os] + : 292.1311, found 292. 1318.

Entry 8 : 72 h. run 1 : [L: B] = 13 : 1, [E:Z] = 12 : 1; run 2 : [L: B] =12 : 1, [E : Z] =12 : 1 ; average: [L: B] =13 : 1, [E : Z] = 12 : 1 (24h, [L: B] =37 : 1,48h, [L: B] =21 : 1). Purification by flash chromatography (15% EtOAc/hexanes eluent) provided the desired linear (E)- allylic acetate as the major product (run 1 : 183. 0 mg, 0. 66 mmol, 66%; run 2 : 170. 2 mg, 0. 61 mmol, 61%; average yield : 64%). After column : [L: B] =14 : 1; [E:Z] = 12 : 1. 1H NMR (400 MHz, CDC13) 5 7. 38 (bd, J= 7. 6 Hz, 2H), 7.30 (t, J= 7. 2 Hz, 2H), 7.06 (t, J=7. 2Hz, 1H), 6.69 (brs, 1H), 5. 78 (dt, J = 15. 2,6. 4 Hz, 1H), 5.6 (dt, J = 15. 6,7. 2 Hz, 1H), 4.52 (dd, J = 6. 0,0. 4 Hz), 4.17 (t, J = 6.4 Hz, 2H), 2.18 (brq, J = 7.2 Hz, 2H), 2.06 (s, 3H), 1.78 (m, 2H); 13C NMR (100 MHz, CDCl3) # 170. 9,153. 5,137. 9, 134.9, 129.0, 124.7, 123.4, 118. 6,65. 0,64. 6,28. 7,28. 1,21. 0; IR (film, ciel) : 3329 (br), 3138,3080, 3044,2953, 2851,1736 (br, shoulder 1715), 1601,1539, 1445, 1225; HRMS (EI) m/z calc'd for [Ci5Hl9N04] + : 277.1314, found 277.1315.

Entry 9 : 48 h. run 1 : [L: B] =24 : 1, [E:Z] = 12 : 1; run 2 : [L: B] =21 : 1, [E:Z] = 12 : 1; average: [L: B] =23 : 1, [E:Z] = 12 : 1 (24h, [L: B] =44 : 1). Purification by flash chromatography (35% EtOAc/hexanes eluent) provided the desired linear (E)-allylic acetate as the major product (run 1: 148. 0 mg, 0. 61 mmol, 61%; run 2 : 150. 5 mg, 0. 62 mmol, 62% yield; average yield : 62%). After column : [L: B] =21 : 1, [E : Z] =12 : 1.'HNMR (400 MHz, CDCl3) # 5. 75 (dt, J=16, 6. 4 Hz, 1H), 5.58 (dt, J = 15. 2,6. 0 Hz, 1H), 4.5 (d, J= 6. 4 Hz, 2H), 3.36 (q, J= 7. 6 Hz, 2H), 3.28 (q, J= 7. 6 Hz, 2H), 2.28 (t, J= 7. 6 Hz, 2H), 2.11 (brq, J= 7. 2 Hz, 2H), 2.04 (s, 3H), 1.75 (q, J= 7. 6 Hz, 2H), 1.15 (t, J = 7. 2 Hz, 3H), 1.09 (t, J=7. 2Hz, 3H) ; 13C NMR (400 MHz, CDC13) 5 172. 0, 171. 1, 135. 9,124. 8,65. 4,42. 2,40. 3,32. 4,32. 0,24. 7,21. 2,14. 6,13. 3; IR (film, cm~l) : 2974,2936, 2878,1740, 1641,1433, 1233; HRMS (ESI) calc'dforCi3H23N03 [M+H] + : 242.1756, found 242.1747.

Entry 10 : 48 h. run 1 : [L: B] =>99 : 1, [E : Z] = 13 : 1; run2 : [L: B] =>99 : 1, [E:Z] = 12 : 1 ; average: [L: B] = >99 : 1, [E : 2] = 13: 1. Purification by flash chromatography (15% EtOAc/hexanes eluent) provided the desired linear acetate as the major product (run 1: 114. 1mg, 0. 65 mmol, 65%; run 2 : 112. 1 mg, 0. 64 mmol, 64%; average yield : 65%).

After column : [L: B] = >99 : 1; [E : Z] =13 : 1.'H NMR (400 MHz, CDC13) 8 7. 39 (m, 2H), 7.32 (m, 2H), 7.27 (m, 1H), 6.65 (d, J= 15. 6 Hz, 1H), 6.29 (dt, J= 15. 8,6. 4 Hz, 1H), 4.73 (dd, J = 6.8, 1.6 Hz, 2H), 2.1 (s, 3H); 13C NMR (100 MHz, CDCl3) # 170. 8, 136.2, 134.2, 128.6, 128.0, 126.6, 123.1, 65.0, 21.0 ; IR (film, cm-1) : 3082,3059, 3028,2943, 2882, 1738, 1495,1449, 1379,1364, 1233; HRMS (EI) nalz calc'd for [C11H12O2]+ : 176.0837, found 176.0841.

Example 4 1 (10 mol %) OAc TBDPSO BQ (2 eq) TBDPSO' CH2CI2 : AcOH (1 : 1) 40°C, 72h 65% yield, [L : B] = 1 : 6 H H ° H OAc above 69 % yield, [L : B] = 1 : 5 69 % yield, [L : B] = 1 : 5 General procedure for catalyst 1 (equations 2,3) : A 40 mL borosilicate glass vial was

charged with the following solids: catalyst 1 (53. 2 mg, 0.1 mmol, 10 mol%), benzoquinone (217 mg, 2.0 mmol, 2 eq). A separate 4 mL borosilicate glass vial was charged with olefin substrate (0.1 mmol) which was diluted with CH2Cl2 and transferred to the solids vial via pipette (3 x 1 mL, total volume of CH2C12 was always 3 mL). The 40 mL vial was charged with AcOH (3 mL), a stir bar, capped and allowed to heat at 40°C. Aliquots were taken 50 pL filtered through a silica plug with Et2O) at t= 24 h, 48 h, and 72 h to determine linear : branched ratios [L: B]. The reaction was quenched with saturated NH4Cl (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H2O (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown/red oil. Purification of the crude by flash chromatography afforded a mixture of the branched and linear (E)-allylic acetates (trace amounts of the Z isomer was detected by 1H NMR) with the branched allylic acetate as the major product.

Equation 2 : 72 h. run 1 : [L: B] = 1 : 6, run 2 : [L: B] = 1 : 5.5, average reported : [L: B] = 1 : 6 (24h, [L: B] = 1 : 7,48h, [L: B] = 1 : 6). Purification by flash chromatography (3% EtOAc/hexanes eluent) provided the branched allylic acetate as the major product (run 1: 256. 5 mg, 0. 67 mmol, 67% ; run 2 : 240. 8 mg, 0. 63 mmol, 63%; average yield reported : 65%). After column [L: B] = 1: 6.'H NMR (400 MHz, CDC13) 8 7.65 (m, 4H), 7.40 (m, 6H), 5.78 (ddd, J= 17. 0,10. 4,6. 0 Hz, 1H), 5.46 (m, 1H), 5.23 (app dt, J= 17. 2,1. 2 Hz, 1H), 5.15 (app dt, J = 10. 0,1. 6 Hz, 1H), 3.69 (t, J= 6. 4 Hz, 2H), 2.0 (s, 3H), 1.87 (m, 2H), 1.05 (s, 9H); 13C NMR (100 MHz, CDC13) 8 170.1, 136.4, 135.56 and 135.53 (d), 133.68 and 133.6 (d), 129.6, 127.6, 116.5, 71.9, 59.7, 37.0, 26.8, 21.2, 19.1 ; IR (film, cm'') : 3073,3050, 3000,2957, 2932,2891, 2859,1742, 1474,1427, 1371, 1236,1111 ; HRMS (CI, NH3) m/z calc'd for C23H34NO3Si [M+NH4] + : 400.2308, found 400.2308.

Equation 3: 72 h. run 1,2 : [L: B] = 1 : 5 (24h, [L: B] = 1 : 7; t = 48h, [L: B] = 1: 7).

Purification by flash chromatography (12% EtOAc/hexanes eluent) provided the branched allylic acetate as the major product (run 1 : 190. 4mg, 0. 69 mmol, 69%; run 2 : 189. 9mg, 0.68 mmol, 68%; average yield reported: 69%). After column [L: B] = 1 : 5. 1H NMR (400 MHz, CDC13) d 7. 38 (brd, J= 7. 6 Hz, 2H), 7.30 (t, J= 7.6 Hz, 2H), 7.05 (t, J= 7.2 Hz, 1H), 6.71 (brs, 1H), 5. 78 (ddd, J= 17. 4,10. 4,6. 4, 1H), 5.32 (m, 1H), 5.25 (app dt, J

= 17. 2,1. 6,1H), 5.19 (app dt, J= 10. 4,1. 2 Hz, 1H) 4.17 (t, J=6. 0Hz, 2H), 2.07 (s, 3H), 1.73 (m, 4H) ; 13C NMR (100 MHz, CDC13) 5 170.5, 153.4, 137.8, 136.1, 129.0, 123.4, 118. 6,117. 0,74. 2,64. 8,30. 8,24. 6,21. 2; IR (film, cm~l) : 3329 (br), 3196,3138, 3063,2957, 2859,1734 (br, shoulder 1716), 1601,1539, 1225; HRMS (EI) m/zzalc'd for [CisHi9N04]'' : 277.1314, found277. 1318.

Example General Information: All allylic oxidation reactions described below were conducted in 40 mL VWRbrand borosilicate glass vials with a teflon-lined solid cap under an air atmosphere. Vials were used as received (no cleansing or drying was done prior to reaction). All commercially obtained reagents for the allylic oxidation reaction (Sigma- Aldrich Chemical Company, unless otherwise stated) were used as received: anhydrous (Sure/Seal) DMSO; 4A (powdered, <5 micron) activated molecular sieves; 1,4- benzoquinone; glacial acetic acid (Mallinckrodt Chemicals); Pd (OAc) 2 (Strem Chemicals).

Pd (OAc) 2 was stored in a glove box under a nitrogen atmosphere and weighed out under an air atmosphere prior to use. Solvents tetrahydrofuran (THF), diethyl ether (Et2O), and methylene chloride (CH2C12) were purified prior to use by passage through a bed of activated alumina (Glass Contour, Laguna Beach, California). Methanol (MeOH) was distilled from magnesium. Anhydrous N, N-dimethylformamide (DMF) (Sure/Seal) was obtained from Sigma-Aldrich and used as received. (-)-B- Methoxydiisopinocampheylborane was obtained from Sigma-Aldrich. Propionic acid (1R, 2S)-2- [N-benzyl-N- (mesitylenesulfonyl) amino]-l-plienylpropyl ester was obtained from TCI-US Chemical Company. Dess-Martin periodinane was obtained from Sigma-Aldrich.

Dicyclohexylboron triflate (Cy2BOTf) was prepared according to the published procedure (Abiko, A. Org. Syrath. Collective Vol. X2004, 103). Isobutyraldehyde was distilled at 65°C external temperature (760 mm Hg) before use. Achiral gas chromatographic (GC) analyses were performed on Agilent Technologies 6890N Series instrument equipped with FID detectors using a HP-5 (5%-Phenyl)-methylpolysiloxane column (30m, 0.32mm, 0. 25pm).

Linear to branched allylic acetate ratios [L: B] were determined by GC analysis of the crude and were not corrected for small response factor variations. Retention times for the branched isomers were determined by independent synthesis using the previously described literature procedure (Chen, M. S.; White. M. C J. Am. Chem. Soc. 2004, 126, 1346). Chiral

GC analysis was performed on Agilent 5890 Series instrument equipped with FID detectors using a cyclodex-P column (30m, 0.25mm, 0. 251lm). Thin-layer chromatography (TLC) was conducted with E. Merck silica gel 60 F254 precoated plates (0.25 mm) and visualized with UV and potassium permanganate staining. Flash column chromatography was performed as described by Still et al using EM reagent silica gel 60 (230-400 mesh; Still, W. C.; Kahn, M.; Mitra, A. J. Org Chem. 1978, 43, 2923). lH NMR spectra were recorded on a Varian Mercury-400 (400 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 7.26 ppm). Data reported as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad; coupling constant (s) in Hz; integration.

Ratios of E to Z isomers for the allylic acetates and allylic alcohols were determined by lH NMR analysis of the crude upon workup and are based on integration of the allylic hydrogens of the acetoxy-or hydroxy-bearing carbon of the two isomers. Proton- decoupled 13C NMR spectra were recorded on a Varian Mercury-400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 77.0 ppm). IR spectra were recorded as thin films on NaCl plates on a Matterson FTIR 3000 and are reported in frequency of absorption (cm 1). High resolution mass spectra were obtained at the Harvard University Mass Spectrometry Laboratory. Optical rotations were measured using a 2 mL cell with a 1 dm path length on a Jasco DIP 370 digital polarimeter. Optical rotations were obtained with a sodium lamp and are reported as follows: [a] T C (C = g/100 mL, solvent).

Procedure for Equation 4--Synthesis of (E)-5- [ (4R, 5S)-2, 2, 5-trimethyl-1, 3-dioxan-4- yl] pent-2-enyl acetate: A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added DMSO (2.5 mL) and (2S, 3R)-2- methyloct-7-ene-1, 3-acetonide (198. 3 mg, 1.0 mmol). DMSO (0.5 mL) was used to rinse any residual acetonide to the bottom of the vial. The vial was then charged with AcOH (3.0 mL) and a stir bar, capped, and allowed to heat at 40°C. Aliquots were taken at t = 24h and 48h to determine the linear: branched isomeric ratio [L: B]. After 48h the reaction was

quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H20 (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil. Crude product: 24h: [L: B] = 34 : 1; 48h: [L: B] = 20 : 1, [E: Z] = 12: 1. Immediate purification by flash chromatography (10% EtOAc/hexanes) provided the desired linear (E)-allylic acetate as a yellow oil. After column : (run 1: 134.6 mg, 0.53 mmol, 53% yield; run 2: 130.6 mg, 0.51 mmol, 51% yield; run 3: 139.5 mg, 0.54 mmol, 54% yield; average yield: 53%). After column: [L: B] = 19: 1, [E: Z] =11 : 1.'H NMR (400 MHz, CDC13) 8 5.76 (dt, J= 15.4, 6.6 Hz, 1H), 5.58 (dt, J= 15.2, 6. 8 Hz, 1H), 4.50 (d, J= 6. 8 Hz, 2H), 3.67 (dd, J = 11. 2,5. 2 Hz, 1H), 3.48 (t, J = 11. 2 Hz, 1H), 3.42 (dt, J= 2.4, 9.4 Hz, 1H), 2.23 (m, 1H), 2.10 (m, 1H), 2. 05 (s, 3H), 1.66 (m, 2H), 1.45 (m, 1H), 1.40 (s, 3H), 1.37 (s, 3H), 0.73 (d, J= 6.8 Hz, 3H); Z isomer: 4.63 (d, J = 6.4 Hz, 2H) ;'3C NMR (100 MHz, CDC13) 8 170.9, 136.1, 124.1, 98.2, 74.0, 66.1, 65.2, 34.0, 32.0, 29.7, 27.6, 21.0, 19.1, 12.7 ; IR (film, cm'') : 2992,2944, 2855,1742, 1460, 1381,1368, 1233,1202. HRMS (ESI) m/z calc'd for C14H2504 [M+H] + : 257.1753, found 257.1750 ; [a] u = +40. 7° (c = 0.97, CHC13).

Procedure for Equation 5--Synthesis of (E)-1'-acetoxy-2'-penten-5'-yl-3- benzenesulfonyl-3-carbomethoxy-propanoate (Trost, B. M.; Verhoeven, T. R. J. Am.

Chemin. Soc. 1980, 102, 4743): A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added a solution of l'-penten-5'-yl 3- benzenesulfonyl-3-carbomethoxypropanoate (340.4 mg, 1.0 mmol) in DMSO (2 mL) and AcOH (4 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C.

Aliquots were taken at t = 24h and 48h to determine [L: B]. After 48h the reaction was quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H2O (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography (47.5 : 47.5 : 5 hexanes: CHCl3 : acetone) provided the desired linear (E)-allylic acetate as a yellow, viscous oil. Crude product 24h: [L: B] = 38 : 1; 48h: [L: B] = 26: 1, [E : Z] = 13: 1.

After column (run 1: 253mg, 0.64 mmol, 64% yield; run 2: 260.2mg, 0.65 mmol, 65%

yield; run 3: 270.3mg, 0.68 mmol, 68% yield; average yield: 66%). After column: [L: B] = 26: 1, [E: Z] = 12 : 1.'H NMR (400 MHz, CDC13) 8 7.87 (dd, J= 8. 4,0. 8 Hz, 2H), 7.72 (tt, J = 7.2, 1.2 Hz, 1H), 7.60 (t, J= 7.6 Hz, 2H), 5.67 (m, 2H), 4.51 (d, J= 5.2 Hz, 2H), 4.43 (dd, J= 9.6, 5.2 Hz, 1H), 4.13 (m, 2H), 3.67 (s, 3H), 3.12 (m, 2H), 2. 37 (bq, J= 6.4Hz, 2H), 2.06 (s, 3H); Z isomer: 4.60 (d, J= 6.4 Hz, 2H); 13C NMR (100 MHz, CDC13) 8 170.8, 169.5, 165.4, 137. 0,134. 6, 130. 3,129. 3,129. 1,127. 1,66. 3,64. 6,64. 4, 53. 2,31. 4, 31. 1, 20.9 ; IR (film, cm-1) : 2957,1740, 1449,1327, 1235, 1152. HRMS (ESI) m/z calc'd for CigH23OgS [M+H] + : 399.1113, found 399. 1118.

Equation 6--Synthesis of Methyl 10-hydroxy- (E)-dec-8-enoate (Ranganathan, D.; Ranganathan, S.; Mehrotra, M. M. Tetrahedron 1980, 36, 1869): A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added DMSO (2.3 mL), 9-methyl decenoate (184.3 mg, 1.0 mmol), and AcOH (3.7 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C. Aliquots were taken at t = 24h and 48h to determine [L: B]. After 48h the reaction was quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H20 (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil (crude methyl 10-acetoxy- (E)-dec-8-enoate). Linear acetate crude product 48h : [L: B] = 11 : 1, [E: Z] = 13 : 1. Crude product was taken on without purification.

A flame-dried 25 mL round bottom flask was charged with a stir bar and potassium carbonate (415 mg, 3.0 mmol). A solution of the crude linear acetate in MeOH (3.5 mL) was added via cannula. The reaction was allowed to stir at room temperature for lh then diluted with Et2O (150 mL). The Et2O layer was washed with saturated NH4C1 (5 mL), H20 (5 mL), and brine (5 mL). The organic layer was dried over MgS04, filtered, and concentrated in vacuo. Purification by flash chromatography (25% EtOAc/hexanes) provided the desired linear (E)-allylic alcohol as a yellow, viscous oil. Linear alcohol crude product: [L: B] = 13: 1 (by 1H NMR), [E: Z] = 13: 1. After column (run 1: 118.1 mg, 0.59 mmol, 59% yield; run 2: 119.1 mg, 0.59 mmol, 59% yield ; run 3: 111.8 mg, 0.56 mmol, 56% yield; average yield: 58%). After column : No branched product observed by I NMR

or GC), [E : Z] = 13 : 1. IH NMR (400 MHz, CDC13) 8 5.65 (m, 2H), 4.08 (d, J= 5.2 Hz, 2H), 3.66 (s, 3H), 2. 30 (t, J= 7.6Hz, 2H), 2.03 (m, 2H), 1.61 (m, 2H), 1.24-1. 42 (m, 6H); Z isomer: 4.19 (d, J= 6.4 Hz, 2H) ; 13C NMR (100 MHz, CDC13) 8 174.3, 133.2, 129.0, 63.8, 51.4, 34.0, 32.1, 29.0, 28.8, 28.7, 24.8 ; IR (film, cm-1) : 3401 (br), 2928,2857, 1740,1437, 1366,1254, 1202,1175. HRMS (ESI) m/z calc'd for CIlH2103 [M+H] + : 201.1491, found 201.1487.

Characterization of methyl 10-acetoxy- (E)-dec-8-enoate :'H NMR (400 MHz, CDC13) 8 5.75 (dt, J= 15.6, 6.8 Hz, 1H), 5.55 (dt, J= 15.2, 6.4 Hz, 1H), 4.50 (d, J= 6.0 Hz, 2H), 3.66 (s, 3H), 2.30 (t, J= 7.6 Hz, 2H), 2.06 (s, 3H), 2.03 (m, 2H), 1.61 (m, 2H), 1.25-1. 40 (m, 6H); 13C NMR (100 MHz, CDC13) b 174.2, 170.8, 136.4, 123. 8, 65.2, 51.4, 34.0, 32.1, 28.9, 28.7, 28.6, 24.8, 21.0 ; HRMS (ESI) filz calc'd for C13H2304 [M+H] + : 243.1596, found 243.1591.

Procedure for Equation 7--Synthesis of (E)-6-phthalimidohex-2-enyl acetate: A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added a solution of N- (5-hexenyl) phthalimide (184.3 mg, 1.0 mmol) in DMSO (2.5 mL), and AcOH (3.5 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C. Aliquots were taken at t = 24h and 48h to determine [L: B]. After 48h the reaction was quenched with saturated NH4Cl (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H2O (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography (20% EtOAc/hexanes) provided the desired linear (E)-allylic acetate.

Crude product 24h: [L: B] = 29: 1; 48h: [L: B] = 17: 1, [E: Z] = 12: 1. After column: (run 1 : 206.8 mg, 0.72 mmol, 72% yield; run 2: 199.5 mg, 0.69 mmol, 69% yield; run 3: 206.1 mg, 0.72 mmol, 72% yield; average yield: 71%). After column: [L: B] = 17: 1, [E: Z] = 12: 1.'H NMR (400 MHz, CDC13) 8 7.84 (dd, J= 5. 4,3. 6 Hz, 2H), 7.71 (dd, J= 5.4, 3.2 Hz, 2H),

5.77 (dt, J= 15.6, 6. 4 Hz, 1H), 5.61 (dt, J= 15.6, 6. 4 Hz, 1H), 4.47 (dd, J= 6. 4,0. 8 Hz, 2H), 3.69 (t, J= 7.2 Hz, 2H), 2.13 (m, 2H), 2.05 (s, 3H), 1.79 (m, 2H); Z isomer: 4.60 (d, J = 6.4 Hz, 2H) ; 13C NMR (100 MHz, CDC13) 8 170.8, 168.4, 134.5, 133.9, 132.1, 124.8, 123.2, 64.9, 37.5, 29.5, 27.6, 21.0 ; IR (film, cm'') : 2942,1771, 1736, 1711, 1615,1468, 1439,1397, 1370,1235. HRMS (ESI) m/z calc'd for C16Hl8N04 [M+H] + : 288.1236, found 288.1230.

Procedure for Equation 8--Synthesis of (E)-6-bromohex-2-enyl acetate (Shimada, T.; Yamamoto, Y. Tetrahedron Lett. 1998, 39, 471) : A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added the following: DMSO (2 mL), 6-bromo-1-hexene (163.1 mg, 1.0 mmol), and AcOH (4 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C. Aliquots were taken at t = 24h, 48h, and 72h to determine [L: B]. After 72h the reaction was quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H20 (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo at 0°C to give a brown oil. Purification by flash chromatography (10% EtzO/n-pentane) provided the desired linear (E)-allylic acetate as a light yellow oil. Crude product 24h: [L: B] = 32 : 1; 48h: [L: B] = 30 : 1; 72h: [L: B] = 29 : 1, [E: Z] = 14 : 1. After column: (run 1: 149.0 mg, 0.67 mmol, 67%; run 2: 138. 3 mg, 0.63 mmol, 63%; run 3 138.5 mg, 0.63 mmol, 63% yield; average yield: 64%) [L: B] = 29: 1, [E: Z] = 13: 1 1H NMR (400 MHz, CDC13) 8 5. 73 (dt, J= 15. 2,6. 4 Hz, 1H), 5.63 (dt, J= 15.2, 6.4 Hz, 1H), 4.51 (d, J= 6.0 Hz, 2H), 3.40 (t, J= 6.8 Hz, 2H), 2.23 (m, 2H), 2.06 (s, 3H), 1.95 (m, 2H); Z isomer: 4.64 (d, J= 5.2 Hz, 2H); 13C NMR (100 MHz, CDC13) 8 170.9, 133.9, 125.4, 64.9, 32.9, 31.7, 30.5, 21.0 ; IR (film, cm~l) : 3017,2938, 2851,1740, 1441,1381, 1366,1240. HRMS (CI, NH3) m/z calc'd for C8Hl7BrNO2 [M+NH4] + : 238.0443, found 238.0455.

Procedure for Equation 9--Synthesis of (4R, 2E)-4- (p-methoxybenzyloxy)-5- methylhex-2-enyl acetate: A 40 mL borosilicate glass vial was charged with the following solids: Pd (OAc) 2 (22.4 mg, 0.1 mmol), benzoquinone (217 mg, 2.0 mmol), and 4A MS (217 mg). To the solids vial was sequentially added a solution of (S)-3-(p- methoxybenzyloxy) -2-methyl-5-hexene (172.5 mg, 0.94 mmol) in DMSO (2 mL), and AcOH (4 mL). The vial was charged with a stir bar, capped and allowed to heat at 40°C.

After 48h the reaction was quenched with saturated NH4C1 (10 mL) and extracted with CH2C12 (3 x 100 mL). The combined organic layers were washed with H2O (2 x 100 mL), dried over MgS04, filtered and concentrated in vacuo to give a brown oil. Crude product 48h: No (Z) -linear or branched acetate observed by lH NMR or GC. Purification by flash chromatography (10% EtOAc/hexanes) provided the desired linear (E)-allylic acetate as a viscous, yellow oil with no degradation of enantiomeric purity (see"Determination of Enantiomeric Excess"section below). After column: (run 1: 191.1 mg, 0.65 mmol, 70% yield; run 2: 202.7 mg, 0.69 mmol, 74% yield; run 3: 183.1 mg, 0.63 mmol, 67% yield; run 4: 175.7 mg, 0.60 mol, 64% yield, run 5: 176.3 mg, 0.60 mmol, 64% yield; average yield: 68% yield).'H NMR (400 MHz, CDCl3) 8 7.25 (d, J= 9.2 Hz, 2H), 6.87 (d, J= 8.4 Hz, 2H), 5.72 (dt, J= 15.6, 6.0 Hz, 1H), 5.65 (dd, J= 15. 8,7. 6 Hz, 1H), 4.61 (d, J= 4.8 Hz, 2H), 4.51 (d, J= 11.2 Hz, 1H), 4.26 (d, J= 12.0 Hz, 1H), 3. 80 (s, 3H), 3.43 (t, J= 7.2 Hz, 1H), 2.09 (s, 3H), 1.78 (m, 1H), 0.93 (d, J= 6.8 Hz, 3H), 0. 85 (d, J= 7.2 Hz, 3H); 13C NMR (100 MHz, CDC13) 8 170.8, 159.0, 133.7, 130.9, 129.2, 127.5, 113.7, 84.2, 70.0, 64.3, 55.2, 32.7, 21.0, 18.7, 18.4 ; IR (film, cm'') : 3077,2928, 2857,1742, 1642,1460, 1362,1248, 1200,1171. HRMS (ESI) m/z calc'd for C17H28NO4 [M+NH4] + : 310.2018, found 310.2017 ; [oc] D29 = +43. 3° (c = 1.00, CHC13).

Determination of Enantiomeric Excess--Synthesis and Charaterization of (4R, 2E)-4- (acetoxy)-5-methylhex-2-enyl acetate: A portion of the PMB-protected (E)-allylic acetate was transformed into the acetate-protected (E)-allylic acetate for enantiomeric excess determination. A 25 mL round bottom flask was charged sequentially with a stir bar, (4R)- (p-methoxybenzyloxy)-5-methyl- (2E)-hexen-1-acetate (19.0 mg, 0.07 mmol), CH2C12 (330

gel), H20 (20 wIL), and 2,3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) (15.5 mg, 0.07 mmol). The reaction was allowed to stir at room temperature for 10 min then diluted with CH2Cl2 (20 mL). The organic layer was washed with H20 (3 mL), dried over MgS04, filtered, and concentrated in vacuo. Purification by flash chromatography (20% EtOAc/hexanes) provided the desired linear allylic alcohol (12.3 mg, mass above theoretical yield). A 25 mL round bottom flask containing the entire mixture of linear allylic alcohol (12.3 mg) was charged with a stir bar, Et2O (0.5 mL), pyridine (11 µL, 0.13 mmol), acetic anhydride (12 gel, 0.13 mmol), and DMAP (1.0 mg, 0. 01 mmol). The reaction was allowed to stir at room temperature for lh then diluted with Et2O (20 mL) and quenched with 1.0 M HCl (0.1 mL). The organic layer was washed with 1.0 M HCl (1 x 3 mL) and H20 (1 x 3 mL), dried over MgS04, filtered, and concentrated in vacuo.

Purification by flash chromatography (20% EtOAc/hexanes) provided the desired acetate- protected linear (E)-allylic acetate (7.9 mg, 0.04 mmol, 57% yield, 2 steps) as a pale yellow oil. 1H NMR (400 MHz, CDC13) 8 5.76 (dt, J= 16.0, 5.2 Hz, 1H), 5.67 (dd, J= 15.6, 6. 8 Hz, 1H), 5.07 (t, J= 6. 4 Hz, 1H), 4.55 (d, J= 5. 2 Hz, 2H), 2.06 (s, 6H), 1. 86 (m, 1H), 0.90 (d, J= 6.4 Hz, 3H), 0. 89 (d, J= 6.8 Hz, 3H); 13C NMR (100 MHz, CDC13) 8 170.7, 170.3, 130.8, 127.3, 78.1, 64.1, 31.9, 21.1, 20.9, 18. 0,17. 9. Enantiomeric excess was determined by chiral GC analysis (Cyclodex-P, 95°C, isothermal); major enantiomer tR=28. 2 min, minor enantiomer tR=26.6 min; 94% ee.

Example 6 Procedure for Equation 10--Synthesis of a 14-member macrocycle : A 1 dram vial was charged with the phenyl bis-sulfoxide catalyst (10.1 mg, 0.02 mmol). Another 1 dram vial was charged with 2- ( (dec-9-enyloxy) carbonyl) benzoic acid (60.9 mg, 0.2 mmol). To a 100 mL round bottom flask was sequentially charged benzoquinone (43.2 mg, 0.4 mmol), the phenyl bis-sulfoxide catalyst (transferred using 10 mL CH2C12), and the acid substrate (transferred using 10 mL CH2C12). The flask was charged with a stir bar, topped with a

condenser, and allowed to heat at 40°C with an empty balloon on the top of the flask. After 72h the reaction was quenched with saturated NH4C1 (5 mL) and extracted with CH2C12 (3 x 30 mL). The combined organic layers were washed with H20 (2 x 30 mL), dried over MgS04, filtered and concentrated in vacuo to give a yellow solid. Purification by Si02 flash chromatography (10% EtOAc/hexanes) provided the desired 14-member macrocycle (29.1 mg, 0.10 mmol, 48% yield) as a yellow oil. 1H NMR (400 MHz, CDC13) 8 7.74 (m, 2H), 7.53 (m, 2H), 5.92 (ddd, J= 17.2, 10.4, 5.8 Hz, 1H), 5.68 (m, 1H), 5.34 (dt, J= 17.2, 1.2 Hz, 1H), 5.20 (dt, J= 10.4, 1.2 Hz, 1H), 4.74 (ddd, J= 11.0, 6.2, 2.8 Hz, 1H), 4.01 (ddd, J= 11.2, 9.0, 2.0 Hz, 1H), 1.25-1. 77 (m, 12H; 13C NMR (100 MHz, CDC13) 8 167.9, 166.5, 136. 5,132. 8,132. 2,131. 1, 130. 7,129. 2,128. 9,116. 3,74. 0,64. 4,32. 8,26. 5,25. 4, 24.9, 22.0, 20.7 ; HRMS (CI, NH3) iizlz calc'd for C18H26NO4 [M+NH4] + : 320.1862, found 320.1859.

Procedure for Equation 11--Synthesis of a 16-Member macrocycle : A 1 dram vial was charged with the phenyl bis-sulfoxide catalyst (10.1 mg, 0.02 mmol). Another 1 dram vial was charged with 2-((dodec-11-enyloxy) carbonyl) benzoic acid (66.5 mg, 0.2 mmol).

To a 100 mL round bottom flask was sequentially charged benzoquinone (43.2 mg, 0.4 mmol), the phenyl bis-sulfoxide catalyst (transferred using 10 mL CH2C12), and the acid substrate (transferred using 10 mL CH2Cl2). The flask was charged with a stir bar, topped with a condenser, and allowed to heat at 40°C with an empty balloon on the top of the flask.

After 72h the reaction was quenched with saturated NH4C1 (5 mL) and extracted with CH2C12 (3 x 30 mL). The combined organic layers were washed with H2O (2 x 30 mL), dried over MgS04, filtered and concentrated in vacuo to give a yellow solid. Purification by Si02 flash chromatography (10% EtOAc/hexanes) provided the desired 16-member macrocycle (40.7 mg, 0.12 mmol, 62% yield) as a yellow oil. lH NMR (400 MHz, CDC13) # 7. 90 (dd, J = 7. 6,1. 6 Hz, 1H), 7.55 (m, 3H), 5.90 (ddd, J= 17. 2,10. 8,6. 0 Hz, 1H), 5.68 (m, 1H), 5.31 (dm, J= 17.2 Hz, 1H), 5.17 (dm, J= 10.8 Hz, 1H), 4. 55 (m, 1H), 4.24 (m, 1H), 1.85 (m, 1H), 1.25-1. 75 (m, 15H) ; 13C NMR (100 MHz, CDC13) 8 168. 9,165. 4,136. 7,

134.7, 131.8, 130.1, 130.0, 129.3, 128.2, 116.4, 74.0, 64.8, 33. 8, 29.7, 28.1, 26.6, 26.5, 25. 8, 24.4, 23.7 ; HRMS (EI) m/z calc'd for C20H2604 : 330. 1831, found 330.1827.

ExamPle ? General Information: Unless stated otherwise, 0.2 mmol and 0.4 mmol scale reactions were conducted in 2mL or 4mL VWRbrand borosilicate glass vials (respectively, also depending on total volume) with red PTFE-faced silicone lined plastic screw caps or Wheaton Brand black plastic caps with teflon liners (respectively) under an air atmosphere.

Reactions run on a 1.0 mmol olefin scale with 4 eq. of acetic acid were conducted in a 25 mL pear-shaped flasks equipped with condensors and empty balloon outlets. All other 1.0 mmol olefin scale reactions with non-volatile acids were run in 40mL VWRbrand borosilicate glass vials (for convenience) with teflon lined solid caps under an air atmosphere. Vials were used as received (no cleansing or drying was done prior to reaction). All commercially obtained reagents (Sigma-Aldrich Chemical Company, unless stated otherwise) were used as received: anhydrous (Sure/Seal) dioxane; anhydrous (Sure/Seal) dimethylsulfoxide (DMSO); anhydrous (Sure/Seal) N, N-dimethylformamide (DMF); HPLC grade chloroform (CHC13), 1,4-benzoquinone, glacial acetic acid (Mallinckrodt Chemicals); phenyl vinyl sulfoxide ; Pd (OAc) 2 (Strem Chemicals). Both palladium sources were stored in a glove box under a nitrogen atmosphere. Pd (OAc) 2 was weighed in the air. Solvents tetrahydrofuran (THF), diethyl ether (Et2O), ethylene glycol dimethyl ether (DME), methylene chloride (CH2Cl2), toluene, benzene were purified prior to use by passage through a bed of activated alumina (Glass Contour, Laguna Beach, California). Acetonitrile (CH3CN) was distilled from CaH2. Gas chromatographic (GC) analyses were performed on Agilent Technologies 6890N Series instrument equipped with FID detectors using a HP-5 (5%-Phenyl) -methylpolysiloxane column (30m, 0. 32mm, 0. 25, um). GC yields reported relative to an internal standard (nitrobenzene) and corrected for response factor variations. Unless otherwise noted, branched to linear allylic acetate ratios [B: L] were determined by GC analysis of the crude and were not corrected for small response factor variations. Retention times for the linear isomers were determined by independent syntheses: linear (E)-allylic acetates were synthesized using the previously reported DMSO/Pd (OAc) 2 method (Chen, M. S.; White. M. C J. Ain. Chem. Soc. 2004, 126, 1346 and described herein), linear (E)-allylic benzoic acid esters were synthesized via 1,3-

dicyclohexyl-carbodiimide (DCC) coupling of the appropriate benzoic acid with linear (E)- allylic alcohol. Thin-layer chromatography (TLC) was conducted with E. Merck silica gel 60 F254 precoated plates (0.25 mm) and visualized with W and potassium permanganate staining. Reaction progression was monitored by both GC and TLC analysis. Flash column chromatography was performed as described by Still et al. (Still, W. C.; Kahn, M.; Mitra, A.

J. Org. Chem. 1978, 43, 2923) using EM reagent silica gel 60 (230-400 mesh). 1H NMR spectra were recorded on a Varian Mercury-400 (400 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 7.26 ppm). Data reported as: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, app = apparent; coupling constant (s) in Hz; integration. Proton-decoupled 13C NMR spectra were recorded on a Varian Mercury-400 (100 MHz) spectrometer and are reported in ppm using solvent as an internal standard (CDC13 at 77.0 ppm). IR spectra were recorded as thin films on NaCI plates on a Matterson FTIR 3000 and are reported in frequency of absorption (cm''). High resolution mass spectra were obtained at the Harvard University Mass Spectrometry Laboratory.

1, 2-bis (phenylsulfinyl) ethane: A 100 mL round bottom flask was charged with a stir bar, 2.5 g (10.2 mmol) of 1, 2-bis (phenylthio) ethane (commercial, Alfa Aesar), and 15 mL of glacial acetic acid. To the mixture was added dropwise at room temperature a solution of H202 (50 wt%, 20.3 mmol, 1.17 mL) in acetic acid (4.2 mL). Soon after addition of the HxOx (approximately 15 min), the mixture became homogeneous and was allowed to stir overnight. The acetic acid was removed with mild heating (40°C) under high vacuum and the white solid was washed with EtOH (3 x 40 mL). The white solid was dried under high vacuum overnight to give 2.0 g (7.14 mmol) of 1, 2-bis (phenylsulfinyl) ethane in 70% yield.

1 H NMR (400 MHz, CDC13) 8 7.56-7. 48 (m, 10H), 3.40 (m, 2H, rac), 3.05 (s, 4H, meso), 2.74 (m, 2H, rac) ; 13C NMR (100 MHz, CDC13) 8 142.3, 142.1, 131.4, 131.3, 129.5, 129.4, 123.92, 123.85 ; IR (film, cm-1) : 3048,2970, 2922,2361, 2342,1478, 1441,1209, 1084, 1036. HRMS (EI) m/z calc'd for [Cl4HlsO2S2] + : 279. 0513, found 279.0518. This compound has previously been characterized by lHNMR : Ternay, A. L.; Lin, J.; Sutliff, T.

J. Org. Chemin. 1978 (43) 3024; and IR: Cattalini, L.; Michelon, G.; Marangoni, G.; Pelizzi, G. J. C72eiii. Soc. Dalton Trans. 1979,96.

Example 8 General Procedure for Screens (Figure 11,14-19) : Vials (2 mL or 4mL borosilicate) were charged with the following solids: Pd (OAc) 2 (10 mol%) ; ligands (10 mol%), and oxidant (2 eq). It is important for attaining good yields that phenyl vinyl sulfoxide ligand 2 and Pd (OAc) 2 are well-mixed neat before the addition of solvent. Therefore, reactions were found to proceed in highest yields when the order of addition was as follows: ligand, Pd (OAc) 2, oxidant. Separate vials (2 mL, borosilicate) were charged with the following: 1- undecene (0.2 mmol or 0.4 mmol), nitrobenzene (internal GC standard, 40 mol%), AcOH (x eq) and 0.6 mL (0.2 mmol scale) or 1.2 mL (0.4 mmol scale) solvent. When 1-20 eq. of AcOH was used, the AcOH was weighed out into a clean vial followed by 1-undecene, nitrobenzene, solvent. When 52 eq. of AcOH was used, the order of addition was as follows: 1-undecene, nitrobenzene, solvent, AcOH. Aliquots were taken from the liquid vials (~10, uL filtered with Et20 through a short pipette plug of silica), to determine GC initial ratios of 1-undecene to nitrobenzene. The liquids were transferred via pipette into the appropriate solids vial, charged with a stir bar, capped and allowed to heat at 40-43°C.

When 1-20eq of AcOH were used, 0.5 + 0.1 mL (0.2 mmol scale) or 1.0 + 0.2 mL (0.4 mmol scale) of solvent were sequentially used to ensure complete transfer of the liquids.

This reaction has a very narrow temperature range. Heating the reactions even a few degrees below 40°C (i. e. 38°C,) resulted in noticable decreases in GC yields. Aliquots were taken at 24h, 48h (shown) and 72h to determine GC yields. Response factors relative to undecene were determined for the branched and linear allylic acetates.

Figure 11: 0.2 mmol scale: Solids vial (2 mL borosilicate): ligands (10 mol%): 1,2- bis (phenylsulfinyl) ethane (0.02 mmol, 5.6 mg) or 2 (0.02 mmol, 3. 0mg) ; benzoquinone (BQ, 2 eq, 0.4 mmol, 43.2 mg), Cu (OAc) 2 (2eq, 0.4 mmol, 72.7 mg), methyl-1,4- benzoquinone [BQ (Me), 2 eq, 0.4 mmol, 48.8 mg], 2,6-dimethyl-benzoquinone [BQ (Me) 2, 2 eq. , 0.4 mmol, 54.5 mg], duroquinone (DQ, 2 eq. , 0.4 mmol, 65.7 mg). Liquids vial (2 mL borosilicate): AcOH (4 eq, 0.8 mmol, 48 mg, 46 pL), l-undecene (31 mg, 41.1 pL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8. 2 pL, 0.08 mmol), 0.6 mL dioxane.

Or 1-undecene (31 mg, 41.1 LL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8.2 pL, 0.08 mmol), 0.6 mL dioxane, AcOH (52 eq. , 10.4 mmol, 0.6 mL). Results are reported as an average of three runs.

Figure 14: 0.2 mmol scale: Solids vial (2 mL borosilicate) : 2 (0.02 mmol, 3. 0mg), Pd (OAc) 2 (4. 5mg, 0.02 mmol, 10 mol%), benzoquinone (BQ, 2 eq, 0.4 mmol, 43.2 mg).

Liquids vial (2 mL borosilicate): 1-undecene (31 mg, 41. 1 uL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8.2 ! 1L, 0.08 mmol), 0.6 mL solvent, AcOH (52 eq. , 10.4 mmol, 0.6 mL). Results are reported as an average of 2 runs.

Figure 15: 0.4 mmol scale (entries 1-5): Solids vial (2 mL borosilicate), 2 (0.04 mmol, 6.1 mg, 10 mol%), Pd (OAc) 2 (9mg, 0.04 mmol, 10 mol%), BQ (2 eq, 0.8 mmol, 86. 5 mg).

Liquids vial (2 mL, borosilicate): AcOH : 1 eq. (0.4 mmol, 24mg, 23 µL), 1.5 eq. (0.6 mmol, 36mg, 34AL), 2.0 eq. (0.8 mmol, 48mg, 46µL), 3.0 eq. (1.2 mmol, 72mg, 69 RL), 4.0 eq. (1.6 mmol, 96 mg, 92 IlL) ; 1-undecene (61.7 mg, 82. 2 µL, 0.4 mmol), nitrobenzene (internal GC standard, 19.7 mg, 16.5 IlL, 0.16 mmol); 1.2 mL dioxane. Results are reported as an average of 2 runs. 0.2 mmol scale (entries 6-9): Solids vial (2 mL borosilicate): 2 (0.02 mmol, 3. 0mg), Pd (OAc) 2 (4. 5mg, 0.02 mmol, 10 mol%), benzoquinone (BQ, 2 eq, 0.4 mmol, 43.2 mg). Liquids vial (2 mL borosilicate), AcOH : 10 eq. (2.0 mmol, 120 mg, 114 µL), 15 eq. (3.0 mmol, 180 mg, 172 iL), 20 eq. (4.0 mmol, 240 mg, 229 pL) ; 1- undecene (31 mg, 41. 1 nul, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8. 2 RL, 0.08 mmol), 0.6 mL dioxane. Or: 1-undecene (31 mg, 41. 1, uL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8. 2, uL, 0.08 mmol), 0.6 mL dioxane, AcOH : 52 eq. (10.4 mmol, 625 mg, 0.6 mL). Results are reported as an average of two runs.

Figures 16-18: 0.2 mmol scale: Solids vial (2 mL, borosilicate): 2 (0.02 mmol, 3. 0mg, 10 mol%); Pd (OAc) 2 (4. 5mg, 0.02 mmol, 10 mol%) ; BQ (2 eq, 0.4 mmol, 43.2 mg; or 20 mol%, 0.04 mmol, 4.3 mg), or DQ (duroquinone, 2 eq, 0.4 mmol, 65.7 mg), Cu (OAc) 2 (2eq, 0.4 mmol, 72.7 mg; or 5 mol%, 0.01 mmol, 1.8 mg), or Mn02 (manganese (IV) oxide, <5 micron activated, 2 eq, 0.4 mmol, 34.8 mg), methyl-1, 4-benzoquinone (0.4 mmol, 48. 8 mg), 2-t-butyl-1, 4-benzoquinone (0.4 mmol, 65.7 mg), 2,6-dimethyl-benzoquinone (0.4 mmol, 54.5 mg). Liquids vial (2 mL, borosilicate): 1-undecene (31 mg, 41. 1 pL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8. 2, ut, 0.08 mmol); 0.6 mL dioxane; AcOH 52 eq. (10.4 mmol, 625 mg, 595 I1L). Or: AcOH 4 eq. (0.8 mmol, 48 mg, 46, uL) ; 1-

undecene (31 mg, 41. 1 uL, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8.2 gel, 0.08 mmol), 0.6 mL dioxane. Results are reported as an average of 3 runs.

Graph of Pd (II)-mediated isomerization study (Figure 18): 0.2 mmol scale w/out α- olefin : Solids vial (2 mL, borosilicate): 2 (0.02 mmol, 3. 0mg, 10 mol%); Pd (OAc) 2 (4. 5mg, 0.02 mmol, 10 mol%); BQ (2 eq, 0.4 mmol, 43.2 mg). Liquids vial (2 mL, borosilicate): AcOH 4 eq. (0.8 mmol, 48 mg, 46 I1L), branched allylic acetate (undec-l-en-3-yl acetate, 42.5 mg, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8.2 1L, 0.08 mmol); 0.6 mL dioxane. Or: branched allylic acetate (undec-l-en-3-yl acetate, 42.5 mg, 0.2 mmol) nitrobenzene (internal GC standard, 9.9 mg, 8. 2 µL, 0.08 mmol), 0.6 mL dioxane, AcOH 52 eq. (10.4 mmol, 625 mg, 595, uL). 0.2 mmol scale w/a-olefin : Solids vial (2 mL, borosilicate): 2 (0.02 mmol, 3. 0mg, 10 mol%); Pd (OAc) 2 (4. 5mg, 0.02 mmol, 10 mol%); BQ (2 eq, 0.4 mmol, 43.2 mg). Liquids vial (2 mL, borosilicate): AcOH 4 eq. (0.8 mmol, 48 mg, 46 I1L), branched allylic acetate (undec-l-en-3-yl acetate, 42.5 mg, 0.2 mmol), oc-olefin [(tert-butyldiphenylsiloxy)-l-pentene, 64.8 mg, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8. 2 µL, 0.08 mmol); 0.6 mL dioxane. Or: branched allylic acetate (undec- l-en-3-yl acetate, 42.5 mg, 0.2 mmol), a-olefin [(tert-butyldiphenyl-siloxy)-l-pentene, 64.8 mg, 0.2 mmol), nitrobenzene (internal GC standard, 9.9 mg, 8.2 p1L, 0.08 mmol), 0.6 mL dioxane, AcOH 52 eq. (10.4 mmol, 625 mg, 595 gel). Aliquots were take at t=24, 48,72, 96h to determine [B: L] ratios of undec-l-en-3-yl acetate by GC. All data is reported as an average of two runs; data plotted is of one run.

Example 9 General Procedure for Figure 12: All data reported is an average of three to four runs. It is critical for obtaining high yields that phenyl vinyl sulfoxide 2 and Pd (OAc) 2 are thoroughly mixed prior to addition of any other reaction component or solvent (see conditions below). When AcOH or other low molecular weight acids are used, it is important for achieving reliably good yields to run the reaction in a round bottomed flask fitted with a condensor. Aliquots were taken (-10 pL) and filtered through a silica plug with Et2O at t= 24h, 48h, 72h to monitor B: L ratios. The reaction was quenched with saturated NH4C1 (20 mL) and extracted with CH2Cl2 (3 x 50 mL). The combined organic

layers were washed with H20 (2 x 50 mL), dried over MgS04, filtered and concentrated iii vacuo. Purification of the crude by flash chromatography afforded the branched allylic acetates as the major products with trace amounts of the linear allylic acetates. Branched to linear allylic ester ratios do not change over time. Unless otherwise noted, all [B: L] ratios were measured by GC. Branched to linear allylic ester ratios for entries 7,8, 12,14 were measured from 1H NMR (500 MHz) spectra of the crude reactions. Linear (E)-allylic acetates for entries 1-8 were synthesized using our previously reported Pd (OAc) 2/DMSO/BQ/AcOH allylic acetoxylation method (Chen, M. S. ; White. M. C J. Am.

Clzefn. Soc. 2004, 126, 1346 and described herein). Linear (E)-allylic acetates for entries 9- 13 were synthesized using our allylic acetoxylation method followed by deactylation and DCC coupling with the respective acids.

Procedure for entries 1-3,5-8, 13: A 25 mL round bottomed flask was charged with the following: 2 (phenyl vinyl sulfoxide, 15.2 mg by weight, 0.1 mmol, 10 mol%), Pd (OAc) 2 (22.4 mg, 0.1 mmol, 10 mol%), BQ (216 mg, 2.0 mmol, 2 eq) and a magnetic stir bar.

Mixing was ensured by placing the Pd (OAc) 2 directly in the area occupied by the phenyl vinyl sulfoxide and gently swirling for-1 minute by hand. A 1 dram vial was charged with a-olefin substrate (1.0 mmol, by weight): and AcOH (240.1 mg by weight, 4.0 mmol) or isobutyric acid (132.2 mg, 1.5 mmol). This mixture was taken up in 2 x 1.5 mL of dioxane and sequentially transferred via pipette into the round bottomed flask. A second rinse with 1.5 mL of dioxane was done to ensure that all a-olefin substrate and AcOH were transferred. The reaction flask was equipped with a reflux condensor and an empty balloon outlet and allowed to heat at 40°C for 72 h.

Procedure for entry 4: As above with the following change: 2 (phenyl vinyl sulfoxide, 30.4 mg by weight, 0.2 mmol, 20 mol%).

Procedure for entry 5: As above with the following change: phenyl-carbamic acid hex-5- enyl ester (1.0 mmol, 219.3 mg) was added following BQ to the round bottomed flask.

Procedure for entries 9-12,13, 14: A 40 mL borosilicate vial was charged with the following: 2 (phenyl vinyl sulfoxide, 15.2 mg by weight, 0.1 mmol, 10 mol%), Pd (OAc) 2 (22.4 mg, 0.1 mmol, 10 mol%), solid acid (1.5 eq.), BQ (216 mg, 2.0 mmol, 2 eq) and a magnetic stir bar. Mixing as described above. A 1 dram vial was charged with a-olefin substrate (1.0 mmol, by weight) that was taken up in 2 x 1.5 mL of dioxane and sequentially transferred via pipette into the borosilicate tube.

Entry 1: 1-undecene (1.0 mmol, 154.3 mg). 48 h. Purification by flash chromatography (2% EtOAc/hexanes). run 1 (78%, [B: L] = [28 : 1]), run 2 (80%, [28: 1] ), run 3: (75% yield, [B: L] = 28: 1). Average three runs: 78%, [B: L] = [97: 3]. lH NMR (400 MHz, CDC13) 8 5.77 (ddd, J = 17.2, 10.8, 6.4 Hz, 1H), 5.22 (app dt, J= 17.6, 1.2 Hz, 1H), 5.21 (m, 1H), 5.15 (app dt, J= 10.4, 1.2 Hz, 1H), 2.06 (s, 3H), 1.59 (m, 2H), 1.26 (m, 12H), 0.87 (t, J= 6.8 Hz, 3H); 13C NMR (100 MHz, CDC13) 8 170.4, 136. 6,116. 5,74. 9,34. 2,31. 8,29. 4, 29.3, 29.2, 25.0, 22.6, 21.2, 14.1 ; IR (film, cm'') : 2928,2857, 1742,1657, 1466, 1371, 1238,1098, 1020,930, 841,723, 623; LRMS (CI, NH3) nzlz calc'd for C13H28NO2 [M+NH4] + 230, found 230.

Entry 2: (tert-butyldiphenylsiloxy)-1-pentene (1.0 mmol, 324.2 mg). 72h. Purification by flash chromatography (3% EtOAc/hexanes). run 1 (74%, [B: L] = [16: 1] ), run 2 (71%, [16: 1] ), run 3: (71% yield, [B: L] = 16: 1). Average three runs: 71%, [B : L] = [94: 6]. IH NMR (400 MHz, CDC13) 87. 65 (m, 4H), 7.40 (m, 6H), 5.78 (ddd, J= 17. 0,10. 4,6. 0 Hz, 1H), 5.46 (m, 1H), 5.23 (app dt, J = 17. 2,1. 2 Hz, 1H), 5.15 (app dt, J = 10. 0,1. 6 Hz, 1H), 3.69 (t, J=6. 4Hz, 2H), 2.0 (s, 3H), 1.87 (m, 2H), 1.05 (s, 9H) ; 13C NMR (100 MHz, CDC13) 8 170. 1,136. 4,135. 56 and 135.53 (d), 133.68 and 133.6 (d), 129.6, 127.6, 116.5, 71.9, 59.7, 37.0, 26.8, 21.2, 19.1 ; IR (film, cm'') : 3073,3050, 3000,2957, 2932,2891, 2859,1742, 1474,1427, 1371,1236, 1111; HRMS (CI, NH3) m/z calc'd for C23H34NO3Si [M+NH4] + : 400. 2308, found 400. 2308.

Entry 3: 2-hydroxy-benzoic acid hex-5-enyl ester (1.0 mmol, 220.3 mg). 72h. The crude was placed under high vacumn for-6h to remove BQ in order to facillitate purification.

Purification by flash chromatography (5% EtOAc/hexanes). run 1 (65%, [B : L] = [24: 1]),

run2 (66%, [22: 1] ), run 3 : (64% yield, [21: 1] ), run4 : (62%, [21: 1] ). Average four runs : 64%, [B: L] = [96: 4].'HNMR (400 MHz, CDC13) 8 10.79 (s, 1H), 7.83 (app dd, J = 8,1. 6 Hz, 1H), 7.46 (td, J = 7.2, 1.6 Hz, 1H), 6.98 (dd, J = 12,0. 8 Hz, 1H), 6.89 (td, J = 7.6, 1.2 Hz, 1H), 5.79 (ddd, J = 17.2, 10.6, 6.4 Hz, 1H), 5.31 (m, 1H), 5.28 (app dt, J = 17.2, 1. 2 Hz, 1H), 5.21 (app dt, J = 10,1. 2 Hz, 1H), 4.36 (t, J = 6 Hz, 2H), 2.08 (s, 3H), 1. 80 (m, 4H); 13C NMR (100 MHz, CDC13) 6 170.3, 170.1, 161.7, 135.9, 135.7, 129.8, 119.1, 117.6, 117.2, 112.4, 74.1, 64.8, 30.6, 24.3, 21.2 ; IR (film, cm-1) : 3188,3154, 3092,2959, 1740,1676, 1615,1586, 1485,1371, 1302,1238, 1159,1140, 1090,1020, 968,928, 758,702, 530; HRMS (CI, NH3) nzlz calc'd C15H22NO5 [M+NH4] + : 296.1498, found 296.1496.

Entry 4: N, N-diethyl-6-heptenamide (1.0 mmol, 183.3 mg). 72h. Purification by flash chromatography (40% EtOAc/hexanes). run 1 (57%, [B: L] = [17: 1] ), run 2 (54%, [18: 1] ), run 3: (58% yield, [17: 1] ), run 4: (54%, [18: 1] ). Average four runs: 56%, [B: L] = [95: 5].

'H NMR (400 MHz, CDC13) 6 5.78 (ddd, J = 17.2, 11.2, 6.4 Hz, 1H), 5.24 (m, 1H), 5.24 (app dt, J = 17.6, 1.2 Hz, 1H), 5.16 (app dt, J = 10.4, 1.2 Hz), 3.36 (q, J = 7.2 Hz, 2H), 3.28 (q, J = 7. 2 Hz, 2H), 2.30 (m, 2H), 2.06 (s, 3H), 1.68 (m, 4H), 1.16 (t, J = 7.2 Hz, 3H), 1.10 (t, J = 7. 2 Hz, 3H); 13C NMR (100 MHz, CDC13) 5 171.5, 170.4, 136. 3,116. 8,74. 4,41. 9, 40.1, 33. 8, 32.5, 21.2, 20.8, 14.3, 13.1 ; IR (film, cm-1) : 2972,2936, 1738, 1642,1460, 1429,1373, 1240,1144, 1098,1020, 964,928, 797,608 ; HRMS (ESI) tnlz calc'd C13H24NO3 [M+H] + : 242.1756, found 242.1753.

Entry 5: 1-benzyloxy-4-pentene (1.0 mmol, 176.3 mg). 72h. Purification by flash chromatography (3% EtOAc/hexanes). run 1 (58%, [B: L] = [18: 1] ), run 2 (62%, [18: 1] ), run 3 : (57% yield, [18: 1]). Average three runs : 59%, [B: L] = [95: 5]. 1H NMR (400 MHz, CDC13) 5 7.36-7. 26 (m, 5H), 5.80 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.42 (m, 1H), 5.24 (app dt, J = 17. 2,1. 6 Hz, 1H), 5.17 (app dt, J = 10.4, 1.2 Hz, 1H), 4.48 (d, J = 2 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 2.02 (s, 3H), 1.94 (m, 2H) ; 13C NMR (100 MHz, CDC13) 8 170.2, 138. 2, 136.2, 128.3, 127.7, 127.6, 116.7, 73.0, 72.1, 66.1, 34.3, 21.1 ; IR (film, cm-1) : 3088,3065, 3030,2926, 2863,1740, 1647,1497, 1454,1371, 1238, 1101,1022, 932,739, 698,608 ; HRMS (ESI) m/z calc'd Cl4Hl903 [M+H] + : 235.1334, found 235.1335.

Entry 6: phenyl-carbamic acid hex-5-enyl ester (1.0 mmol, 219.3 mg). 72h. Purification by flash chromatography (12% EtOAc/hexanes # 15% EtOAc/hexanes). run 1 (66%, [B: L] [25: 1] ), run 2 (66%, [25: 1] ), run 3: (60% yield, [27: 1] ). Average three runs: 64%, [B: L] = [96: 4]. 1H NMR (400 MHz, CDC13) d 7. 38 (brd, J= 7. 6 Hz, 2H), 7. 30 (t, J= 7.6 Hz, 2H), 7.05 (t, J= 7.2 Hz, 1H), 6.71 (brs, 1H), 5. 78 (ddd, J = 17. 4,10. 4,6. 4, 1H), 5. 32 (m, 1H), 5.25 (app dt, J = 17. 2,1. 6, 1H), 5.19 (app dt, J= 10. 4,1. 2 Hz, 1H) 4.17 (t, J = 6.0 Hz, 2H), 2.07 (s, 3H), 1.73 (m, 4H) ; 13C NMR (100 MHz, CDCl3) # 170. 5,153. 4, 137.8, 136.1, 129.0, 123.4, 118.6, 117.0, 74.2, 64. 8, 30.8, 24.6, 21.2 ; IR (film, cm'') : 3329 (br), 3196,3138, 3063,2957, 2859, 1734 (br, shoulder 1716), 1601,1539, 1225; HRMS (ESI) m/z calc'd for ClsH2oNo4 [M+H] + : 278.1392, found 278. 1391.

Entry 7: (tert-butyldiphenylsiloxy)-2, 7-octadiene (1.0 mmol, 364.6 mg). 72h. Dioxane was removed by stripping the crude with 3 x 10 mL of chloroform and placing it under high vacumn for 15-30 min. Branched to linear allylic acetate ratios were determined from 1H NMR (500 MHz) spectra of the crude. Purification by flash chromatography (3% EtOAc/hexanes). run 1 (53%, [B: L] = [26: 1] ), run 2 (58%, [35: 1] ), run 3: (58% yield, [32: 1] ). Average three runs: 56%, [B: L] = [>95 : 5].'H NMR (400 MHz, CDC13) 8 7.68 (m, 4H), 7.39 (m, 6H), 5. 78 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.65 (dtt, J = 15.2, 6.4, 1.2 Hz, 1H), 5. 55 (dtt, J = 15.2, 4.8, 1.2 Hz, 1H), 5.24 (m, 1H), 5.24 (app dt, J = 17.2, 1.2 Hz, 1H), 5.18 (app dt, J = 10.4, 1.2 Hz, 1H), 4.15 (dd, J = 5.2, 1.2 Hz, 2H), 2.07 (s, 3H), 2.06 (m, 2H), 1.69 (m, 2H), 1.06 (s, 9H) ; 13C NMR (100 MHz, CDC13) 8 170.3, 136.3, 135.5, 133.8, 129.61, 129.56, 129.5, 127.6, 116.8, 74.3, 64.4, 33.6, 27.8, 26.8, 21.2, 19.2 ; IR (film, cm'') : 3073,3050, 3017,2932, 2859,1740, 1472,1427, 1371, 1238, 1111,1047, 1024,968, 823, 741,702, 611, 505,405 ; HRMS (ESI) m/z calc'd C26H3503Si [M+H] + : 423.2355, found 423.2358.

Entry 8: 7-methyl-1, 6-octadiene (1.0 mmol, 124.2 mg). 72h. Dioxane was removed by stripping the crude with 3 x 10 mL of chloroform and placing it under high vacumn for 15- 30 min. Branched to linear allylic acetate ratios were determined from 1H NMR (500 MHz) spectra of the crude. Purification by flash chromatography (3% EtOAc/hexanes). run 1 (54%, [B: L] = [15: 1] ), run 2 (58%, [20: 1] ), run 3: (58% yield, [22: 1] ). Average three runs: 57%, [B: L] = [95: 5]. lH NMR (400 MHz, CDC13) 8 5.77 (ddd, J = 17.2, 10.8, 6.4 Hz, 1H),

5.22 (app dt, J = 17.2, 1.2 Hz, 1H), 5.21 (m, 1H), 5.16 (app dt, J = 10.4, 1.2 Hz, 1H), 5. 08, 2.06 (s, 3H), 2.00 (m, 2H), 1.68 (bd, J = 1.2 Hz, 3H), 1.66-1. 58 (m, 2H), 1. 58 (bs, 3H); 13C NMR (100 MHz, CDC13) 8 170.4, 136. 5,132. 3,123. 2,116. 6,74. 4,34. 2,25. 7,23. 7,21. 2, 17.6 ; IR (film, cm-1) : 3086,2969, 2928, 2859, 1742,1647, 1439,1373, 1238,1099, 1020, 990, 961,930, 833,610 ; LRMS (CI, NH3) m/z calc'd for CllHz2NOz [M+NH4] + 200, found 200.

Entry 9: 1-undecene (1.0 mmol, 154.3 mg). 48h. Purification by flash chromatography (2% EtOAc/hexanes). run 1 (71%, [B: L] = [43: 1] ), run2 (74%, [31 : 1]), run 3: (68% yield, [36: 1] ). Average three runs: 71%, [B: L] = [97: 3]. 1H NMR (400 MHz, CDC13) 8 8.06 (m, 2H), 7. 56 (tt, J = 8,1. 6 Hz), 7.44 (app td, J = 6.4, 1.6 Hz, 2H), 5.90 (ddd, J = 17.2, 11.2, 6.4 Hz, 1H), 5.49 (m, 1H), 5.32 (app dt, J = 17.2, 1.2 Hz, 1H), 5.20 (app dt, J = 10.8, 1.2 Hz, 1H), 1.75 (m, 2H), 1.26 (m, 12H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDC13) 8 165.9, 136.6, 132.8, 130.6, 129.6, 128.3, 116. 5, 75.4, 34.3, 31. 8, 29.44, 29.39, 29.2, 25. 1, 22.6, 14.1 ; IR (film, cm-1) : 3090,3071, 2928,2857, 2361,2340, 1723,1657, 1603,1452, 1271,1177, 1111,1069, 1026,932, 712; HRMS (EI) m/z calc'd [C18H26O2]+ : 274.1933, found 274.1926.

Entry 10: 1-undecene (1.0 mmol, 154.3 mg). 72h. Purification by flash chromatography (2% EtOAc/hexanes). run 1 (72%, [B: L] = [44: 1] ), run 2 (71%, [35: 1] ), run 3: (67% yield, [45: 1] ). Average three runs: 70%, [B: L] = [98: 2].'HNMR (400 MHz, CDC13) 8 8. 02 (app dt, J = 9.2, 2.4 Hz, 2H), 6.92 (app dt, J = 9.2, 2.4 Hz, 2H), 5. 89 (ddd, J = 17.2, 10.8, 6 Hz, 1H), 5.46 (m, 1H), 5.30 (app dt, J = 17.2, 1.2 Hz, 1H), 5. 18 (app dt, J = 10.4, 1.2 Hz, 1H), 3.86 (s, 3H), 1.73 (m, 2H), 1.26 (m, 12H), 0.87 (t, J = 7.6 Hz); 13C NMR (100 MHz, CDC13) 8 165.7, 163.3, 136.9, 131.6, 123.0, 116.3, 113.6, 75.0, 55.4, 34.4, 31. 8, 29.5, 29.4, 29.2, 25.1, 22.6, 14.1 ; IR (film, cm-1) : 3082,2928, 2857,1713, 1657, 1607,1512, 1464, 1422,1258, 1167,1101, 1032,930, 847,770, 696,611 ; HRMS (ESI) 771/Z calc'd ClsH2go3 [M+H] + : 305. 2116, found 305. 2118.

Entry 11: 1-undecene (1.0 mmol, 154.3 mg). 48h. Purification by flash chromatography <BR> <BR> <BR> (2% EtOAc/hexanes). run 1 (75%, [B: L] = [48: 1] ), run 2 (77%, [48 : 1] ), run 3: (71% yield,

[43: 1] ). Average three runs: 74%, [B: L] = [98: 2]. lH NMR (400 MHz, CDC13) 8 7.92 (app dt, J = 8.8, 2 Hz, 2H), 7. 58 (app dt, J = 8.4, 2 Hz, 2H), 5. 88 (ddd, J = 17.2, 10.8, 6.4 Hz, 1H), 5.46 (m, 1H), 5. 30 (app dt, J = 17.2, 1.2 Hz, 1H), 5.20 (dt, J = 10.4, 1.2 Hz, 1H), 1.74 (m, 2H), 1.26 (m, 12H), 0. 87 (t, J = 7. 2 Hz, 3H) ; 13C NMR (100 MHz, CDC13) 8 165.1, 136.4, 131.7, 131.1, 129.5, 127.9, 116.8, 75.8, 34.3, 31. 8, 29.42, 29.36, 29.2, 25.1, 22.6, 14.1 ; IR (film, cm'') : 3088,2926, 2857, 1723,1591, 1466,1398, 1269,1173, 1101,1013, 932,847, 756; HRMS (EI) m/z calc'd [Cl8H25BrO2] + : 352.1038, found 352.1031.

Entry 12: 1-undecene (1.0 mmol, 154.3 mg). 48h. Dioxane was removed by stripping the crude with 3 x 10 mL of chloroform and placing it under high vacumn for 15-30 min.

Branched to linear allylic acetate ratios were determined from 1H NMR (500 MHz) spectra of the crude. Purification by flash chromatography (2% EtOAc/hexanes). run 1 (83%, [B: L] = [42: 1] ), run 2 (82%, [52: 1] ), run 3: (83% yield, [33: 1]). Average three runs: 83%, [B: L] = [>95: 5]. lH NMR (400 MHz, CDC13) 8 8.29 (app dt, J = 9.2, 2 Hz, 2H), 8.22 (app dt, J = 9.2 Hz, 2 Hz), 5.89 (dd, J = 17.2, 10.8, 6.4 Hz, 1H), 5.50 (m, 1H), 5.33 (app dt, J = 17.2, 1.2 Hz, 1H), 5.24 (app dt, J = 10.4, 1.2 Hz), 1. 78 (m, 2H), 1.29 (m, 12H), 0.87 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDC13) 6 164.0, 150.1, 136.0, 135.9, 130.7, 124.9, 123.5, 117.5, 34.2, 31.8, 29.4, 29.3, 29.2, 25.1, 22.6, 14.1 ; IR (film, cm-1) : 3086,2928, 2857,1726, 1657, 1609,1530, 1466, 1412, 1348, 1319,1273, 1170,1117, 1106,1014, 988, 934,874, 835, 785,719 ; HRMS (EI) m/z calc'd [Cl8H25NO41+ : 319.1784, found 319.1783.

Entry 13: 1-undecene (1.0 mmol, 154.3 mg). 48h. Purification by flash chromatography (2% EtOAc/hexanes). run 1 (63%, [B: L] = [32: 1] ), run 2 (65%, [31 : 1] ), run 3: (64% yield, [33: 1] ). Average three runs: 64%, [B: L] = [97: 3]. lH NMR (400 MHz, CDC13) 8 5. 78 (ddd, J = 17.6, 10.4, 6.4 Hz, 1H), 5.22 (m, 1H), 5.22 (app dt, J = 17.2, 1.2 Hz, 1H), 5.13 (app dt, J = 10.4, 1.2 Hz, 1H), 2.55 (app, J = 6.8 Hz, 1H), 1.27 (m, 14H), 1. 18 (d, J = 7.2 Hz, 3H), 1.17 (d, J = 7.2 Hz), 0. 88 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDC13) 8 176.4, 136.8, 116.1, 74.3, 34.2, 31.8, 31.6, 29.4, 29.3, 29.2, 25.0, 22.6, 19.0, 18.9, 14.1 ; IR (film, cm-1) : 3086,2957, 2928,2857, 1738,1657, 1468,1387, 1256,1192, 1157,1069, 970,930 ; HRMS (EI) m/z calc'd [ClsH2sO2] + : 240.2089, found 240.2093.

Entry 14: 2-hydroxy-benzoic acid hex-5-enyl ester (1.0 mmol, 220.3 mg). 72h. Dioxane was removed by stripping the crude with 3 x 10 mL of chloroform and placing it under high vacumn for 15-30 min. Branched to linear allylic acetate ratios were determined from 1H NMR (500 MHz) spectra of the crude. Purification by flash chromatography (5% EtOAc/hexanes). run 1 (63%, [B: L] = [26: 1] ), run 2 (62%, [35: 1] ), run 3: (65% yield, [19: 1] ), run 4 : (68% yield, [19: 1]). Average three runs : 65%, [B: L] = [>95: 5].'H NMR (400 MHz, CDC13) 8 10.76 (s, 1H), 7.91 (app dt, J = 8.8, 2 Hz, 2H), 7.82 (app dd, J = 8,2 Hz, 1H), 7. 58 (app dt, J = 8.8, 2 Hz, 2H), 7.46 (m, 1H), 6. 98 (app dd, J = 12.2, 2 Hz, 1H), 6.87 (m, 1H), 5.90 (ddd, J = 17.2, 10.4, 6.4 Hz, 1H), 5.56 (m, 1H), 5.36 (app dt, J = 17.2, 1.2 Hz, 1H), 5.27 (app dt, J = 10.4, 1.2 Hz, 1H), 4.39 (m, 2H), 1.92 (m, 4H); 13C NMR (100 MHz, CDC13) 8 170.1, 165.0, 161.7, 135. 73, 135. 69,131. 8, 131.1, 129.8, 129.1, 128.2, 119.1, 117.61, 117.57, 112.4, 75.0, 64.8, 30. 7,24. 4; IR (film, cm'') : 3190,3150, 3096, 2957,2859, 1721,1674, 1615,1589, 1485, 1398, 1327,1302, 1267,1213, 1157,1101, 1013,951, 847, 756,702 ; HRMS (CI, NH4) m/z calc'd C2oH23BrNO5 [M+NH4] + : 437.0760, found 436.0743.

Incorporation by Reference All of the U. S. patents and U. S. patent application publications cited herein are hereby incorporated by reference.

Equivalents Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.