Epoxides are widely utilized as versatile synthetic intermediates. Their reactions are dominated by the electrophilic nature of the epoxiue, generally involving cleavage of the strained three-membered ring and include a wide range of nucleophilic ring openings and acid-and base-induced isomerization reactions. The alkylative deoxygenation of epoxides using organolithiums to give substituted alkenes is known.

The present invention is based on the finding that the alkylative deoxygenation can be applied to epoxides of oxygen-containing and heterocycles thereby giving rise to substituted alkenediols. This is particularly surprising for 5- membered heterocycles because p-elimination from the presumed lithiated intermediate is the reverse of a stereoelectronically disfavoured 5-endo-trig cyclisation. These alcohols find utility as intermediates in organic synthesis.

According to the present invention there is provided a process for preparing a substituted alkene diol of the formula: wherein n is 0 to 4, R is an unsubstituted or substituted aliphatic or aromatic radical, R'is hydrogen or an aliphatic (or aromatic) radical and each of R2, R3, R4 and R5 which are the same or different, is hydrogen, or an unsubstituted or substituted aliphatic or aromatic radical or R2 and R3 together form a divalent radical having 1 to 4 chain carbon atoms which comprises reacting an epoxide of the formula:

wherein n, R', R2, R3, R4 and R5 are as defined above with an organolithium compound of the formula: RLi wherein R is as defined above.

The alkylative double ring-opening process of the present invention can be illustrated by the following reaction scheme where, for simplicity, R', R2 and R3 are all hydrogen.

The process of the present invention is typically carried out in a solvent.

Suitable solvents include ethereal solvents such as dialkyl ethers, for example diethyl ether, as well as cyclic ethers such as tetrahydrofuran which is particularly preferred.

In addition, hydrocarbon solvents can also be used. These can be aliphatic such as hexane and pentane or aromatic such as cumene.

In order to control the decomposition of the lithiated intermediate which is believed to be formed, it is desirable to carry out the lithiation reaction at a temperature not exceeding room temperature (20°C) and desirably not exceeding 0°C. In general, temperatures from-78°C to-90°C are suitable. Thus, typically, a

solution of the epoxide in the solvent is cooled and the organolithium added to it. As one of skill in the art will know, lithiation reactions can be very rapid or they can take up to, say, two hours. After the reaction, generally involving warming to room temperature, the desired product can be worked up in a standard way, quenching the reaction, typically using methanol.

Typically, roughly 2 equivalents of organolithium are employed per mole of epoxide. In general, 2 to 5 times, e. g. about 2.5 to 3.5, times the stoichiometric amount of organolithium compound can generally be employed. n is 0 to 4, preferably 0 or 1 i. e. the starting materials are preferably epoxides of reduced furans or pyrans. The ring can itself be substituted-by R', R2 and R3.

The process has broad applicability in that a wide variety of lithium compounds can be used. Thus R can be, for example, an optionally substituted primary, secondary or tertiary alkyl group, especially with 1 to 6, for example 3 or 4, carbon atoms and preferably branched, such as methyl, isopropyl and primary, secondary and tertiary butyl or an aryl group such as phenyl or heteroaryl such as furanyl, especially 2-furanyl. Similar comments apply to R2, R3, R4 and R5 which are typically methyl such as methoxy methyl. Thus the aliphatic groups are typically alkyl groups although they can be unsaturated e. g. ethylenically unsaturated i. e. alkenyl, especially in the terminal position as in but-4-enyl. R2 and R3 can also together form a divalent radical thus forming a bridge, typically possessing 1,2, which is preferred, or 3 chain carbon atoms. These carbon atoms can be substituted as in disubstituted ethylene, typically by the substituents given below, for example alkoxy, alkoxyalkyl such as methoxymethyl or trialkylsilyloxy such as t- butyldimethylsilyloxy, and can form part of a fused ring which can be aromatic as in benzene or cycloaliphatic, for example 1,2-phenylene or 2,3-cyclopropylene 1-one or a protected derivative thereof such as an acetal e. g. the neopentyl acetal.

As indicated R'is hydrogen or an aliphatic or aromatic radical especially an alkyl radical, for example one as indicated above for R, i. e. the epoxide ring can be substituted. Typical substituents include methyl and pentyl.

The various groups which R, R, R2, R3, R4 and R5 can represent can be substituted.

The nature of the substituents present is generally unimportant although it is preferred to exclude any substituent which is sensitive to base or is susceptible to nucleophilic attack, since this can result in the organolithium reacting with this substituent rather than at the desired epoxide position. Thus, in general, the presence of carbonyl group-containing substituents derived from aldehydes, ketones and esters should be avoided, although it is possible to protect them with base-stable protecting groups.

As used herein, an alkyl group is typically a linear or branched alkyl group containing from 1 to 6 carbon atoms, such as a C,-C4 alkyl group, for example methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl and t-butyl or a higher alkyl group having 6 to 18, typically 6,8 or 10, carbon atoms.

An alkyl group may be unsubstituted or substituted at any position.

Typically, it is unsubstituted or carries one or two substituents. Suitable substituents include aryl, halogen and silyl-oxy, for example trialkylsilyloxy e. g. tert-butyl dimethyl silyloxy as in 3-tertbutyl dimethyl silyloxy propyl, especially for R, and trialkylsilyl, for example trimethylsilyl as, for example, in 1-trimethylsilyl-hexyl, especially for R. The presence of such a trialkylsilyl substituent on a C, substitutent e. g. methyl is particularly useful, especially for R. By this means a wide range of electrophiles can subsequently be introduced into the molecule if an appropriate lithium compound of the type LiCXY (TAS) where TAS is typically trimethylsilyl and X and Y are independently hydrogen or alkyl groups is used.

Unsaturated aliphatic groups include ethylenically unsaturated groups having, typically, the same number of atoms and substituents as indicated above for the alkyl group. Typically the terminal group is unsaturated as in, for example, but-4-enyl.

As used herein, an aryl group is typically a C6-Clo aryl group such as phenyl or naphthyl. Phenyl is preferred. An aryl group may be unsubstituted or substituted at any position. Typically, it carries 1,2, 3 or 4 substituents. Suitable substituents

include aryl, heteroaryl and heterocyclic groups, halogen, alkyl, for example haloalkyl, alkylthio, alkoxy, for example chloroalkoxy and hydroxy.

An aryl group may optionally be fused to a further said aryl group or to a carbocyclic, heterocyclic or heteroaryl group. For example, it may be fused to a pyridine ring to form a quinoline group, or to a 1,4 dioxane or 1,3 dioxolane ring.

As used herein, a silyl group is typically a tri (alkyl/aryl) silyl group i. e. a silyl group substituted by 3 alkyl and/or aryl groups, typically by 3 alkyl groups, which is preferred, or 3 aryl groups. The alkyl (and aryl) groups need not all be the same. A specific example is t-butyl, dimethylsilyl.

As used herein, a halogen is typically chlorine, fluorine or bromine As used herein, a heterocyclic group is typically a non-aromatic, saturated or unsaturated C5-Cxo carbocyclic ring in which one or more, for example 1,2 or 3, of the carbon atoms are replaced by a heteroatom selected from N, O and S. Saturated heterocyclic groups are preferred. Examples of suitable heterocyclic groups include piperidine, morpholine, 1,4 dioxane and 1,3 dioxolane.

A heterocyclic group may be unsubstituted or substituted at any position.

Suitable substituents include nitro, halogen, alkyl, for example haloalkyl, alkylthio, alkoxy, for example haloalkoxy or hydroxy.

This process has a particular advantage in that if the starting material is a particular isomer then the end products will also be a particular isomer i. e. the stereochemistry of the starting material faithfully translates into the stereochemistry in the product. Thus methylation and epoxidation of cis-2, 5-bis (hydroxymethyl)-2, 5- dihydrofuran gave a chromatographically separable mixture of epoxides and as shown below: OR OMe OMe CF3COCH3, Oxone, 2. 5%, 3. 5% r NaHC03. Na2EDTAn 0/~D0 + O D° MeCN, HzO, 0 °C, 3 h, 76% . 8°/u J 1. 0% OR OMe OMe 10 : 7 17 R = H 1NaH, Mel, THF, $ 19 R = Me oJ25 °C, 16 h, 75%

On treatment with n-BuLi each diastereomeric epoxide gave a geometric isomer of the same trisubstituted olefin. Thus cis, trans-A exclusively gave the E- olefin B in 90% yield, and cis, cis-C exclusively gave the Z-olefin D in 65% yield see below:

Furthermore the process can be used for asymmetric/enantioselective reactions if an external chiral ligand is present using similar reaction conditions. For epoxides which are achiral a racemate will normally be obtained. However a specific enantiomer can be obtained using an external chiral base, typically a ditertiarydiamine such as (-) -sparteine or a bisoxazoline typically having the formula :

where each R, and R2, which may be the same or different, is an alkyl substituent, typically of 1 to 4 carbon atoms, such as ethyl, isopropyl, isobutyl and tert. butyl.

Preferred compounds include valine and tert. leucine derived ligands where R, = isopropyl or tert. butyl and R2= ethyl or R, = isopropyl and R2= isobutyl. This is useful for the preparation of, for example, cycloheptene and arene-1, 2-diols.

Some of the epoxide starting materials are commercially available or, at least, known. Others are novel, in particular those where R'is not hydrogen and those where one or both of R2 is and R3 are not hydrogen.

The cyclic epoxides can generally be obtained from the corresponding cyclic- ene; this can, in turn, be obtained from an a, m-diene, as follows: 0 <\0 () metathesis g)) P ; 0-n 6- n = 14

Bridged compounds can generally be obtained by cycloaddition, for example by reacting benzyne with furan and then epoxidising the unsaturation. 8-oxa bicyclo [3.2. 1] octanes can be obtained from furans by an oxyallyl [4+3] cycloaddition reaction.

Compounds where R and/or R3 is a substituent can generally be prepared from the corresponding dihydro ring compound by epoxidation.

Particularly useful compounds which can be prepared by the process include the allylsilane of formula: Compounds wherein R is trialkylsilylalkyl, especially trimethylsilylmethyl and 1-trimethylsilylhexyl, trialkylsilyloxy such as trimethylsilyloxy, alkenyl, especially where the double bond is terminal or heteroaryl form another aspect of the present invention along with compounds where at least one of R'R'and R'is not hydrogen.

The reaction can also be carried out with the corresponding nitrogen heterocycles provided the nitrogen atom is protected, as one skilled in the art will appreciate.

The following Examples further illustrate the present invention.

Example 1: 3-Methylideneheptane-1, 2-diol

To a stirred solution of 3, 4-epoxytetrahydrofuran (80 mg, 0.93 mmol) in THF (5.0 mL) at-78 °C was added dropwise over 10 min n-BuLi (2.20 M in hexanes, 1.06 mL, 2.33 mmol). The reaction mixture was then allowed to warm to 25 °C over 1 h, followed by addition of MeOH (0.5 mL) and preabsorption onto silica gel (2.5 g). Purification by column chromatography on silica gel (petrol/diethyl ether 1/9) gave the product as a colourless oil (121 mg, 90%); Rf 0. 35 (diethyl ether); vmax/cm-1 (Thin Film) 3368, 2957, 2930, 1458, 1074,1029, 903; SH (400 MHz) 5.05 (1 H, s), 4.87 (1 H, s), 4.12 (1 H, d, J6. 8Hz), 3.97 (1 H, brs), 3.89 (1 H, brs), 3.62 (1 H, d, J 11. 2 Hz), 3.44 (1 H, dd, J 11. 2 and 8. 0 Hz), 2.05-1. 88 (2 H, m), 1.43-1. 36 (2 H, m), 1.33-1. 24 (2 H, m), 0.87 (3 H, t, J7. 2 Hz); #C (100 MHz) 148.5, 110.2, 75.1, 66.2, 32.3, 30.5, 22.5, 13.91 ; m/z [CIMS] 162 (M + NH4+, 100), 128 (50); HRMS cald for C8H20NO2 162.1494, found 162.1494.

Example 2: 4-(Trimethylsilyl)-3-methylidenebutane-1, 2-diol Following Example 1,3, 4-epoxytetrahydrofuran was reacted with TMSCH2Li (1.0 mol dm~3 in pentane, 2.32 cm3), giving the product as a colourless oil (119 mg, 73%); Rf0. 27 (75% Et20 in petrol); vmax/cm-1 (Thin Film) 3392,2954, 1743,1638, 1418,1249, 1158,1074, 844; i (400 MHz) 4.83 (1 H, s), 4.59 (1 H, s), 3.91-3. 86 (1 H, m), 3. 57-3. 50 (1 H, m), 3.34-3. 20 (3 H, m), 1.46 (1 H, d, J 14. 0 Hz), 1.21 (1 H, d, J 14.0 Hz), -0.12 (9 H, s); gc (100 MHz) 146.0, 108.2, 75.6, 65.5, 23.3,-1. 5.

Example 3: 3-Phenylbut-3-ene-1, 2-diol

Following Example 1,3, 4-epoxytetrahydrofuran was reacted with PhLi (1.5 mol dm-3 in cyclohexane/Et23O, 1. 55 cm3), giving the product as a white solid (85 mg, 56%); Rf 0.24 (90% Et20 in petrol); mp. 93.0-95. 0 °C ; vma"/cm~l (KBr) 3223,2926, 1494,1442, 1126,1045, 933,784s ; #H (400 MHz, MeOH-d4) 7.40 (2 H, d, J 8.6 Hz), 7. 33 - 7. 24 (3 H, m), 5.44 (1 H, s), 5. 36 (1 H, s), 4.93 (2 H, s) 4.71 (1 H, dd, J 7. 6 and 3. 2 Hz), 3.56 (1 H, dd, J 11. 4 and 3. 2 Hz), 3. 38 (1 H, dd, J 11.4 and 7.6 Hz) ; dC (100 MHz, MeOH-d4) 150.7, 141.6, 129.5, 128.8, 127.8, 114.1, 75.5, 66.9.

Example 4: cis-2, 5-Bis (methoxymethyl) -2, 5-dihydrofuran To a solution cis-2, 5-bis (hydroxyoxymethyl) -2, 5-dihydrofuran (C. de Micheli, M. de Amici, E. Grana, F. Zonta, M. Giannella and A. Piergentili, Farmaco, 1993,48, 1333) (1.28 g, 10 mmol) and MeI (6.4 cm3, 100 mmol, 10 eq. ) in THF (10 cm 3mmol-', 100 cm3) was added NaH (60% suspension on mineral oil, 2.0 g, 50 mmol, 5 eq. ) portionwise over 20 min.

After stirring at room temperature for 16 h the reaction mixture was poured into sat. aq. NH4Cl (200 cm3) and extracted with CH2Cl2 (2 x 100 cm3), the combined

organics were dried (MgSO4), filtered and concentrated under reduced pressure.

Purification of the residue by column chromatography (SiO2, 75% Et2O in petrol) gave the product as a colourless oil (1.18 g, 75%); Rf 0. 30 (75% Et2O in petrol); vmax/cm-1 (Film) 2878,1453, 1358,1195, 1096,949, 922,761 ; i (400 MHz) 5.85 (2 H, s), 4.93-4. 90 (2 H, m), 3.46-3. 38 (4 H, m), 3.36 (6 H, s); dC (100 MHz) 128.6, 85.4, 75.8, 59.2. cis, trans-and cis, cis-2, 5-Bis (methoxymethyl) -3, 4-epoxytetrahydrofuran Following the procedure of D. Yang, M. K. Wong and Y. C. Yip, J. Org. Chem., 1995,60, 3887, to a solution of cis-2, 5-bis (methoxymethyl) -2, 5-dihydrofuran (1.26 g, 7.95 mmol) and Na2EDTA (400 µmol dm-3 in H2O, 40 cm3, 16 µmol, 0.002 eq. ) in MeCN (7.5 cm3 mmol'', 60 cm3) at 0 °C was added trifluoroacetone (7.9 cm3, 87.5 mmol, 11 eq. ) from a pre-cooled syringe. The resulting homogeneous mixture was treated with a mixture of Oxonee (24.5 g, 39.8 mmol, 5 eq. ) and NaHCO3 (5.4 g, 63.6 mmol, 8 eq. ) portionwise over 20 minutes, and then stirred at 0 °C for 3 h.

H2O (230 cm3) was added and the reaction mixture extracted with CH2Cl2 (3 x 170 cm3). The combined organics were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% then 75% Et2O in petrol) gave both diastereomers of the epoxide.

First to elute was the cis, trans-isomer, a colourless oil (0.65 g, 45%); Rf 0.31 (75% Et2O in petrol); t/cm-' (Film) 2928,1458, 1197,1126, 1089, 851 ; #H(400

MHz) 4.20 (2 H, t, J 4.8 Hz), 3.74 (2 H, s), 3.46 (4 H, dq, J 10. 0 and 4. 8 Hz), 3. 36 (6 H, s); dc (100 MHz) 77.5, 72.8, 59.2, 58.9 ;'H NOE experiments: irradiation at 8 3.74 saw enhancement at 4.20 (2.5%) and at 3.46 (1.8%).

Second to elute was the cis, cis-isomer, a pale yellow oil (0.45 g, 31%) ; Rf 0.23 (75% Et2O in petrol) ; vmax/cm-1 (Film) 2897,1461, 1199,1136, 1109,967, 929, 892; #H (400 MHz) 4.01 (2 H, t, J6. 4 Hz), 3.75 (2 H, s), 3. 53 (4 H, d, J 6. 4 Hz), 3. 39 (6 H, s); #C (100 MHz) 76.3, 71.1, 59. 3, 56. 6 ;'H NOE experiments: irradiation at 8 3.75 saw enhancement at 4.01 (3.5%) and at 3.53 (1.0%).

(E)-(2SR,3RS)-1-Methoxy-4-(2-methoxyethylidene)-octane-2, 3-diol Following Example 1, cis, trans-2, 5-bis (methoxymethyl) -3, 4- epoxytetrahydrofuran (80 mg, 459 punol was reacted with n-BuLi (2.3 mol dm-3 in hexanes, 0.50 cm3, 1. 15 mmol, 2.5 eq. ), giving the product as a pale yellow oil (96 mg, 90%); Rf 0. 23 (75% EtOAc in petrol); vmax/cm-1 (Film) 3436,2929, 2821,1456, 1379, 1193,1092, 958 ; #H (400 MHz) 5.69 (1 H, t, J6. 4 Hz), 4.19 (1 H, br d, J 5. 6 Hz), 4.05-3. 95 (2 H, m), 3.82-3. 78 (1 H, m), 3.54-3. 50 (2 H, m), 3.36 (3 H, s), 3. 32 (3 H, s), 2.98 (1 H, br s), 2.91 (1 H, br s), 2.19-2. 11 (1 H, m), 1.97-1. 90 (1 H, m), 1.42-1. 23 (4 H, m), 0.89 (3 H, t, J7. 2 Hz); #C (100 MHz) 142.5, 123.5, 76.4, 73.3, 70.7, 68.5, 59.2, 58.1, 31.8, 28.2, 23.0, 13.8.

(Z)- (2RS, 3RS)-1-Methoxy-4- (2-methoxyethylidene)-octane-2, 3-diol

Likewise, cis, cis-2, 5-bis (methoxymethyl)-3, 4-epoxytetrahydrofuran (80 mg, 459 pmol) was reacted with n-BuLi (2.3 mol dm~3 in hexanes, 0.50 cm3, 1.15 mmol, 2.5 eq. ), giving the product as a pale yellow oil (66 mg, 65%); Rf 0.19 (75% EtOAc in petrol) ; vmax/cm-1 (Film) 3401,2929, 1658,1457, 1194,1092 ; #H(400 MHz) 5.54 (1 H, t, J 6. 4 Hz), 4.42 (1 H, br d, J 7. 2 Hz), 4.07 (1 H, dd, J 12. 0 and 7. 2 Hz), 3. 95 (1 H, dd, J 12. 0 and 6. 0 Hz), 3.78-3. 74 (1 H, m), 3.45-3. 29 (2 H, m), 3.36 (3 H, s), 3.34 (3 H, s), 3.05 (2 H, br s), 2.19-2. 12 (1 H, m), 2.01-1. 93 (1 H, m), 1.49-1. 41 (2 H, m), 1. 38-1. 29 (2 H, m), 0.90 (3 H, t, J7. 2 Hz) ; #C (100 MHz) 142.7, 128.6, 73.2, 72.1, 71.6, 68.2, 59.1, 58.1, 31.6, 30.8, 22.6, 14.0.

Example 5: 4-Methylidene-octane-1, 3-diol

Following Example 1,3, 4-epoxytetrahydropyran (se G. Berti, G. Catelani, M.

Ferretti & L. Monti, Tetrahedron, 1974,4013) (80 mg, 800 pool) was reacted with n- BuLi (2.3 mol dm-3 in hexanes, 0.87 cm3, 2.0 mmol, 2.5 eq. ), giving the product as a colourless oil (75 mg, 60%); Rf 0.22 (90% Et20 in petrol) ; vma, cm~l (Film) 3350, 2929,2872, 1456,1052 ; #H (400 MHz) 5.06 (1 H, s), 4.85 (1 H, s), 4.28 (1 H, dd, J 8. 2 and 3. 2 Hz), 3.84-3. 73 (2 H, m), 3.30 (2 H, br s), 2.07-1. 93 (2 H, m), 1.84- 1.70 (2 H, m), 1.47-1. 29 (4 H, m), 0.90 (3 H, t, J7. 2 Hz); (5c (100 MHz) 151.7, 108.9, 74.6, 61. 1, 36.8, 31.5, 30.1, 22.6, 14.0 ; m/z [CI + NH3] 176 (M +NH4+, 100%) and 158 (M + H+, 20) (Found: M + H+, 159.1386. C9H, 902 requires 159.1385).

Example 6: 3,4-Epoxy-4-methyltetrahydropyran To a solution of tetrahydropyran-4-one (5.4 g, 54 mmol) in Et2O (2 cm3 mmol'', 100 cm3) was added dropwise a solution of MeMgBr in Et2O (3.0 mol dm-3, 36 cm3, 108 mmol, 2 eq. ) over 30-45 min, a water bath being used to prevent vigorous reflux. After complete addition external heating was applied such that a gentle reflux was maintained for 2 h. HCl (6 mol dm-3 in H2O, 60 cm') was cautiously added to the cooled solution, the organic layer separated, dried (MgSO4), filtered and concentrated under reduced pressure to give crude 4- methyltetrahydropyran-4-ol as a pale yellow oil (3.12 g, #50%).

To this material was added solid KHSO4 (2.85 g, 21 mmol,-1 eq. ), the mixture was heated at 140 °C for 1 h, then under distillation conditions at 150 °C,

affording a mixture of endo-and exo-cyclic alkenes (-4 : 1,'H NMR) as a colourless oil (bp. 130 °C) (2.30 g, quant.).

To a solution of the mixture of alkenes in CH2Cl23 (4 cm3 mmol'', 90 cm3) at- 10 °C was added mCPBA (55% in H2O, 7.7 g, 24.7 mmol, 1. 1 eq. ) and the mixture was allowed to attain room temperature over 16 h.

Sat. aq. Na2SO3 (80 cm3) was added and the mixture stirred vigorously for 5 min. The organic phase was separated, washed with brine (50 cm3), dried (MgSO4), filtered and concentrated under reduced pressure.

Purification of the residue by column chromatography (SiO2, 50% Et2O in petrol) gave the product as a colourless oil (0.67 g, 26%) ; Rf 0.27 (50% Et2O in petrol); tcm-' (Film) 2962,2848, 1446,1421, 1387,1297, 1250,1137, 1096, 1019, 952,859 ; #H (400 MHz) 4.00 (1 H, dd, J 13.2 and 3.2 Hz), 3.86 (1 H, d, J 13.2 Hz), 3.50-3. 43 (2 H, m), 3.01 (1 H, d, J 3. 2 Hz), 1.89-1. 86 (2 H, m), 1.37 (3 H, s); dC (100 MHz) 65.2, 61.5, 57.8, 55.5), 30.2, 23.0 ; m/z [CI + NH3] 132 (M + NH4+, 100%) (Found: M + NH4+, 132.1027. C6H, 402N requires 132.1025).

3-Methyl-4-methylidene-octane-1, 3-diol Following the typical procedure, 3,4-epoxy-4-methyltetrahydropyran (80 mg, 701 J. mol) was reacted with n-BuLi (2.3 mol dm~3 in hexanes, 0.76 cm3, 1.75 mmol, 2.5 eq. ), giving the product as a colourless oil (85 mg, 70%); Rf 0.34 (75% Et2O in petrol) ; vmax/cm-1 (Film) 3369,2930, 2822,1456, 1372,1124, 1085,1053, 906; #H(400 MHz) 5.20 (1 H, s), 4.91 (1 H, s), 3.77-3. 69 (2 H, m), 3.24 (1 H, br s), 3.15

(1 H, br s), 1.98-1. 92 (2 H, m), 1.84-1. 83 (2 H, m), 1.49-1. 42 (2 H, m), 1.39- 1.31 (2 H, m), 1. 35 (3 H, s, ) 0.91 (3 H, t, J7. 2 Hz); i5c (100 MHz) 154.2, 108.0, 77.0, 60.1, 40.7, 31.0, 30.7, 28.4, 22.7, 14.0 ; m/z [CI + NH3] 190 (M + NH4+, 40%), 173 (M + H+, 40) and 155 (100) (Found: M + NH4+, 190.1809. C10H24O2N requires 190.1807).

Example 7: Allyl 2-pentyl allyl ether To a solution of 2-methylidene heptanol (see L. E. Overman & D. Lesuisse, Tetrahedron Lett. , 1985,4167) (3.48 g, 27.1 mmol) and allyl bromide (11.7 cm3, 136 mmol, 5 eq. ) in THF (2.0 cm3 mmol'', 54 cor') at 0 °C was added NaH (60% dispersion on oil, 2.7 g, 68 mmol, 2.5 eq. ) in portions over 15 min. The reaction mixture was allowed to attain room temperature over 2 h then poured into sat. aq.

NH4Cl (200 cm') and extracted with CH2Cl2 (3 x 100 cm3). The combined organics were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by bulb-to-bulb distillation (70 °C, 0.5 mbar) gave the product as a colourless oil (4.38 g, 96%); vmaxcm-1 (Film) 2956,2928, 2857,1648, 1460,1087, 901; dom400 MHz) 5.96-5. 86 (1 H, m), 5. 30-5. 24 (1 H, m), 5. 18-5.15 (1 H, m), 4.99 (1 H, s), 4.88 (1 H, s), 3.96-3. 94 (2 H, m), 3.90 (1 H, s), 2.04 (2 H, t, J7. 5 Hz), 1.48-1. 40 (2 H, m), 1.34-1. 24 (4 H, m), 0.91-0. 86 (3 H, m) ; #C (100 MHz) 146.3, 134.8, 116.8, 111.1, 73.0, 70.6, 33.1, 31.6, 27.3, 22.5, 14.0 (CH3) ; m/z [EI] 168 (M + H+, 100%).

3-Pentyl-2,5-dihydrofuran

A solution of allyl 2-pentyl allyl ether (1.68 g, 10 mmol) and bis (tricyclohexylphosphine) benzylidene ruthenium (IV) dichloride (0.41 g, 500 pmol, 0.05 eq. ) in CH2C12 (100 cm3 mmol~, 1000 cm3) was stirred at room temperature for 5 days. Following concentration under reduced pressure, purification by column chromatography (SiO2, 2% then 5% Et2O in petrol) afforded two compounds, first to elute was recovered starting material (0.58 g, 35%), second to elute was the product, which was further purified by bulb-to-bulb distillation (75-80 °C, 0.4 mbar) giving a colourless oil (0.78 g, 56%) ; Rf 0.29 (5% Et2O in petrol); vma, cm-} (Film) 2956,2929, 2860, 1750,1467, 1067m; #H (400 MHz) 5.48-5. 43 (1 H, m), 4.65-4. 60 (2 H, m), 5.54-4. 49 (2 H, m), 2.10-2. 03 (2 H, m), 1.50-1. 42 (2 H, m), 1.35-1. 26 (4 H, m), 0.91-0. 85 (3 H, m); #C (100 MHz) 140.6, 125.3, 77.1, 76.0, 31.6, 27.3, 27.0, 22.4, 14.0.

3,4-Epoxy-3-pentyl-tetrahydrofuran 3-Pentyl-2,5-dihydrofuran was epoxidised using the procedure of Yang et al. (see Example 5) : To a solution of 3-pentyl-2, 5-dihydrofuran (0.76 g, 5.42 mmol) and Na2EDTA (400 µmol dm-3 in H2O, 27 cm3, 10.9 pmol, 0.002 eq. ) in MeCN (7.5 cm3 mmol-', 41 cm3) at 0 °C was added trifluoroacetone (5.3 cm', 59.6 mmol, 11 eq. ) from a pre-cooled syringe. The resulting homogeneous mixture was treated with a

mixture of Oxone# (16.7 g, 27.1 mmol, 5 eq. ) and NaHCO3 (3.6 g, 43.4 mmol, 8 eq.) portionwise over 20 minutes, and then stirred at 0 °C for 90 min.

H20 (200 cm3) was added and the reaction mixture extracted with CH2Cl2 (3 x 150 cm3). The combined organics were dried (MgS04), filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 15 i) 25% EtOAc in petrol, 5% steps) gave the product as a colourless oil (0.62 g, 73%); Rf 0.26 (20% EtOAc in petrol) ; vmax/cm-1 (Film) 2923,2859, 1467,1078, 908,864 ; i (400 MHz) 3.80 (2 H, dd, J 21.0 and 10.5 Hz), 3.72 (2 H, dd, J. 21.0 and 10.0Hz), 3.54 (1 H, s), 1.92-1. 74 (2 H, m), 1.44-1. 37 (2 H, m), 1.38-1. 28 (4 H, m, 0.90-0. 86 (3 H, m); dc (100 MHz) 69.0, 67.6, 67.1, 60.5, 31.8, 27.9, 25.2, 22.4, 13.9.

3-Methylidene-2-pentyl-heptane-1,2-diol Following the typical procedure, 3, 4-epoxy-3-pentyl-tetrahydrofuran (80 mg, 512 pmol) was reacted with n-BuLi (1.0 mol dm-3 in hexanes, 1.28 cm3, 1.28 mmol, 2.5 eq. ), giving the product as a colourless oil (99 mg, 90%); Rf 0.24 (20% EtOAc in petrol); vmax/cm-1 (Film) 3421,2955, 2872,1467, 1059,903 ; d (400 MHz) 5.13 (1 H, s), 5.01 (1 H, s), 3.62 (1 H, d, J 11.0 Hz), 3.44 (1 H, d, J 11.0 Hz), 2. 25-1. 70 (2 H, br s), 1.96-1. 91 (2 H, m), 1. 51-1. 49 (2 H, m), 1.46-1. 17 (10 H, m), 0.91 (3 H, t, J 7.2 Hz), 0.85 (3 H, t, J7. 0 Hz); dc (100 MHz) 150.6, 110.4, 78.4, 68.2, 35.5, 32.2, 31.0, 30.4, 22.7, 22.6, 22.5, 14.0.

Example 8: (1S, 2R) *- (-)-3-Isopropyl-1, 2-dihydronaphthalene-1,2-diol

To a solution of isopropyllithium (1.1 mol du-'in petrol; 1.60 cm3, 1.75 mmol, 3.5 eq. ) in Et2O (2.0 cm3) at-78 °C was added (-) -sparteine (0.40 cm3, 1.75 mmol, 3.5 eq. ) and this mixture was stirred at that temperature for 1 h. After this time a solution of exo-1, 2,3, 4-tetrahydro-1,4-2, 3-diepoxynaphthalene (see LG French and TP Charlton, Heterocycles, 1993,35, 305) (80 mg, 499 umol) in Et2O (3.0 cm3) was added dropwise such that a temperature of-78 °C was maintained. The mixture was stirred at-78 °C for 5 h and then allowed to warm to room temperature over 16 h.

MeOH (0.5 cm3) was added and the mixture concentrated under reduced pressure, purification of the residue by column chromatography (SiO2, 80% Et2O in Petrol) gave the diol as an off-white solid (45 mg, 44%); Rf 0.27 (80% Et2O in Petrol); [a] D25-96. 0 (¢ 1.0 in CHCl3) ; vmax/cm-1 (KBr) 3306,2959, 2866,1454, 1384,1263, 1196,1112, 1086,1032, 953,894, 805,752, 705; c' ;, (400 MHz) 7.59-7. 57 (1 H, m), 7.29-7. 23 (2 H, m), 7.09-7. 07 (1 H, m), 6.28 (1 H, s), 4.71 (1 H, m), 4.15 (1 H, d, J 4. 2 Hz), 2.66-2. 57 (1 H, m), 1.21 (3 H, d, J 10. 8 Hz), 1.19 (3 H, d, J 10. 8 Hz) ; dC (100 MHz) 146.9, 135. 1,132. 1,128. 0,127. 6,126. 4,126. 0,122. 0,71. 8,69. 3,32. 6, 21.8, 21.3 ; m/z [CI + (NH3)] 222 (M + NH4+, 10%), 206 (20), 187 (100), 170 (50), 155 (40) (Found: M + NH4+, 222.1489. C, 3H20NO2 requires 222.1494) ; The ee was determined to be 68% by chiral HPLC (OD column, 20% EtOH in Hexane, 0.3 cm3/min), tR mn, 14.2 ; tR mj, 16.1.

In this and the following Examples, absolute stereochemistries have not been established. All stereochemistries are tentative assignments based on previous

observations of preferential removal of the proton at the R-stereocentre by organolithium/ (-)-sparteine mixtures.

Example 9: (l S, 2R) *-(-)-3-Butyl-1, 2-dihydronaphthalene-1, 2-diol Following Example 8, n-BuLi (1.90 mol drri 3 in hexanes, 0. 55 cm3, 1.05 mmol, 2.1 eq. ) in Et2O (2.0 cm3) and (-) -sparteine (0.24 cm3, 1. 05 mmol, 2.1 eq. ) were reacted with a solution of exo-1, 2,3, 4-tetrahydro-1, 4-2,3-diepoxynaphthalene (French et al, see Example 8) (80 mg, 499 umol) in Et20 (3.0 cm3), giving the diol as an off-white solid (55.0 mg, 50%); Rf 0.21 (50% Et2O in petrol); [a] D-53. 9 t 0.76 in CHCl3) ; vmax/cm-1 (CHCl3) 3292,2955, 2928,2858, 1456,1377, 1267,1099, 1079,1042, 959, 753; #H (400 MHz) 7.56-7. 52 (1 H, m), 7.28-7. 22 (2 H, m), 7.08-7. 04 (1 H, m), 6.26 (1 H, s), 4.70 (1 H, br s), 4.10 (1 H, br s), 2.65 (1 H, br d, J 9.2 Hz), 2. 38 - 2.28 (2 H, m), 1.92 (1 H, br s), 1.60-1. 50 (2 H, m), 1.47-1. 38 (2 H, m), 0.98-0. 94 (3 H, m); #C (100 MHz) 141.1, 134.8, 132.3, 128.1, 127.5, 126.3, 126.1, 123.8, 71.4, 70.4, 34.1, 30.3, 22.5, 14.0 ; The ee was determined to be 46% by chiral HPLC (OD Column, 10% EtOH in Hexane, 0.3 cm3min~'), tR mn, 19.7 ; tR mj, 22.4.

Example 10: (1R, 2S, 4S)*-(-)-4-(Tertbutyldimethylsilyloxy)-7-isopropylcyclohept- 6- ene-1, 2-diol

Following Example 8, isopropyllithium (1.3 mol dm-3 in petrol; 0.84 cm3, 1.09 mmol, 3.5 eq. ) in toluene (2.0 cm3) and (-) -sparteine (0.25 cm3, 1.09 mmol, 3.5 eq. ) were reacted with a solution of exo,exo-3-(terbutyldimethylsilyloxy)-6, 7-epoxy-8- oxabicyclo [3.2. 1] octane (obtained from 8-oxabicyclo [3.2. 1] oct-6-en-3-one (see J Mann and LC de Almeida Barbosa, J Org. Chem., Perkin Trans. I, 1992,787 and H Kim and HMR Hoffmann, Eur. J. Org Chem., 2000,2195) via highly stereoselective reduction of the ketone functionality) (80 mg, 312 pmol) in toluene (3.0 cm3), giving the diol as a colourless oil (50 mg, 58%); Rf 0. 46 (Et2O) ; [a] D-12. 1 C) 0.76 in CHC13) ; vmax/cm-1 (Film) 3381,2957, 2858,1464, 1383,1362, 1256,1089, 1036, 1005,937, 878; SH (400 MHz) 5.40 (1 H, dd, J6. 0 and 6.0 Hz), 4.14 (1 H, br s), 3.89 - 3. 84 (1 H, m), 3.77-3. 73 (1 H, m), 3.25 (1 H, br s), 2. 58-2. 44 (2 H, m), 2. 37 (1 H, sept, J 6. 8 Hz), 2.22-2. 05 (3 H, m), 1. 05 (3 H, d, J 6. 8 Hz) 1.04 (3 H, d, J 6. 8 Hz), 0.89 (9 H, s), 0.08 (3 H, s), 0.06 (3 H, s) ; dc (100 MHz) 147.4, 119.8, 75.8, 71.5, 67.4, 42.5, 35. 6,34. 8,25. 7,22. 0,21. 9,18. 0, -4.9,-5. 1; m/z [CI + (NH3)] 318 (M + NH4+, 25%), 301 (M + H+, 90), 283 (100), 151 (20), 135 (30) (Found: M + H+, 301.2202.

C, 6H3303Si requires 301.2199). The ee was determined to be 66% following derivatisation as the bis (3,5-dinitrobenzoate).

Example 11: (lS, 2R) *-(-)-3-Isopropylcyclohept-3-ene-1, 2-diol

Following Example 8, isopropyllithium (1.3 mol dm~3 in petrol; 1.71 cm3, 2.22 mmol, 3.5 eq. ) in cumene (2.0 cm3) and (-) -sparteine (0.51 cm3, 2.22 mmol, 3.5 eq. ) were reacted with a solution of exo-6, 7-epoxy-8-oxabicyclo [3.2. 1] octane (80 mg, 614 pmol) in cumene (3.0 cm3), giving the diol as a white solid (47 mg, 44%); Rf 0.30 (Et2O) ; mp 100.5-102. 0 °C ; [a] D-39. 5 t 0.66 in CHCl3) ; vmax/cm-1 (KBr) 3339,2965, 2948,2920, 2878,2852, 1466,1444, 1420,1391, 1364,1302, 1264, 1119, 1101, 1071,1045, 1014; #H (400 MHz) 5.75 (1 H, dd, J 8. 8 and 4. 8 Hz), 4.20 (1 H, br s), 3.64 (1 H, ddd, J 11. 0,4. 2 and 1. 6 Hz), 2.49-2. 21 (4 H, m), 2.18-2. 07 (1 H, m), 2.04-1. 95 (1 H, m), 1.94-1. 85 (1 H, m), 1.74-1. 66 (1 H, m), 1.49-1. 36 (1 Hi m), 1.02 (3 H, d, J6. 8 Hz), 1. 01 (3 H, d, J 6. 8 Hz); dc (100 MHz) 146.0, 128.2, 75.9, 73.0, 36.2, 34.1, 26.4, 25.8, 21.5, 21.4 ; m/z [CI + (NH3)] 183 (M + NH4+, 100%), 186 (40), 170 (M + H+, 85), 154 (40), 153 (40), 137 (90) (Found: M + NH4+, 188.1653. C10H22NO2 requires 188.1651) ; The ee was determined to be 85% following derivatisation as the bis (3,5-dinitrobenzoate).

Example 12: (lR, 2S, 4R) *- (-)-4- (Tertbutyldimethylsilyloxy)-7-isopropylcyclohept-6- ene-1, 2-diol

Following Example 8, isopropyllithium (0.93 mol dm~3 in petrol, 1.17 cm3, 1.09 mmol, 3.5 eq. ) in toluene (2.0 cm3) and (-) -sparteine (0.25 cm3, 1.09 mmol, 3.5 eq. ) were reacted with a solution of endo, exo-3- (tertbutyldimethylsilyloxy)-6, 7- epoxy-8-oxabicyclo [3.2. 1] octane (80 mg, 312 pool) in toluene (3.0 cm3).

Following column chromatography a colourless oil was eluted, (lR, 2S, 4R) *-4- (tertbutyldimethylsilyloxy)-7-isopropylcyclohept-6-ene-1, 2-diol (58 mg, 59%); Rf 24 0.33 (Et20) ; [a] D-54. 4 0 0.66 in CHCl3); vmax/cm-1 (Film) 3377,2956, 2857,1472, 1362,1253, 1083,1040, 1003,908, 838,773 ; i (400 MHz) 5.48 (1 H, dd, J 8. 0 and 5. 2 Hz), 4.25 (1 H, br s), 4.09-4. 00 (2 H, m), 2.47 (1 H, dd, J 15. 2 and 5. 2 Hz), 2. 35 (1 H, sept, J 7.0 Hz), 2.28-2. 17 (2 H, m), 2.05-1. 91 (3 H, m), 1.04 (3 H, d, J 7. 0 Hz), 1.03 (3 H, d, J 7. 0 Hz), 0.86 (9 H, s), 0.04 (3 H, s), 0.03 (3 H, s); diC (100 MHz) 146.0, 122.6, 75.7, 69.0, 67.8, 41.6, 35.7, 34.3, 25. 7, 21.6, 21.5, 18.0,-5. 0; The ee was determined to be 77% following derivatisation as the bis (3,5-dinitrobenzoate).

Example 13 ()-3-Methylenehept-6-ene-1, 2-diol

To a solution of 4-iodobut-1-ene (90% wt. solution in Et2O, 0.940 g, 4.64 mmol, 5 equiv. ) in Et2O (10 cm3) at-78 °C was added dropwise t-BuLi (1.60 mol dm-3 in pentane, 6.0 cm3, 9.8 mmol, 10.5 equiv. ). The resulting solution was stirred at-78 °C for 1 h and then at 25 °C for 1 h, and concentrated under a stream of argon. Addition of pentane (5 cm3) to the residue precipitated LiI, the mixture was collected in a syringe and added to a solution of 3, 4-epoxytetrahydrofuran (80 mg, 930 pool) in THF (5 cm3) at-78 °C over 10 min through a syringe filter [Gelman Acrodisc GF Syringe Filter; Glass Filter 25 mm diameter, 1.0 pm pores (Aldrich) ]. The reaction mixture was stirred at-78 °C for 1 h and then at 25 °C for 1 h. Phosphate buffer (pH 7,5 cm') was added and the mixture extracted with EtOAc (2 x 10 cm3). The organic layers were dried, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, 90% Et20 in petrol) to give the ene diol as a colourless oil (0.105 g, 80%) ; Rf 0.25 (90% Et2O in petrol); vmax/cm-1 (Film) 3369s br, 2928s, 1641m, 1439m and 1074s; #H (500 MHz) 5.81 (1 H, ddt, J 17.5, 10.3 and 6.5, (C (6) -H), 5.14 (1 H, s, C=CH2), 5.06-4. 96 (2 H, m, 2 x C (7) -H), 4.96 (1 H, s, C=CH2), 4.18 (1 H, dd, J7. 5 and 2.5, C (2) -H), 3.67 (1 H, dd, J 11.5 and 8.0, C (1)-H), 3.51 (1 H, dd, J 11. 5 and 6. 4, C (1)-H), 3.28 (1 H, br s, OH), 3.14 (1 H, br s, OH), 2.27 - 2. 13 (3 H, m, C (4) -H and 2 x C (5) -H) and 2.10-2. 03 (1 H, m, C (4) -H) ; dC (125 MHz) 147.5 (C (3) ), 137.8 (C (6) ), 114.9 (C (7)), 110.9 (C=CH2), 75.0 (C (2) ), 65.5 (C (1)), 31.9 (C (5) ) and 31.6 (C (4) ) ; m/z [CI + (NH3)] 160 (M +NH4+, 100%) (Found: M + NH4+, 160.1340. C8H18NO2 requires 160.1338).

Example 14

To a solution of 1-iodo-3- (tert-butyldimethylsilyloxy) propane (1.40 g, 4.65 mmol, 5 equiv. ) in Et20 (10 cm3) at-78 °C was added dropwise t-BuLi (1.60 mol dm~3 in pentane, 5.9 cm', 9.8 mmol, 10.5 equiv. ). The resulting solution was stirred at-78 °C for 1 h and then at 25 °C for 1 h, and concentrated under a stream of argon. Addition of pentane (5 cm') to the residue precipitated LiI, the mixture was collected in a syringe and added to a solution of 3, 4-epoxytetrahydrofuran (80 mg, 930 pool) in THF (5 cm3) at-78 °C over 10 min through a syringe filter [Gelman Acrodisc GF Syringe Filter; Glass Filter 25 mm diameter, 1.0 pm pores (Aldrich) ]. The reaction mixture was stirred at-78 °C for 1 h and then at 25 °C for 1 h. Phosphate buffer (pH 7,5 cm3) was added and the mixture extracted with EtOAc (2 x 10 cm3). The organic layers were dried, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, 90% Et20 in petrol) to give the ene diol as a colourless oil (0. 207 g, 86%) ; Rf 0.15 (75% Et20 in petrol); vmax/cm-1 (Film) 3369m br, 2953s, 2925s, 2857s, 1472m, 1256s and 1103s; #H (400 MHz) 5.13 (1 H, s, C=CH2), 4.96 (1 H, s, C=CH2), 4.19 (1 H, dd, J 7. 2 and 3.2 C (2) -H), 3.67 (1 H, dd, J 11. 2 and 3. 2, C (1)-H), 3.64 (2 H, t, J6. 4, 2 x C (6) -H), 3.53 (1 H, dd, J 11. 2 and 7. 2, C (1)-H), 2.98 (1 H, br s, OH), 2.64 (1 H, br s, OH), 2.18-2. 01 (2 H, m, 2 x C (4) -H), 1.76-1. 64 (2 H, m, 2 x C (5) -H), 0.89 (9 H, s, C (CH3) 3) and 0.05 (6 H, s, 2 x SiCH3) ; dc (100 MHz) 148.1 (C (3)), 111.0 (C=CH2), 75.1 (C (2) ), 65.6 (C (1)), 62.6 (C (6)), 31. 1 (C (5)), 28.6 (C (4) ), 25.9 (C (CH3) 3), 18.3 (C (CH3) 3) and-5. 3 (2 x SiCH3) ; m/z [CI + (NH3)] 261 (M + H+, 100%), 243 (35), 185 (20), 129 (45) and 111 (25) (Found: M + H+, 261.1885. C, 3H2903Si requires 261.1886).

Example 15 3-(Furan-2-yl) but-3-ene-1, 2-diol

To a solution of furan (0.34 cm3, 4.7 mmol, 5 equiv. ) in THF (5 cm3) at-78 °C was added n-BuLi (2.00 mol dm-3 in hexanes, 2.3 cm3, 4.7 mmol, 5 equiv. ) dropwise over 10 min. The mixture was stirred at 0 °C for 2 h then recooled to-78 °C before a solution of 3, 4-epoxytetrahydrofuran (80 mg, 930 pool) in THF (3 cm3) was added dropwise over 10 min. After stirring at-78 °C for 1 h and then at 25 °C for 1 h phosphate buffer (pH 7,5 cm3) was added. The mixture was extracted with EtOAc (2 X 10 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO2, 80% Et20 in petrol) gave the ene diol as a pale yellow oil (70 mg, 49%); Rf 0.20 (80% Et2O in petrol); vmax/cm-1 (CHCl3) 3369m br, 2935m and 1215s; J (400 MHz) 7.35 (1 H, s, ArH), 6.37-6. 35 (2 H, m, 2 x ArH), 5.66 (1 H, s, C=CH2), 5.34 (1 H, s, C=CH2), 4.66 (1 H, d, J 7. 2, C (2) -H), 3.84-3. 75 (2 H, m, C (1)-H and OH) and 3.62-3. 57 (2 H, m, C (1)-H and OH); dc (lOO MHz) 152.1 (C (3) ), 142.1 (ArC-H), 137. 1 (ArC), 111.2 (ArC-H), 110.3 (=CH2), 106.6 (ArC-H), 72.6 (C (2) ) and 66.5 (C (1)) ; m/z [CI + (NH3)] 172 (M + NH4+, 100%), 155 (M + H+, 80) and 121 (25) (Found: M + NH4+, 172.0973.

C8Hl4NO3 requires 172.0974).

Example 16 ()-3-Methylene-4- (trimethylsilyl) nonane-1, 2-diol To a solution of vinyltrimethylsilane (0.25 g, 2.51 mmol, 2.7 equiv. ) in THF (5 cm3) at-78 °C was added n-BuLi (2.20 mol dm~3 in hexanes, 1. 1 cm3, 2.3 mmol, 2.5 equiv. ) dropwise. The solution was stirred at-78 °C for 2 h and then at-30 °C for 1

h. 67 After recooling to-78 °C a solution of 3, 4-epoxytetrahydrofuran (80 mg, 929 pmol) in THF (3 cm') was added dropwise, the mixture was stirred at-78 °C for 1 h and then at 25 °C for 1 h. Phosphate buffer (pH 7,5 cm3) was added and the mixture extracted with EtOAc (2 x 10 cm3), the combined organics were dried, filtered and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO2, 50% Et2O in petrol) gave the ene diol (2: 1 mixture of diastereomers) as a colourless oil (0.140 g, 81%); Rf 0.20 (50% Et2O in petrol); vmax/cm-1 (Film) 3369s br, 2956s, 2933s, 2858s, 1248s, 1072m and 838s; #H (400 MHz, major diastereomer) 5.18 (1 H, s, C=CH2), 4.75 (1 H, s, C=CH2), 3.95-3. 93 (1 H, m, C (2) -H), 3.73-3. 71 (1 H, m, C (1)-H), 3.40-3. 38 (1 H, m, C (1)-H), 2.81-2. 61 (2 H, m, 2 x OH), 1.54-1. 47 (2 H, m, CH2), 1.43-1. 38 (1 H, m, C (4) -H), 1. 30-1. 16 (6 H, m, 3 x CH23), 0.86 (3 H, t, J 7. 0, CH3) and 0.00 (9 H, s, 3 x SiCH3) ; 4 (400 MHz, minor diastereomer) 5. 04 (1 H, s, C=CH2), 4.77 (1 H, s, C=CH2), 4.05-4. 00 (1 H, m, C (2) -H), 3.70-3. 66 (1 H, m, C (1)-H), 3.54-3. 49 (1 H, m, C (1)-H), 2.81-2. 61 (2 H, m, 2 x OH), 1.54-1. 47 (2 H, m, CH2), 1.43-1. 38 (1 H, m, C (4) -H), 1.30-1. 16 (6 H, m, 3 x CH2), 0.86 (3 H, t, J7. 0, CH3) and 0.00 (9 H, s, 3 x SiCH3) ; #C (100 MHz, CDCl3, major diastereomer) 150.6 (C (3) ), 105.8 (C=CH2), 76.2 (C (2) ), 65.6 (C (1)), 33.8 (CH2), 32.0 (CH2), 29.3 (CH2), 28.7 (CH2), 22.5 (C (4) ), 14.1 (C (9) ) and-3.1 (3 x SiCH3) ; dC (100 MHz, minor diastereomer) 151. 1 (C (3) ), 108.6 (C=CH2), 75.9 (C (2)), 65.7 (C (1)), 32.6 (CH2), 31.6 (CH2), 29.1 (CH2), 28.7 (CH23), 22.5 (C (4) ), 14.1 (C (9)) and-2.3 (3 x SiCH3) ; m/z [CI + (NH3)] 262 (M + NH4+, 60%), 245 (M + H+, 70), 227 (85) and 211 (100) (Found: M + NH4+, 262.2202. C13H32NO2Si requires 262. 2202).

Example 17 (+)- (lSR, 2RS, SSR, 6SR)-3-Butyl-5, 6-bis (methoxymethyl) cyclohex-3-ene-1, 2-diol

To a stirred solution of (-) -sparteine (0.20 cm3, 840 µmol, 2.1 equiv. ) in Et2O (2 cm3) at-78 °C was added dropwise n-BuLi (2.40 mol dm-3 in hexanes, 0. 35 cm3, 840 pmol, 2.1 equiv. ). After stirring at-78 °C for 1 h a solution of exo, exo-2,3- bis (methoxymethyl) -5, 6-epoxy-7-oxabicyclo [2.2. 1] heptane (80 mg, 400 pmol) in Et2O (3 cm3) was added dropwise over 10 min. The reaction mixture was stirred at -78 °c for 5 h and then allowed to warm to 25 °C over 16 h. HCl (1 mol dm-3, 5 cm3) was added and the layers separated, the organic phase was washed with further HCl (1 mol dm-3, 5 cm3), the combined aqueous washings extracted with Et2O (10 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure.

Column chromatography (75% Et2O in light petroleum) gave the ene diol as a colourless oil (48 mg, 46%); Rf 0. 15 (75% Et20 in petrol) ; [aa] D25 +28 # 1. 00, CHC13) ; t/cm-'3370s br, 2926s, 1458m and 1100s ; i (500 MHz) 5.32 (1 H, d, J 3.2, C (4) -H), 4.37 (1 H, d, J 10.0, OH), 3.97 (1 H, br s, C (2) -H), 3.84-3. 80 (1 H, m, C (1)-H), 3.60-3. 52 (2 H, m, C (6)-CH2), 3.44-3. 36 (2 H, m, C (5)-CH2), 3.39 (3 H, s, OCH3), 3.36 (3H, s, OCH3), 2.99 (1 H, d, J 10.0, OH), 2.56 (1 H, br s, C (6) -H), 2.35 (1 H, dq, J 7. 5 and 3.0, C (5)-H), 2.32-2. 26 (1 H, m, CHH), 2.08-2. 02 (1 H, m, CHH), 1.54-1. 23 (4 H, m, 2 x CH2) and 0.91 (3 H, t, J7. 0, CH3) ; #C (125 MHz) 140.3 (C (3) ), 122.6 (C (4) ), 71.6 (C (6)-CH2), 71.2 (C (5)-CH2), 69.1 (C (2) ), 67.4 (C (1)), 58.8 (OCH3), 58. 7 (OCH3), 39.1 (C (5) ), 36.6 (C (6) ), 32.9 (CH2), 30.0 (CH2), 22.4 (CH2) and 13.9 (CH3) ; m/z [CI + (NH3)] 259 (M + H+, 20%), 241 (100) and 193 (35) (Found: M + H+, 259.1907. C14H27O4 requiresd 259.1909). The ee of the bis (3,5- dinitrobenzoate) was determined to be 34% by chiral HPLC (OD Column, 80% EtOH in heptane, 1.0 cm3 min~', tR mj, 19.0 ; tR mn, 41.8).

Example 18 (+)- (lSR, 2RS, SSR, 6SR)-5, 6-Bis (methoxymethyl)-3-isopropylcyclohex-3-ene-1, 2-diol

To a stirred solution of (-) -sparteine (0.20 cm3, 840 µmol, 2.1 equiv. ) in Et2O (2 cm3) at-78 °C was added dropwise i-PrLi (1.55 mol dm-3 in light petroleum, 0.64 cm3, 1.00 mmol, 2.5 equiv. ). After stirring at-78 °C for 1 h a solution of exo, exo-2, 3- bis (methoxymethyl) -5, 6-epoxy-7-oxabicyclo [2.2. 1] heptane (80 mg, 400 pmol) in Et2O (3 cm3) was added dropwise over 10 min. The reaction mixture was stirred at - 78 °C for 5 h and then allowed to warm to 25 °C over 16 h. HCl (1 mol dm-3, 5 cm3) was added and the layers separated, the organic phase was washed with further HCl (1 mol dm-3, 5 cm3), the combined aqueous washings extracted with Et2O (10 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure.

Column chromatography (75% Et2O in light petroleum) gave the ene diol as a pale yellow oil (33 mg, 34%); Rf 0. 15 (75% Et2O in light petroleum); [aa] D25 +33 # 1. 00, CHC13); vmax/cm-1 3382m br, 2893s, 1460m, 1387m and 1100s ; i (400 MHz) 5.28 (1 H, br d, J 3. 6, C (4) -H), 4. 33 (1 H, d, J 10.0, OH), 4.0-4. 04 (1 H, m, C (2) -H), 3.81 (1 H, ddd, J 10.0, 4.4 and 2.8, C (1)-H), 3.60-3. 51 (2 H, m, C (6)-CH2), 3.41 (2 H, dq, J 9.6 and 4.0, C (5)-CH2), 3.38 (3 H, s, OCH3), 3. 35 (3 H, s, OCH3), 3.03 (1 H, d, J 10.4, OH), 2.61 (1 H, sept., J7. 0, CH (CH3) 2), 2.57-2. 53 (1 H, m, C (6) -H), 2.33 (1 H, ddd, J 14.0, 7.2 and 2.8, C (5) -H), 1.06 (3 H, d, J 7. 0, CH (CH3) 2) and 1. 05 (3 H, d, J7. 0, CH (CH3) 2) ; #C(100 MHz) 145.6 (C (3)), 120. 3 (C (4) ), 71.6 (CH2), 71.5 (CH2), 68.6 (C (2) ), 67.9 (C (1)), 58.9 (OCH3), 58.8 (OCH3), 38. 9 (C (5)), 36. 7 (C (6) ), 29.4 (CH (CH3) 2), 22.4 (CH (CH3) 2) and 20.9 (CH (CH3) 2) ; m/z [CI + (NH3)] 262 (M + NH4+, 25%) and 245 (M + H+, 100) (Found: M + H+, 245.1756. C13H25O4 requires 245.1753).

The ee of the bis (3,5-dinitrobenzoate) was determined to be 63% by chiral HPLC (OD Column, 80% EtOH in heptane, 1.0 cm3 mini', tR mj, 16.8 ; tR mn, 42.2).

Example 19 (+)- (lSR, 4RS, SSR, 6SR)-3-Butyl-4, 5-dihydroxybicyclo [4.1. 0] hept-2-en-7-one neopentyl acetal

To a stirred solution of (-) -sparteine (0.17 cm3, 750 µmol, 2.1 equiv. ) in Et2O (2 cm3) at-78 °C was added dropwise n-BuLi (2.40 mol dm~3 in hexanes, 0.31 cm3, 750 pmol, 2.1 equiv. ) After stirring at-78 °C for 1 h a solution of exo, exo-6, 7-epoxy-8- oxatricyclo [3.2. 1. 02, I] octan-3-one neopentyl acetal (80 mg, 360 mol) in Et20 (3 cor') was added dropwise over 10 min. The reaction mixture was stirred at-78 °C for 5 h and then allowed to warm to 25 °C over 16 h. HCl (1 mol dm-3, 5 cm3) was added and the layers separated, the organic phase was washed with further HCl (1 mol dm-3, 5 cm3), the combined aqueous washings extracted with Et2O (10 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure. Column chromatography (75% Et2O in light petroleum) gave the ene diol as a colourless oil (57 mg, 57%); Rf 0.20 (75% Et2O in light petroleum) ; [aa] D25+21 # 1. 00, CHCl3) ; vmax/cm-1 3437s br, 2958s, 2871s, 1470s, 1435s, 1254m, 1135s and 1065s; #H (400 MHz) 5.59 (1 H, d, J 5. 6, C (2) -H), 4.15 (1 H, dt, J9. 6 and 5.6, C (5) -H), 3.90 (1 H, dd, J 12.0 and 5.6, C (4) -H), 3.74 (1 H, d, J 12.0, OH), 3.57-3. 46 (3 H, m, OCH2 and OCHH), 3.26 (1 H, d, J 10.8, OCHH), 3.06 (1 H, d, J 9. 6, OH), 2.14-2. 10 (2 H, m, CH2), 1.92 (1 H, dd, J9. 6 and 5.6, C (6) -H), 1.81 (1 H, dd, J 10. 4 and 5.6, C (1)-H), 1.47-1. 25 (4 H, m, 2 x CH2), 1. 22 (3 H, s, CCH3), 0. 90 (3 H, t, J7. 2, CH3) and 0.80 (3 H, s, CCH3) ; (100 MHz) 138. 8 (C (3) ), 126.0 (C (2) ), 92.6 (C (7) ), 77.2 (OCH23), 76.0 (OCH2), 68.1 (C (4) ), 66.2 (C (5) ), 34.8 (CH2), 30.6 (C (CH3) 2), 30.1 (CH23), 28.7 (C (6) ), 25.2 (C (1)), 22.9 (C (CH3)23), 22.4 (CH2), 21.8 (C (CH3)2) and 13.9 (CH3) ; m/z [CI + (NH3)] 300 (M + NH4+, 10%), 283 (M + H+, 10), 265 (100), 148 (50) and 131 (65) (Found: M + NH4+, 300.2178. C, 6H30NO4 requires 300.2175). The ee of the bis (3,5-dinitrobenzoate) was determined to be 27% by chiral HPLC (OD Column, 80% EtOH in heptane, 1.0 cm'min', tR mj, 19.9 ; tR mn, 26.3).

EXAMPLE 20 (+)- (lSR, 4RS, SSR, 6SR)-4, 5-Dihydroxy-3-isopropylbicyclo [4.1. 0] hept-2-en-7-one neopentyl acetal

To a stirred solution of (-)-sparteine (0.20 cm3, 890 pLmol, 2.5 equiv. ) in Et2O (2 cm3) at-78 °C was added dropwise i-PrLi (1.40 mol dm-3 in light petroleum, 0.64 cm3, 890 µmol, 2.5 equiv. ). After stirring at-78 °C for 1 h a solution of exo, exo-6, 7-epoxy-8- oxatricyclo [3.2. 1. 02, I] octan-3-one neopentyl acetal (80 mg, 360 pool) in Et2O (3 cm3) was added dropwise over 10 min. The reaction mixture was stirred at-78 °C for 5 h and then allowed to warm to 25 °C over 16 h. HCl (1 mol dm-3, 5 cm3) was added and the layers separated, the organic phase was washed with further HCl (1 mol dm-3, 5 cm3), the combined aqueous washings extracted with Et2O (10 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure. Column chromatography (75% Et2O in light petroleum) gave the ene diol as a colourless oil (47 mg, 49%); Rf 0.20 (75% Et2O in light petroleum); [aa] D +35 t 1.00, CHCl3) ; vmax/cm-1 3432s br, 2958s, 2870m, 1471m, 1434m, 1136m and 1064s; 4 (400 MHz) 5.63 (1 H, d, J 5. 6, C (2) -H), 4.16-4. 11 (1 H, m, C (5) -H), 4.00 (1 H, dd, J 12.0 and 5.6, C (4) -H), 3.80 (1 H, d, J 12.0, OH), 3.57-3. 47 (3 H, m, OCH2 and OCHH), 3.25 (1 H, d, J 11.2, OCHH), 3.09 (1 H, d, J9. 2, OH), 2.41 (1 H, sept. , J 6.8, CH (CH3)2), 1.93 (1 H, dd, J 10.4 and 6.0, C (6) -H), 1.83 (1 H, dd, J 10.4 and 5.6, C (1)-H), 1.22 (3 H, s, CCH3), 1. 08 (3 H, d, J 6.8, CH (CH3) 2), 1.03 (3 H, d, J 6.8, CH (CH3) 2) and 0.80 (3 H, s, CCH3) ; dC (100 MHz) 144.6 (C (3) ), 115.1 (C (2) ), 92.7 (C (7) ), 77.2 (OCH2), 76.0 (OCH23), 67.3 (C (4) ), 66.4 (C (5)), 32. 8 (CH (CH3) 2), 30. 5 (C (CH3)2), 29.0 (C (6)), 25.1 (C (1)), 22.8 (C (CH3) 2), 22.3 (CH (CH3) 23) 21. 8 (CH (CH3) 2) and 21.7 (C (CH3) 2); m/z [ES +] 291 (M + Na+, 100%), 251 (50) and 172 (25) (Found: M + Na+, 291.1573.

C, 5H24NaO4 requires 291.1572). The ee of the bis (3,5-dinitrobenzoate) was

determined to be 59% by chiral HPLC (OD Column, 80% EtOH in heptane, 1.0 cm3 min-1, tR mj, 18.9 ; tR mn, 23.7).

Example 21 (-)- 2RS)-1, 2-Dihydro-1, 4-dimethyl-3-isopropylnaphthalene-1, 2-diol To a stirred solution of (-) -sparteine (0.31 cm3, 1.3 mmol, 2.5 equiv. ) in Et2O (3 cm3) at-78 °C was added dropwise i-PrLi (1.50 mol dm-3 in light petroleum, 0.89 cm3, 1.3 mmol, 2.5 equiv. ). After stirring at-78 °C for 1 h a solution of exo-1, 4-dimethyl- 1, 4: 2, 3-diepoxy-1, 2,3, 4-tetrahydronaphthalene (0.100 g, 531 µmol) in Et20 (5 cm3) was added dropwise over 10 min. The reaction mixture was stirred at-78 °C for 5 h and then allowed to warm to 25 °C over 16 h. HCl (1 mol dm-3, 10 cm3) was added and the layers separated, the organic phase was washed with further HCl (1 mol dm-3, 10 cm3), the combined aqueous washings extracted with Et2O (15 cm3), the combined organic layers dried, filtered and concentrated under reduced pressure. Column chromatography (50% Et2O in light petroleum) gave the ene diol as a white solid (52 mg, 42%); Rf 0.25 (50% Et2O in light petroleum); mp. 108-109 °C (Et2O/light petroleum); (Found: C, 77.2 ; H, 8.8. C15H20O2 requires C, 77.5 ; H, 8.7%) ; [aa] D -108 C 1. 00, CHCl3) ; vmax/cm-1 (KBr) 3306m br, 2964s, 2930m, 1390m, 1330m, 1090s and 1001s ; i (500 MHz) 7.70-7. 68 (1 H, m, ArH), 7.32-7. 25 (3 H, m, 3 x ArH), 3.83 (1 H, d, J 8. 0, C (2) -H), 3.15 (1 H, sept., J 7.0, CH (CH3)2), 3.09 (1 H, s, OH), 2.08 (3 H, s, C (4)-CH3), 1.44 (1 H, d, J 8. 0, OH), 1.32 (3 H, s, C (1)-CH3), 1.17 (3 H, d, J7. 0, CH (CH3) 2) and 1.12 (3 H, d, J 7. 0, CH (CH3)2; #C (125 MHz) ) 140.9 (C=C), 140.1 (C=C), 133.9 (C (8a) ), 127.6 (ArC-H), 127.3 (ArC-H), 126.5 (C (4a)),