PREPARATION THEREOF

FIELD OF THE INVENTION

The present invention relates to a vinylic 3-amino-l,2 diol compound of formula (I). Particularly, present invention relates to a one pot cost-effective process for the synthesis of vinylic-3-amino-l,2-diol compound of formula (I) with good yields and excellent enantio- and diastereoselectivities. More particularly, present invention relates to a process for the synthesis of D-ribo-phytosphingosine tetraacetate (7) from compound of formula (I).

BACKGROUND AND PRIOR ART OF THE INVENTION

The vicinal amino diol motif is an important stereotriad pattern present in many pharmaceutical compounds and biologically active natural products. Enantiopure vicinal amino diols are useful building blocks for asymmetric synthesis and their utility has been largely demonstrated in a variety of organic transformations. Although, several methodologies have been developed for the synthesis of this unit. Of these, dihydroxylation or epoxidation of allylic amine, or aminohydroxylation or epoxidation of an allylic alcohol are the most commonly used methods. Another approach for the construction of vicinal aminodiols involves diastereoselective additions to a- aminoaldehydes. More recently, the reaction of allenyl zinc with enantiopure a-alkoxy t- BS imines has been reported for the enantiopure synthesis of anti, anti and syn, anti acetylenic 2- amino- 1,3 -diol. However, these methods are limited because of costly reagent, complex chiral pool resources and involves multistep asymmetric transformations. Inspired by their unique biological properties and natural prevalence, we were interested to develop a new one-pot protocol for the synthesis of vicinal amino diols.

Recently, proline - catalyzed a-amination of aldehydes and ketones has emerged as a reliable method for the enantioselective synthesis of a-amino acid derivatives. ⁴ In other ways, the in situ generated a-amino aldehydes were further utilized in the subsequent tandem reaction to transform into several functionalized organic derivatives eg. 1,2- aminoalcohols, 3,6-dihydropyridazines, functionalized β-aminoalcohols, γ-amino- α- β- unsaturated esters and 4-hydroxypyrazolidine derivatives.

The synthetic methodology leading rapidly to structural complexity from readily available starting material through one-pot reaction sequence is widely recognized.3 In particular, proline catalyzed sequential reaction such as a-amination of aldehydes4 followed by Wittig, (S. P. Kotkar et al. Org. Lett., 2007, 9, 1001) aldol (N. S. Chowdari et al. Org. Lett., 2003, 5, 1685) or Corey-Chaykovsky (B. S. Kumar et al. Org. Lett., 2012, 14, 2468) have gained more prominence in recent years.

There is ample literature available on the synthesis of vicinal amino diols.

Article titled "Direct Catalytic Asymmetric a-Amination of Aldehydes" by B List published in . Am. Chem. Soc, 2002, 124 (20), pp 5656-5657 reports the first direct catalytic asymmetric a-amination of aldehydes. The a-Unbranched aldehydes reacts with dialkyl azodicarboxylates in presence of proline-catalyst to give a-amino aldehydes in excellent yields and enantioselectivities.

n ^ (S)-Proline _

^Cbz - _N (10 mol%) ^{0 Cbz}

I I ^ N. bz

^{H N} bz CH ₃ CN, 0 ^° C-rt ^H _Ξ

R 3h R

1 -5 eq 1 eq > _90% yy _eW

>95% ee

Article titled "Direct Organo-Catalytic Asymmetric a-Amination of Aldehydes— A Simple Approach to Optically Active a-Amino Aldehydes, a-Amino Alcohols, and a- Amino Acids" by A Bogevig et al. published in Angewandte Chemie International Edition, 2002, 41 (10), pp 1790-1793 reports the first direct asymmetric a-amination of aldehydes using 1-proline as the catalyst. The reactions proceed in high yields and excellent enantioselectivities with as little as 2 mol % of the catalyst.

Article titled "Organocatalytic Sequential a-Amination/Corey-Chaykovsky Reaction of Aldehydes: A High Yield Synthesis of 4-Hydroxypyrazolidine Derivatives" by BS Kumar et al. published in Org. Lett., 2012, 14 (10), pp 2468-2471 reports a tandem reaction of in situ generated a-amino aldehydes with dimethyloxosulfonium methylide under Corey-Chaykovsky reaction conditions proceeds efficiently to give 4- hydroxypyrazolidine derivatives in high yields with excellent enantio- and diastereoselectivities.

Article titled "Zn mediated regioselective Barbier reaction of propargylic bromides in THF/aq. NH ₄ C1 solution" by A Jogi et al. published in Molecules, 2001, 6, ppSS 964-968 reports the reaction of substituted and unsubstituted propargylic bromides with butanal in presence of zinc power in THF/saturated aqueous NH4C1 solution gave corresponding allenic and propargylic alcohols with high selectivity.

Article titled "A highly concise and practical route to clavaminols, sphinganine and (+)- spisulosine via indium mediated allylation of a-hydrazino aldehyde and a theoretical insight into the stereochemical aspects of the reaction" by M Pandey et al. published in RSC Adv., 2013,3, 15442-15448 reports a conceptually different approach for the synthesis of 1,2-amino alcohols by proline-catalyzed a-amination of aldehyde and one- pot indium mediated allylation of the crude a-hydrazino aldehydes.

Article titled "Stereoselective synthesis of Ν,Ο,Ο,Ο-tetraacetyl-D-ribo-phytosphingosine, N,0,0-triacetyl-D-erythro-sphingosine and Ν,Ο,Ο-triacetyl sphingonine from a common chiral intermediate derived from D-mannitol" by R mettu et al. published in an efficient protocol for the stereoselective synthesis of tetraacetyl-D-ribo-phytosphingosine, triacetyl-D-erythro-sphingosine and triacetyl sphinganine from a common chiral intermediate derived from commercially available D-mannitol.

As seen above, prior art fails to teach the synthesis of vicinal amino diols under feasible reaction conditions such as pressure and temperatures as the maintenance of highly low temperature is very difficult on industrial scale. There is therefore still a need in the art to provide cost-effective organocatalytic method for the synthesis of vicinal amino diols, an important stereotriad pattern present in many pharmaceutical compounds and biologically active natural products.

OBJECTIVE OF INVENTION

The main objective of the present invention is to provide a vinylic 3-amino-l,2 diol compounds of formula (I).

Another objective of the present invention is to provide a one pot cost-effective process for the synthesis of vinylic-3 -amino- 1,2-diol compound of formula (I) with good yield and excellent enantio- and diastereoselectivities which comprises tandem a-amination- benzoyloxyallylation of aldehydes.

Still another objective of the present invention is to provide a cost-effective asymmetric synthesis of biologically active molecules using organocatalysis from compounds of formula (I).

BRIEF DISCRPTION OF THE DRAWING

Scheme 1 represents process step for the preparation of vinylic-3 -amino- 1,2-diol compound of formula (I) (a-i), wherein (i) L-proline (10 mol%), amine R'OC ₂ N=NC0 ₂ R' (1 equiv.), CH ₃ CN 0°C, 3h ; (ii) Zn powder (2 equiv.), 3- benzoyloxyallyl bromide (2 eqviv.), sat. aq. NH ₄ C1, -20 °C, 2h.

Scheme 2 represents process steps for the synthesis of D-ribo-phytosphingosine tetraacetate 7, wherein Reagents and conditions are (i) D-Proline (10 mol%), DBAD (1 equiv.), CH ₃ CN, 0 °C, 3 h; then Zn powder (2 equiv.), aq. NH ₄ CI, (2 equiv.), 3- benzoyloxyallyl bromide (2 equiv.), -20 °C, 2h, 85%. (ii) LiOH.H ₂ 0 ( 2.2 equiv.), MeOH, 3h, 70 %. (iii) Grubbs second generation catalyst (10 mol%), tetradecene (3 equiv.), DCM, reflux, 72%.

SUMMARY OF THE INVENTION

Accordingly, present invention provides a compound of formula (I) I o

q\ NH 11

OH

Formula (I)

wherein;

R is straight or branched chain alkyl or substituted alkyl or aryl alkyl selected from group consisting of methyl, ethyl, propyl, isopropyl, CH ₃ OCH ₂ O-CH ₂ CH _2,

BnO-CH ₂ , CH ₂ =CH-CH ₂ , Ph-CH ₂ , p-MeO-Ph-CH ₂ ;

R' is selected from the group consisting of C0 ₂ -iPr, C0 ₂ -Bn and C0 ₂ -tBu.

In an embodiment of the present invention, compound of formula I is selected from group consisting of:

a. Diisopropyl l -((2R,3R,4S)-4-(benzoyloxy)-3-hydroxyhex-5-en-2- yl)hydrazine- 1 ,2-dicarboxylate ( la);

b. Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxyhept-6-en-3- yl)hydrazine- 1 ,2-dicarboxylate( lb) ;

c. Diisopropyl l -((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy-2-methylhept-6-en-3- yl)hydrazine- 1 ,2-dicarboxylate( lc);

d. Diisopropyl l-((4R,5R,6S)-6-(benzoyloxy)-5-hydroxyoct-7-en-4- yl)hydrazine- 1 ,2-dicarboxylate( Id) ;

e. Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy- l- (methoxymethoxy)hept-6-en-3-yl)hydrazine- 1 ,2-dicarboxylate( le); f. Di-tert-butyl l -((3R,4R,5S)-5-(benzoyloxy)- l -(benzyloxy)-4-hydroxyhept-6- en-3-yl)hydrazine- 1 ,2-dicarboxylate( If);

g. Diisopropyl l-((3S,4R,5R)-3-(benzoyloxy)-4-hydroxynona- l ,8-dien-5- yl)hydrazine- 1 ,2-dicarboxylate( 1 g) ;

h. Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy- l-phenylhex-5-en-2- yl)hydrazine- 1 ,2-dicarboxylate( lh) ;

i. Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy- l-(4- methoxyphenyl)hex-5-en-2-yl)hydrazine- 1 ,2-dicarboxylate( 1 i); j. Dibenzyl l-((2R,3R,4S)-4-(benzoyloxy)-l-(benzyloxy)-3-hydroxyhex-5-en -2- yl)hydrazine- 1 ,2-dicarboxylate( lj );

In another embodiment, present invention provides a process for the preparation of compound of formula 1 comprising the steps of:

i. subjecting substituted aldehydes of formula (II) and azodicarboxylate (ROC ₂ N=NC0 ₂ R') in acetonitrile to a-amination at 0°C for 2 to 3 h followed by subjecting to benzoyloxyallylation reaction in presence of zinc powder, 3-benzoyloxyallyl bromide and saturated aq. NH ₄ C1 at 0 to (-) 25°C to afford vinylic-3 -amino- 1,2-diol compound of formula (I).

Formula II

wherein R is straight or branched chain alkyl or substituted alkyl or aryl alkyl selected from group consisting of methyl, ethyl, propyl, isopropyl, CH3OCH ₂ O-CH ₂ CH ₂ , BnO- CH ₂ , CH ₂ =CH-CH ₂ , Ph-CH ₂ , p-MeO-Ph-CH ₂ ;

R' is selected from the group consisting of CC iPr, C0 ₂ -Bn and C0 ₂ -tBu.

In yet another embodiment of the present invention, a-amination is carried out in presence of catalyst such as L-proline.

In yet another embodiment of the present invention, substituted aldehydes of formula (II) are selected from the group consisting of Propanal, Butaraldehyde, isovalraldehyde, valraldehyde, 4-(methoxymethoxy)butanal, 3-(Benzyloxy)butanal, hex-5-enal, 3- phenylpropanal, 3-(4-methoxyphenyl)propanal or 2-(Benzyloxy)propanal.

In yet another embodiment of the present invention, azodicarboxylate are selected from the group consisting of Dibenzyl azadicarboxylate, Di-tert-buty\ azadicarboxylate or Diisopropyl azadicarboxylate.

In yet another embodiment, present invention provides a process for the preparation D- ribo-phytosphingosine tetraacetate from compounds of formula (lj) wherein said process comprising the steps of:

a) deprotecting benzoate group of formula (lj) using Deprotecting agent lithium hydroxide monohydrate to afford oxazolidinone (5); b) refluxing the compound (5) as obtained in step (a) with tetradecene and Grubbs second generation catalyst in dichloromethane at temperature in the range of 40-60°C for period in the range of 4-6 hrs to afford desired cross- coupled product (6);

c) subjecting the compound of steep (b) to catalytic hydrogenation under hydrogen atmosphere followed by basic hydrolysis and acetylation to afford D-ribo-phytosphingosine tetraacetate (7).

In yet another embodiment of the present invention, hydrogenating agent used in step (c) for catalytic hydrogenation is raney nickel.

In yet another embodiment of the present invention, hydrolyzing agent and acetylating agent used in step (c) is potassium carbonate and acetic anhydride (Ac ₂ 0) respectively. In yet another embodiment of the present invention, in step (c) acetylation is carried out presence of catalyst 4-Dimethylaminopyridine (DMAP).

DETAILED DESCRIPTION OF THE INVENTION

Present invention provides a vinylic 3 -amino- 1,2 diol compounds of formula (I)

R"

I o

Ή O' h

OH

Formula (I)

wherein

R is straight or branched chain alkyl or substituted alkyl or aryl alkyl selected from the group consisting of methyl, ethyl, propyl, isopropyl, CH ₃ OCH ₂ O-CH ₂ CH _2, BnO-CH ₂ , CH ₂ =CH ₂ -CH ₂ , Ph-CH ₂ , p-MeO-Ph-CH ₂ ;

R' is selected from the group consisting of C0 ₂ -iPr, C0 ₂ -Bn and C0 ₂ -tBu.

The compounds of formula (I) are selected from the group consisting of

a. Diisopropyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxyhex-5-en-2- yl)hydrazine- 1 ,2-dicarboxylate (la);

b. Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxyhept-6-en-3- yl)hydrazine- 1 ,2-dicarboxylate( lb) ; c. Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy-2-methylhept-6-en-3- yl)hydrazine- 1 ,2-dicarboxylate( lc);

d. Diisopropyl l-((4R,5R,6S)-6-(benzoyloxy)-5-hydroxyoct-7-en-4- yl)hydrazine- 1 ,2-dicarboxylate( Id) ;

e. Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy-l- (methoxymethoxy)hept-6-en-3-yl)hydrazine- 1 ,2-dicarboxylate( le); f. Di-tert-butyl l-((3R,4R,5S)-5-(benzoyloxy)-l-(benzyloxy)-4-hydroxyhept-6- en-3-yl)hydrazine- 1 ,2-dicarboxylate( If);

g. Diisopropyl l-((3S,4R,5R)-3-(benzoyloxy)-4-hydroxynona-l,8-dien-5- yl)hydrazine- 1 ,2-dicarboxylate( 1 g) ;

h. Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy- l-phenylhex-5-en-2- yl)hydrazine- 1 ,2-dicarboxylate( lh) ;

i. Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy-l-(4- methoxyphenyl)hex-5-en-2-yl)hydrazine- 1 ,2-dicarboxylate( 1 i);

j. Dibenzyl l-((2R,3R,4S)-4-(benzoyloxy)-l-(benzyloxy)-3-hydroxyhex-5-en -2- yl)hydrazine- 1 ,2-dicarboxylate( lj );

1 a 1 b 1 c 1 d

C0 ₂ /-Pr C0 ₂ f-Bu I C0 ₂ f-Bu

O C0 ₂ /-Pr

NH I O I O

/ ^' -PrOoC. II

f-Bu0 ₂ C NH II

N O Ph -Pr0 ₂ C^NH i »*°2

"N O^Ph <ΗΓ _o A _ph

BnO"

OH OH OH OH

1 e 1 f i g 1 h

p-M

1 i 1j

These compounds may find tremendous applications in the synthesis of various biologically active organic molecules possess vicinal amino diol stereotriad. The present invention provides a cost-effective asymmetric synthesis of chiral vinylic-3- amino- 1,2-diols of formula I via intermediate A starting from substituted aldehydes of formula (II). The reaction proceeds with L-proline catalysed one pot procedure for a tandem a-amination-reaction of aldehydes followed by Zn promoted benzoyloxyallylation reaction (Barbier protocol) in one-pot to obtain the corresponding chiral vinylic-3-amino-l, 2-diol of formula (I).

The pre invention provides a cost-effective asymmetric synthesis of chiral vinylic-3- amino- 1,2-diols of formula (I) from substituted aldehydes of formula (II) comprises subjecting substituted aldehydes of formula (II) and azodicarboxylate in acetonitrile to examination at 0°C for 3 h followed by subjecting to benzoyloxyallylation reaction in presence of zinc powder, 3-benzoyloxyallyl bromide and saturated aq. NH ₄ CI at 0°C to - 25°C to afford vinylic-3-amino- 1,2-diols of formula (I). The a-amination is carried out in presence of suitable catalyst such as L-proline.

The invention may also be performed using other cheaper metal catalysts such as Indium metal, Chromium (III) chloride etc instead of Zinc.

The substituted aldehydes of formula (II) are selected from the group consisting of Propanal, Butaraldehyde, isovalraldehyde, valraldehyde, 4-(methoxymethoxy)butanal, 3- (Benzyloxy)butanal, hex-5-enal, 3-phenylpropanal, 3-(4-methoxyphenyl)propanal or 2- (Benzyloxy)propanal.

The azodicarboxylate are selected from the group consisting of Dibenzyl azadicarboxylate, Di-feri-butyl azadicarboxylate or Diisopropyl azadicarboxylate.

The one pot procedure for a tandem L-proline catalyzed one pot procedure for a tandem a-amination- benzoyloxyallylation reaction of aldehydes of various aldehydes of formula (II) that proceed to give vinylic-3-amino-l, 2-diol of formula (I) in a highly enantio- and diastereoselective manner as given in scheme 1.

Propinaldehyde 11(a) is treated with 10 mol % of L-proline and diisopropyldiazodicarboxylate in acetonitrile at 0 °C for 3 h, and then reacted with zinc powder, 3-benzoyloxyallyl bromide and saturated aq. NH ₄ CI at 0 °C, to afford Diisopropyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxyhex-5-en-2-yl)hydrazin e-l,2- dicarboxylate (la) in a diastereomeric mixture (60: 40). In an alternate process variant, the suitability of the temperature is optimized and accordingly a dramatic improvement in diastereoselectivity (80: 20) is achieved by performing the reaction at - 10 °C for 2h; however, the best result is obtained when the addition of 3-benzoyloxyallyl bromide is conducted at -20 °C (ee 90%, dr> 99).

The invention provides substrate scope of aliphatic aldehydes bearing different functionality Formula Il(a-j). Accordingly, the aldehydes bearing different functionality such as aryl, alkenyl, benzoyloxy or methoxymethyl were reacted under the same reaction conditions which confirms that the instant process displayed a wide substrate scope and was compatible with various functionalities. Further, the corresponding products of the aldehydes were indeed obtained in high yield (81-87%) and excellent enantioselectivity (92-99% ee) with dr> 99%. The stereochemistry of this tandem transformation is assigned according to the previous established absolute configuration of a- aminoaldehyde. The anti-anti stereochemistry in vinylic-3-amino-l,2-diol is proven from X-ray crystallographic analysis.

To rationalize the observed high αηύ,αηύ diastereselectivity of vicinal amino diols, the inventors have proposed both Fekin-Ahn ^6d (TS 1) and six membered transition state (TS II) model. Anti relationship at Ci-C ₂ carbons is governed by the Felkin-Ahn model in which Zn atom of benzoyloxyallylzinc reagent is coordinated to the carbonyl oxygen and the nucleophilic attack of the corresponding reagent takes place at 'Si' face predominantly perpendicular to the bulky R N-NHR ¹ group. Also, anti relationship at C ₂ - C ₃ carbons can be explained based on the six membered transition state model (TS II) in which hydrazino alkyl group of aldehyde and OBz group of nucleophile are oriented in the pseudoequatorial position to deliver anti diol.

Proposed transition state model for compound of formula I

(R ¹ = C0 ₂ Pr, C0 ₂ iBu, C0 ₂ Bn; R = alkyl, alkyl aryl; Bz=C ₆ H ₅ CO). The present invention provide a process for the preparation of D-ribo-phytosphingosine tetraacetate 7 from compounds of formula (I) wherein said process comprising the steps of:

a) deprotecting benzoate group of formula (I) using suitable Deprotecting agent to afford oxazolidinone (5);

b) refluxing the compound of step (a) with tetradecene and Grubbs second generation catalyst in dichloromethane at temperature in the range of 40-60 °C for period in the range of 4-6 hrs to afford desired cross- coupled product (6);

c) subjecting the compound of steep (b) to catalytic hydrogenation followed by basic hydrolysis and acetylation to afford D-ribo-phytosphingosine tetraacetate (7).

The deprotecting agent is selected from Lithium hydroxide monohydrate or potassium carbonate.

The catalytic hydrogenation in step (c) is carried out using hydrogenating agents selected from raney nickel and under hydrogen atmosphere.

The basic hydrolysis in step (c) is carried out using hydrolyzing agent selected from potassium carbonate, sodium dicarbonate or lithium hydroxide.

The acetylation in step (c) is carried out in using acetylating agent selected from acetic anhydride (Ac ₂ 0) or acetic chloride (AcCl) and in presence of suitable catalyst such as 4- Dimethylaminopyridine (DMAP).

Among the potential applications of this methodology, for example, a short asymmetric synthesis of D-ribo-phytosphingosine tetraacetate 7, a key backbone component of sphingolipids is synthesized (Scheme 2). Accordingly, for the preparation of D-ribo- phytosphingosine tetraacetate 7, 3-(benzyloxy)propanal formula II j) is subjected to one- pot a-amination-benzoyloxyallylation sequence (DBAD, D-proline, CH ₃ CN followed by Zn powder, 3-benzoyloxyallyl bromide and saturated aq. NH ₄ CI ) to produce vinylic amino diol ent-l ) (85 %). In the next step, the installation of appropriate long chain of natural product is accomplished by cross-metathesis of vinylic amino diol ent-l ) with 3 eq. of tetradecene using Grubbs second generation catalyst, however, did not observe any cross-coupled product, that might be due to the steric hindrance of bulky benzoate group. Therefore, benzoate group is deprotected using LiOH.H ₂ 0 in methanol to produce free allylic alcohol with concomitant formation of oxazolidinone 5 in 75% yields. The oxazolidinone is refluxed in DCM with 3 eq. of tetradecene and Grubbs second generation catalyst (10 mol%) to give the desired cross- coupled product 6 in 72% isolated yield after 4h. Further, compound 6 is converted into target molecule, D-ribo- phytosphingosine tetraacetate 7 . The catalytic hydrogenation [Raney Ni, H ₂ (60 psig), 24 h] of 6 followed by basic hydrolysis (K ₂ C0 ₃ , MeOH) and its acetylation (Ac ₂ 0, py, DMAP) produced the target D-ribo-phytosphingosine tetraacetate 7 in 76% yield and 93% ee. The process for the synthesis of phytosphingosine 7 is as shown in Scheme: 2. To further extend its synthetic utility la was subjected to hydroboration/oxidation sequence that gave functionalized amino triol 3 in high yield. Also lc was hydrogenated over Raney Ni followed by its Boc protection giving 4 in 89% yield.

Bo

1c, R'= Bn

Examples

Following examples are given by way of illustration and therefore should not be construed to limit the scope of the invention.

General experimental procedure for sequential a-amination/benzoyloxyallylation of Aldehydes

To a cooled solution of azadicarboxylate (5.0 mmol) and L-proline (10 mol%) in dry CH ₃ CN (20 mL) at 0°C was added aldehydes (Formula Il(a-j)), 5 mmol) and the mixture was stirred for 3 h at 0°C. This was followed by the addition of zinc powder (7.5 mmol), 3-benzoyloxyallyl bromide (7.5 mmol) and saturated aq. NH ₄ CI (20 ml) at -20°C for 2 h. The progress of the reaction can be monitored by TLC. After completion of the reaction, it was concentrated in vacuum to remove acetonitrile and the concentrate was extracted with ethyl acetate (3x40 mL). The combined organic layers were washed with brine, dried over anhyd. Na ₂ S0 ₄ , and concentrated under reduced pressure to give the crude products, which were then purified by flash column chromatography (100-200 mesh) using petroleum ether and ethyl acetate (4: 1) as eluents to afford the pure products of formula I(a-j).

Table L-Proline-catalyzed Asymmetric Sequential a-Amination/Benzoyloxyallylation of Aldehydes ³

^a Aldehyde (5 mmol), amine (R'0 ₂ C-N=N-C0 ₂ -R') (5 mmol), L-proline (10 mol %), CH ₃ CN (25 ml), 0 °C, 3 h followed by 3-benzoyloxyallyl bromide (7.5 mmol), Zn (7.5 mmol), saturated aq. NH ₄ C1 (10 mL), -20 °C, 2 h. isolated yield. ^c from chiral HPLC analysis

Example 1

Diisopropyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxyhex-5-en-2-yl)hydrazin e-l,2- dicarboxylate (la)

Yield: 79%; colorless solid; mp 110-112°C; IR (CHC1 ₃ ): 3303, 2982, 2932, 1708, 1386, 1267, 1105, 753, 712 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.20-1.34 (m, 15H), 4.17 (brs, IH), 4.38 (brs, IH), 4.9-5.03 (m, 2H), 5.30-5.48 (m, 3H), 5.98-6.15 (m, IH), 6.53 (brs, NH), 7.45 (t, = 8.9 Hz, 2H), 7.57 (t, = 6.3 Hz, IH), 8.09 (d, = 8.9 Hz, IH); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 11.0, 21.7, 54.6, 69.6, 69.9, 70.5, 73.9, 118.1, 128.2, 129.6, 132.9, 155.2, 156.5, 165.3; HRMS (ESI, m/z): calcd for C ₂ iH ₃₀ N ₂ O ₇ [M+Na] ⁺ 445.1945, found 445.1938; HPLC: [Chiralpack ADH, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (minor) 20.92 min, (major) 25.13 min, ee 77%]; [a] ^D ₂₅ +25.81 (c 3.78, CHC1 ₃ ).

Example 2

Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxyhept-6-en-3-yl)hydrazi ne-l,2- dicarboxylate (lb)

Yield: 87%; gum; IR (CHC1 ₃ ): 3317, 2982, 1705, 1307, 1237, 741 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 0.91 (brs, 3H), 1.27 (s, 12H), 1.73 (brs, 2H), 4.13 (brs, 2H), 4.91-5.03 (m, 2H), 5.33-5.54 (m, 3H) 5.99-6.16 (m, IH), 6.46 (brs, NH), 7.45 (t, = 6.3 Hz, 2H), 7.58 (t, = 6.7 Hz, IH), 8.1 (s, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 11.2, 18.1, 21.9, 61.1, 70.1, 70.6, 73.6, 75.1, 118.6, 128.3, 129.6, 129.7, 129.9, 133, 155.3, 156, 165.1; HRMS (ESI, m/z): calcd for C ₂₂ H ₃₂ N ₂ 0 ₇ [M+Na] ⁺ 459.2107, found 459.2091. HPLC: Chiracel AS-H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 18.49 min and (minor) 28.39 min, ee 91%]; [a] ^D 25 -2.8 (c 2.2, CHC1 ₃ ).

Example 3 Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy-2-methylhept-6-en-3- yl)hydrazine-l,2-dicarboxylate (lc)

Yield: 83%; gum; IR (CHC1 ₃ ): 3306, 2962, 1267, 1105, 754 cm ^"1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 0.94 (d, 7 = 6.7 Hz, 3H), 1.11 (d, 7 = 3.4 Hz, 3H), 1.23-1.32 (m, 12H), 2.12- 2.34 (m, IH), 4- 4.11 (m, IH), 4.26 (t, 7 = 4.5 Hz, IH), 4.86-5.06 (m, 2H), 5.35-5.63 (m, 3H), 6.0-6.17 (m, IH), 6.88 (brs, NH), 7.43 (t, 7 = 6.9 Hz, 2H), 7.56 (t, 7 = 6.9 Hz, IH), 8.07 (d, 7 = 4.1 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 19.6, 22, 27.7, 29.6, 63.7, 70.3, 70.8, 71.8, 72.5, 119.4, 128.4, 129.7, 129.8, 130, 133.1, 156, 156.2, 165.3; HRMS (ESI, m/z): calcd for C ₂₃ H ₃₄ N ₂ O ₇ [M+Na] ⁺ 473.2263, found 473.2253; HPLC: [Chiralpack AD-H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 16.47 min and (minor) 19.82 min, ee 95%]; [a] ^D 25 +212.69 (c 0.54, CHCI ₃ ).

Example 4

Diisopropyl l-((4R,5R,6S)-6-(benzoyloxy)-5-hydroxyoct-7-en-4-yl)hydrazin e-l,2- dicarboxylate (Id)

Yield: 86%; viscous oil; IR (CHC1 ₃ ): 3316, 2983, 1705, 1267, 1106, 749 cm ^"1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 0.98 (t, 7 = 6.2 Hz, 3H), 1.28 (s, 12H), 1.6-1.87 (m, 4H), 4.14 (brs, IH), 4.21 (brs, IH), 4.92-5.0 (m, 2H), 5.30-5.57 (m, 3H), 5.99-6.16 (m, IH), 6.69 (brs, NH), 7.44 (t, 7 = 6.8 Hz, 2H), 7.57 (t, 7 = 5.5 Hz, IH), 8.09 (d, 7 = 5.9 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 13.6, 19.3, 21.7, 26.5, 58.5, 69.8, 70.3, 73.5, 74.9, 118.3, 128.1, 129.5, 132.8, 155.3, 156.7, 165.4; HRMS (ESI, m/z): calcd for C ₂₃ H ₃₄ N ₂ O ₇ [M+Na] ⁺ 473.2258, found 473.2249; HPLC: [Chiralpack AD-H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (minor) 27.2 min and (minor) 30.607 min, ee 93%]; [a] ^D 25 +65.68 (c 1.94, CHC1 ₃ ).

Example 5

Diisopropyl l-((3R,4R,5S)-5-(benzoyloxy)-4-hydroxy-l-(methoxymethoxy)hep t-6-en- 3-yl)hydrazine-l,2-dicarboxylate (le)

Yield: 87%; gum; IR (CHC1 ₃ ): 3405, 2982, 2938, 1706, 1379, 1231, 1103 cm ^"1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.26 (s, 12H), 2.0 (brs, 2H), 3.24 (s, 3H), 3.54 (brs, 2H), 4.14 (brs, IH), 4.38 (brs, IH), 4.49 (s, 2H), 4.87-4.99 (m, 2H), 5.32-5.53 (m, 3H), 6.0- 6.17 (m, IH), 6.87 (brs, NH), 7.44 (t, = 6.9 Hz, 2H), 7.54 (t, = 7.1 Hz, IH), 8.1 (d, = 6.2 Hz, 2H) ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 21.8, 30.6, 54.8, 57.5, 65.2, 69.9, 70.4, 73.6, 74.7, 118.3, 128.2, 129.6, 132.9, 155.4, 165; HRMS (ESI, m/z): calcd for C ₂₄ H ₃₆ N ₂ 0 ₉ [M+Na] ⁺ 519.2318, found 519.2316; HPLC: [Chiralpack AD-H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time :(major) 24.01 min and (minor) 29.12 min, ee 93%]; [a] ^D ₂₅ -6.61 (c 0.66, CHC1 ₃ ).

Example 6

Di-tert-butyl l-((3R,4R,5S)-5-(benzoyloxy)-l-(benzyloxy)-4-hydroxyhept-6-e n-3- yl)hydrazine-l,2-dicarboxylate (If)

Yield: 84%; gum; IR (CHC1 ₃ ): 3364, 2980, 1707, 1269, 1216, 749, 711 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.48 (s, 18H), 2.05 (brs, 2H), 3.61 (brs, 2H), 4.17 (brs, IH), 4.42 (s, 2H), 4.51 (s, IH), 5.31-5.54 (m, 3H), 6.02-6.18 (m, IH), 6.81 (brs, NH), 7.27 (s, 5H), 7.44 (t, = 7.3 Hz, 2H), 7.56 (t, = 7.2 Hz, IH), 8.11 (d, = 7.3 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 28.1, 29.6, 57.9, 68.1, 73.1, 73.7, 74.9, 81.1, 81.9, 118.3, 127.5, 128.3,

129.7, 129.8, 130.1, 132.9, 133.1, 137.9, 154.9, 165.2; HRMS (ESI, m/z): calcd for C ₃ iH ₄₂ N ₂ 0 ₈ [M+Na] ⁺ 593.2838, found 593.2841 ; HPLC: [Chiralpack AD-H, 2- Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time : (minor) 22.79 min and (major) 26.14 min, ee 93%]; [a] ^D ₂₅ -5.88 (c 0.76, CHC1 ₃ ).

Example 7

Diisopropyl l-((3S,4R,5R)-3-(benzoyloxy)-4-hydroxynona-l,8-dien-5-yl)hyd razine- 1,2-dicarboxylate (lg)

Yield: 82%; gum; IR (CHC1 ₃ ): 3305, 2981, 2923, 1704, 1267, 1105, 754 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.26 (s, 12H), 1.69-2.15 (m, 4H), 4.14 (brs, IH), 4.22 (brs, IH), 4.81-5.03 (m, 4H), 5.32-5.48 (m, 3H), 5.65-5.82 (m, IH), 5.98-6.15 (m, IH), 6.71 (brs, NH), 7.44 (t, = 7.7 Hz 2H), 7.57 (t, = 7.2 Hz, IH), 8.09 (d, = 6.7 Hz, 2H), ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 22, 29.7, 30.6, 58.5, 70.2, 70.7, 73.8, 74.4, 115.3, 118.7, 128.3,

129.8, 133.1, 137.5, 155.4, 155.8, 165.5; HRMS (ESI, m/z): calcd for C ₂₄ H ₃₄ N ₂ 0 ₇ [M+Na] ⁺ 485.2264, found 485.2267; HPLC: [Chiralpack AD-H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time : (major) 12.530 min and (minor) 15.123 min, ee 95%]; [a] ^D ₂₅ +133.85 (c 0.84, CHC1 ₃ ).

Example 8

Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy-l-phenylhex-5-en-2- yl)hydrazine-l,2-dicarboxylate (lh)

Yield: 84%; gum; IR (CHC1 ₃ ): 3323, 2981, 1704, 1267, 1109, 842, 741 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.26-1.48 (m, 18H), 3.05 (brs, 2H), 4.35 (t, = 7.9 Hz, 1H), 4.63 (brs, 1H), 5.32-5.64 (m, 3H), 6.04-6.21 (m, 1H), 7.11-7.26 (m, 5H), 7.44 (t, = 7.5 Hz, 2H), 7.54 (d, = 6.9 Hz 1H,), 8.12 (t, = 6.3 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 28.1, 30.6, 60.5, 74.4, 74.8, 81.6, 82.1, 118.2, 126.4, 128.4, 128.6, 129.7, 130.1, 133,

134.1, 138.7, 154.7, 165.3; HRMS (ESI, m/z): calcd for C ₂₉ H ₃₈ N ₂ 0 ₇ [M+Na] ⁺ 549.2577, found 549.2579; HPLC: [Chiralpack ADH, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 21.64 min and (minor) 32.11 min, ee 97%]; [a] ^D ₂₅ +130.4 (c 0.86, CHC1 ₃ ).

Example 9

Di-tert-butyl l-((2R,3R,4S)-4-(benzoyloxy)-3-hydroxy-l-(4-methoxyphenyl)he x-5- en-2-yl)hydrazine-l,2-dicarboxylate (li)

Yield: 81%; gum; IR (CHC1 ₃ ): 3364, 2981, 2922, 1708, 1351, 1263, 1105, 833, 711 cm ^{" l} ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.34-1.47 (s, 18H), 2.97 (brs, 2H), 3.74 (s, 3H), 4.26 (brs, 1H), 4.38 ( brs, 1H), 5.34 (t, = 8.5 Hz, 1H), 5.45 (dd, = 5.4, 11.6 Hz, 1H), 5.6 (t, = 5.4 Hz, 1H), 6.03-6.15 (m, 1H), 6.36 (brs, NH), 6.75 (d, = 8.8 Hz, 2H), 7.02 (d, = 8.8 Hz, 2H), 7.45 (t, = 7.6 Hz, 2H), 7.57 (q, = 7.6 Hz, 1H), 8.11 (dd, / = 7.1, 12.5 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 28.2, 29.7, 55.1, 59.6, 74.4, 74.8, 81.4, 82.1, 114.1,

118.2, 128.3, 128.4, 129.3, 129.8, 130.1, 133.3, 134.2, 165.1, 165.3, 170.1 ; HRMS (ESI, m/z): calcd for C ₃₀ H ₄ oN ₂ 0 ₈ [M+H] ⁺ 557.2862, found 557.2875; HPLC: [Chiralpack AD- H, 2-Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 26.608 min and (minor) 43.61 min, ee 99%]; [a] ^D ₂₅ +288.75 (c 0.4, CHC1 ₃ ).

Example 10 Dibenzyl l-((2R,3R,4S)-4-(benzoyloxy)-l-(benzyloxy)-3-hydroxyhex-5-en -2- yl)hydrazine-l,2-dicarboxylate (lj)

Yield: 85%; gum; IR (CHC1 ₃ ): 3309, 2979, 1706, 1262, 752 cm ^"1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 3.81 (brs, 2H), 4.36 (s, 2H), 4.42 (brs, 1H), 4.57 (brs, 1H), 5.13 (s, 4H), 5.29- 5.39 (m, 2H), 5.52 (brs, 1H), 5.94-6.08 (m, 1H), 6.79 (brs, NH), 7.19-7.28 (m, 15H), 7.41 (d, = 7.3 Hz, 2H), 7.52 (s, 1H), 8.06 (d, = 6.8 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 58.6, 67.9, 68.2, 68.7, 73.1, 74.7, 75.6, 118.7, 127.7, 127.8, 128.2, 128.4, 128.4, 128.5, 129.8, 133.1, 135.4, 135.7, 137.5, 155.6, 165.3; HRMS (ESI, m/z): calcd for C ₃₆ H ₃₆ N ₂ O ₈ [M+H] ⁺ 625.255, found 625.2517; HPLC: [Chiralpack AD-H, 2- Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 86.00 min and (minor) 93.6 min, ee 93%]; [a] ^D ₂₅ -288.75 (c 0.4, CHCI ₃ ).

Example 11

Dibenzyl l-((2S,3S,4R)-4-(benzoyloxy)-l-(benzyloxy)-3-hydroxyhex-5-en -2- yl)hydrazine-l,2-dicarboxylate (ent-lj)

Yield: 85%; gum; IR (CHC1 ₃ ): 3309, 2979, 1706, 1262, 752 cm ^-1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 3.81 (brs, 2H), 4.36 (s, 2H), 4.42 (brs, 1H), 4.57 (brs, 1H), 5.13 (s, 4H), 5.29- 5.39 (m, 2H), 5.52 (brs, 1H), 5.94-6.08 (m, 1H), 6.79 (brs, NH), 7.19-7.28 (m, 15H), 7.41 (d, = 7.3 Hz, 2H), 7.52 (s, 1H), 8.06 (d, = 6.8 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 58.6, 67.9, 68.2, 68.7, 73.1, 74.7, 75.6, 118.7, 127.7, 127.8, 128.2, 128.4, 128.4, 128.5, 129.8, 133.1, 135.4, 135.7, 137.5, 155.6, 165.3; HRMS (ESI, m/z): calcd for C ₃₆ H ₃₆ N ₂ O ₈ [M+H] ⁺ 625.255, found 625.2517; HPLC: [Chiralpack AD-H, 2- Propanol/n-Hexane = 10/90, flow rate 0.5 mL/min, λ = 220 nm, retention time: (major) 86.00 min and (minor) 93.6 min, ee 93%]; [a] ^D ₂₅ +288.75 (c 0.4, CHCI ₃ ).

Example 12

Experimental procedure for the preparation of diisopropyl l-((2R,3R,4S)-4- (benzoyloxy)- 3,6-dihydroxyhexan-2-yl)hydrazine-l,2-dicarboxylate (3)

Aminodiol la (0.22 g; 0.5 mmol) was added dropwise to a solution of BH ₃ .DMS (0.023 mL, 0.025 mmol) in dry THF (10 mL) at room temperature and then mixture was stirred for 3 h. The reaction flask was cooled at 0°C and NaOH (0.02 g; 0.5 mmol) in ethanol (2 mL) was added to the reaction mixture followed by 30% ¾(¾ (0.06 mL, 0.7 mmol). It was then allowed to stir at rt for 2 h and the product was extracted with ethyl acetate washed with brine, dried over Na ₂ S04 and concentrated in vacuum. Purification by column chromatography over silica gel using petroleum ether and ethyl acetate as eluents (4: 1) gave 3 as a colorless oil.

Yield: 75%; colorless oil; IR (CHC1 ₃ ): 3372, 2091, 1706, 1671, 1511, 1363, 711 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 1.11-1.20 (m, 15H), 1.91-2.15 (m, 2H), 2.67 (brs, OH), 3.39 (brs, OH), 3.52-3.70 (m, 2H), 4.04 (brs, 1H), 4.30 (brs, 1H), 4.84-4.89 (m, 2H), 5.04 (t, = 4.4 Hz, 1H), 7.03 (brs, NH), 7.36 (t, = 7.8 Hz, 2H), 7.49 (t, = 6.8 Hz, 1H), 7.98 (d, = 6.8 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 9.9, 21.9, 34.4, 54.5, 58.3, 70.1, 72.4, 73.8, 128.3, 129.7, 133.1, 155.2, 166.4; HRMS (ESI, m/z): calcd for C ₁₇ H ₂₅ N ₂ O ₈ [M+H] ⁺ 441.2237, found 441.2238; [a] ^D ₂₅ +32.9 (c 0.21, CHC1 ₃ ).

Example 13

Experimental procedure for the preparation of (3S,4R,5R)-5-((tertbutoxycarbonyl) amino)-4-hydroxyhexan-3-yl benzoate (4)

The solution of vicinal amino diol lc (lg, 1.9 mmol) in MeOH (20 mL) was treated with Raney Ni (0.5 g, excess) under H2 atmosphere (80 psig) for 24 h. The reaction mixture was filtered over celite and concentrated to give crude product, which was dissolved in CH2C12 (15 mL) and added NEt3 (0.26 mL, 1.9 mmol) followed by Boc20 (0.42 g, 1.9 mmol) and reaction mixture was stirred for 1 h at room temperature. After completion of reaction was quenched with water and extracted with CH2C12 (3 X 15 mL) and concentrate to give crude product which was purified by flash column chromatography (100-200 mesh) using petroleum ether and ethyl acetate (4: 1) as eluents to afford the pure product 4.

Yield: 89%; gum; IR (CHC1 ₃ ): 3335, 2918, 1734, 1695, 749 cm ^-1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 0.98 (t, = 7.3 Hz, 3H), 1.17 (d, = 6.8 Hz, 2H), 1.45 (s, 9H), 1.70 (brs, 1H), 1.78-1.85 (m, 1H), 1.93-1.99 (m, 1H), 3.87 (brs, 1H), 4.78-4.83 (m, 1H), 5.09-5.15 (m, 1H), 7.45 (t, = 7.3 Hz, 2H), 7.58 (t, = 7.7 Hz, 1H), 8.05-8.07 (dd, = 1.3, 8.2 Hz, 2H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 9.6, 15.7, 23.7, 28.4, 48.4, 75.1, 76.2, 79.6, 128.5, 129.7, 133.1, 155.8, 166.3; HRMS (ESI, m/z): calcd for C18H27NO5 [M+Na] ⁺ 360.1786, found 360.1792; [a] ^D ₂₅ +29.1 (c 1.0 in CHC1 ₃ ).

EXAMPLE 14

Experimental procedure for the preparation of Benzyl ((4S,5S)-4- ((benzyloxy)methyl)-5- ((R)-l-hydroxyallyl)-2-oxooxazolidin-3-yl)carbamate (5):

To a solution of vicinal amino diol 4 (2 g, 3.6 mmol) in MeOH (20 ml) at room temperature was added LiOH.H ₂ 0 (296 mg, 7.2 mmol) and the reaction mixture was stirred for 3 h. After completion of the reaction, it was diluted with water and the mixture was concentrated in vacuum to remove MeOH and the concentrate was extracted with ethyl acetate (3 x 40 ml). The combined organic layers were washed with brine, dried over anhydrous Na ₂ S0 ₄ and concentrated under reduced pressure to give crude product, which was then purified by flash column chromatography using petroleum ether: ethyl acetate (2:3) to afford pure oxazolidinone 5.

Yield: 71%; gum; IR (CHC1 ₃ ): 3368, 2084, 1707, 1675, 1261, 750 cm ^-1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 3.72 (q, = 9.6 Hz, 2H), 4.08 (brs, 1H), 4.33 (s, 1H), 4.48 (t, = 6.9 Hz 1H,), 5.07 (s, 2H), 5.2 (d, = 10.5 Hz, 1H), 5.35 (d, = 17.4 Hz, 1H), 5.84-5.92 (m, 1H), 7.23-7.3 (m, 9H), 7.44 (t, = 9.1 Hz, 1H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 58.4, 64.5, 67.7, 69.4, 71.1, 73.3, 117.3, 127.5, 127.7, 128, 128.1, 128.2, 128.4, 128.5, 135.2, 135.7, 136.6, 155.5, 156.6; HRMS (ESI, m/z): calcd for C ₂₂ H ₂₄ N ₂ 0 ₆ [M+H] ⁺ 413.1712, found 413.1792; [a] ^D ₂₅ -88.96 (c 4.46, CHC1 ₃ ).

EXAMPLE 15

Experimental procedure for the preparation of benzyl ((4S,5S)-4- ((benzyloxy)methyl)-5-((R,E)-l-hydroxypentadec-2-en-l-yl)-2- oxooxazolidin-3-yl) carbamate (6)

To a solution of oxazolidinone 5 (1.3 g, 3.16 mmol) in 20 ml of dry CH2C12 was added Grubbs II ^nd generation catalyst (5 mol%, 15 mg) followed by tetradecene (2.1 g, 10.8 mmol) and the resulting mixture was heated at reflux for 6 h. After completion of the reaction, it was concentrated to give the crude product, which was then purified by flash column chromatography (100-200 mesh) using petroleum ether and ethyl acetate (7:3) as eluents to afford the pure product 6.

Yield: 81%; gum; IR (CHC1 ₃ ): 3368, 2084, 1708, 1671, 1352, 642 cm ^"1 ; 1H NMR (200 MHz, CDCI ₃ ): δ 0.88 (t, = 7.1 Hz, 3H), 1.26 (s, 20 H), 2.03 (q, J = 7 Hz, 2H), 2.9 (brs, OH), 3.69- 3.79 (m, 2H), 4.09 (brs, 1H), 4.31 (brs, 1H), 4.42 (brs, 1H), 4.51 (q, J = 11.6 Hz, 2H), 5.11 (q, J= 12.2 Hz, 2H), 5.49 (dd, = 5.8, 9.7 Hz, 1H) 5.78 (m, 1H), 6.89 (brs,NH), 7.25-7.33 (m, 10H); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 14.1, 22.7, 28.9, 29.2, 29.4, 29.5, 29.6, 29.7, 31.9, 32.3, 58.6, 64.5, 67.9, 69.6, 73.6, 77.8, 127.4, 128, 128.2, 128.3, 128.4, 128.5, 128.7, 135.3, 136.3, 155.4, 156.5; HRMS (ESI, m/z): calcd for C ₃₄ H ₄₈ N ₂ O ₆ [M+Na] ⁺ 581.3591, found 581.3573; [a] ^D ₂₅ - 232.9 (c 0.34, CHCI ₃ ).

EXAMPLE 16

Experimental procedure for the preparation of D-ri ^' io-phytosphingosine tetraacetate (7)

A solution of olefin 6 (1 g, 1.7 mmol) in MeOH (20 mL) was treated with Raney Ni (0.5 g, excess) under H ₂ atmosphere (80 psig) for 24 h. The reaction mixture was filtered over celite to give crude product, in which was added K ₂ C0 ₃ (248 mg, 1.8 mmol) and the reaction mixture was stirred for 6 h until consumption of the starting material and methanol was removed in vacuum. H ₂ 0 was added to the crude product and extracted with ethyl acetate (3 X 10 mL), dried over Na ₂ S0 ₄ and concentrated. The crude material was subsequently acetylated with acetic anhydride (0.72 mL, 7.65 mmol), pyridine (0.62 mL, 7.65 mmol) and DMAP (cat). After overnight stirring, the solvent was evaporated and the residue was purified on a silica gel column using petroleum ether and ethyl acetate (5: 1) as eluent to give tetraacetate 7 as a white solid. Spectroscopic data of tetraacetate are in full agreement with those reported in literature.

Yield: 76%; white solid; mp: 45-46°C; IR (CHC1 ₃ ): 2920, 1734, 1685, 749 cm ^"1 ; 1H NMR (200 MHz, CDC1 ₃ ): δ 0.88 (t, = 7 Hz, 3H), 1.25 (brs, 24 H), 1.6-1.69 (m, 2H), 2.02 (s, 3H), 2.04 (s, 6H), 2.08 (s, 2H), 3.98 (dd, / = 2.9, 11.7 Hz, 1H), 4.29 (dd, = 4.7,

11.6, Hz, 1H), 4.42-4.48 (m, 1H), 4.92 (dt, = 3.1, 9.7 Hz, 1H), 5.09 (dd, 7 = 3.1, 8.3 Hz, 1H), 6.01 (d, = 9.3 Hz, NH); ¹³ C NMR (50 MHz, CDC1 ₃ ): δ 14.1, 20.7, 20.8, 21.0,

22.7, 23.2, 25.5, 28.1, 29.3, 29.4, 29.5, 29.6, 29.6, 29.6, 29.7, 31.9, 47.6, 62.8, 71.9, 73.0, 169.5, 169.9, 170.7, 171.0; HRMS (ESI, m/z): calcd for C26H47NO7 [M+H] ⁺ 486.3431, found 486.3435; [a] ^D ₂₅ +20.1 (c 1.0 in CHC13); {lit. [a] ^D ₂₅ +20.9 (c 1.1 in CHCI3)}.

ADVANTAGES OF INVENTION

1. Novel compounds of formula (I)

2. Novel compounds of formula (I) are used for the preparation of phytosphin

and epi-jaspine B

3. Simple, cost-effective and easy to operate process

4. The process gives high yield and selectivity

5. Use of cheap and easily available proline as organocatalysts.