Enantioselective process for the preparation of enantiomers of sex pheromones

Patent metadata

Field	Value
Publication number	US-9598346-B2
Application number	US-201414763449-A
Country	US
Kind code	B2
Filing date	Jan 24, 2014
Priority date	Jan 24, 2013
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

The invention disclosed herein relates to an enantioselective process for preparation of biologically active (R) and (S) enantiomers of sex pheromones of the long-tailed Mealybug with high enantiopurity having significant biological activity. Further, the invention provides absolute configuration of synthesized R and S enantiomers.(I)

First claim

I claim:

1. An enantioselective process for preparation of biologically active (R) and (S) enantiomers of sex pheromones:

wherein, the process comprises the steps of:
a) subjecting 3,3-dimethylhex-5-en-2-one (2) to Meyer-Schuster rearrangement reaction in presence of ethoxyacetylene and an organolithium reagent, followed by treatment with Lewis acid catalyst and then reduction to obtain racemic 3,4,4-trimethylhepta-2,6-dien-1-ol (3);

b) conducting Claisen rearrangement reaction on compound (3) in presence of alkyl vinyl ether and source of mercury ion, followed by reduction to obtain racemic 3,4,4-trimethyl-3-vinyl-hept-6-en-1-ol (4);

c) esterifying alcohol (4) with a chiral acid in presence of a coupling agent and base to obtain a mixture of diastereomers (5a) and (5b) followed by chiral separation;

d) hydrolyzing diastereomer (5a) and (5b) separately in alkaline medium followed by acetylation in presence of acetic anhydride, acetic acid, or acetyl chloride to obtain R and S enantiomer of (3,4,4-trimethyl-3-vinyl-hept-6-enyl) acetate (6a) and (6b); and

e) subjecting compound (6a) and (6b) to ring closure metathesis in presence of (Grubbs-II catalyst) [1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene) (tricyclohexyl phosphine) ruthenium to obtain the S and R enantiomers 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate.

2. The process as claimed in claim 1 , wherein the organolithium reagent is selected from the group consisting of n-butyllithium, methyllithium, t-butyllithium, and hexyllithium.

3. The process as claimed in claim 1 , wherein the Lewis acid catalyst is selected from the group consisting of copper (II) triflate, indium(III)chloride, and scandium(III) triflate.

4. The process as claimed in claim 1 , wherein the alkyl group in alkyl vinyl ether is selected from the group consisting of methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, isobutyl and mercury ion source is selected from the group consisting of mercury acetate, mercury formate, mercury oxide or mixtures thereof.

5. The process as claimed in claim 1 , wherein the reduction is carried out in presence of reducing agent selected from the group consisting of lithium aluminium hydride, sodium borohydride, sodium amalgam, diborane, and diisobutylaluminium hydride.

6. The process as claimed in claim 1 , wherein the chiral acid is selected from the group consisting of (−)-10,2-Camphorsultam; (+)-10,2-Camphorsultam; N-(2-Carboxybenzoyl)-(−)-10,2-camphorsultam; N-(2-Carboxybenzoyl)-(+)-10,2-camphorsultam or camphorsultam phthalic acid (CSP); N-(2-Carboxy-4,5-dichlorobenzoyl)-(−)-10,2-camphorsultam; N-(2-Carboxy-4,5-dichlorobenzoyl)-(+)-10,2-camphorsultam or camphorsultam dichlorophthalic acid (CSDP).

7. The process as claimed in claim 1 , wherein the coupling agent is selected from the group consisting of pyridine, 4-Dimethylaminopyridine (DMAP), N,N′-Dicyclohexylcarbodiimide (DCC), Hydroxybenzotriazole (HOBT), (Benzotriazol-1-yloxy) tris(dimethylamino)phosphonium hexafluorophosphate (BOP), N,N-Diisopropyl ethylamine (DIEA), O-Benzotriazole-N,N,N′,N′-tetramethyl-uronium-hexafluoro-phosphate, and N,N,N′,N′-tetramethyl-o-(benzotriazol-1-yl)uronium tetrafluoroborate (TBTU).

8. The process as claimed in claim 1 , wherein the base is an organic base selected from the group consisting of dimethylamine, diethylamine, trimethylamine, triethylamine, tributylamine, dimethylaniline, pyridine or mixtures thereof.

9. The process as claimed in claim 1 , wherein the alkaline medium is selected from the group consisting of alkali metal hydroxide, alkali metal carbonate, alkali metal bicarbonates in lower alcohol such as (C1-C6) alcohol.

10. The process as claimed in claim 1 , wherein the yield of S and R enantiomers 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate is in the range of 70-80%.

11. The process as claimed in claim 3 , wherein the Lewis acid catalyst is scandium(III) triflate [Sc(OTf) 3 ].

12. The process as claimed in claim 5 , wherein the reduction is carried out in presence of Diisobutylaluminium hydride (DIBAL-H).

Assignees

• Council Scient Ind Res
• Council Scient Ind Res

Inventors

• Reddy Dumbala Srinivasa

Classifications

• C07B2200/07

  Optical isomers · CPC title

• C07C29/143

  of ketones · CPC title

• C07C29/147

  of carboxylic acids or derivatives thereof · CPC title

• C07C29/92

  by a consecutive conversion and reconstruction · CPC title

• C07C67/293 Primary

  by isomerisation; by change of size of the carbon skeleton · CPC title