Process for synthesizing highly optically active 1,3-disubstituted allenes

Patent metadata

Field	Value
Publication number	US-9873713-B2
Application number	US-201414405092-A
Country	US
Kind code	B2
Filing date	Oct 10, 2014
Priority date	Aug 6, 2014
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

The present invention relates to a process for efficiently synthesizing highly optically active 1,3-disubstituted allenes, i.e., a one-step process for preparing highly optically active 1,3-disubstituted allenes by using a functionalized terminal alkyne, an aldehyde and a chiral α,α-diphenyl prolinol as reactants under the catalysis of a divalent copper salt. The operation of the process is simple, and the raw materials and reagents are readily available. The process has a broad-spectrum of substrates and a good compatibility for a wide variety of functional groups such as glycosidic units, primary alcohols, secondary alcohols, tertiary alcohols, amides, malonates, etc., and does not require the protection for the functional groups. The obtained axially chiral allene has a moderate to high yield and a good diastereoselectivity or enantioselectivity.

First claim

What is claimed:

1. A process for synthesizing optically active 1,3-disubstituted allenes, in a heated reaction comprising a functionalized terminal alkyne, an aldehyde and a chiral secondary amine as reactants, a divalent copper salt as a catalyst and an organic solvent, thereby producing a variety of functionalized axially chiral 1,3-disubstituted allenes; wherein the process consists of:
adding in sequence to a reaction under nitrogen atmosphere: a divalent copper salt, a chiral secondary amine, a terminal alkyne, an aldehyde and an organic solvent;
subjecting the reaction to anhydrous and anaerobic treatment by heating for 12-24 h in an oil bath;
returning the reaction to room temperature,
diluting the reaction with the organic solvent,
washing the reaction with dilute hydrochloric acid,
separating the organic phase,
extracting the aqueous phase with the organic solvent,
washing with saturated brine,
drying with anhydrous sodium sulfate, filtering, concentrating and subjecting reaction products to column chromatography, so as to obtain the axially chiral allene; wherein the reaction has a following reaction equation:

wherein R 1 comprises functional groups selected from glycosidic units, primary alcohols, secondary alcohols, tertiary alcohols, amides, malonates, alkyl group or aryl group, and R 2 is an alkyl group or an aryl group.

2. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1 , wherein the catalyst is copper bromide, copper chloride, copper acetate, copper sulfate or copper triflate.

3. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1 , wherein the chiral secondary amine is selected from the group consisting of (S)-3a and enantiomers thereof:

4. The process for synthesizing optically active 1,3-disubstituted allenes of claim 1 , wherein the organic solvent is 1,4-dioxane, toluene, benzene, chlorobenzene, p-xylene, o-xylene, m-xylene, or mesitylene.

5. The process for synthesizing optically active 1,3-disubstituted allenes of claim 3 , wherein the organic solvent is 1,4-dioxane, toluene, benzene, chlorobenzene, p-xylene, o-xylene, m-xylene, or mesitylene.

Assignees

• Univ Zhejiang

Inventors

• Ma Shengming
• Huang Xin
• Fu Chunling

Classifications

• C07C67/343

  by increase in the number of carbon atoms · CPC title

• C07H15/18 Primary

  Acyclic radicals, substituted by carbocyclic rings · CPC title

• C07C2527/122

  Compounds comprising a halogen and copper · CPC title

• C07C67/30

  by modifying the acid moiety of the ester, such modification not being an introduction of an ester group · CPC title

• C07C303/40

  by reactions not involving the formation of sulfonamide groups · CPC title