Method of synthesizing (1S, 5R)-lactone

Patent metadata

Field	Value
Publication number	US-10316012-B1
Application number	US-201916246531-A
Country	US
Kind code	B1
Filing date	Jan 13, 2019
Priority date	Jan 15, 2018
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

Disclosed is a method of synthesizing a series of compounds with the structure of (1S, 5R)-lactone. In the method, under the catalysis of a chiral phosphonic acid, substituted bicyclo[3.2.0]-hept-2-en-6-one (II) as a substrate is reacted with hydrogen peroxide for enantioselective Baeyer-Villiger oxidation to produce a chiral lactone (I). This method involves mild reaction conditions, simple operation, quantitatively recyclable catalyst and high reaction selectivity and stereoselectivity, which is suitable for industrial production.

First claim

What is claimed is:

1. A method of synthesizing a (1S,5R)-lactone of formula (I), comprising:

in the presence of a chiral phosphonic acid catalyst, substituted bicyclo[3.2.0]-hept-2-en-6-one reacting with a hydrogen peroxide in an organic solvent under normal, elevated or reduced pressure for enantioselective Baeyer-Villiger oxidation to produce a chiral lactone; where the substituted bicyclo[3.2.0]-hept-2-en-6-one is presented by structural formula (II)

wherein:
in formula (I), R is selected from the group consisting of hydrogen, halogen comprising chlorine, bromine and iodine, C 1 -C 8 alkyl or cycloalkyl, phenyl, monosubstituted or polysubstituted aryl or aralkyl, thienyl, furyl and naphthyl;
in formula (II), R is selected from the group consisting of hydrogen, halogen comprising chlorine, bromine and iodine, C 1 -C 8 alkyl or cycloalkyl, phenyl, monosubstituted or polysubstituted aryl or aralkyl, thienyl, furyl and naphthyl;
the chiral phosphonic acid catalyst is an (11aR)-spirophosphonic acid of formula (A):

wherein, R 1 and R 2 are selected independently from the group consisting of hydrogen, halogen comprising chlorine, bromine and iodine, C 1 -C 8 alkyl or cycloalkyl, phenyl, monosubstituted or polysubstituted aryl or aralkyl, thienyl, furyl and naphthyl;
hydrogen peroxide is selected from a 10%-80% hydrogen peroxide solution, an adduct of hydrogen peroxide and urea, peroxyacetic acid or m-chloroperoxybenzoic acid;
a molar ratio of cyclobutanone to hydrogen peroxide to chiral catalyst is 1:1-10:0.05-1.1;
the organic solvent is a single solvent or mixture solvent;
a reaction temperature is −80-25° C.; and
a reaction time is 10-80 hours.

2. The method of claim 1 , wherein the chiral phosphonic acid catalyst is (11aR)-10,11,12,13-tetrahydro-5-hydroxy-3,7-bis[2,4,6-triisopropyl-phenyl]-5-oxide-diindeno[7,1-de:1′,7′-fg][1,3,2]dioxaphosphocin.

3. The method of claim 1 , wherein the hydrogen peroxide is a 10%-80% hydrogen peroxide solution.

4. The method of claim 1 , wherein the molar ratio of cyclobutanone and the hydrogen peroxide and the chiral catalyst is 1:1-5:0.05-1.

5. The method of claim 1 , wherein the organic solvent is selected from the group consisting of dichloromethane, chloroform, 1,2-dichloroethane, carbon tetrachloride, hexane, heptane, decane, acetonitrile, ethyl acetate, benzene, toluene, xylene, nitrobenzene, diethyl ether, dioxane and tetrahydrofuran.

6. The method of claim 1 , wherein the reaction temperature is −40-25° C.

7. The method of claim 1 , wherein the reaction time is 24-72 hours.

Assignees

• Univ Fudan

Inventors

• Chen Fener
• Peng Haihui
• Hu Sha
• Meng Ge
• Wu Yan
• Cheng Dang
• Huang Zedu
• Liang Guanfeng

Classifications

• C07D307/93 Primary

  condensed with a ring other than six-membered · CPC title

• C07D307/935

  Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans · CPC title

• Y02P20/584

  Recycling of catalysts · CPC title