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

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.

Claims

1. A method of synthesizing a (1S,5R)-lactone of formula (I), comprising: ##STR00004## 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) ##STR00005## wherein: in formula (I), R is selected from the group consisting of hydrogen, halogen comprising chlorine, bromine and iodine, C.sub.1-C.sub.8alkyl 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.sub.1-C.sub.8alkyl 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): ##STR00006## wherein, R.sup.1 and R.sup.2 are selected independently from the group consisting of hydrogen, halogen comprising chlorine, bromine and iodine, C.sub.1-C.sub.8alkyl 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.

Description

DETAILED DESCRIPTION OF EMBODIMENTS

(1) The invention will be further described below with reference to embodiments, but the invention is not limited to these embodiments.

Example 1

(2) 7,7-Dichlorobicyclo[3.2.0]-hept-2-en-6-one (1.77 g, 0.01 mol), (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 (0.35 g, 0.005 mmol), hydrogen peroxide solution (30%, 2.5 mL, 0.03 mol) and chloroform (20 mL) were added to a dry reaction flask and stirred at 20-0 C. for 36-72 hours. After the reaction was completed, the solvent was recycled under vacuum, and the residue was added with diethyl ether (50 mL) and stirred for 15 minutes after the residue was cooled to room temperature. Hydrochloric acid (10%, 50 mL) was added and stirred for 30 minutes followed by standing to form an organic layer. The organic layer was separated, dried with anhydrous sodium sulfate, and filtered to produce a filtrate. The filtrate was processed under vacuum to recycle the solvent and to produce a solid product. The solid product was dried to obtain a white powder, which was recrystallized from diethyl ether to obtain product II (RCl, 46% yield, 96.9% ee).

(3) .sup.1HNMR (CDCl.sub.3): 5.99 (s, 1H), 5.74 (s, 1H), 5.28 (s, 1H), 4.10 (s, 1H), 2.81 (s, 2H).

Example 2

(4) 7,7-Dichlorobicyclo[3.2.0]-hept-2-en-6-one (1.77 g, 0.01 mol), (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 (0.35 g, 0.005 mmol), hydrogen peroxide solution (30%, 2.5 mL, 0.03 mmol) and chloroform (20 mL) were added to a dry reaction flask, and stirred at 40 C. to 20 C. for 48-72 hours. After the reaction was completed, the solvent was recycled under vacuum, and the residue was added with diethyl ether (50 mL) and stirred for 15 minutes after the residue was cooled to room temperature. Hydrochloric acid (10%, 50 mL) was added and stirred for 30 minutes followed by standing to form an organic layer. The organic layer was separated, dried with anhydrous sodium sulfate and filtered to produce a filtrate. The filtrate was processed under vacuum to recycle the solvent and to produce a solid product. The solid product was dried to obtain a white powder, which was recrystallized from diethyl ether to obtain product II (RCl, 46% yield, 96.9% ee).

(5) .sup.1HNMR (CDCl.sub.3): 5.99 (s, 1H), 5.74 (s, 1H), 5.28 (s, 1H), 4.10 (s, 1H), 2.81 (s, 2H).

Example 3

(6) 7,7-Dichlorobicyclo[3.2.0]-hept-2-en-6-one (1.77 g, 0.01 mol), (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 (0.35 g, 0.005 mmol), hydrogen peroxide solution (30%, 2.5 mL, 0.03 mmol) and chloroform (20 mL) were added to a dry reaction flask, and stirred at 20 C. to 20 C. for 36-72 hours. After the reaction was completed, the solvent was recycled under vacuum, and the residue was added with diethyl ether (50 mL) and stirred for 15 minutes after the residue was cooled to room temperature. Hydrochloric acid (10%, 50 mL) was added and stirred for 30 minutes followed by standing to form an organic layer. The organic layer was separated, dried with anhydrous sodium sulfate, and filtered to produce a filtrate. The filtrate was processed under vacuum to recycle the solvent and to produce a solid product. The solid product was dried to obtain a white powder, which was recrystallized from diethyl ether to obtain product II (RCl, 46% yield, 96.9% ee).

(7) .sup.1HNMR (CDCl.sub.3): 5.99 (s, 1H), 5.74 (s, 1H), 5.28 (s, 1H), 4.10 (s, 1H), 2.81 (s, 2H).