Cyclopropanation method

Patent metadata

Field	Value
Publication number	US-11465966-B2
Application number	US-201816635475-A
Country	US
Kind code	B2
Filing date	Aug 17, 2018
Priority date	Aug 18, 2017
Publication date	Oct 11, 2022
Grant date	Oct 11, 2022

Abstract

A cyclopropanation method includes reacting an alcohol, an ester, or an aldehyde with a sulfone in an organic solvent containing a base providing a counter cation to form a cyclopropane; and isolating the cyclopropane. When using the alcohol or ester, the organic solvent further contains a catalyst having an alcohol dehydrogenation activity.

First claim

The invention claimed is:

1. A cyclopropanation method, comprising:
reacting an alcohol, an ester, or an aldehyde with a phenyl sulfone in an organic solvent containing a base providing a counter cation to form a cyclopropane; and,
isolating the cyclopropane;
wherein,
the aldehyde is paraformaldehyde or R 3 CHO, in which R 3 is hydrogen, alkyl, or cycloalkyl, and the alkyl is optionally intervened by oxygen, sulfur, or nitrogen;
R 3 is saturated or unsaturated, provided that a double bond does not exist between a β carbon and a γ carbon of the aldehyde;
R 3 is unsubstituted or substituted with at least one substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided that the α carbon of the alcohol is unsubstituted;
the substituent is further substituted or unsubstituted when the aldehyde is reacted; and,
the organic solvent further contains a catalyst having an alcohol dehydrogenation activity when the alcohol or the ester is reacted.

2. The cyclopropanation method according to claim 1 ;
wherein, the alcohol is reacted;
the alcohol is R 1 CH 2 OH, in which R 1 is hydrogen, alkyl, or cycloalkyl, and the alkyl is optionally intervened by oxygen, sulfur, or nitrogen;
R 1 is saturated or unsaturated, provided that a double bond does not exist between a β carbon and a γ carbon of the alcohol;
R 1 is unsubstituted or substituted with at least one substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided that the β carbon of the alcohol is unsubstituted; and,
the substituent is further substituted or unsubstituted.

3. The cyclopropanation method according to claim 2 ,
wherein the alcohol is selected from the group consisting of:

4. The cyclopropanation method according to claim 1 ,
wherein, the ester is reacted;
the ester is formed from R 1 CH 2 OH and R 2 COOH;
R 1 is hydrogen, alkyl, or cycloalkyl, and the alkyl is optionally intervened by oxygen, sulfur, or nitrogen;
R 1 is saturated or unsaturated, provided that a double bond does not exist between a β carbon and a γ carbon of the alcohol;
R 1 is unsubstituted or substituted with at least one substituent selected from the group consisting of alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, provided that the β carbon of the alcohol is unsubstituted;
the substituent is further substituted or unsubstituted; and,
R 2 is saturated or unsaturated alkyl, saturated or unsaturated cycloalkyl, saturated or unsaturated heterocycloalkyl, aryl, or heteroaryl, and R 2 is unsubstituted or substituted.

5. The cyclopropanation method according to claim 4 ,
wherein the ester is selected from the group consisting of

6. The cyclopropanation method according to claim 1 ,
wherein the aldehyde is selected from the group consisting of:

and C 5 H 11 CHO.

7. The cyclopropanation method according to claim 1 , wherein the sulfone is represented by R 4 CH 2 SO 2 R 5 ;
R 4 is hydrogen, alkyl, alkylthio, cycloalkyl, heterocycloalkyl, aryl, or hetroraryl; and,
R 5 is unsubstituted or substituted phenyl.

8. The cyclopropanation method according to claim 1 , wherein the phenyl sulfone is selected from the group consisting of:

9. The cyclopropanation method according to claim 1 , wherein the base provides a potassium cation or a cesium cation.

10. The cyclopropanation method according to claim 1 , wherein the base is at least one selected from the group consisting of potassium hydroxide, potassium methoxide, potassium ethoxide, potassium propoxide, potassium butoxide, potassium tert-butoxide, potassium bis(trimethylsilyl)amide, and potassium hydride.

11. The cyclopropanation method according to claim 1 , wherein the catalyst contains Pt, Cu, Fe, Co, Pd, Ru, V, Ni, or Os.

12. The cyclopropanation method according to claim 1 , wherein the catalyst is a Ru catalyst, an Os catalyst, or a Ni catalyst.

13. The cyclopropanation method according to claim 1 , wherein the catalyst is selected from the group consisting of:

14. The cyclopropanation method according to claim 1 , wherein the organic solvent is selected from ether based solvents and aromatic hydrocarbons.

15. The cyclopropanation method according to claim 1 , wherein the organic solvent is selected from the group consisting of tetrahydrofuran, dioxane, 1,2-dimethoxyethane, benzene, and toluene.

16. The cyclopropanation method according to claim 1 , wherein an amount of the catalyst is 0.2 to 1.0 mol % with respect to an amount of the alcohol or the ester.

17. The cyclopropanation method according to claim 1 , wherein an amount of the base is 50 to 300 mol % with respect to an amount of the alcohol or the ester.

18. The cyclopropanation method according to claim 1 , wherein the solvent is anhydrous.

19. The cyclopropanation method according to claim 1 , wherein the molar ratio of sulfones:the alcohol, the ester, or the aldehyde is approximately 2:1.

20. The cyclopropanation method according to claim 1 , wherein a cyano compound is also reacted in the reacting step.

21. The cyclopropanation method according to claim 1 , wherein a yield of the cyclopropane is 70% or more.

22. The cyclopropanation method according to claim 1 , wherein the isolating is carried out by a chiral chromatography.

23. The cyclopropanation method according to claim 1 , wherein the reacting is carried out in a closed system.

24. The cyclopropanation method according to claim 1 , wherein the reacting is carried out at above room temperature.

25. The cyclopropanation method according to claim 1 , wherein the reacting is carried out at 80° C. or more.

26. The cyclopropanation method according to claim 1 , wherein the reacting is carried out for 16 to 72 hours.

Assignees

• Okinawa Inst Science & Tech School Corp

Inventors

• Khaskin Eugene

Classifications

• C07C2603/74

  Adamantanes · CPC title

• B01J31/226

  Sulfur, e.g. thiocarbamates · CPC title

• B01J2231/4288

  using O nucleophiles, e.g. alcohols, carboxylates, esters · CPC title

• B01J2531/821

  Ruthenium · CPC title

• C07C2601/02

  with a three-membered ring · CPC title