Cross-coupling of unactivated secondary boronic acids

Patent metadata

Field	Value
Publication number	US-10072028-B2
Application number	US-201415034102-A
Country	US
Kind code	B2
Filing date	Nov 3, 2014
Priority date	Nov 3, 2013
Publication date	Sep 11, 2018
Grant date	Sep 11, 2018

Abstract

Provided are methods for site- and stereo-retentive cross-couplings with unactivated secondary boronic acids, which methods are particularly useful in building block-based approach for small molecule synthesis. Also provided is a method of forming an air-stable chiral secondary boronic acid.

First claim

We claim:

1. A method of forming a chiral non-racemic secondary boronic acid, comprising:
combining a chiral compound of formula (I)

wherein, independently for each occurrence, R 1 and R 2 are selected from the group consisting of substituted C 1 -C 6 alkyl and unsubstituted C 1 -C 6 alkyl; a chiral iminodiacetic acid, wherein the chiral iminodiacetic acid is not a racemic mixture; pyridinium p-toluenesulfonate (PPTS); and a polar aprotic solvent, thereby forming a mixture of chiral boronates;
resolving the mixture of chiral boronates into individual diastereomers; and
hydrolyzing an individual diastereomer,
thereby forming the chiral non-racemic secondary boronic acid.

2. The method of claim 1 , wherein the hydrolyzing is with aqueous hydroxide.

3. The method of claim 1 , wherein the chiral iminodiacetic acid has an enantiomeric excess of at least 80 percent.

4. The method of claim 1 , wherein the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA).

5. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 80 percent.

6. The method of claim 1 , wherein the resolving is by crystallization.

7. The method of claim 1 , wherein the resolving is by chromatography.

8. The method of claim 1 , wherein the hydrolyzing is with aqueous NaOH.

9. The method of claim 1 , wherein the chiral iminodiacetic acid has an enantiomeric excess of at least 90 percent.

10. The method of claim 1 , wherein the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent.

11. The method of claim 1 , wherein the polar aprotic solvent is CH 3 CN.

12. The method of claim 1 , wherein the compound of formula (I) is a racemic mixture.

13. The method of claim 1 , wherein the compound of formula (I) is not a racemic mixture.

14. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 90 percent.

15. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent.

16. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 80 percent; and the chiral iminodiacetic acid has an enantiomeric excess of at least 80 percent.

17. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 90 percent; and the chiral iminodiacetic acid has an enantiomeric excess of at least 90 percent.

18. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; and the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent.

19. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 80 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 80 percent; and the compound of formula (I) is a racemic mixture.

20. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 90 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 90 percent; and the compound of formula (I) is a racemic mixture.

21. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; and the compound of formula (I) is a racemic mixture.

22. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; and the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA).

23. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA); and the compound of formula (I) is a racemic mixture.

24. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA); the compound of formula (I) is a racemic mixture; and the hydrolyzing is with aqueous hydroxide.

25. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA); the compound of formula (I) is a racemic mixture; and the hydrolyzing is with aqueous NaOH.

26. The method of claim 1 , wherein the chiral non-racemic secondary boronic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid has an enantiomeric excess of at least 95 percent; the chiral iminodiacetic acid is benzylcyclopentyl iminodiacetic acid (BIDA); the compound of formula (I) is a racemic mixture; the hydrolyzing is with aqueous NaOH; and the polar aprotic solvent is CH 3 CN.

Assignees

• Univ Illinois

Inventors

• Burke Martin D
• Wang Pulin
• Crouch Ian

Classifications

• C07C69/76

  Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring · CPC title

• C07B37/04

  Substitution · CPC title

• C07C67/343

  by increase in the number of carbon atoms · CPC title

• C07C15/24

  containing two rings · CPC title

• C07F5/025 Primary

  Boronic and borinic acid compounds · CPC title