Combinatorial approach to chiral reagents or catalysts having amine or amino alcohol ligands

• US 20040053775A1
• Filed: 08/04/2003
• Published: 03/18/2004
• Est. Priority Date: 10/23/1998
• Status: Abandoned Application

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Petasis, Nicos A.
• Application Number:
  US10/633,760
• Publication Number:
  US 20040053775A1
• Time in Patent Office: Days
• US Class Current: 502/150
• CPC Class Codes: B01J 2219/00738 Organic catalysts
• CPC Class Codes: B01J 2219/00745 Inorganic compounds
• CPC Class Codes: B01J 2219/00747 Catalysts
• CPC Class Codes: B01J 2531/10 Complexes comprising metals of Group I (IA or IB) as the central metal
• CPC Class Codes: B01J 2531/20 Complexes comprising metals of Group II (IIA or IIB) as the central metal
• CPC Class Codes: B01J 2531/30 Complexes comprising metals of Group III (IIIA or IIIB) as the central metal
• CPC Class Codes: B01J 2531/40 Complexes comprising metals of Group IV (IVA or IVB) as the central metal
• CPC Class Codes: B01J 2531/82 Metals of the platinum group
• CPC Class Codes: B01J 2531/84 Metals of the iron group
• CPC Class Codes: B01J 31/1805 the ligands containing nitrogen
• CPC Class Codes: B01J 31/223 At least two oxygen atoms present in one at least bidentate or bridging ligand
• CPC Class Codes: B01J 31/2243 At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07C 215/28 and containing six-membered aromatic rings
• CPC Class Codes: C07C 215/30 containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 215/50 with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• CPC Class Codes: C07C 229/36 with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07K 5/06026 the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
• CPC Class Codes: C40B 30/08 : by measuring catalytic activity
• CPC Class Codes: C40B 40/18 : Libraries containing only inorganic compounds or inorganic materials

Abstract

Functionalized amine derivatives are prepared by reacting an amine, a carbonyl derivative, and an organoboron compound under mild conditions. Organoboronic acids (4) react with amines (2) and alpha-hydroxy aldehydes (3) to give anti-alpha-amino alcohols (1) with very high diastereoselectivities (>99% de). When optically pure alpha-hydroxy aldehydes are used in this process, no racemization occurs and the products are obtained with very high enantioselectivities (>99% ee). The reaction also works with unprotected glyceraldehyde to give the corresponding amino diol derivatives, while unprotected carbohydrates give the corresponding amino polyols. The chiral amino alcohol products of this process or their derivatives, react further with metals or non-metals to give adducts that are effective catalysts for a variety of asymmetric reactions. Overall, the present invention relies on the facile synthesis of the chiral amino alcohol ligands for the rapid construction of combinatorial libraries of chiral catalysts. These libraries can then be used to identify the most suitable catalyst for a particular asymmetric transformation.

Claims

1. A process for preparing a chiral reagent or catalyst comprising reacting a metal or metal derivative with one or more chiral amino ligands.

2. The process according to claim 1 wherein the amino ligand is an amino alcohol.

3. The process according to claim 2 wherein the metal or metal derivative is reacted directly with the amino alcohol.

4. The process according to claim 2 wherein the metal or metal derivative is reacted with the amino alcohol concurrent to synthesis of the amino alcohol.

5. The process according to claim 2 wherein the amino alcohol is prepared by a one-step reaction comprising:

a) an organoboronic acid;

b) an amine;

c) a compound selected from the group consisting of an alpha-hydroxy aldehyde, an alpha-keto acid and a carbohydrate.

6. The process according to claim 1 wherein the amino ligand is prepared by the reaction of comprising:

a) an organoboronic acid;

b) an amine;

c) a compound selected from the group consisting of an alpha-hydroxy aldehyde, an alpha-keto acid and a carbohydrate.

7. The process according to claim 6 wherein the amino ligand is further modified prior to reaction with the metal or metal derivative.

8. The process according to claim 1 wherein the chiral amino ligand has an enantiomeric and/or diastereomeric purity of greater than 50%.

18. The process according to claims 5 or 6 wherein at least one of the organoboronic acid, the amine and/or the alpha-hydroxy aldehyde, alpha-keto acid or monosaccharide is attached to a solid support.

25. The process according to claim 1 wherein the chiral amino ligand is selected from the group consisting of:

9. A process for preparing a combinatorial library of chiral reagents or catalysts comprising reacting a metal or metal derivative with one or more chiral amino ligands.

10. The process according to claim 9 wherein the amino ligand is an amino alcohol.

14. The process according to claim 9 wherein the amino ligand is prepared by the reaction of comprising:

a) an organoboronic acid;

b) an amine;

c) a compound selected from the group consisting of an alpha-hydroxy aldehyde, an alpha-keto acid and a carbohydrate.

15. The process according to claim 14 wherein the amino ligand is further modified prior to reaction with the metal or metal derivative.

16. The process according to claim 9 wherein the chiral amino ligand has an enantiomeric and/or diastereomeric purity of greater than 50%.

17. A combinatorial library of chiral reagents or catalysts prepared according to claim 9.

26. The process according to claim 9 wherein the chiral amino ligand is selected from the group consisting of:

11. The process according to claim 11 wherein the metal or metal derivative is reacted directly with the amino alcohol.

12. The process according to claim 11 wherein the metal or metal derivative is reacted with the amino alcohol concurrent to synthesis of the amino alcohol.

13. The process according to claim 11 wherein the amino alcohol is prepared by a one-step reaction comprising:

a) an organoboronic acid;

b) an amine;

c) a compound selected from the group consisting of an alpha-hydroxy aldehyde, an alpha-keto acid and a carbohydrate.

19. A process for producing a compound of formula M(L)n comprising reacting a metal or metal derivative with one or more chiral amino ligands, wherein

M is an atom selected from the group consisting of B, Li, Mg, Al, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Zr, Mo, Ru, Rh, Pd, Ag, Re, Os, Ir, Pt, La, Ce and Yb;

L is one or more same or different ligands selected from the group consisting of chloro, bromo, iodo, fluoro, oxo, hydroxy, hydroperoxy, alkoxy, aryloxy, acyloxy, acetoacetyl, carboxy, nitro, amino, alkylamino, dialkylamino, azido, carbonyl, alkyl, alenyl, dienyl, aryl, triflate and arylsulfonyl; and

n=1-6.

20. A compound produced by the process according to claim 19.

21. A combinatorial library produced by the process according to claim 19.

22. The use of the compound according to claim 20 for the preparation of an industrial chemical.

23. The use of the compound according to claim 20 for the preparation of a pharmaceutical.

24. The use of the compound according to claim 20 for the preparation of an agrochemical.