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

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.

What is claimed:  
     
         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%.  
     
     
         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.  
     
     
         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.  
 
     
     
         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 .  
     
     
         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.  
     
     
         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.  
     
     
         25 . The process according to  claim 1  wherein the chiral amino ligand is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein one or more bonds exists among M and a heteroatom of the ligand; 
 M=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 or Yb;  
 and R 1 -R 10 =alkyl, alyl, alkenyl, aryl, allenyl, or alkynyl group.  
 
     
     
         26 . The process according to  claim 9  wherein the chiral amino ligand is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
       wherein one or more bonds exists among M and a heteroatom of the ligand; 
 M=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 or Yb;  
 and R 1 -R 10 =alkyl, alyl, alkenyl, aryl, allenyl, or alkynyl group.