Hydride reduction of alpha, beta-unsaturated carbonyl compounds using chiral organic catalysts

Abstract

Nonmetallic, chiral organic catalysts are used to catalyze the 1,4-hydride reduction of an α,β-unsaturated carbonyl compound. The α,β-unsaturated carbonyl compound may be an aldehyde or cyclic ketone, and the hydride donor may be a dihydropyridine. The reaction is enantioselective, and proceeds with a variety of hydride donors, catalysts, and substrates. The invention also provides compositions effective in carrying out the 1,4-hydride addition of α,β-unsaturated carbonyl compounds.

1 . A composition comprising a hydride donor and an imidazolidinone catalyst. 
     
     
         2 . The composition of  claim 1 , wherein the hydride donor and the catalyst are selected so as to be effective in catalyzing an enantioselective 1,4-hydride reduction of an α,β-unsaturated carbonyl compound. 
     
     
         3 . The composition of  claim 1 , wherein the hydride donor is a dihydropyridine. 
     
     
         4 . The composition of  claim 3 , wherein the hydride donor has the structure of formula (X) 
       
         
           
           
               
               
           
         
         wherein R 34  and R 35  are independently selected from H and deactivating groups, and R 36 , R 37 , R 38  and R 39  are independently selected from H and activating groups. 
       
     
     
         5 . The composition of  claim 1 , further comprising an acid selected from Brønsted acids, carboxylic acids, and mixtures thereof. 
     
     
         6 . The composition of  claim 1 , wherein the imidazolidinone catalyst is in the form of an acid addition salt comprising an acid selected from Brønsted acids, carboxylic acids, and mixtures thereof. 
     
     
         7 . The composition of  claim 1 , wherein the imidazolidinone catalyst has the structure of formula (IIA) or (IIB) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is selected from C 1 -C 24  hydrocarbyl, substituted C 1 -C 24  hydrocarbyl, heteroatom-containing C 1 -C 24  hydrocarbyl, and substituted heteroatom-containing C 1 -C 24  hydrocarbyl; 
 R 2  has the structure -(L) m -CR 6 R 7 R 8  wherein m is zero or 1, L is C 1 -C 6  alkylene, and R 6 , R 7  and R 8  are C 1 -C 24  hydrocarbyl; 
 R 3  is selected from H and —CR 9 R 10 R 11  wherein R 9  and R 10  are independently selected from H, halo, hydroxyl, C 1 -C 24  hydrocarbyl, substituted C 1 -C 24  hydrocarbyl, heteroatom-containing C 1 -C 24  hydrocarbyl, and substituted heteroatom-containing C 1 -C 24  hydrocarbyl, and R 11  is a cyclic group optionally substituted with 1 to 4 non-hydrogen substituents and containing zero to 3 heteroatoms, 
 or is an acid addition salt thereof. 
 
     
     
         8 . The composition of  claim 1 , wherein the imidazolidinone catalyst has the structure of formula (VIIA) or (VIIB) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 20  is selected from C 1 -C 24  hydrocarbyl, substituted C 1 -C 24  hydrocarbyl, heteroatom-containing C 1 -C 24  hydrocarbyl, and substituted heteroatom-containing C 1 -C 24  hydrocarbyl; and 
 R 13  and R 15  are independently selected from substituted and unsubstituted C 1 -C 24  alkyl, C 5 -C 24  aryl, substituted C 1 -C 24  aryl, heteroatom containing C 1 -C 24  aryl, substituted heteroatom-containing C 1 -C 24  aryl, C 1 -C 24  alkaryl, substituted C 1 -C 24  alkaryl, heteroatom containing C 1 -C 24  alkaryl, and substituted heteroatom-containing C 1 -C 24  alkaryl, 
 or is an acid addition salt thereof. 
 
     
     
         9 . The composition of  claim 1 , wherein the hydride donor and the imidazolidinone catalyst are present in a molar ratio in the range of about 4:1 to about 20:1. 
     
     
         10 . The composition of  claim 1 , wherein an acid addition salt of the imidazolidinone catalyst is capable of lowering the energy level of the lowest unoccupied molecular orbital (LUMO) of an α,β-unsaturated carbonyl compound and further wherein the hydride donor is capable of reacting with the α,β-unsaturated carbonyl compound by virtue of the lowered LUMO of the α,β-unsaturated carbonyl compound in the presence of the acid addition salt of the imidazolidinone catalyst.