| Abstract
| - The catalytic enantioselective Henry reaction of α-keto esters with nitromethane has been developed.The reaction conditions have been optimized by the screening of different chiral Lewis acids, solvents,and bases, and it was found that the copper(II)−tert-butyl bisoxazoline complex in combinationwith triethylamine catalyzed a highly enantioselective reaction giving optically active β-nitro-α-hydroxy esters in high yields and with excellent enantiomeric excesses. The scope of the reactionis demonstrated by the reaction of a variety of different α-keto esters. The catalytic enantioselectiveHenry reaction of β,γ-unsaturated-α-keto esters proceeds as a 1,2-addition reaction exclusively, incontrast to the uncatalyzed reaction where both the 1,2- and 1,4-addition products are formed. Itis demonstrated that the β-nitro-α-hydroxy esters can be converted into, e.g., Boc-protected β-amino-α-hydroxy esters in high yields and without loss of optical purity. The mechanism for the reactionis discussed, and it is postulated that both the α-keto ester and nitromethane/nitronate is coordinatedto the metal center during the reaction course.
|
