Rh-BINAP Induced 1,4-Conjugate Addition Leads to Chiral α-Amino Esters

Significance

For an asymmetric route to α-amino esters, several groups have attempted rhodium-catalyzed conjugate addition followed by ­diastereoselective protonation of the putative rhodium enolate with water, but ee values were generally modest (e.g., M. Reetz et al. Org. Lett. 2001, 3, 4083). In the present study the authors report Rh-induced 1,4-addition reactions of hydroamino esters with potassium arylfluoroborates with 2-methoxyphenol as proton source to provide α-amino esters in high yields and enantioselectivities. A series of deuterium-labeling and DFT studies indicate that the reaction proceeds via hydride transfer from the amido substituent to the α-carbon explaining the high levels of enantioselectivity.