Catalytic Asymmetric Synthesis of Cyclopentyl β-Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates

Abstract

Chiral cyclopentyl β-amino esters are formed catalytically by [3+2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 % ee and excellent diastereocontrol. Use of β-silyl-substituted enoldiazoacetates with a chiral dirhodium catalyst and trans-β-arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen-bond association between the vinylcarbamate and the intermediate metalloenolcarbene. Reductive conversion of the protected amino esters forms highly functionalized cyclopentyl β-amino acids and 3-aminocyclopentanones.

Keywords: amino acids; cycloaddition; diazo compounds; enantioselectivity; rhodium.