Synthesis of Chiral Tetrasubstituted Azetidines from Donor-Acceptor Azetines via Asymmetric Copper(I)-Catalyzed Imido-Ylide [3+1]-Cycloaddition with Metallo-Enolcarbenes.

ABSTRACT

The all-cis stereoisomers of tetrasubstituted azetidine-2-carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl-protected Z-γ-substituted enoldiazoacetates and imido-sulfur ylides by asymmetric [3+1]-cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p-methoxybenzyl azetine-2-carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.