Efficient Remote Axial-to-Central Chirality Transfer in Enantioselective SmI₂-Mediated Reductive Coupling of Aldehydes with Crotonates of Atropisomeric 1-Naphthamides

Control of enantioselectivity by remote amide conformation has been studied in SmI2-mediated reductive
coupling of aldehydes with the crotonates possessing different 2-substituted 8-methoxy-1-naphthamides.
The enantiomers of atropisomeric 8-methoxy-1-naphthamides were prepared through a chemical resolution
process, and their absolute stereochemistry was determined by X-ray crystal structural analysis. It was
found that the linkage between crotonate and the C2 position of 8-methoxy-1-naphthamides remarkably
influenced the efficiency of remote chirality transfer originated from the amide conformation. Among
the four crotonates examined, the one derived from 2-hydroxy-8-methoxy-1-naphthamide reacted with
pentanal to afford the highest ee of >99% for the cis-γ-butyrolactone and in 90% combined yield with
a cis/trans ratio of 90:10. We developed a new procedure for attaching the chiral crotonate via the C8
oxygen to a Rink amide resin under mild conditions and obtained the same level of highly remote axial-to-central chirality transfer in the solid-phase reaction.