α-Alkylation of Aldehydes by Combining Transition-Metal and Organocatalysis

Significance

A catalytic, intermolecular allylic α-alkylation of aldehydes and cyclic ketones employing enamine intermediates is presented. Initial experiments towards an organocatalytic, intermolecular alkylation using alkyl halides proved futile, since the amine catalyst was N-alkylated itself. However, when electrophilic π-complexes of palladium, generated in a second catalytic reaction, are present, the desired α-alkylation proceeds smoothly. The reaction was found to be highly regioselective in case of substituted allylic acetates and carbonates, and it gives good to high yields. Moreover, an asymmetric version of this reaction is presented. This variant achieves good enantiomeric excesses, yet so far only poor yields and is currently under investigation.