Cascade Reaction for Synthesizing Piperidines

Significance

The authors report a catalytic tandem reaction which leads to highly enantioenriched 2,4,6-substituted, N-Boc-protected piperidines. In the reaction sequence, an initial chiral phosphoric acid mediated aza-ene type reaction between an N-Boc aldimine and an enecarbamate leads to a second aldimine as product. This undergoes a further aza-ene type reaction with a second enecarbamate molecule, and the resulting aldimine cyclizes to yield the six-membered ring product. The reaction is usually found to give only two of the possible four diastereoisomers, with high selectivity for the trans product. Moreover, good to excellent yields and excellent enantio­selectivities are found for a variety of different N-Boc imines.