Access to optically active 3-substituted piperidines by ring expansion of prolinols and derivatives

Abstract

The ring expansion of prolinols via an aziridinium intermediate gives C3-substituted piperidines in good yields and enantiomeric excess, the substituent at the C3 position being derived from the most reactive nucleophile in the reaction mixture. Depending on the nucleophile, the reaction proceeds under thermodynamic or kinetic control. The regioselectivity of attack of nucleophiles on the aziridinium intermediate depends on the nature of the substituents on the nitrogen atom and the C4 position of the starting prolinols.

Keywords: enantioselectivity; piperidines; pyrrolidinols; rearrangements; ring expansion.