1,3-allylic strain as a strategic diversification element for constructing libraries of substituted 2-arylpiperidines.

Minimization of 1,3-allylic strain is a recurring element in the design of a stereochemically- and spatially-diverse collection of 2-arylpiperidines. Here, stereochemically-diverse scaffolding is first constructed using A strain to guide the regioselective addition of nucleophiles, which serve as handles for further substitution. -substitution with alkyl and acyl substituents again leverages A strain to direct each stereoisomer to two different conformer populations, doubling the number of library members.