1,3-Allylic Strain as a Strategic Diversification Element For Constructing Libraries of Substituted 2-Arylpiperidines

Abstract

Flipping diversity—Minimization of 1,3-allylic strain is a recurring element in the design of a stereochemically- and spatially-diverse collection of 2-arylpiperidines. Here, stereochemicallydiverse scaffolding is first constructed using A1,3 strain to guide the regioselective addition of nucleophiles, which serve as handles for further substitution. N-substitution with alkyl and acyl substituents again leverages A1,3 strain to direct each stereoisomer to two different conformer populations, doubling the number of library members