Pd(II)-Catalyzed, Picolinamide-Aided γ-(sp²)-C–H Functionalization of Racemic and Enantiopure α-Methylbenzylamine and Phenylglycinol Scaffolds

Abstract

In this paper, we report the Pd(II)-catalyzed, picolinamide DG-aided sp² γ-C–H functionalization and expansion of the library of enantiopure α-methylbenzylamine and phenylglycinol scaffolds. We have shown the synthesis of a wide range of racemic and enantiopure ortho-C–H arylated, alkylated, brominated, and iodinated α-methylbenzylamine and phenylglycinol scaffolds. Various racemic and R and S (chiral) sp² γ-C–H functionalized α-methylbenzylamine and phenylglycinol scaffolds were synthesized with good enantiopurities. Racemic and enantiopure α-methylbenzylamine and phenylglycinol derivatives are important building blocks in organic synthesis and medicinal chemistry. Accordingly, this work contributes to the expansion of the libraries of α-methylbenzylamine and phenylglycinol motifs and substrate scope development through the Pd(II)-catalyzed bidentate directing group picolinamide-aided site-selective C–H activation and functionalization method.

Key words

amino alcohols - bidentate directing groups - biaryls - C–H functionalization - cross-coupling - α-methylbenzylamine - palladium - stereoselective synthesis

Publication History

Received: 16 March 2022

Accepted after revision: 20 April 2022

Accepted Manuscript online:
20 April 2022

Article published online:
20 June 2022

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