Pd-Catalyzed Remote δ-C(sp2)–H Functionalization in Phenylalaninol: Expanding the Library of Phenylalaninols

Abstract

We report the Pd(II)-catalyzed, picolinamide-directed δ-C(sp2)-H (ortho) functionalization of phenylalaninol scaffolds. Assembling of (ortho) δ-C-H arylated, alkylated, benzylated, alkenylated, brominated and iodinated phenylalaninol scaffolds was accomplished. The δ-C(sp2)-H arylation reaction of phenylalaninol occurred in a neat condition. Hydrolysis of the picolinamide moiety and synthetic utility of the δ-C(sp2)-H arylated substrates were explored. We have also shown the preparation of some modified Matijin-Su (aurantiamide) derivatives using the bis δ-C-H (ortho) arylated phenylalaninol compounds obtained from the δ-C(sp2)-H arylation reaction (it may be noted that Matijin-Su is an anti-HBV agent possessing phenylalaninol unit). Considering the importance of phenylalaninols, this work contributes to expanding the phenylalaninol library and demonstrates the substrate scope development in remote δ-C(sp2)-H functionalization reactions.