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

We report the Pd(II)-catalyzed, picolinamide-directed dC(sp(2))-H (ortho) functionalization of phenylalaninol scaffolds. Assembling of (ortho) 8-C-H arylated, alkylated, benzylated, alkenylated, brominated, and iodinated phenylalaninol scaffolds was accomplished. The d-C(sp(2))-H arylation reaction of phenylalaninol occurred under neat conditions. Hydrolysis of the picolinamide moiety and synthetic utility of the d-C(sp(2))-H arylated substrates were explored. We have also shown the preparation of some modified Matijin-Su (aurantiamide) derivatives using the bis d-C-H (ortho) arylated phenylalaninol compounds obtained from the d-C(sp(2))-H arylation reaction (Matijin-Su is an anti-HBV agent possessing the phenylalaninol unit). Considering the importance of phenylalaninols, this work contributes to expanding the phenylalaninol library and demonstrates the substrate scope development in remote dC(sp(2))-H functionalization reactions.