Pd‐Catalyzed Arylation and Benzylation of Tyrosine at the <i>δ</i>−C(sp<sup>2</sup>)−H and C(2) Positions: Expanding the Library of Unnatural Tyrosines
Prabhakar Singh, Srinivasarao Arulananda Babu
Abstract
Abstract This paper describes Pd(II)‐catalyzed picolinamide‐directed intermolecular arylation and benzylation of remote δ −C(sp 2 )−H bond (C(2) position) of the aryl ring in tyrosine derivatives and expansion of the library of unnatural tyrosine. Various racemic and enantiopure bis C(2) ( ortho C−H) arylated and benzylated tyrosine derivatives were assembled in good yields. Removal of the picolinoyl moiety after the C(2)−H arylation and assembling of tyrosine‐based peptides using C(2)−H arylated tyrosines were shown. Tyrosine derivatives and biaryl amino acids are vital scaffolds in medicinal chemistry. Correspondingly, this work is a contribution towards the expansion of the unnatural tyrosine library with biaryl‐ or terphenyl and diarylmethane‐based tyrosine scaffolds.