Metal-free sp2 -C7-H Borylation of Tryptophan Containing Peptides and Late-stage Modification

Abstract

The discovery of milder and robust strategies to enable the introduction of organoboronates in peptides remains conspicuously underdeveloped. Herein, we demonstrate an efficient method for the site-selective sp² -C7-H borylation of tryptophan under metal-free condition using BBr₃ directed by pivaloyl group. The versatility of this approach is that gram scale synthesis and C7-borylated N-Phth-Trp(N-Piv)(C7-BPin)-OMe was modified into various C7-substituted derivatives. Moreover, the strategy enables for the peptide elongation and late-stage borylation of peptides, natural product Brevianamide F and drug Oglufanide.

Keywords: Brevianamide F; C−H activation; Metal-free borylation; Oglufanide; Tryptophan borylation.