Picolinamide-assisted ortho-C-H functionalization of pyrenylglycine derivatives using aryl iodides.

Abstract

Chemical transformations involving the pyrenylglycine motif (an unnatural amino acid) and practical methods toward it are seldom known. This work aimed at developing a method for synthesizing novel pyrenylglycine (pyrene-based glycine) unnatural amino acid derivatives. To realize this, initially, a new pyrenylglycine substrate possessing the picolinamide moiety was assembled via the Ugi multicomponent reaction. The picolinamide moiety linked to amine substrates is a well-known bidentate directing group for accomplishing the site-selective γ-C-H functionalization of amines. Subsequently, it was aimed at using a Pd(II)-catalyzed bidentate directing group-aided γ-C-H arylation strategy for generating a wide range of unprecedented examples of C(2)-H arylated pyrenylglycines. Accordingly, pyrenylglycine possessing the picolinamide moiety was subjected to Pd(II)-catalyzed C(2)-H arylation in the non-K-region to afford a library of C(2)-arylated pyrenylglycines (π-extended pyrenes). Additionally, pyrenylglycine-based small peptides were assembled using C(2)-arylated pyrenylglycines. The X-ray structure of a representative compound was obtained, which corroborated the structure of pyrenylglycine and the regioselectivity of C(2)-H arylation of the pyrene in the non-K-region.