Successive diastereoselective C(sp3)–H arylation and Suzuki coupling toward enantioenriched polyaryl unnatural amino acid motifs

Abstract

This paper reports the preliminary efforts in constructing (teraryl-, quateraryl- and hexaryl-based) polyaryl unnatural amino acid motifs. At first, chemo- and diastereoselective Pd(II)-catalyzed bidentate directing group-aided arylation of prochiral β-C(sp³)–H bonds of carboxamides of amino acids with 4-bromo-4′-iodo-1,1′-biphenyl was performed. This process generated amino acid motifs possessing the 4-bromobiphenyl unit. Subsequently, the Suzuki–Miyaura coupling reaction with the 4-bromobiphenyl unit present in amino acid motifs has led to the assembling of a library of teraryl-, quateraryl-, and hexaaryl-based polyaryl unnatural amino acid motifs. Emission spectra of representative teraryl-, quateraryl-, and hexaaryl-based unnatural amino acid motifs are recorded, and some are found to be fluorescent. In the literature, various teraryl- and quateraryl-based molecules have been reported as medicinally relevant compounds. Consequently, there is scope for synthesizing novel and functionalized teraryl-, quateraryl-, and hexaaryl-based molecules to aid future investigations into the biological activities of such scaffolds. Thus, this work on the construction of teraryl-, quateraryl-, and hexaaryl-based unnatural amino acid motifs via successive sp³ C–H arylation and Suzuki coupling would be a valuable effort toward strengthening the library of polyaryl-based unnatural amino acid scaffolds.