Late-Stage Diversification of Phosphines by C-H Activation: A Robust Strategy for Ligand Design and Preparation.

Abstract

ConspectusThe advent of the twenty-first century marked a golden era in the realm of synthetic chemistry, exemplified by groundbreaking advancements in the field of C-H activation, which is a concept that quickly transitioned from mere academic fascination to an essential element within the synthetic chemist's toolkit. This methodological breakthrough has given rise to a wealth of opportunities spanning a wide range of chemical disciplines. It has facilitated the late-stage diversification of elaborate organic frameworks, encompassing the spectrum from simple methane to complex polymers, thus refining the lead optimization process and easing the production of diverse molecular analogues. Among these strides forward, the development of phosphorus(III)-directed C-H activation stands out as an increasingly significant and inventive approach for the design and synthesis of ligands, substantially redefining the contours of synthetic methodology.Phosphines, renowned for their roles as ligands and organocatalysts, have become fundamentally important in modern organic chemistry. Their efficiency as ligands is significantly affected by coordination with transition metals, which is essential for their involvement in catalytic processes, influencing both the catalytic activity and the selectivity. Historically, the fabrication of phosphines predominantly relied on synthesis employing complex, multistep procedures. Addressing this limitation, our research has delved into ligand design and synthesis through innovative catalytic P(III)-directed C-H activation strategies. In this Account, we have explored a spectrum of procedures, including direct arylation using metal catalysis, and ventured further into domains such as C-H alkylation, alkenylation, aminocarbonylation, alkynylation, borylation, and silylation. These advances have enriched the field by providing efficient methods for the late-stage diversification of biaryl-type monophosphines as well as enabled the C-H activation of triphenylphosphine and its derivatives. Moreover, we have successfully constructed libraries of diverse axially chiral binaphthyl phosphine ligands, showcasing their potency in asymmetric catalysis. Through this Account, we aim to illuminate the exciting possibilities presented by P(III)-directed C-H activation in propelling the boundaries of organic synthesis. By highlighting our pioneering work, we hope to inspire further developments in this promising field of chemistry.