Planar chiral [2.2]paracyclophane biarylphosphine (PCP-BPhos) libraries: rational design, catalytic synthesis, and...

The advent of privileged chiral ligands has marked a transformative milestone in the realm of asymmetric catalysis, underscoring the imperative for developing efficient synthetic methodologies to access these compounds. Such advancements are crucial for the rapid generation of diverse chemical libraries endowed with varied steric and electronic properties. In this study, we unveil a highly efficient and streamlined approach for the construction of a broad spectrum of planar chiral [2.2]paracyclophane biarylphosphine (PCP-BPhos) ligands. Our innovative strategy leverages P(III)-directed C-H activation, which entails the direct arylation of triarylphosphines with enantiomerically enriched PCP bromides. A cornerstone of this methodology is the intrinsic phosphine moiety within the substrates, which serves as a directing group, thereby facilitating the formation of a benzo-fused four-membered metallacycle during the catalytic cycle. These in situ modified chiral ligands have exhibited exceptional efficacy in Pd-catalyzed asymmetric allylic alkylation and Suzuki-Miyaura coupling, underscoring their potential for widespread applications in asymmetric catalysis. Our comprehensive experimental and computational studies provide detailed mechanistic insights into these transformations, further elucidating the underlying principles of these catalytic processes.