Abstract:
Palladium-catalyzed enantioselective C(sp3)-H functionalization reactions has attracted considerable attention due to its ability for the synthesis of enantiomerically enriched molecules and stimulation of novel retrosynthetic disconnections. Understanding the reaction mechanism, especially the stereochemical process of the reaction, is crucial for the rational design of more efficient catalytic systems. Previously, we developed a Pd(II)/sulfoxide-2-hydroxypridine (SOHP) catalytic system for asymmetric C(sp3)-H functionalization reactions. In this study, we focused on unraveling the chemistry of chiral palladacycles involved in the Pd(II)-catalyzed enantioselective C(sp3)-H functionalization. We have isolated key palladacycle intermediates involved in the enantioselective β-C(sp3)-H arylation of carboxylic acids catalyzed by the Pd(II)/SOHP system. These palladacycles, exhibiting ligand-induced chirality, provided a significant opportunity to investigate the stereochemical process and the ligand effect in this asymmetric C-H functionalization. Our investigation provided direct evidence for the C-H palladation step as the enantioselectivity-determining step, which forms diastereomeric palladacycles that exhibited preservation of chirality in the functionalization step. DFT calculations provided insights into the chiral induction in palladacycle formation. This work highlights the value of chiral palladacycle chemistry in offering mechanistic insights into the Pd(II)-catalyzed asymmetric C(sp3)-H functionalization reactions.
摘要:
钯催化的对映选择性C(sp3)-H官能化反应由于其合成富含对映异构体的分子和刺激新型逆合成分离的能力而引起了广泛关注。了解反应机理,尤其是反应的立体化学过程,对于合理设计更有效的催化系统至关重要。以前,我们开发了用于不对称C(sp3)-H官能化反应的Pd(II)/亚砜-2-羟基吡啶(SOHP)催化体系。在这项研究中,我们专注于揭示参与Pd(II)催化的对映选择性C(sp3)-H官能化的手性钯环的化学。我们已经分离出涉及Pd(II)/SOHP系统催化的羧酸对映选择性β-C(sp3)-H芳基化的关键palladacycle中间体。这些palladacycle,表现出配体诱导的手性,为研究这种不对称C-H官能化的立体化学过程和配体效应提供了重要的机会。我们的调查为C-Hpalladation步骤作为对映选择性测定步骤提供了直接证据,其形成在官能化步骤中表现出手性保留的非对映异构体钯环。DFT计算提供了对palladacycle形成中的手性诱导的见解。这项工作强调了手性钯环化学在提供对Pd(II)催化的不对称C(sp3)-H官能化反应的机理见解方面的价值。