Iron/phosphine-catalyzed reductive cross-coupling to construct quaternary carbon centers

作者：Qiao Zhang, Xiangyu Liu, Yuyu Li, Ming‐Yao Huang, Shou‐Fei Zhu · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-64781-5 · 被引用次数：3 · 研究领域：Catalytic C–H Functionalization Methods、Catalytic Cross-Coupling Reactions、Asymmetric Hydrogenation and Catalysis

Transition metal-catalyzed C–C reductive coupling reactions avoid the direct use of sensitive metal reagents, representing a practical approach for constructing the skeletons of organic compounds. However, such reactions face significant challenges in constructing quaternary carbon centers. Herein, we report an example of iron-catalyzed reductive cross-coupling reaction of tertiary alkyl halides with allyl halides by using phosphine ligands. A directing strategy is developed for diverse reductive couplings of 3o C(sp3) with 1o C(sp3) and even 2o C(sp3). The directing effect of the carbonyl of amides and esters facilitates the iron catalyst in overcoming the substantial steric hindrance and numerous competing side reactions, allowing the reaction to proceed smoothly. The current study develops a directing strategy for highly steric reductive coupling reactions, and offers new insights into the efficient construction of complex C(sp3)–C(sp3) bonds using iron catalysts modified with phosphine ligands. Iron-catalyzed C–C reductive coupling avoids sensitive reagents but struggles to build quaternary centers. Using phosphine-ligated Fe and carbonyl directing groups, this work enables tertiary–primary/secondary C(sp³) coupling under mild conditions.