化学
组合化学
选择性
钯
立体选择性
芳基
烷基
催化作用
基质(水族馆)
立体化学
有机化学
海洋学
地质学
作者
Yan Liang,Tiancen Bian,Komal Yadav,Qixin Zhou,Liejin Zhou,Rui Sun,Zuxiao Zhang
标识
DOI:10.26434/chemrxiv-2024-v3dsv
摘要
1,4-cis-disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective and modular synthesis remains a long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing cyclic 1,3-dienes/alkyl(aryl)halides and amines. This procedure exhibits a wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated in the efficient synthesis of a TRPV6 inhibitor, CFTR modulator and other bioactive molecules. Combined experimental and computational studies suggest that the hybrid palladium-catalyzed radical-polar crossover mechanism is crucial for achieving the exceptional 1,4-syn-addition selectivity (dr > 20:1).
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