Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, 18 Shilongshan Road, Hangzhou 310024, China.
Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China.
J Am Chem Soc. 2020 Jul 15;142(28):12039-12045. doi: 10.1021/jacs.0c05113. Epub 2020 Jul 1.
With the aid of a class of newly discovered Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the Pd-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved with high efficiency [0.2-1.0 mol% Pd(dba)/], good generality, and high enantioselectivity (>30 examples, 82-99% yield and 90-96% ee). Moreover, a diversity-oriented synthesis (DOS) of previously unreachable flavaglines is disclosed. It features a reliable and scalable sequence of the freshly developed Tsuji-Trost-Stoltz AAA, a Wacker-Grubbs-Stoltz oxidation, an -benzoin condensation, and a conjugate addition, which allows the efficient construction of the challenging and compact cyclopenta[]benzofuran scaffold with contiguous stereocenters. This strategy offers a new avenue for developing flavagline-based drugs.
在一类新发现的具有手性环烷骨架的 Trost 型双膦配体的辅助下，高效地实现了苯并呋喃的 Pd 催化脱羧去芳构化不对称烯丙基烷基化反应（AAA）[0.2-1.0 mol% Pd(dba)/]，具有很好的通用性和高对映选择性（>30 个实例，82-99%产率和 90-96%ee）。此外，还公开了一种以前无法获得的黄烷类化合物的多样性导向合成（DOS）。它具有新开发的 Tsuji-Trost-Stoltz AAA、Wacker-Grubbs-Stoltz 氧化、-苯偶姻缩合和共轭加成的可靠和可扩展序列，可有效地构建具有连续立体中心的具有挑战性和紧凑的环戊[]苯并呋喃骨架。该策略为基于黄烷类化合物的药物开发提供了新途径。
