Optically Active Flavaglines-Inspired Molecules by a Palladium-Catalyzed Decarboxylative Dearomative Asymmetric Allylic Alkylation
Meng‐Yue Cao, Binjie Ma, Zhiqi Lao, Hongliang Wang, Jing Wang, Juan Liu, Kuan Xing, Yu-Hao Huang, Kang‐Ji Gan, Wei Gao, Huaimin Wang, Xin Hong, Hai‐Hua Lu
Abstract
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% Pd2(dba)3/L], 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 intra-benzoin condensation, and a conjugate addition, which allows the efficient construction of the challenging and compact cyclopenta[b]benzofuran scaffold with contiguous stereocenters. This strategy offers a new avenue for developing flavagline-based drugs.