Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C–H Olefination

• DOI: 10.1021/jacs.7b01718
• Publication Date: 2017-03-08T16:14:58Z
• Authors: Zhongyin Zhang; Jinxin Wang; Jian Li; Fan Yang; Guodu Liu; Wenjun Tang; Weiwei He; Jian-Jun Fu; Yun-Heng Shen; Ang Li; Wei-Dong Zhang
• Keywords: Kinetic resolution; Isoquinoline; Indene; Asymmetric hydrogenation; Indane

Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) commercially available starting materials. We exploited an construction strategy developed two reactions, namely Rh-catalyzed asymmetric hydrogenation indene-type tetrasubstituted olefins kinetic resolution β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. substrate scope the reaction covered unfunctionalized those containing polar functionalities such as sulfonamides. provided collection enantioenriched indane- tetralin-based triflamides, including bearing quaternary chiral centers. selectivity factor (s) exceeded 100 for number substrates. These reactions enabled different yet related approaches to key intermediate 28 excellent enantiopurity. In synthesis, triflamide served not only effective directing group bond activation but also versatile functional further elaborations. relative absolute configurations delavatine were unambiguously assigned by syntheses natural product its three stereoisomers. Their cytotoxicity against series cancer cell lines evaluated.