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.
作者：Zhongyin Zhang,# Jinxin Wang, # Jian Li, # Fan Yang, Guodu Liu, Wenjun Tang, Ang Li,*
關鍵字：Total synthesis
論文來源：期刊
具體來源：J. Am. Chem. Soc. 2017, 139, 5558–5567. (Z.Z., J.W. and J.L. contributed equally, Citation;20）
發(fā)表時間：2017年
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) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C–H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane- and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C–H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines was evaluated.