Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure

Chemical Science
Yang LiuQi-Lin Zhou

Abstract

A divergent enantioselective approach to hapalindole-type alkaloids is described. The route features a ruthenium-catalyzed asymmetric hydrogenation of a ketone via DKR to construct the chiral trans-1-indolyl-2-isopropenylcyclohexane skeleton and a switchable sequence of methylation and acetylation/aldol reaction to access a chiral quaternary stereocenter. (+)-Hapalindole Q (1, 13 steps, 5.9% overall yield), (-)-12-epi-hapalindole Q isonitrile (2, 15 steps, 5.5% overall yield), (-)-hapalindole D (3, 14 steps, 2.3% overall yield), and (+)-12-epi-fischerindole U isothiocyanate (4, 14 steps, 3.0% overall yield) were synthesized in 13-15 steps from a commercially available material to demonstrate the application of this approach.

References

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Citations

Dec 7, 2018·Angewandte Chemie·Huai-Yu BinQi-Lin Zhou
Jun 18, 2019·Natural Product Reports·Nengzhong WangXuefeng Jiang
Aug 5, 2020·Chemical Communications : Chem Comm·Takumi AbeToshiki Yamashiro
Apr 16, 2018·Chemistry : a European Journal·Dattatraya Hanumant DetheNisar Ahmed Mir
Aug 15, 2017·Angewandte Chemie·Yun-Ting LiuQi-Lin Zhou
Sep 17, 2020·Organic Letters·Liu-Yang PuQi-Lin Zhou

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Methods Mentioned

BETA
NMR
X-ray

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