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Construction of Chiral 2‐Substituted Octahydroindoles from Cyclic Ketones and Nitroolefins Bearing only One α‐Substituent
Author(s) -
Han Yong,
Zheng Bo,
Peng Yungui
Publication year - 2015
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400851
Subject(s) - substituent , chemistry , nitro , amination , phosphoric acid , medicinal chemistry , amine gas treating , catalysis , intramolecular force , organic chemistry , stereoselectivity , alkyl
Abstract A dual catalytic system has been developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitroolefins bearing only one α‐substituent. The resulting γ‐nitro ketones, which contain a substituent on the carbon connected to the nitro group, were formed in excellent yields (>80%) with high levels of stereoselectivity (up to 94:6 dr and 98% ee ) when the reaction was performed in benzene at 0 °C with 10 mol% of the optimal amine/phosphoric acid combination (1:1) as a catalyst. Subsequent reduction of the nitro group followed by intramolecular reductive amination could afford optically active cis ‐octahydroindole analogues bearing a non‐functional substituent at their 2‐position.