One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence
Yanqing Liu 1,†, Liang Ouyang 2,†
, Ying Tan 3, Xue Tang 1, Jingwen Kang 1, Chunting Wang 2, Yaning Zhu 3, Cheng Peng 1,* and Wei Huang 1,*
, Ying Tan 3, Xue Tang 1, Jingwen Kang 1, Chunting Wang 2, Yaning Zhu 3, Cheng Peng 1,* and Wei Huang 1,*
1
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
3
China Resources Sanjiu (Ya’an) Pharmaceutical Company Limited, Ya’an 625000, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Aurelio G. Csákÿ
Catalysts 2017, 7(2), 46; https://doi.org/10.3390/catal7020046
Received: 14 December 2016 / Revised: 18 January 2017 / Accepted: 22 January 2017 / Published: 4 February 2017
(This article belongs to the Special Issue Metal-free Organocatalysis)
Abstract
A highly enantioselective organocatalytic Wolff rearrangement–amidation–Michael–hemiaminalization stepwise reaction is described involving a cyclic 2-diazo-1,3-diketone, primary amine and α,β-unsaturated aldehyde. Product stereocontrol can be achieved by adjusting the sequence of steps in this one-pot multicomponent reaction. This approach was used to synthesize various optically active spirocyclic piperidones with three stereogenic centers and multiple functional groups in good yields up to 76%, moderate diastereoselectivities of up to 80:20 and high enantioselectivities up to 97%. View Full-TextKeywords:
organocatalysis; asymmetric synthesis; one-pot reaction; multicomponent reaction; aminocatalysis; spirocyclic piperidone
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Liu, Y.; Ouyang, L.; Tan, Y.; Tang, X.; Kang, J.; Wang, C.; Zhu, Y.; Peng, C.; Huang, W. One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence. Catalysts 2017, 7, 46.
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