One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

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

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

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)

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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-Text

Keywords: organocatalysis; asymmetric synthesis; one-pot reaction; multicomponent reaction; aminocatalysis; spirocyclic piperidone

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MDPI and ACS Style

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. https://doi.org/10.3390/catal7020046

AMA Style

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(2):46. https://doi.org/10.3390/catal7020046

Chicago/Turabian Style

Liu, Yanqing, Liang Ouyang, Ying Tan, Xue Tang, Jingwen Kang, Chunting Wang, Yaning Zhu, Cheng Peng, and Wei Huang. 2017. "One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence" Catalysts 7, no. 2: 46. https://doi.org/10.3390/catal7020046

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One-Pot Two-Step Organocatalytic Asymmetric Synthesis of Spirocyclic Piperidones via Wolff Rearrangement–Amidation–Michael–Hemiaminalization Sequence

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