Copper(I)-Catalyzed Asymmetric Desymmetrization through Inverse-Electron-Demand aza-Diels-Alder Reaction: Efficient Access to Tetrahydropyridazines Bearing a Unique α-Chiral Silane Moiety

Liang Wei; Yu Zhou; Zhi-Min Song; Hai-Yan Tao; Zhenyang Lin; Chun-Jiang Wang

doi:10.1002/chem.201700912

Copper(I)-Catalyzed Asymmetric Desymmetrization through Inverse-Electron-Demand aza-Diels-Alder Reaction: Efficient Access to Tetrahydropyridazines Bearing a Unique α-Chiral Silane Moiety

Chemistry. 2017 Apr 11;23(21):4995-4999. doi: 10.1002/chem.201700912. Epub 2017 Mar 27.

Authors

Liang Wei^{1

2}, Yu Zhou³, Zhi-Min Song¹, Hai-Yan Tao^{1

2}, Zhenyang Lin³, Chun-Jiang Wang^{1

2}

Affiliations

¹ College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, P. R. China.
² State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071, P. R. China.
³ Department of Chemistry, The Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong.

PMID: 28261883
DOI: 10.1002/chem.201700912

Abstract

An unprecedented copper(I)-catalyzed asymmetric desymmetrization of 5-silylcyclopentadienes with in situ formed azoalkene was realized through an inverse-electron-demand aza-Diels-Alder reaction (IEDDA) pathway, in which 5-silylcyclopentadienes served as efficient enophiles. This new protocol provides a facile access to the biologically important heterocyclic tetrahydropyridazines containing a unique α-chiral silane motif and three adjoining stereogenic centers in generally good yield (up to 92 %) with exclusive regioselectivity, high diastereoselectivity (>20:1 diastereomeric ratio), and excellent enantioselectivity (up to 98 % enantiomeric excess). DFT calculations and control experiments further confirmed the proposed reaction mechanism.

Keywords: Diels-Alder reaction; asymmetric catalysis; desymmetrization; mechanism investigation; α-chiral silanes.