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He et al. Chem Synth 2023;3:35 Chemical Synthesis
DOI: 10.20517/cs.2023.14

Research Article Open Access

Enantioselective synthesis of 6-(Indole-2-yl)-3,4-
dihydropyran-2-one skeletons by N-Heterocyclic

carbene-catalyzed asymmetric [3 + 3] cycloaddition
of α-bromocinnamaldehyde

1
2,*
1,#
1,#
Gao He , Xiaoyu Chen , Siqi Xia , Guofu Zhong , Limin Yang 1,*
1
College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 311121, Zhejiang, China.
2
Department of Chemistry, Eastern Institute for Advanced Study, Ningbo 315200, Zhejiang, China.
#
Authors contributed equally.
*
Correspondence to: Prof. Guofu Zhong, Department of Chemistry, Eastern Institute of Technology, No.568 Tongxin Road,
Ningbo 315200, Zhejiang, China. E-mail: guofuzhong@eias.ac.cn; Prof. Limin Yang, College of Material, Chemistry and Chemical
Engineering, Hangzhou Normal University, No.2318 Yuhangtang Road, Hangzhou 311121, Zhejiang, China. E-mail:
myang@hznu.edu.cn;
How to cite this article: He G, Chen X, Xia S, Zhong G, Yang L. Enantioselective synthesis of 6-(Indole-2-yl)-3,4-dihydropyran-2-
one skeletons by N-Heterocyclic carbene-catalyzed asymmetric [3 + 3] cycloaddition of α-bromocinnamaldehyde. Chem Synth
2023;3:35. https://dx.doi.org/10.20517/cs.2023.14
Received: 02 Mar 2023 First Decision: 28 Mar 2023 Revised: 29 Apr 2023 Accepted: 16 May 2023 Published: 21 Jul 2023
Academic Editors: Bao-Lian Su, Feng Shi Copy Editor: Dan Zhang Production Editor: Dan Zhang

Abstract
The enantioselective construction of chiral 6-(indole-2-yl)-3,4-dihydropyran-2-one skeleton was demonstrated by
the formal [3 + 3] cycloaddition reaction of α-bromocinnamaldehyde with β-ketoester indole catalyzed by chiral N-
heterocyclic carbene (NHC). The reaction proceeds smoothly via a vinyl acyl azolium intermediate (electron-poor
enone) generated from NHC-aldehyde adducts, providing 6-(indole-2-yl)-3,4-dihydropyran-2-one derivatives in
good yields with excellent enantioselectivities (up to 98% ee).

Keywords: Organocatalysis, enantioselective synthesis, N-heterocyclic carbene (NHC), acyl azolium intermediate,
6-(indole-2-yl)-3, 4-dihydropyran-2-one skeleton

INTRODUCTION
Indole skeletons are widely present in many important biomolecules and possess a heterocyclic structure
with diverse properties. Their structural characteristics can offer unique features, such as modifying electron

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