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Wu et al. Chem Synth 2023;3:6 Chemical Synthesis
DOI: 10.20517/cs.2022.42

Research Article Open Access

Organocatalytic Nazarov-type cyclization of 3-

alkynyl-2-indolylmethanols: construction of axially
chiral cyclopenta[b]indole scaffolds

2,*
2
2
1,2
2
Ping Wu , Xin-Yu Yan , Song Jiang , Yi-Nan Lu , Wei Tan , Feng Shi 1,2,*
1
School of Petrochemical Engineering, Changzhou University, Changzhou 213164, Jiangsu, China.
2
School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
* Correspondence to: Prof. Wei Tan, School of Chemistry and Materials Science, Jiangsu Normal University, Shanghai Road No.
101, Xuzhou 221116, Jiangsu, China. E-mail: wtan@jsnu.edu.cn; Prof. Feng Shi, School of Petrochemical Engineering, Changzhou
University, Gehu Road No. 21, Changzhou 213164, Jiangsu, China. E-mail: fshi@jsnu.edu.cn; fshi@cczu.edu.cn
How to cite this article: Wu P, Yan XY, Jiang S, Lu YN, Tan W, Shi F. Organocatalytic Nazarov-type cyclization of 3-alkynyl-2-
indolylmethanols: construction of axially chiral cyclopenta[b]indole scaffolds. Chem Synth 2023;3:6.
https://dx.doi.org/10.20517/cs.2022.42
Received: 20 Dec 2022 First Decision: 4 Jan 2023 Revised: 12 Jan 2023 Accepted: 28 Jan 2023 Published: 3 Feb 2023

Academic Editor: Bao-Lian Su Copy Editor: Ke-Cui Yang Production Editor: Ke-Cui Yang

Abstract
In recent years, it has become an urgent task to design new types of indole-based platform molecules for Nazarov-
type cyclizations and develop organocatalytic Nazarov-type cyclizations for synthesizing indole derivatives. To
fulfill this task, in this work, by changing the alkynyl terminal substituent from t-Bu to an aryl group, the reactivity of
3-alkynyl-2-indolylmethanols is modulated and the new platform molecules serve as competent substrates for
Brønsted acid-catalyzed Nazarov-type cyclization. Based on this new reactivity, the first organocatalytic Nazarov-
type cyclization of aryl-substituted 3-alkynyl-2-indolylmethanols with 2-naphthols is accomplished, leading to the
efficient construction of a new class of axially chiral 3, 4-dihydrocyclopenta[b]indole scaffolds. This preliminary
investigation of organocatalytic asymmetric Nazarov-type cyclization provides an optional strategy for the
atroposelective construction of this new class of axially chiral cyclopenta[b]indole scaffolds. In addition, the first
preparation of axially chiral 3, 4-dihydrocyclopenta[b]indole with optical purity is established through chiral
resolution, which could serve as a complementary method to catalytic asymmetric approaches.

Keywords: 2-indolylmethanol, Nazarov cyclization, organocatalysis, asymmetric organocatalysis, axial chirality

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