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Page 8 of 17 Wu et al. Chem Synth 2023;3:6 https://dx.doi.org/10.20517/cs.2022.42

Scheme 3. One mmol scale reaction and control experiments.

substrate 2k was used as a nucleophile to react with 1a and still no reaction occurred. This result
demonstrated that the OH group of substrate 2 was necessary for performing the reaction.

Based on the control experiments, a possible reaction pathway and activation mode of this Brønsted acid-
catalyzed reaction were proposed [Scheme 4]. As exemplified by the model reaction, 3-alkynyl-2-
indolylmethanol 1a was initially transformed into allene-iminium intermediate A under the activation of
Brønsted acid 4a via hydrogen-bonding interaction. Subsequently, catalyst 4a simultaneously activated
allene-iminium intermediate A and 2-naphthol 2a via forming two hydrogen bonds, thus facilitating a 1, 4-
addition between them to generate intermediate B. Intermediate B then experienced a dehydration process
under the catalysis of Brønsted acid 4a to give carbocation C, which was easily converted into 4π
carbocation D due to electron delocalization. Finally, activated by catalyst 4a via the interactions of
hydrogen bonding and ion pairing, intermediate D underwent a Nazarov-type cyclization to form the cyclic
carbocation intermediate E, which immediately underwent α-H elimination to deliver 3, 4-
dihydrocyclopenta[b]indole 3aa with the regeneration of catalyst 4a.

Because this class of 3, 4-dihydrocyclopenta[b]indole scaffolds 3 contains a carbon-carbon chiral axis, we
then carried out a preliminary investigation on the organocatalytic asymmetric version of the Nazarov-type
cyclization. In fact, in recent years, the catalytic asymmetric construction of axially chiral indole-based
scaffolds has become an emerging area of study [8,78] due to the importance of such scaffolds in many natural