ChemistryMedicine

Hao-Hui Zhang, Yi-Fan Wang, Kuiyong Dong, Feng Shi

2026.5.20ORGANIC LETTERS

DOI: 10.1021/acs.orglett.6c01670

Abstract

A catalyst-controlled asymmetric chemodivergent reaction of C,N-cyclic azomethine imines with 2-indolylacetates has been developed. By simply switching the chiral isothiourea catalyst, the reaction proceeds via either a catalytic asymmetric (3 + 2) cycloaddition or an addition reaction in a chemodivergent manner, affording two distinct families of chiral indole-based hydroisoquinolines in high yields (up to 90%) with excellent stereoselectivities (up to 99% ee). This work not only represents the first catalytic asymmetric chemodivergent reaction of C,N-cyclic azomethine imines but also serves as an excellent example of catalyst-controlled chemodivergent enantioselective transformation. Furthermore, it demonstrates a new application of 2-indolylacetates as reaction partners displaying either α- or γ-selectivity, thereby offering a powerful strategy for the synthesis of enantioenriched indole-based hydroisoquinolines.

Citation format

ZHANG, Hao-Hui, et al. Catalyst-controlled asymmetric chemodivergent reaction of c,n-cyclic azomethine imines with 2-indolylacetates. ORGANIC LETTERS, 2026, 28 22(22): 6981–6986.