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Organocatalytic Access to <scp>C1</scp>‐Functionalized Indolizines via Remote Stereocontrolled Construction of Axially Chiral Allenes

Xuan Zhang, Xu‐Hua Jiang, Chun‐Dong Huang, Cheng Gao, Shao‐Fei Ni, Qijian Ni

2025Chinese Journal of Chemistry6 citationsDOIOpen Access PDF

Abstract

Comprehensive Summary We present here a straightforward protocol for the enantioselective synthesis of axially chiral tetrasubstituted allenes enabled by chiral phosphoric acid (CPA)‐catalyzed 1,8‐addition of indolizines to propargylic alcohols. This strategy achieves enantioselective and regioselective C1‐functionalization of indolizines under mild reaction conditions with low catalyst loading, broad functional group tolerance (35 examples), and excellent enantioselectivities (up to 96% ee). Moreover, the scale‐up reaction and late‐stage C3‐functionalizations demonstrated its potential applications. DFT calculations were carried out to clarify the reaction mechanism and the origin of enantio‐ and regioselective control.

Topics & Concepts

ChemistryAxial symmetryCombinatorial chemistryStructural engineeringEngineeringSynthesis and Reactivity of HeterocyclesCyclopropane Reaction MechanismsCatalytic C–H Functionalization Methods