Authors
- Yuxuan Ye
MIT, University of Pittsburgh ,
- Ilia Kevlishvili ,
- Sheng Feng ,
- Peng Liu ,
- Stephen L. Buchwald
Abstract
C3-substituted 1H-indazoles are useful and important substructures in many pharmaceuticals. Methods for direct C3- functionalization of indazoles are relatively rare, compared to reactions developed for the more nucleophilic N1 and N2 positions. Herein, we report a highly C3-selective allylation reaction of 1H-N-(benzoyloxy)indazoles using CuH catalysis. A variety of C3-allyl 1H-indazoles with quaternary stereocenters were efficiently prepared with high levels of enantioselectivity. Density functional theory (DFT) calculations suggest that the indazole addition to copper allyl complex proceeds through an enantioselectivity-determining six- membered Zimmerman-Traxler-type transition state. The enantioselectivity is governed both by the ligand-substrate steric interac- tions and the steric repulsions with the pseudoaxial substituent in the six-membered allylation transition state.
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