Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: scope and DFT study

Dmitry Katayev; Evgeny Larionov; Masafumi Nakanishi; Céline Besnard; E Peter Kündig

doi:10.1002/chem.201403985

Palladium-N-heterocyclic carbene (NHC)-catalyzed asymmetric synthesis of indolines through regiodivergent C(sp3)-H activation: scope and DFT study

Chemistry. 2014 Nov 10;20(46):15021-30. doi: 10.1002/chem.201403985. Epub 2014 Sep 26.

Authors

Dmitry Katayev¹, Evgeny Larionov, Masafumi Nakanishi, Céline Besnard, E Peter Kündig

Affiliation

¹ Department of Organic Chemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211Geneva 4 (Switzerland), Fax: (+) 41 22-237-3215.

PMID: 25262613
DOI: 10.1002/chem.201403985

Abstract

Two bulky, chiral, monodentate N-heterocyclic carbene ligands were applied to palladium-catalyzed asymmetric C-H arylation to incorporate C(sp(3))-H bond activation. Racemic mixtures of the carbamate starting materials underwent regiodivergent reactions to afford different trans-2,3-substituted indolines. Although this CAr-Calkyl coupling requires high temperatures (140-160 °C), chiral induction is high. This regiodivergent reaction, when carried out with enantiopure starting materials, can lead to single structurally different enantiopure products, depending on the catalyst chirality. The C-H activation at a tertiary center was realized only in the case of a cyclopropyl group. No C-H activation takes place alpha to a tertiary center. A detailed DFT study is included and analyses of methyl versus methylene versus methine C-H activation is used to rationalize experimentally observed regio- and enantioselectivities.

Keywords: CH activation; asymmetric catalysis; carbenes; chirality; density functional calculations.