Pd(0)-Catalyzed Bidentate Auxiliary Directed Enantioselective Benzylic C-H Arylation of 3-Arylpropanamides Using the BINOL Phosphoramidite Ligand

Hua Rong Tong, Sujuan Zheng, Xinghua Li, Zhiqiang Deng, Hao Wang, Gang He, Qian Peng, Gong Chen

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Palladium-catalyzed enantioselective C(sp3)-H functionalization could provide valuable reactions for organic synthesis. While significant progress has been made on monodentate directing-group-mediated (DG-mediated) enantioselective C-H functionalization using amino acid or N-heterocycle-based chiral ligands, methods for enantioselective C(sp3)-H functionalization mediated by bidentate DGs have lagged far behind. For Pd-catalyzed C(sp3)-H functionalization reactions, 8-aminoquinoline (AQ) is a powerful N,N-bidentate auxiliary. The bidentate binding mode of AQ can stabilize high-valent Pd intermediates, enabling challenging transformations through a PdII/IV catalytic manifold. Recently, Duan reported an enantioselective Pd-catalyzed AQ-directed benzylic C-H arylation of 3-arylpropanamides using PdII catalyst and the BINOL phosphoramide (PV) ligand. Herein, we report a protocol for Pd-catalyzed AQ-mediated enantioselective benzylic C-H arylation of 3-arylpropanamides using Pd0 catalyst and the BINOL-phosphoramidite (PIII) ligand. These reactions give good to high yield and improved enantioselectivity (up to 95% ee). Mechanistic studies indicate that the reactions proceed via a Pd0/II catalytic cycle, unprecedented for AQ-directed reactions. DFT calculations suggest that both the phosphoramidite ligand and cesium carbonate base are involved in the enantiodetermining C-H palladation step, and that the AQ directing group converts between binding modes to accommodate the C-H palladation and reductive elimination steps.

Original languageEnglish (US)
Pages (from-to)11502-11512
Number of pages11
JournalACS Catalysis
Volume8
Issue number12
DOIs
StatePublished - Dec 7 2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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