Open AccessSilver-Catalyzed Enantioselective Propargylic C–H Bond Amination through Rational Ligand Design
Author(s) -
Minsoo Ju,
Emily E. Zerull,
Jessica M. Roberts,
Minxue Huang,
Ilia A. Guzei,
Jennifer M. Schomaker
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.0c05726
Subject(s) - chemistry , amination , nitrene , enantioselective synthesis , ligand (biochemistry) , oxazoline , catalysis , combinatorial chemistry , hydrogen bond , transfer hydrogenation , stereochemistry , medicinal chemistry , organic chemistry , molecule , ruthenium , biochemistry , receptor
Asymmetric C-H amination via nitrene transfer is a powerful tool to prepare enantioenriched amine precursors from abundant C-H bonds. Herein, we report a regio- and enantioselective synthesis of γ-alkynyl γ-aminoalcohols via a silver-catalyzed propargylic C-H amination. The protocol was enabled by a new bis(oxazoline) (BOX) ligand designed via a rapid structure-activity relationship (SAR) analysis. The method utilizes accessible carbamate esters bearing γ-propargylic C-H bonds and furnishes versatile products in good yields and excellent enantioselectivity (90-99% ee ). The putative Ag-nitrene is proposed to undergo enantiodetermining hydrogen-atom transfer (HAT) during the C-H amination event. Density functional theory calculations shed insight into the origin of enantioselectivity in the HAT step.