High-Throughput Discovery and Evaluation of a General Catalytic Method for N-Arylation of Weakly Nucleophilic Sulfonamides

被引：21

作者：

Becica, Joseph ^{[1
,2
]}

Hruszkewycz, Damian P. ^{[2
]}

Steves, Janelle E. ^{[2
]}

Elward, Jennifer M. ^{[3
]}

Leitch, David C. ^{[2
,4
]}

Dobereiner, Graham E. ^{[1
]}

机构：

[1] Temple Univ, Dept Chem, Philadelphia, PA 19122 USA

[2] GlaxoSmithKline, Chem Dev, Collegeville, PA 19426 USA

[3] GlaxoSmithKline, Mol Design Data & Computat Sci, Collegeville, PA 19426 USA

[4] Univ Victoria, Dept Chem, Victoria, BC V8P 5C2, Canada

来源：

ORGANIC LETTERS | 2019年 / 21卷 / 22期

基金：

美国国家科学基金会;

关键词：

PHOSPHINE-LIGANDS; DRUG DISCOVERY; ARYL HALIDES; AMINATION; EXPERIMENTATION; ACCELERATION; AMIDATION; COMPLEXES; BIPPYPHOS; SECONDARY;

D O I：

10.1021/acs.orglett.9b03380

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Through targeted high-throughput experimentation (HTE), we have identified the Pd/AdBippyPhos catalyst system as an effective and general method to construct densely functionalized N,N-diaryl sulfonamide motifs relevant to medicinal chemistry. AdBippyPhos is particularly effective for the installation of heteroaromatic groups. Computational steric parametrization of the investigated ligands reveals the potential importance of remote steric demand, where a large cone angle combined with an accessible Pd center is correlated to successful catalysts for C-N coupling reactions.

引用

页码：8981 / 8986

页数：6

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