American Chemical Society
jo3c01072_si_001.pdf (6.16 MB)

Decarboxylative Cross-Electrophile Coupling of (Hetero)Aromatic Bromides and NHP Esters

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journal contribution
posted on 2023-08-23, 07:55 authored by Ethan M. DeCicco, Simon Berritt, Thomas Knauber, Steven B. Coffey, Jie Hou, Matthew S. Dowling
Aryl bromides are known to be challenging substrates in the decarboxylative cross-electrophile coupling with redox-active NHP esters–the majority of such processes utilize aryl iodides. Herein, we describe the development of conditions that are suitable for the decarboxylative cross-electrophile coupling of NHP esters and a wide range of (hetero)aryl bromides. The key advances that allowed for the use of aryl bromides in this reaction are (1) the identification of ligand L3 as an optimal ligand for the use of electron-neutral and deficient aryl bromides and (2) the significant improvement in yield that iodide salts and excess heterogenous zinc impart to this reaction. A wide variety of NHP esters perform well under the optimized conditions, including methyl, primary, secondary, and several strained tertiary systems. Likewise, a variety of aromatic and heteroaromatic bromides relevant to medicinal chemistry perform well in this transformation, including an aryl bromide precursor to the known drug dapagliflozin.