posted on 2023-08-23, 07:55authored byEthan
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.