Journal Article

Decarboxylative borylation

Yu, Shan, Chatterjee, Arnab K., Peters, David S., Barton, Lisa M., Yan, Ming, Yu, Antony W., Li, Chao, Tian, Maoqun, Johnson, Kristen A., Baran, Phil S., Wang, Jie, Kumar, Manoj

2017

Overview

Carbon-bound boronic acids and their esters are widely used as coupling partners to make carbon-carbon bonds. More recently, these chemicals have garnered pharmaceutical interest in their own right. Li et al. report a versatile nickel-catalyzed process to replace carboxylic acids with boronate esters by using a phthalimide activator. The reaction is well suited to late-stage modification of complex molecules. The authors used the approach to produce a potent in vitro inhibitor of human neutrophil elastase, a target of interest in treating inflammatory lung diseases. Science , this issue p. eaam7355 Nickel catalyzes replacement of carboxylic acid groups with boronic acids and esters in a wide variety of compounds. The widespread use of alkyl boronic acids and esters is frequently hampered by the challenges associated with their preparation. We describe a simple and practical method to rapidly access densely functionalized alkyl boronate esters from abundant carboxylic substituents. This broad-scope nickel-catalyzed reaction uses the same activating principle as amide bond formation to replace a carboxylic acid moiety with a boronate ester. Application to peptides allowed expedient preparations of α-amino boronic acids, often with high stereoselectivity, thereby facilitating synthesis of the alkyl boronic acid drugs Velcade and Ninlaro as well as a boronic acid version of the iconic antibiotic vancomycin. The reaction also enabled the discovery and extensive biological characterization of potent human neutrophil elastase inhibitors, which offer reversible covalent binding properties.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Acids / Alcohols / Alkenes / Amides / Amination / Bonding / Boron / Boron - chemistry / Boronic Acids - chemistry / Carbamates (tradename) / Carbon / Carboxylic acids / Carboxylic Acids - chemistry / Chemical bonds / Chemical reactions / Chemical sensors / Chemical synthesis / Chemoreceptors / Clinical trials / Compatibility / Drug development / Drug discovery / Elastase / Esters / Functional anatomy / Functional groups / Halides / Inhibitors / Ketones / Lead compounds / Lung diseases / Materials science / Media / Natural products / Neutrophils / Nickel / Nucleophiles / Organic Chemistry / Oxidation / Peptides / Pharmaceutical Preparations - chemical synthesis / Pharmacokinetics / Phthalimide / Phthalimides / RESEARCH ARTICLE SUMMARY / Stereoselectivity / Vancomycin