Decarboxylative Cross-Electrophile Coupling of (Hetero)Aromatic Bromides and NHP Esters
Ethan M DeCicco1, Simon Berritt1, Thomas Knauber1
1Medicine Design, Pfizer, Inc., Eastern Point Road, Groton, Connecticut 06340, United States.
Abstract:
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.
More Related Videos
07:06A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
19:58Palladium N-Heterocyclic Carbene Complexes: Synthesis from Benzimidazolium Salts and Catalytic Activity in Carbon-carbon Bond-forming Reactions
Published on: July 30, 2017
Related Concept Videos
Electrophilic 1,2- and 1,4-Addition of HX to 1,3-Butadiene
α-Bromination of Carboxylic Acids: Hell–Volhard–Zelinski Reaction
Radical Substitution: Allylic Bromination
Electrophilic 1,2- and 1,4-Addition of X2 to 1,3-Butadiene
β-Dicarbonyl Compounds via Crossed Claisen Condensations
Nucleophilic Aromatic Substitution: Elimination–Addition
![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)