A mild robust generic protocol for the Suzuki reaction using an air stable catalyst

• Published in: Tetrahedron 2012-07, Vol.68 (30), p.6010-6017
• Main Authors: Moseley, Jonathan D., Murray, Paul M., Turp, Edward R., Tyler, Simon N.G., Burn, Ross T.
• Format: Article
• Language: English
• Subjects: Aromatic compounds; B derivatives; Catalysis; Catalysts: preparations and properties; Chemical reactions; Chemistry; Chlorides; Conversion; Exact sciences and technology; General and physical chemistry; Noncondensed benzenic compounds; Optimization; Organic chemistry; Organometalloidal and organometallic compounds; Preparations and properties; Solvents; Theory of reactions, general kinetics. Catalysis. Nomenclature, chemical documentation, computer chemistry; Transformations; Utilities
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.05.030

A mild but robust procedure has been developed as a first pass generic protocol for the Suzuki–Miyaura reaction. The protocol employs an air stable palladium pre-catalyst at low loading (≤1mol%) in aqueous solvent mixtures at moderate temperature using potassium carbonate as base. Under these mild conditions, most aryl bromides will react with sterically and electronically demanding aryl boronic acids to give complete conversion to the product biphenyls in less than 1h. Aryl chlorides are also fully converted in most cases either under identical conditions in 8–24h, or in 2h at elevated temperature. A further advantage of these mild conditions of moderate temperature, weak base and benign solvent is that sensitive functional groups and structural motifs are well tolerated. In addition, the lipophilic biphenyl products are readily isolated after a simple work-up procedure. These generic conditions are ideal for proof of transformation, and as the starting point for development and optimization of a specific process. The discovery and fine-tuning of this generic protocol will be presented, supported extensively by examples to illustrate its scope and utility. [Display omitted]