2,5-Dihydro-1H-pyrrol-3-yl Boronic Derivatives: Multigram Synthesis and Coupling Reactions

A protocol for the multigram synthesis of 3-substituted 2,5-dihydro-1H-pyrrole boronic derivatives is reported. The method relied on the triflation of N-Boc-3-oxopyrrolidine and subsequent palladium-catalyzed borylation. Optimization studies demonstrated the high efficiency of t-BuOK as a base for the triflation step and good performance of the one-pot protocol as compared with the conventional step-by-step synthesis. The method allowed the production of up to 60 g of the target compound (as pure trifluoroborate or technical-grade boropinacolate) in one run using commercially available reagents and common laboratory equipment. Application of the obtained building block for the preparation of compounds relevant to medicinal chemistry through C-C coupling reactions is also illustrated. It is suggested that the boropinacolate form of the title building block is advantageous when immediate synthesis of the coupling products is envisaged, whereas trifluoroborate is more convenient for storage and commercialization.