Carbonylation reactions play a crucial role in organic and industrial chemistry, enabling the introduction of carbonyl groups into organic substrates using carbon monoxide (CO). While CO is cost-effective and atom-efficient reagent, its toxicity and high-pressure handling present significant challenges in traditional batch processes. In recent years, flow chemistry has revolutionized these transformations, offering enhanced efficiency, safety, and precise control of reaction parameters. Sulfoximines are valuable scaffold in pharmaceutical, agricultural, and organic chemistry as chiral auxiliars and intermediates. Despite their synthetic potential, previous approaches often rely on toxic reagents, excessive oxidants, and tedious purification steps, leading to low conversions and undesirable by-products. Here, we report a continuous flow protocol for the N-aroylation of different functionalized aryl halides with sulfoximines under CO pressure using a palladium-based catalyst, a base, and a ligand. Comprehensive screening of organic bases in batch mode allowed to identify optimal conditions, which were then translated into a flow system operating at 80 °C and 6 bar for 40 minutes. This innovative strategy provides rapid reactions, high selectivity, and good to excellent yields (up to 90%) across a small library, demonstrating the advantages of continuous flow technology in carbonylation chemistry.
Moroni et al. (Tue,) studied this question.