The development of a conjugate addition reaction of non-activated alkyl bromides to Michael acceptors under visible-light photoredox catalysis is disclosed. A diverse set of alkyl bromides was successfully added to α,β-unsaturated esters and amides. This transformation allowed access to a key intermediate of Vorinostat®, an HDAC inhibitor used to fight cancer and HIV.

Continuous flow has been used widely in process chemistry and academic settings for various applications. However, initial reaction discovery has generally remained “batch-exclusive” despite the existence of efficient, reproducible flow systems. We hereby disclose a workflow to bridge the gap between early medicinal chemistry efforts and process-scale development, showcased by the discovery and optimization of a metallaphotoredox-catalyzed cross-coupling between benzylic chlorides and aryl bromides, followed by two library syntheses of complex drug-like compounds.

Here we disclose a sulfurane-mediated method for the formation of dimeric dibenzofuran helicenes via the reaction between diaryl sulfoxides and hexadehydro-Diels–Alder (HDDA) derived benzynes. A variety of S-shaped and U-shaped helicenes were formed under thermal conditions. Both experimental and DFT studies support a sulfur­(IV)-based coupling (aka ligand coupling) mechanism involving tetracarbo-ligated S­(IV) intermediates undergoing reductive elimination to afford the helicene products. This process involves the de novo generation of five new rings in a single operation and constitutes a new method for the construction of topologically interesting, polycyclic aromatic compounds.