Reported is a modular one-step three-component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza-Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2-alkyl- and 2-aryl-substituted aziridines to access 1,3-cis-substituted and 1,4-cis-substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.

Ramelteon is the first medicine in human history that treat insomnia as a melatonin receptor agonist. Herein, we report an efficient three-step synthetic route to access it from commercially available 2,3-dihydrobenzofuran-4-amine, which represents as the shortest racemic synthesis to date with a 26 % overall yield. Key to the success is the application of the intermolecular Catellani-type alkylation and intramolecular redox-relay Heck cyclization cascade for preparation of the key indane-containing aldehyde. The unique primary amide-involved reductive amination of aldehyde is another feature of this route. New process of ramelteon can be developed based on this chemistry.[a] S.

Reported is a modular one‐step three‐component synthesis of tetrahydroisoquinolines using a Catellani strategy. This process exploits aziridines as the alkylating reagents, through palladium/norbornene cooperative catalysis, to enable a Catellani/Heck/aza‐Michael addition cascade. This mild, chemoselective, and scalable protocol has broad substrate scope (43 examples, up to 90 % yield). The most striking feature of this protocol is the excellent regioselectivity and diastereoselectivity observed for 2‐alkyl‐ and 2‐aryl‐substituted aziridines to access 1,3‐cis‐substituted and 1,4‐cis‐substituted tetrahydroisoquinolines, respectively. Moreover, this is a versatile process with high step and atom economy.