Modular One-Step Three-Component Synthesis of Tetrahydroisoquinolines Using a Catellani Strategy.

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.

Epoxides as Alkylating Reagents for the Catellani Reaction.

We report a cooperative catalytic system comprising a PdII complex, XPhos, and the potassium salt of 5-norbornene-2-carboxylic acid that enables the use of epoxides as alkylating reagents in the Catellani reaction, thereby expanding the existing paradigm of this powerful transformation. The potassium salt of inexpensive 5-norbornene-2-carboxylic acid acts as both mediator and base in the process. This mild, chemoselective, scalable, and atom-economical protocol is compatible with a wide variety of readily available functionalized aryl iodides and epoxides, as well as terminating olefins. The resulting products undergo facile oxa-Michael addition to furnish ubiquitous isochroman scaffolds.

Rhodium-catalyzed direct C-H bond cyanation of arenes with isocyanide.

An efficient rhodium-catalyzed regioselective C-H bond cyanation of arenes was developed using tert-butyl isocyanide as the cyanide source. A wide range of (hetero)aryl and cycloalkenyl nitriles could be afforded with high regioselectivity and good functional group tolerance.

Rhodium-catalyzed regioselective C-H chlorination of 7-azaindoles using 1,2-dichloroethane.

An unexpected rhodium-catalyzed regioselective C-H chlorination of 7-azaindoles was developed using 1,2-dichloroethane (DCE) as a chlorinating agent and 7-azaindole as the directing group. This protocol provides an efficient access to ortho-chlorinated azaindoles with operational simplicity, good functional group tolerance, and a wide substrate scope.