Enantioselective palladium-catalyzed C(sp2)-H carbamoylation

An enantioselective palladium-catalyzed C(sp²)-H carbamoylation for the preparation of chiral isoindolines was described for the first time. With chiral monophosphorus ligand (R)-AntPhos as the ligand, a series of chiral isoindolines were prepared from diarylmethyl carbamoyl chlorides in excellent yields and enantioselectivities with the palladium loading as low as 1 mol%. Initial mechanistic studies indicated the asymmetric cyclization catalyzed a palladium species with a single chiral monophosphorus ligand.     

Transition-metal-free synthesis of primary to tertiary carboxamides: A quick access to prodrug-pyrazinecarboxamide

One-pot expedient and direct carbamoylation of heterocyclics is described. The transformation is realized via direct dehydrogenative aminocarbonylation of heterocyclic compounds under transition-metal-free conditions. This method is regioselective and the protocol is proved to be scalable on a gram scale. Further, the therapeutically useful antitubercular agent pyrazinecarboxamide is successfully synthesized by employing this protocol.     

Photoinduced carbamoylation of ethereal C-H bonds using pentafluorophenyl isocyanate

An intermolecular carbamoylation of ethers has been achieved via photoinduced functionalization of ethereal C-H bonds in the presence of benzophenone at ambient temperature. The carbamoyl group, a one-carbon unit with a high oxidation state, derived from pentafluorophenyl isocyanate (C₆F₅NCO) is chemoselectively introduced at the position geminal to the oxygen functionality in a single step. The present reaction system effectively activates the tertiary C-H bond at the sterically hindered site of fused bicyclic systems, and enables introduction of the carbamoyl group, which is then available for further synthetic elaborations.     

Asymmetric desymmetrization of meso-vic-diols by carbamoylation catalyzed with a chiral Cu(II) complex

Asymmetric desymmetrization of meso-vic-diols was achieved by carbamoylation in the presence of copper triflate and (S,S)-Ph-BOX as a catalyst without any use of bases. The method was successfully applied to asymmetric desymmetrization of five- to eight-membered cyclic meso-vic-diols in high enantioselectivity with up to 93% ee.