Hydrogen atom transfer from transition-metal hydrides: Applications to radical cyclization

Radical cyclization reactions are important tools for the synthesis of complex molecules. These reactions rely on tin hydrides, the toxicity of which has precluded their use in the pharmaceutical industry. Many tin hydride substitutes that react through an analogous mechanism have been developed; however, they have either (1) still used tin in some form, or (2) contained a bond to hydrogen stronger than that in Bu3SnH and are therefore less reactive at H· transfer. Furthermore, these methods are stoichiometric in some other heavy element, typically a halogen, selenium, or sulfur.;Rate studies of H· transfer from CpCr(CO)3H to substituted olefins predict the favored site of transfer. This allows the design of diene substrates that are likely to cyclize. CpCr(CO)3H and the cobaloxime (H2O)2 Co(dmgBF2)2 are competent radical cyclization catalysts, with respectable H· transfer rates and easy regeneration of M-H from M· by H2. A series of HV(CO) 4P-P complexes initiates radical cyclization, but the V-H bond is so weak as to not undergo regeneration with H2. These V-H complexes initiate cyclization stoichiometrically under very mild conditions. All of these transition-metal hydride systems can perform catalytically without the stoichiometric use of H2 with substrates that offer sterically unhindered hydrogen atoms beta to the formed radical. Abstraction of this H· by M· regenerates M-H and leads to an unsaturated product.;Transition-metal hydrides have been developed as alternatives to tin hydrides. The weakness of the transition-metal-hydrogen bond (as weak as 55 kcal/mol) allows a different approach to generating radicals: direct transfer of H· from M-H to an olefin. The metalloradical M· that remains after H· transfer can be converted back to M-H by reaction with H 2. Transition-metal hydrides not only alleviate the toxicity concerns associated with tin reagents but also eliminate the need for a stoichiometric amount of another heavy element, providing a green alternative to toxic tin hydrides for radical-mediated carbon-carbon bond forming reactions.