Titanocene-mediated radical cyclization:: An emergent method towards the synthesis of natural products

The reaction of the Cp2TiCl complex with oxiranes leads to homolytic opening of the heterocycle with high regioselectivity. Although the resulting beta-titanoxyl radical can evolve in different ways, when the epoxide reacting with Cp2TiCl possesses suitable unsaturated moieties such as olefins, triple bonds, carbonyls or nitriles in its structure, intramolecular addition of this beta-titanoxyl radical to these unsaturated groups can take place, leading to a cyclization process. Structures containing from three- to seven-membered rings have been synthesized using either stoichiometric or catalytic quantities of titanocene. Although a number of applications for these titanium-mediated cyclization reactions have been reported in the synthesis of natural products and bioactive compounds such as antibiotic gamma-lactones, lignans and beta-lactams, we consider that the strategy involving the opening and ensuing cyclization of the monoepoxides of polyprenes, which resulted in the preparation of C-10, C-15, C-20 and C-30 terpenoids, including mono-, bi- and tricyclic natural products, deserves special mention. Attractive aspects of this reaction are good stereochemical control and the oxidative termination of the process, which leads regioselectively to exocyclic olefins. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinbeim, Germany, 2006.