Synthesis of Oxa-Bridged 7- and 8-Membered Rings via Indium-Mediated Annulation of 1,4- and 1,5-Dicarbonyl Compounds with 3-Iodo-2-[(trimethylsilyl)methyl]propene

A variety of 1,4-and 1,5-dicarbonyl compounds undergo reaction with 3-iodo-2-[(trimethylsilyl)methyl]propene in the presence of indium metal in aqueous media to produce oxa-bridged 7-and 8-membered rings in good yields.The reaction mechanism likely involves intermolecular indium allylation of one carbonyl of the substrate, followed by indium-halide promoted intramolecular allylsilane cyclization.This procedure offers an environmentally friendly alternative to the analogous tin-mediated annulation process.The wide occurrence of seven and eight-membered carbocycles in natural products has stimulated numerous efforts on the part of synthetic chemists to develop a general method for the synthesis of medium rings akin to the Diels-Alder reaction employed for formation of six-membered rings. 1 The development of [m+n] annulation reactions, wherein a carbocyle is generated from two acyclic precursors in a single synthetic operation, remains an important focus of synthetic effort. 2Molander has reported a successful [3+4] and [3+5] annulation approach to seven and eight membered rings involving combination of dicarbonyl compounds with 3-iodo-2-[(trimethylsilyl)methyl]propene (1) as a trimethylenemethane dianion synthon. 3The process is promoted by SnF 2 , which serves to generate allylstannane (2) from 1 in situ (Scheme 1).Carbonyl allylation is then followed by hemiacetal formation and allylsilane cyclization, promoted by the presence of both Sn 4+ and fluoride ions, to provide the oxa-bridged carbocycle in high yields.One undesirable aspect of this procedure is the necessity for use of stoichiometric amounts of a toxic tin reagent.