Application of the Brook Rearrangement in Tandem with Single Electron Transfer Oxidative and Radical Processes
Abstract
Merging rearrangement with radical reactions is a largely unexplored field but may hold promise for approaching scaffolds that are inaccessible by other methodology. Here a tandem nucleophilic substitution/Brook rearrangement/single-electron transfer oxidation/radical oxygenation strategy is presented, through which alpha,gamma-dioxygenated epsilon,zeta-unsaturated amides are efficiently prepared in a single step from enantiomerically enriched allylepoxides and 2-silylacetamides.
The resulting compounds can be easily transformed by persistent radical effect-based 5-exo-trig or 6-endo-trig radical cyclization reactions to functionalized carbocycles bearing three or four stereocenters. The stereochemical outcome of the cyclization reactions can predicted by the Beckwith-Houk model.
The cyclic compounds can be easily diversified by post-cyclization modifications. The tandem process can be further extended by an acylation step leading to beta-dicarbonyl enolates, which were also transformed to cyclopentane and cyclohexane derivatives under oxidative conditions.