Phenylselenoethers as precursors of acyclic free radicals. Creating tertiary and quaternary centers using free radical-based intermediates

In the last two decades, enantioselective and diastereoselective free radical-based processes have started to emerge as viable methods to create stereogenic centers. To this end, chemists have taken advantage of the homolytic carbon-selenium bond cleavage as an efficient way to generate carbon-centered radicals. The reactivity of the radicals generated from beta-hydroxy (or alkoxy) alpha-phenylseleno (or alpha-halo) esters in hydrogen transfer or allylation reactions will be reviewed. The minimization of the allylic-1,3 strain and the intramolecular dipole-dipole effect in the transition states are at the origin of the diastereoselectivities noted in these reactions (acyclic stereocontrol). The predominance of the anti isomer, in the hydrogen transfer reactions, has been shown to be enhanced by taking advantage of the exocyclic effect. Lewis acids were successfully used to create temporary cycles cc to the carbon-centered radical in order to induce the latter effect. Reversing the sense of the diastereoselectivity could be efficiently achieved using bidendate Lewis acids through the endocyclic effect. The synthesis of stereogenic quaternary centers using free radical-based allylation is described. The development of tandem reactions combining the Mukaiyama and the hydrogen transfer reactions, with various Lewis acids, led to the synthesis of propionates and polypropionate motifs. The use of novel phenylselenoenoxysilanes in the Mukaiyama reaction is described.