Free radical-mediated intermolecular conjugate additions. Effect of the Lewis acid, chiral auxiliary, and additives on diastereoselectivity

We have developed a highly diastereoselective method for the conjugate addi tion of carbon radicals to chiral alpha,beta-unsaturated N-enoyloxazolidino nes using Bu3SnH as chain carrier and Et3B/O-2 as radical initiator. Lewis acids have been screened, and Yb(OTf)(3) proved to give optimized results f or both chemical yield (88% for 1a and 94% for 1b) and diastereoselectivity (25:1 for 1a and 46:1 for 1b). The selectivity is solvent-dependent, CH2Cl 2-THF being an ideal combination. Scrupulously dry solvents or reaction con ditions were not required. Substoichiometric amounts of Yb(OTf)(3) provided efficient reaction with minimal sacrifice in diastereoselectivity. Carbon radicals with reasonable nucleophilicity were generally successful, includi ng functionalized radicals such as acetyl or methoxymethyl. Electrophilic r adicals were not successful. A model which accounts for most of our observa tions is presented.