A novel stereoselective tin-free radical protocol for the enantioselective synthesis of pyrrolidinones and its application to the synthesis of biologically active GABA-derivatives

Optically pure 4-alkyl-pyrrolin-2-ones were synthesized from chiral N-allyl-α-bromoacetamides in high selective and stereo-controlled fashion, via a sequential 5-exo-trig radical cyclization-hydrogen or bromine atom-transfer process, under non-tin conditions. Interestingly, when N-allyl-α-bromoacetamides were treated with triethylborane/MeOH(excess)/BF3·OEt2 in toluene at −78 °C, a tandem 5-exo-trig radical cyclization-hydrogen atom-transfer reaction operated, on the other hand, a tandem 5-exo-trig radical cyclization-bromine atom-transfer reaction proceeded in good yield and high stereoselectivity when the reaction was carried out with equimolar amounts of MeOH in THF at −78 °C. Thus, optically pure 4-alkyl-pyrrolin-2-ones were synthesized via this tin-free radical pathway and transformed to their corresponding biologically active GABA-derivatives, Pregabalin and CAMP.