Diastereo- and Enantioselective Synthesis of α-(β-Aminoalkyl)-Substituted γ-Lactams by Michael Addition to Nitroalkenes

α-(β-Aminoalkyl)-substituted γ-lactams 5a-e were synthesized in three steps in good overall yields (37-61%) and diastereo- and enantiomeric excesses (de ≥ 96%, ee = 82-≥ 96%). In the key step metalated N-dialkylamino lactam (S)-1 underwent 1,4-addition to nitroalkenes 2 to afford the Michael adducts 3, which were converted to the protected amines 4. After subsequent reductive cleavage of the N-N-bond with lithium in liquid ammonia the title compounds 5 were obtained. The relative and absolute configuration of the major diastereomer was determined by X-ray structure analysis on (R,R,S′)-3b.

asymmetric synthesis - lactams - Michael addition - nitroalkenes - reduction