406497-17-4

Upstream product

• 406497-11-8 (3R,2'S)-2'-(1-Ethyl-1-methoxy-propyl)-3-((R)-2-nitro-1-phenyl-ethyl)-[1,1']bipyrrolidinyl-2-one 
• 181293-31-2 (S)-2'-(1-Ethyl-1-methoxy-propyl)-[1,1']bipyrrolidinyl-2-one 
• 5153-67-3 nitrostyrene 

Downstream Products

• 406497-22-1 [(R)-2-((R)-2-Oxo-pyrrolidin-3-yl)-2-phenyl-ethyl]-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Asymmetric electrophilic substitutions at the α-position of γ- and δ-lactams

Enantioselective electrophilic substitutions with Michael acceptors and alkylating agents at the α-positions of γ- and δ-lactams are presented. The asymmetric Michael addition of lactam 1a to nitroalkenes 2 was used as the key step for the synthesis, over three steps, of α-(β-aminoalkyl)-γ-lactams 5 in good overall yields (37-61percent) and with very good diastereomeric and enantiomeric excesses (de ≥ 96percent, ee = 82 to ≥ 96percent). Conjugate addition to alkenylsulfones 6a and 6b afforded Michael adducts 7a and 7b in good yields, but with only moderate diastereoselectivities (de = 38-41percent). α-Substituted N-dialkylamino lactams 9a-c were obtained by asymmetric alkylation of N-(dialkylamino)lactam 1a with functionalised electrophiles 8a-c in good yields (66-84percent) and with moderate to excellent diastereomeric excesses (66 to ≥ 96percent). The auxiliary was removed by reductive N-N bond cleavage to afford the lactam 10 (ee = 83percent). A second alkylation of α-alkylated d N-(dialkylamino)lactams 11 yielded α-disubstituted γ-butyrolactams (12a, 12b) in good yields and diastereomeric excesses (de = 83-88percent) and α-disubstituted δ-valerolactams (12c-e) in good yields but with low to moderate diastereoselectivities (de = 6-52percent). The α-silylated γ-lactam 15 was obtained in good yield (53percent over two steps) and with an enantiomeric excess of 83percent by α-silylation of N-(dialkylamino)lactam 1a and subsequent reductive removal of the auxiliary.

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.