A novel synthesis of the carbapen-2-em ring system

Synthesis of Heterocyclic Compounds by Carbenoid Transfer Reactions

“…This and many subsequent applications showed that this N-H carbenoid insertion reaction (5 6) is the most efficient method devised for synthesizing -lactam bicyclic systems (Scheme 5). The synthetic community immediately realized the potential utility of this methodology, e.g., in 1980, Merck researchers incorporated a rhodium(II) acetate catalyzed N-H insertion reaction into the synthesis of the -lactam antibiotic thienamycin [20,21].…”

Recent advances in carbapenem chemistry (review)

“…The most significant synthesis of this class was pioneered at Merck. They used the quite elegant carbenoid-mediated cyclization of a diazo azetidinone 11 (X = H) to form the targeted carbapenem bicyclic nucleus 12 (C(3)--N(4) bond formation) in an excellent yield [13]. Other methods were typical: the intramolecular Wittig-type cyclization of the precursor 13 to directly produce the carbapenem 14 (C(2)--C(3) bond formation) [14] and the Dieckmann-type cyclization of the thiol ester 15 to give the keto ester 12 (C(2)--C(3) bond formation) [15].…”

Selectivity in Rhodium(II)Catalyzed Reactions of Diazo Compounds: Effects of Catalyst Electrophilicity,Diazo Substitution, and Substrate Substitution. From Chemoselectivityto Enantioselectivity

“…For example, in 1980, Merck researchers incorporated a rhodium(II) acetate catalyzed N-H insertion reaction into the synthesis of the b-lactam antibiotic thienamycin (8) (Scheme 2). 8 Nearly complete conversion to bicyclic b-lactam 10 was achieved under Rh 2 (OAc) 4 catalysis, while only a 1:9 ratio of 10 to undesired imide byproduct 11 was obtained with photolysis. The applicability of this methodology continues to be elegantly demonstrated today in numerous syntheses of complex natural product targets ( Figure 1).…”