Preparation of beta-Lactams from beta-Hydroxy Amides, and Annulation of N-Malonyl beta-Lactams by Manganese(III) Acetate-promoted Free Radical Cyclization and by Aldol Cyclization
1995; Elsevier BV; Volume: 40; Issue: 2 Linguagem: Inglês
10.3987/com-94-s57
ISSN1881-0942
AutoresMarvin J. Miller, Peter J. Crocker, Ulrika Karlsson-Andreasson, Bruce T. Lotz,
Tópico(s)Oxidative Organic Chemistry Reactions
ResumoPLactams are formed from bhydroxy amides by base-promoted cyclization of the P-methylsulfonoxyamide.In the system studied, this amidebased mesylate cyclization proceeded in high yields, whereas the analogous P-chloroamide afforded only the a,e-unsaturated amide.Also, two new methods of synthesizing carbacephams by annulation of malonate-substituted P-lactams were demonstrated.The fmt was a manganese(IU) acetate-promoted oxidative free radical cyclization.The second was a spontaneous aldol cyclization of an intermediate aldehyde generated by ozonolysis of an akene.HETEROCYCLES.YO!. 40, No. 2,1995 Penicillium wUm.laThe cephalosporins have been widely used to treat infections by bacteria that are resistant to the penicillins.2Likewise, the carbacephems have proven to be more efkctive per dose than the cephems as they are not degraded as readily.3Our eventual target is the carbacephalosporin Lorabid@ (3, Eli Lilly & Co., Inc., LY163892/KT3777), a new commercially available, orally active antibiotic that is prepared by total synthesis.4(~orabidB) 4 X=C&, Y=Cl, R ' .R ~= P M ~, R~=PNB 0 model 5 X=CHz.Y=OH, R3Q& CO& R1.R2=Phth.R~=PNB 8 9a R = C H ~C H = C ( C H ~~ Our retrosynthetic analysis of Lorabid@ targets the six membered ring initially, as we are already familiar with methods to form the four membered ring5 Recently Snider has published a series of papers regarding ring formation by oxidative free radical cyclization of 1,3-dicarbonyl-walkenes upon treatment with manganeseflIJJ acetate to afford, among other things, exocyclic olefinsfi Or alternatively, Snider also has shown that he can generate such exocyclic olefins by a Mn(OAc)3-promoted free radical cyclization of 1,3-dicarbonyl-o-alkynes in an ~xidativelv n u process by a net hydrogen uansfer cyclization.6b.cWe decided to apply this chemistry to our synthesis of carbacephalospo~s as a potentially useful alternative ta known methods of annulation of p-lactams.7There is precedent for-free radical annulations of P-lactams?thus demonstrating the feasibility of free radical annulations of p-lactams to form the 4,6-fused bicyclic ring system.However, such procedures are not as synthetically amactive as the Mn(OAc)3-promoted procedure as they typically require more complex (k, more functionalized) substrates, afford products in a
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