Heterocycles from lactams

A soln. of N-l-propenyl-N-l-propylbenzamide in methanol irradiated 1 hr. with a 550 w. Hanovia Hg-lamp enclosed in a quartz well 15 85 mixture of cis-and frans- -propylamino-a-methylacrylophenone. Y 85%. F. e. s. N. G. Yang and G. R. Lenz, Tetrah. Let. 1967, 4897 keto-N-heterocyclics from lactams s. M. Fischer, Tetrah. Let. 1968, 4295. 

A study of ketene A, O-acetals has shown that such compounds derived from lactam acetals may be used in the preparation of larger heterocyclic systems via reaction with a 1,3-dipolar species, the initial cycloadducts stabilizing their structures by aromatization. Pyrrolo[2,3-i/]-l,2,3-triazole derivatives, however, do not undergo such elimination reactions and stable cycloadducts may be obtained. Thus, the lactam acetals (133) give the ketene A,0-acetals (134), which on reaction with p-nitrophenyl azide yield substituted pyrrolo[2,3-d]-l,2,3-triazole derivatives (135) <86CB359l>. 

Enaminones were obtained from lactam acetals by reaction with active methylene compounds610. Heterocyclic / -enaminoesters are synthons in the preparation of condensed systems611. Acylated alkyl aminoisobutyrylmalonates (145) can be converted to 3-oxo-2-pyrrolines (146)612,613. 

Finally, there are a mixed bag of oxidases, catalysing ethylene formation in plants and many other diverse reactions, illustrated in Figure 13.20, by isopenicillin N-synthase, IPNS, which catalyses the cyclisation of the heterocyclic P-lactam ring. The importance of penicillin- and cephalosporin-related antibiotics in clinical medicine cannot be underestimated and has stimulated the study of their biosynthetic pathways. A key step in the biosynthesis of these antibiotics involves oxidative ring closure reactions of S-(L-a-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to form isopenicillin N, the precursor of penicillins and cephalosporins, catalysed by IPNS (Figure 13.20). The overall reaction utilizes the full oxidative potential of O2, reducing it to two molecules of H2O. As discussed earlier, these enzymes are technically oxidases and the four electrons required for dioxygen reduction come from the substrate. 

Intramolecular heterocyclization in polyacrylonitrile 86UK62. a-Isocyano acetates, synthesis of N-heterocycles from 85YGK764. Isonitrosotosyl malonates in synthesis of N-heterocycles 80H(14)1581. Lactams, regioselective formation from bridged bicyclic ketones 81T1283. Malononitrile derivatives, synthesis of N-heterocycles condensed from ... 

In addition to several general reviews on enamine chemistry, all of which include heterocyclic syntheses, there is an extensive survey by Hickmott which is entirely concerned with the formation of heterocycles. More specialized reviews deal with heterocyclic enamines, enaminones, the photochemistry of enamides , heterocyclic jS-enamino esters , enamino thiones , the synthesis of indole alkaloids via enamines , formation of pyrimidines, pyridopyrimidines, pyridines and pyrrolizines from enamines , synthesis of lactams , formation of heterocycles from cyclic enamino ketones and 2-acetylcyclohexen-l-ones, the synthesis of 3-cyano-2(l -pyrimidine-thiones and -selenones from jS-enamino ketones and the chemistry of cyclic en-aminonitriles. ... 

TRIFLUOROMETHYLATED HETEROCYCLES FROM p-TRIFLUORO-ACETYLATED LACTAMS AND BENZOLACTAMS... 

This cyclization also affords a route to nitrogen heterocycles from acyclic dienyl-amines and -amides. Pyrrolincs can be obtained from diallylamines. This reaction can also form tetrahydropyridines and -azepines, as well as lactams.3... 

Figure 3 Solid-ph e synthesis of heterocycles from amino acids and peptides through imine formation. Synthesis of (a) isoquinolines 2, (b) thiazolidinones 3 and methathiazanones 4, (c) j8-carbolines 5, (d) -lactams 6, (e) pyrrolidines 7, (f) thia-zolidines 8, and (g) quinolinones 9.

DeTtsova, D.P. Gambaryan, N.P. Mysov, E.I. Knunyants, I.L. Synthesis of four-memhered heterocycles from a perfluoro-a-lactam. Dokl. Akad. Nauk SSSR 1980, 253, 886. 

A practical and general strategy towards such heterocycles from penam precursors was recently disclosed [129, 130] (Scheme 73). Hydroxamic acids 249, formed by cleavage of the P-lactam ring of the penicillinates 248 with hydroxylamine, underwent a smooth Lossen rearrangement in the presence of A/, iV-diethylaminopropyne. The isocyanate intermediates 250 immediately cyclised to give the desired compounds 251 without racemization. 

Methanol added dropwise during 2 h to a refluxing mixture of startg. thiolactam and 12 molar eqs. NaBH4 in tcrt-butanol - product. Y 90%. Ester groups were reduced to prim, alcohols as expected. F.e.s. S.B. Mandal et al., Heterocycles 27, 11-12(1988) with NaBH4/rcrr-BuOH/MeOH, also from lactams, cf. J. Org. Chem. 53, 4236-41 (1988). 

Cyclic imines from lactams via reductive ring closure and reopening of N-heterocycles s. 19, 87 CO... 

Bouillon J-P, Ates C, Janousek Z, Viehe HG (1993) Trifluoromethylated heterocycles from P-trifluoroacetyl-lactams and -benzolactams. Tetrahedron Lett 34 5075-5078... 

Amfidinolides (unique macrolides from marine dinoflagellates) 97H(44)543. Antitumor N-, N,S-, and S-heterocycles and macrocyclic lactams from ascidi-ans 97M122. 

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