Oxime oxalate amides

Scanlan, E.M., Slawin, A.M.Z., and Walton, J.C. (2004) Preparation of [5- and y-lactams from cabamoyl radicals derived form oxime oxalate amides. Organic e[ Biomolecular Chemistry, 2, 716-724. 

An efficient use of triphosgene, as an acid activator, for the synthesis of substituted 2-azetidinones via ketene-imine cycloaddition reaction using various acids and imines has been achieved <02T2215>. Novel routes to monocyclic (3-lactams 13 and 14 through the photochemical decomposition of oxime oxalate amides <02CC2086> and a-oxoamides <02OL1443> have also been described. 

Scheme 17 Oxime oxalate amides as fS-lactam precursors...

Attempts were also made to access penicillin derivatives by this route. Several thiazolidine-containing oxime oxalate amides were prepared and photol-ysed under the same conditions, but without success [84]. It is known that and other conventional cyclisations onto oxime ether acceptors (> C = NOR) are faster than onto alkene acceptors [85]. In the hope that cyclisation onto an oxime ether acceptor would also be more efficient, oxime oxalate amide 80 containing both a thiazolidine ring and oxime ether acceptor was prepared. The photosensitised reaction of 80 did yield the desired carbamoyl radical 81, as shown by EPR spectroscopy. However, the presence of the thiazolidine ring evidently inhibited 4-exo cyclisation because no significant amount of cyclisation to radical 82 took place and none of the penicillin derivative was isolated. 

Scanlan and Walton have described the synthesis of a series of oxime oxalate amides (147). These undergo methoxyacetophenone-sensitized irradiation to afford the radicals (148) formed by CC bond fission and loss of CO2. The radicals can undergo cyclization to afford lactams. Thus, for example, the derivative (147e) cyclizes to yield the radical (149) that is oxidatively converted to the final product (150) obtained in 70% yield. 

A variety of ketones 249 can be directly converted into the secondary amides 253 (the expected product of a Beckmann rearrangement of the corresponding oximes 250) in high yield, by heating them with hydroxylamine hydrochloride and anhydrous oxalic acid (equation 75). Aromatic aldehydes afforded mixtures of nitriles and amides. The... 

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