Aromatization lactam rearrangement

Mercuric acetate Lactam rearrangement with aromatization... 

The hydroxamic acid function in most alicyclic and aromatic compounds is stable to hot dilute acid or alkali, and derivatives cannot undergo normal base-catalyzed Lessen rearrangement. Di Maio and Tardella," however, have shown that some alicyclic hydroxamic acids when treated with polyphosphoric acid (PPA) at 176°-195° undergo loss of CO, CO.2, or H2O, in a series of reactions which must involve earlj fission of the N—0 bond, presumably in a phosphoryl-ated intermediate. Thus, l-hydroxy-2- piperidone(108) gave carbon monoxide, 1-pyrroline (119), and the lactams (120 and 121). The saturated lactam is believed to be derived from disproportionation of the unsaturated lactam. 

JOC2083). The rearrangement does involve presumably the base-promoted ejection of the bridging nitrogen atom, followed by lactam formation and aromatization. Other fused ring heterocycles have also been generated by this chemistry (Scheme 43). 

Certain aromatic N-oxides undergo rearrangement by a process equivalent to that observed in nitrones to give the corresponding lactam. This is illustrated by the conversion of 2,5-dimethylpyrazine 1-oxide (179) into the lactam (180) by photolysis in aqueous solution.150... 

Boger s synthesis commenced with the preparation of the left-hand fi agment 155. A sequence of phenol protection of 151, aldehyde oxidation, Curtius rearrangement, tosylation, nitro reduction, Boc protection, and Pb(OAc)4 mediated oxidation afforded quinodiimide 152. A key Diels-Alder reaction gave 153 in good yield. Treatment of 153 in a sequence of oxonolysis, aromatization, Boc deprotection, cyclization to the lactam, A-tosyl removal, indole reduction, and selective Boc protection afforded 154. Conversion of the lactam to the... 

When pyrrolo[2,l-c][l,4]benzodiazepine-2,5,ll-trione (757) was heated with POCI3 and a catalytic amount of pyridine for 1.5 h, compound 758 was obtained. When the reaction was subjected to MWI for 50 min, compound 757 rearranged and subsequently aromatized to 2,5-dichlorocyclopenta[fe][l,4]benzodiazepine (759) as a major product and its lactam 760 in a ratio 85 15 in 47% yield (97TL2271). Treatment of 758 with POCls/pyridine under MWI also gave 759 and 760 (Scheme 147). 

In the scale up effort of 5,6-disubstituted benz[cc/]indolones 42, a precursor for inhibitors of thymidylate synthase, the Lessen rearrangement was utilized as the key step. A-hydroxylnaphthalimide 38 was converted to activated hydroxamate 40 through aromatic nucleophilic substitution reaction with 39. The Lessen precursor 40 then xmderwent conversion to amino acid intermediate 41, which was subsequently transformed to lactam 42 under acidic conditions. ... 

The Fukuyama synthesis commenced with the copper-catalyzed asymmetric reduction of butenolide 26 to give lactone 27 in 98% enantiomeric excess (Scheme 9). Sequential alkylation with CbzCl followed by methyl acrylate provided lactone 28 and installed both of the required contiguous stereocenters. The key Curtius rearrangement was performed by conversion of the benzyl ester to the acyl azide followed by heating. Subsequent treatment with aqueous HCI provided cyclized lactam 8. This compound was then dibromi-nated to lactam 29 using bromine, ZnCl2, and formic acid, which were the only conditions that were able to introduce the orf/to-bromine. The fully elaborated aromatic compound 29 was treated with methylamine followed by PDC to obtain cyclic A -methylimide 23. 

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