Bicyclopropylidene, reaction with nitrones

This reaction has recently been applied for the preparation of aza-analogs with the basic skeleton and functional groups of the extremely cytotoxic sesquiterpenes illudin (208) and ptaquiloside (209) [139]. Compounds 212-215 were successfully prepared by heating bicyclopropylidene (1) with the enantiomeri-cally pure nitrones 210,211 (Scheme 47) [138]. Some of these simple aza-analogs have indeed been found to exhibit DNA-cleaving abilities [138b,c]. 

Nitrone 81 underwent a dipolar cycloaddition reaction with bicyclopropylidene 82 at 60 °C over a 30-day period to give isoxazolidine 83 in 93% yield (Scheme 14) (96JOC1665). Further heating of 83 in toluene at reflux for 5 days produced pyridone 84 in 63% yield. When a toluene solution of 81 and 82 was heated at reflux for several days, pyridone 84 was isolated in 61% yield. Nitrone 85 produced indolizi-dine 86 when heated with 82 in benzene at reflux temperatures for 7 days. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

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