THE SYNTHESIS OF 5-YLIDENEPYRROL-2(5H)-ONES FROM MALEIMIDES AND FROM PYRROL-2-(5H)-ONES

A series of maleimides 5 have been prepared by reaction of the appropriate maleic anhydrides with either ammonium acetate or methylammonium acetate in boiling acetic acid. The maleimides underwent Wittig-type reactions with stabilised phosphoranes, under moderately forcing conditions, to give 5-ylidenepyrrol-2(5H)-ones 6. The ease of the reaction and the regiochemistry of the addition to unsymmetrical maleimides depended upon the nature of the 3-substituent and on the presence or absence of an N-alkyl substituent. Thus, 3-methoxymaleimides reacted exclusively at C-2; the presence of an N-methyl substituent required the use of more forcing reaction conditions, but did not alter the preference for C-2 attack. With 3-methylmaleimides, however, the slight preference for reaction at C-2 in 5c was overturned by the presence of an N-methyl substituent as in 5d. The related reactions of unstabilised phosphoranes or phosphine oxides usually only afforded intractable gums, and with Julia-type reagents only starting materials were recovered. However, the lithium enolate of methyl trimethylsilylacetate (or other Peterson-type reagents) underwent successful addition to N-methylmaleimides at -78-degrees-C; the 5-ylidenepyrrolone product distributions were similar to those obtained with the stabilised phosphoranes. Variation of the 5-alkylidene side-chain was achieved through the reactions of N-methylmaleimides with alkyl Grignard reagents by dehydrating the first-formed 5-alkyl-5-hydroxypyrrolone. 4-Methoxy-1-methylpyrrol-2(5H)-one could be deprotonated exclusively at the 5-position under kinetic control (i.e. BuLi, THF, -78-degrees-C), and the anion then quenched with a variety of electrophilic agents to give 5-substituted pyrrolones. These derivatives proved amenable to dehydration or dehydrogenation, as appropriate, to afford the corresponding 5-alkylidenepyrrolones.