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 appropr iate maleic anhydrides with either ammonium acetate or methylammonium acetate in boiling acetic acid. The maleimides underwent Wittig-type r eactions with stabilised phosphoranes, under moderately forcing condit ions, to give 5-ylidenepyrrol-2(5H)-ones 6. The ease of the reaction a nd the regiochemistry of the addition to unsymmetrical maleimides depe nded upon the nature of the 3-substituent and on the presence or absen ce of an N-alkyl substituent. Thus, 3-methoxymaleimides reacted exclus ively 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 preferen ce for reaction at C-2 in 5c was overturned by the presence of an N-me thyl substituent as in 5d. The related reactions of unstabilised phosp horanes or phosphine oxides usually only afforded intractable gums, an d with Julia-type reagents only starting materials were recovered. How ever, the lithium enolate of methyl trimethylsilylacetate (or other Pe terson-type reagents) underwent successful addition to N-methylmaleimi des at -78-degrees-C; the 5-ylidenepyrrolone product distributions wer e similar to those obtained with the stabilised phosphoranes. Variatio n of the 5-alkylidene side-chain was achieved through the reactions of N-methylmaleimides with alkyl Grignard reagents by dehydrating the fi rst-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 w ith 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.