Anionic [4 2] cycloaddition reactions of dihydropyrazolin-5-one dienolate with dienophiles: a novel approach for substituted and fused indazolones

The heterocyclic analogs of o-quinodimethane (OQDM, o-xylylene) are of considerable interest both from a theoretical point of view and for their potential in organic synthesis 1 as useful dienes. This has been elegantly demonstrated in the indole series 2 for the synthesis of several naturally occurring and biologically important indole 3 and carbazole 4 alkaloids. However, with the exception of indolo-2,3-quinodimethane, the synthetic potential of other heterocyclic analogs remain largely unexplored, although several studies involving their methods of generation and trapping have been published in recent years. Most widely used routes to these heterocyclic o-quinodimethanes involve flash vacuum pyrolysis, 1,4-elimination 1,6,7 of suitable precursors and thermal extrusion of sulfur dioxide from heteroaromatic fused 3-sulfolenes. Flash pyrolytic 1,4-elimination requires very harsh reaction conditions resulting in formation of polymeric products, thus precluding trapping of o-quinodimethane intermediates except in the most stable cases. However, several heterocyclic o-quinodimethanes have been generated by 1,4-elimination in solution and are efficiently trapped by various dienophiles to afford the corresponding adducts in good yields. Similarly, heterocyclicfused 3-sulfolenes have also been shown to be useful precursors for generation and trapping of heterocyclic o-quinodimethanes (HQDM). However, many of these precursors are not so easily accessible and do not lend themselves readily to structural elaboration, thus limiting the synthetic scope of these heterocyclic o-quinodimethanes, especially for regiocontrolled synthesis of substituted heteroaromatic compounds which have many proven applications. During the course of our continued interest in the synthesis of benzoheterocycles via heteroaromatic annelation, we became interested in the generation and reactions of anionic heteroaromatic o-quinodimethanes which are shown to exhibit pronounced enophilic reactivity and high regiocontrol in cycloadditions as a result of an increased HOMO energy level (or net atomic charge) and charge controlled orientation of two reactive partners in the transition state. It is pertinent to note that neutral HQDM usually affords a mixture of regioisomers on cycloaddition with unsymmetrical dienophiles which limits their synthetic scope for regiocontrolled construction of substituted benzoheterocycles. We have recently reported that enolates derived from 1,2-dimethylindole-3-carbaldehyde are useful anionic α-oxyindolo-2,3-quinodimethane equivalents which undergo facile cycloaddition with a variety of dienophiles, affording a wide range of substituted carbazoles under mild conditions with efficient control of regioselectivity. We have now demonstrated that dihydropyrazolinone dienolate 2 derived from 2,3-dimethyl-4-formyl-1-phenylpyrazolin-5-one is an efficient anionic pyrazolone o-quinodimethane equivalent which undergoes facile regioselective cycloaddition with electron deficient dienophiles to afford substituted indazolones in good yields. We report the results of these studies in this paper.