Regioselectivity miinchnone cycloaddition reactions

Diethylamino-4-(4-methoxyphenyl)-isothiazole 5,5-dioxide 6 is (95T(51)2455) a highly reactive partner in 1,3-dipolar cycloadditions with several dipoles. Azomethine yhdes, such as oxazolones 7 and miinchnones 8, afforded with 6 bicychc pyrrolo[3,4-d]isothiazole 5,5-dioxides 9, 10, 11 in satisfactory yield. The regioselectivity of the reaction was excellent. The thermal behavior of these new bicychc systems was investigated. When heated at their melting point or shghtly above, triarylpyrroles 12, 13 were obtained through SOj and AtiV-diethylcyanamide ehmination. 

The statement made in 1986 by Gingrich and Baum (10), with regard to miinchnones, that the most important reactions (of mtinchnones) from a synthetic point of view are 1,3-dipolar cycloaddition reactions, certainly applies to all mesoionic heterocycles and is more true today than it was in 1986. Although the factors governing the regioselectivity of unsymmetrical mesoionic cycloadditions are not always completely understood, the synthetic utility of this chemistry is enormous and indisputable. 

Similarly, Toupet et al. (76) determined the structures of the pyrrole adducts from the cycloaddition of several miinchnones with methyl phenylpropionate by X-ray crystallography. These highly regioselective cycloadditions are in accord with FMO predictions. This same French team (77) studied the cycloaddition reactions of miinchnones with methyl propiolate and methyl 3-phenylpropiolate to... 

Coppola et al. (81) extensively studied the dipolar cycloaddition of methyl propiolate with unsymmetrical miinchnones. In addition to their own results (Table 10.3), these investigators summarized much previous data on these cycloadditions. In the authors words No single criterion can successfully be used to correlate the experimental observations regarding the regioselectivity in milnch-none cycloaddition reactions. Steric and electronic effects must be considered in... 

Nan ya et al. (97) also reported the synthesis of isoindolediones by the reaction of miinchnones with 1,4-benzoquinones. Reactions with an unsymmetrical mtinchnone were not regioselective. Several groups have examined the reactions of miinchnones with unsaturated nitriles, including 2-chloroacrylonitrile (98), cinna-monitrile (78,99) and fumaronitrile (78) to give unexpected products in several cases. Eguchi and co-workers (100) smdied the cycloaddition of several mtinch-nones with electron-deficient trifluoromethylated olehns. Thus, miinchnones 176... 

An interesting feature of isomiinchnones is their ability to undergo 1,3-dipo-lar cycloaddition with carbonyl compounds, a reaction which is unprecedented with miinchnones [56]. This is illustrated by the reaction of diazoimide 106 with Cu(acac)2 in the presence of several different aldehydes and ketones which resulted in the formation of cycloadducts of type 107 -109. When benzil was used as the dipolarophile, the regioselectivity was reversed giving rise to cycloadduct 110 as the only regioisomer. 

---