Dipolarophiles mesoionic ring systems

Use of mesoionic ring systems for the synthesis of five-membered heterocycles with two or more heteroatoms is relatively restricted because of the few readily accessible systems containing two heteroatoms in the 1,3-dipole. They are particularly suited for the unambiguous synthesis of pyrazoles as the azomethine imine is contained as a masked 1,3-dipole in the sydnone system. An attractive feature of their use is that the precursor to the mesoionic system may be used in the presence of the cyclodehydration agent and the dipolarophile, avoiding the necessity for isolating the mesoionic system. 

The cyclodehydration of 2-substituted-A/-acylthiazolidine-4-carboxylic acids yields bicyclic munchnones. This mesoionic ring system acts as a cyclic azomethine ylid and can undergo 1,3-dipolar cycloaddition reactions with dipolarophiles. A range of chiral pyrrolo[l,2-c]thiazoles have been prepared by this method both intermolecularly and intramolecularly. 

Carbonyl compounds and other dipolarophiles containing heteroatoms react with miinch-nones. Thus benzaldehyde forms the betaine (245) which suffers ring-cleavage to yield the enamine (246 equation 65). Thiocarbonyl compounds and nitrosobenzene behave in an analogous manner. The action of dipolarophiles containing cumulative double bonds results in the formation of new mesoionic systems. Thus carbon disulfide and phenyl isothiocyanate afford a zwitterionic thiazole and imidazole, respectively (Scheme 25). 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

Ring-fused mesoionic anhydro triazolium hydroxide systems 131 (84M11) that incorporate the thiocarbonyl ylide dipole undergo cycloaddition with both olefinic and acetylenic dipolarophiles the unstable 1 1 cycloadducts 132 and 133 yield ring-fused a-pyridinones 134 by elimination of hydrogen sulfide or sulfur, respectively (Scheme 42) (79JOC3803). 

Cycloaddition Reactions.— Acetylenes undergo many types of cycloaddition reaction and provide valuable starting materials for the synthesis of carbo-and hetero-cyclic systems. Many acetylenes are dipolarophiles, and dimethyl acetylenedicarboxylate (DMAD), because of its ready availability, often plays this role in the formation of a variety of heterocycles. Mesoionic systems often function as the 1,3-dipoles, as in the formation of pyrrole (99) from the A -oxazolium-5-olates (munchnones) (100) and DMAD. The procedure can be extended to fuse pyrrole rings on to the piperidine rings of (101) and (102) in moderate yields. Further examples of... 

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