Electrocyclic Processes in Heterocyclic Ring Synthesis

There is a type of electrocyclic process that is of considerable value for heterocyclic ring synthesis 1,3-dipolar cycloadditions producing five-membered heterocycles. 

3-Dipoles always contain a heteroatom as the central atom of the trio, either sp or sp hybridised. Amongst other examples, cycloadditions have been demonstrated with azides (N=N -N-R), nitrile oxides (R-C N -0 ) and nitrile ylides (R-C N -C Ra), where the central atom is sp-hybridised lutrogen, and with nitrones (R2C=N (R)-0 ), carbonyl ylides (R2C=0 -C R2) and azomethine ylides (R2C=N (R)-C R2), where the central atom is sp hybridised. 

General combinations to produce five-membered heterocycles via 1 -dipolar cycloadditions 

Dipolar cycloadditions can, of course, only produce five-membered rings. Addition of dipolarophiles can generate tetrahydro, dihydro or aromatic oxidation level heterocycles, as illustrated above. Alkene dipolarophiles, with a group that can be eliminated following cycloaddition, give the same result as equivalent alkyne dipolarophiles, for example enamines as the dipolarophile, interact with azides, as the 1,3-dipole, with subsequent elimination of the amine, affording 1,2,3-triazoles.  

Many mesoionic substances (2.6) can act as 1,3-dipoles, and, after elimination of a small molecule -carbon dioxide in the example shown - produce aromatic heterocycles.  

There are two types of electrocyclic process which are of considerable value for heterocyclic ring synthesis one of these is 1,3-dipolar cycloaddition, and the second involves a Diels-Alder type addition using some type of azadiene the latter does not in general produce aromatic heterocycles and, important though it is, will not be dealt with here. 

3-Dipoles always contain a heteroatom as the central atom of the trio, either sp or sp hybridised. Amongst other examples, cycloadditions have been demonstrated with azides (NsN -N -R), nitrile oxides (R-CsN -0 ) and nitrile ylides (R- 

The interaction of azides, as the 1,3-dipoles, with enamines, followed by elimination of the amine, affords 1,2,3-triazoles.  

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The last reaction in the previous section is, of course, an example of an electrocyclic process. Other computational studies of electrocyclic reactions in the synthesis of heterocycles are few, but in one recent report high-level calculations predicted that 4 r-electrocyclic ring closures are preferred over 27t for both oxygen and sulfur systems."... 

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