Cycloaddition regiospecific

Chlorotrifluoroethene (15) undergoes cycloadditions regiospecifically giving head-to-head cy-clobutancs. The yields of cycloaddition products depend on the nature of the alkene substituents and the stabilization of the 1,4-diradical intermediate.23-24... 

A-Substituted pyrroles, furans and dialkylthiophenes undergo photosensitized [2 + 2] cycloaddition reactions with carbonyl compounds to give oxetanes. This is illustrated by the addition of furan and benzophenone to give the oxetane (138). The photochemical reaction of pyrroles with aliphatic aldehydes and ketones results in the regiospecific formation of 3-(l-hydroxyalkyl)pyrroles (e.g. 139). The intermediate oxetane undergoes rearrangement under the reaction conditions (79JOC2949). 

A similar regiospecific [2 -I- 2] cycloaddition across a C=S group occurred when benzoyl isothiocyanate (436) and 2,3-diphenyl-1-azirine were heated in refiuxing benzene for 12 hours. The product obtained was shown to be (438) and an intermediate such as (437) could also be involved in this cycloaddition (74JOC3763). In contrast, thiobenzoyl isocyanate added in a [4-1-2] fashion, and after ring expansion gave a thiadiazepine derivative. 

Reactions of fluorinated dipolarophiles. Electron-deficient unsaturated species generally make better dipolarophiles, therefore, fluonnated alkenes become better dipolarophiles when vinylic fluonnes are replaced by perfluoroalkyl groups For example, perfluoro-2-butene is unreactive with diazomethane, but more highly substituted perfluoroalkenes, such as perfluoro-2-methyl-2-pentene, undergo cycloadditions in high yields [5] (equation 2) Note the regiospecificity that IS observed in this reaction... 

Fluorinated a., -unsaturated carbonyl compounds also are reactive dipo-larophiles Because ol the highly activating carbonyl substituent, these 1,3-dipolar cycloadditions are rapid and regiospecific Good examples are the additions of... 

Recently, Burger devised an improved method of carrying out mild, regiospecific cyclizations that involve an intermediate that acts as a synthon for a nitrile ylide of HCN [47 (equation 48). With this methodology, cycloadditions with activated alkenes, alkynes, and azo compounds were earned out [47] (equation 49). All such reported reactions were regiospecific and had the same orientational preference... 

Azidofurazans and -furoxans undergo dipolar cycloaddition reactions with unsaturated compounds, in some cases regiospecifically. Thus, reaction of 3-amino-4-azidofurazan with l-morpholinyl-2-nitroethene (toluene, reflux, 70 hours) gives 4-nitro-l,2,3-triazole 204 in 87% yield (99MI1, 000KGS406). Cycloaddition of the same azide to alkynes was accomplished by formation of a mixture of position isomers 205 and 206. Regiospecific addition was observed only in singular cases... 

Similarly, the regiospecific 1,3-dipolar cycloaddition reaction of 1-methyl-1,2-dihydropyridines 41 with cyanogen azide (50a) and selected organic azides 50c and 50g afforded 2-methyl-2,7-diazabicyclo[4.1.0]hept-4-enes 57, which can be elaborated to 1-methyl-l,2,5,6-tetrahydropyridylidene-2-cyanamide (58) and 1-methyl-2-piperidylidenes 59a-d (85CJC2362). 

Hoomaert has studied Diels-Alder reactions of pyridine oquinodimethane analogs generated from functionalized o-bis(chloromethyl)pyridines <96T(52)11889>. The photochemical cycloaddition of 2-alkoxy-3-cyano-4,6-dimethylpyridine with methacrylonitrile gives a bicyclic azetine, 6-alkoxy-3,5-dicyano-2,5,8-trimethyl-7-azabicyclo[4.2.0]octa-2,7-diene, in moderate yield <96CC1349>. Regiospecific hydroxylation of 3-(methylaminomethyl)pyridine to 5-(methylaminomethyl)-2-(17/)-pyridone by Arthrobacter ureafaciens has been reported <96MI173>. 

In general, nitrilimines are generated in the presence of a suitable dipo-larophile. Thus, heating an equimolar mixture of hydrazone 313, alkene 314, and chloramine-T trihydrate in ethanol under reflux for 3 h provided pyrazolines 315 in 68-90% yield [81]. The cycloaddition in all the cases was regiospecific as indicated by NMR (Table 23). 

Scheme 6 Regiospecific [3+2] cycloaddition of phosphinodiazomethane with phosphaethyne...

Cycloaddition of unsymmetrical 1,3-dienes, such as isoprene 41b, proceeded regiospecifically to give only a single regioisomer 44 (see Equation (13) and Table 7). 

The above complete regiospecificity of the cycloaddition across only the C=S+ bond was rationalized in terms of frontier molecular orbital coefficients in the salt 95. This cycloaddition was considered to be a LUMOsajt -HOMOdiene reaction. MOP AC 93 PM3 calculation of 95 showed the values of LLJMO coefficients for C(6), S, and N are 0.508, —0.502 and 0.364, respectively, as in Figure 1. These values strongly suggest the preference of the reaction site of the C=S+ bond. 

As for the regioselectivity of the nitrone cycloaddition to MCP and its alkyl or aryl derivatives, a tendency of the three-membered ring to end up at the 4-position of the final isoxazolidine ring clearly emerges from the experimental findings. This result is particularly noteworthy if compared to regiospecific formation of the 5,5-disubstituted isoxazolidines in the reactions of nitrones, not... 

Torn0e, C.W., Christensen, C., and Meldal, M. (2002) Peptidotriazoles on solid phase [l,2,3]-triazoles by regiospecific copper) I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 67, 3057-3064. 

If one examines the minimal sequences of reaction steps for [2+2] cycloadditions, Eqs. 12—18, 32—35, one concludes that stereochemistry of addition, and perhaps relative reactivities might be calculable at several points. Oriented complexes could control regiospecificity, or the transition state leading to a biradical could be the important stage. Relative rates of product formation would be derived from relative perturbation stabilization energies for different configurations of the two reactants. 

By regiospecific [4+2] cycloadditions of functional alkenyltin derivatives with dienes such as 1,3-butadiene, 2,3-dimethyl-l,3-butadiene or 1-substituted 1,3-butadienes, polyfunctional cyclic vinyltin compounds 80 are obtained. 

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