1.3- Dipolar additions regiospecificity

An alternative approach to celecoxib using a 1,3-dipolar addition between a trifluoromethyl-containing nitrile imine and an eneamine derived from /i-methyla-cetophenone avoids the issue of regiochemistry. The nitrile imine was readily prepared by reaction of trifluoroacetylated sulfonamidophenyUiydrazine with benzoyl chloride to give the benzenesulfonate 134. Treatment with triethylamine causes elimination of sulfonate to generate the 1,3-dipole for the cycloaddition reaction. The reaction was regiospecific for the formation of celecoxib (Fig. 3.79). " ... 

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... 

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... 

Cycloaddition of p-methoxyphenyl azide to alkynic dipolarophiles at room temperature gives triazoles (697) and (698) (Equation (54)). A regiospecific addition is only observed in the case of Z = CH(OMe)2 <89H(29)967>. Phenyl azide and substituted benzyl azides undergo 1,3-dipolar cycloadditions with DM AD, phenylacetylene, and ethyl propiolate to afford 1-phenyl- and 1-benzyl-... 

Azide addition to enolizable ketones is regiospecific and may be considered as a 1,3-dipolar cycloaddition occurring at the double bond of the enolate, similar to the addition of azides to electron-rich olefins. However, a stepwise reaction appears more probable because glycosyl azides exhibit anomerism when they react with activated methylene compounds, thus indicating the presence of a triazene intermediate.264 On the other hand, the formation of the triazene intermediate may be considered as a limited case of 1,3-dipolar cycloaddition where one of the bonds is formed completely before the other one starts,2 such a limited case being observed for the Diels-Alder reaction.265... 

The number of synthetic routes to the natural 1-hydroxymethyl-pyrrolizidines continues to increase. Robins and Sakdarat have achieved the first synthesis of these necines in optically active form, using natural (-)-4-hydroxy-L-proline as a chiral template.2 The dihydropyrrolizine ester (2) was prepared by regiospecific 1,3-dipolar cycloaddition of ethyl propiolate to the N,0-diformyl derivative (1) of (-)-4-hydroxy-L-proline, followed by deformylation (Scheme 1). Addition... 

A -l,2,3-Triazolines, e.g. (181a), are usually formed by 1,3-dipolar cycloaddition of azides to alkenes (cf. 63AG604, 742, 63AG(E)565, 633,68AG329,68AG(E)32i). The addition always occurs cis and is usually regiospecific. Norbornene condenses with azides to form only the exo... 

Anions from the Schiffs base (78) can be C- or A -alkylated with ethyl iodide or diethyl sulphate. The ratio of the products depends both on the solvent and on the presence of 18-crown-6. In non-polar solvents, the crown ether increases the solubility of the base, and C-alkylation is the major pathway. In dipolar aprotic solvents, the 18-crown-6 breaks up ion pairs by solvation of the Na" cation, and favours A -alkylation. A nerylsulphonamide, formed from (79), undergoes regiospecific reductive desulphonylation to give nerol (80), which implies that (79) is an effective synthon for cisoid iso-prenoids. Chiral complexes of crown ethers, e.g. (81), catalyse the Michael addition reaction of j3-keto-esters and methyl vinyl ketone to give adducts in high optical yields. ... 

---