Diastereoselectivity nitrile imine cycloadditions

Extensive studies on diastereoselectivity in the reactions of 1,3-dipoles such as nitrile oxides and nitrones have been carried out over the last 10 years. In contrast, very little work was done on the reactions of nitrile imines with chiral alkenes until the end of the 1990s and very few enantiomerically pure nitrile imines were generated. The greatest degree of selectivity so far has been achieved in cycloadditions to the Fischer chromium carbene complexes (201) to give, initially, the pyrazohne complexes 202 and 203 (111,112). These products proved to be rather unstable and were oxidized in situ with pyridine N-oxide to give predominantly the (4R,5S) product 204 in moderate yield (35-73%). 

The chiral acrylate 164 was used in a 1,3-dipolar cycloaddition with a nitrile imine. Bis(trityl)nitrile imine was found to undergo a diastereoselective 1,3-dipolar cycloaddition with (f )-a-(acyloxy)-p,p-dimethyl-y-butyrolactone 164 to give the 2-pyrazoline product with a de of 50% (Scheme 12.51) (275). 

Karlsson and Hogberg (291,292) applied the thiocarbonyl ylide 175 in a diastereoselective 1,3-dipolar cycloaddition with 165. The thiocarbonyl yhde was generated in situ by an elimination reaction. The reaction with 165 gave 176 (R = Bu, BnO, Ph) with selectivities of up to 64—80% de. Furthermore, the cycloaddition of a chiral galactose-derived nitrile imine with 165 has been reported (104). 

Aromatic SAMP-hydrazones [45 SAMP = (S)-aminomethoxymethylpyrrolidine] react with the lithio derivative of methoxyaUene to yield enantiopure 3-pyrrolines. Homochiral nitrile imines (46) can be generated in situ by base treatment of hydrazonyl chlorides (47) (46) undergoes diastereoselective formation of furo[3,4-c]pyrazole derivatives [(48), easily separable isomers], via intramolecular cycloaddition. 

A highly regio- and diastereoselective 1,3-dipolar cycloaddition of nitrile oxides to the imine groups in 2,4-dimethyl-3//-l,5-benzodiazepines to afford bis[l,2,4-oxadiazolo[l,5]benzodiazepine] adducts has been reported by Baouid and co-workers stereochemical features were confirmed by single crystal X-ray crystallography on one of the adducts <04SC3565>. 

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