Pyrazolines nitrile imine cycloadditions

Nitrile imine cycloadditions provide access to pyrazolines and pyrazoles. Intramolecular cyclizations to alkynes were first reported in 1974.88 Perhaps the most useful method for generation of nitrile imines involves 1,3-elimination of hydrogen chloride from an a-chlorohydrazone. Tetrazoles and sydnones are also precursors to nitrile imines. 

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). 

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 pyrazoline 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%). 

A mild procedure was developed for polysubstituted pyrazolines synthesis from 2,5-diaryltetrazoles (addition to Section 6.07.5.2.2) <20070L4155>. This procedure involved the in situ photoactivated generation of the reactive nitrile imine dipoles, followed by spontaneous cycloaddition with 1,3-dipolarophiles. 

Dipolar cycloadditions of nitrile imines with alkenes lead to 2-pyrazolines. Moderate select vities are observed in reactions with the acrylate of (/ )-pantolactone. 

Nitrile imines smoothly undergo 1,3-dipolar cycloadditions with alkenes and alkynes to generate 2-pyrazolines and pyrazoles, respectively (Scheme 5.46). 

Dipolar cycloaddition of azomethine imine or nitrile imine-type dipoles with alkenes or alkynes yields nitrogen heterocycles containing two nitrogen atoms in the ring. MeOPEG resin was applied in the solid-phase synthesis of pyrazolines (Scheme 11.13). Resin-bound... 

The regioselectivity and reactivity of the 1,3-dipolar cycloaddition reactions of nitril-imines with acrylonitrile and methyl acrylate have been investigated. The 1,3-dipolar cycloaddition reactions of nitrilimines with isatin imines yielded spiro[indolin-3,3 -1,2,4-triazol] derivatives under classical and microwave conditions/ An extensive study of the 1,3-dipolar cycloaddition reactions of nitrilimines with a,/ -unsaturated lactones, thiolactones, and lactams has been presented. In all cases, regioisomeric mixtures were obtained with the 5-substituted pyrazole as the major cycloadduct. me5 o-Tetrakis(pentafluorophenyl)porphyrin (51) reacts with iminonitriles (52) yielding pyrazolin-fused chlorines (53) via a 1,3-dipolar cycloaddition reaction (Scheme 17). ... 

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