Nitrile imines selectivity

In a manner analogous to classic nitrile iinines, the additions of trifluoro-methylacetonitrile phenylimine occur regiospecifically with activated terminal alkenes but less selectively with alkynes [39], The nitnle imine reacts with both dimethyl fumarate and dimethyl maleate m moderate yields to give exclusively the trans product, presumably via epimenzation of the labile H at position 4 [40] (equation 42) The nitrile imine exhibits exo selectivities in its reactions with norbornene and norbornadiene, which are similar to those seen for the nitrile oxide [37], and even greater reactivity with enolates than that of the nitnle oxide [38, 41], Reactions of trifluoroacetomtrile phenyl imine with isocyanates, isothiocyanates, and carbodiimides are also reported [42]... 

Alternatively, nitriles are selectively reduced by diisobutylaluminium hydride, (DIBAL-H) to imines followed by hydrolysis to aldehydes ... 

The use of organomagnesium reagents as bases leads to complexation of the nitrile imines (e.g., 141), which has been found to have a strong effect in promoting syn selectivity in reactions with methyl 2-(l-hydroxyalkyl)acrylates via coordination of the metal atom with the alcoholic oxygen (e.g., leading to the formation of 142). Lithium complexation had little effect (78). 

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%). 

Complexation has been utilized to control site selectivity. The iron tricarbonyl complex 216 reacts with nitrile imines only at the cyclobutene double bond, whereas the uncomplexed analogue reacts at all three sites (117). 

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). 

McCarthy and co-workers [275] prepared nitrile imines in situ by exposing two hydrazonyl chlorides (210) to basic conditions, and these underwent [2 -i- 3]-cy-cloaddition reaction -with solid-supported-enamines derived from a Merrifield-based piperazine resin and the selected phenylacetaldehyde (209) (Scheme 46). Pyrazoles (212) were then obtained after cleavage from the resin under mildly acidic conditions, the resin functioning as a traceless linker. 

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

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