Regioselectivity nitrile ylide

Frontier molecular orbital theory correctly rationalizes the regioselectivity of most 1,3-dipolar cycloadditions (73JA7287). When nitrile ylides are used as 1,3-dipoles, the dipole... 

The 1,3-dipolar cycloadditions of benzonitrile oxides with tertiary cinnamides yield the 5-phenyl and 4-phenyl regioisomers in a reversal of the expected regioselectiv-ities shown with methyl cinnamate. Calculations have shown that steric factors are responsible for this reversal of regioselectivity." The 1,3-dipolar cycloadditions of benzonitrile oxide with electron-rich and electron-poor dipolarophiles are accelerated by sodium dodecyl sulfate micelles. Phenyl nitrile ylides react with electron-deficient alkenes to produce five-membered -heterocycles where measured rate constants are between 4 x 10 and 7 x 10 lmoP ... 

The highly effective desilylation routes to nonstabihzed azomethine ylides have provided the basis for much of this chemistry. Thus, the reaction of A-(silylmethyl)-thioimidates (30) with AgF in the presence of a range of dipolarophiles (electron-deficient alkenes and alkynes, and aldehydes) led to the isolation of nitrile ylide adducts in generally high yields (20,21). Differences in reactivity and regioselectivity... 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

The imino carbene complexes of tungsten and chromium (e.g., 81) also serve as nitrile ylide synthons (40). The mngsten complexes gave higher yields of the adducts and were strongly regioselective for product 82. For example, for 81 (M=W R = Me, Ph R = Pr, Ph R" = H), the pyrrole 82 was produced in yields of 65-75% with <1% of 83. This route to pyrroles thus has clear advantages over... 

Some interesting work has been carried out on the generation and reactions of nitrile ylides (e.g., 164 and 171) with different substituents at the nitrile carbon. The effect of such substituents on regioselectivity in cycloaddition reactions throws... 

In the first addition of nitrile ylides to a,()-unsaturated lactones (92), it was found that the reaction of benzonitrilio 4-nitrobenzylide with the lactones 178-180 were strongly regioselective. Compounds 178 and 179 reacted to give [e.g., 181 from 178 (51%)] and its methyl analogue from 179 (54%). The exocyclic double bond in 180 was, however, the most reactive and gave 182 (69%). The six-membered analogue of 178 was less reactive (34%) and the seven-membered analogue failed to react. 

Reaction of carbon dioxide with Af-[l-chloro-2,2,2-trifluoro-l-(trifluoromethyl)-ethyl]-A, A -dialkylformamidines has been described as a procedure to prepare 4-(diaLkylamino)-5(2f/)-oxazolones 51 (Scheme 7.13 Table 7.9, Fig. 7.10). Mechanistically, this reaction probably does not proceed via a nitrile ylide given the observed regioselectivities and the dependence of the reaction rate on the solvent. 

These results are rationalized on the basis of the intermediate formation of thio-substituted nitrile ylides 58 that undergo regioselective 1,3-dipolar cycloadditions with the dipolarophiles. Some examples are shown in Scheme 7.15. If a dipolaro-phile is not present in the reaction mixture the nitrile ylides 58 (R2 = Me) isomerize to give the 2-aza-1,3-butadienes 59 that can be trapped in a Diels-Alder reac-... 

Inductive effects exerted by substituents on the nitrile ylide also have an important effect on the regio-selectivity of the cycloaddition. Benzonitriliohexafluoro-2-propanide (73) and methyl acrylate yield products with inverse regioselectivity, as compared with the reactions of the related benzonitrilio-2-pro-panide (76 Scheme 18).83 The difference in regioselectivity has been attributed to the larger coefficient... 

Our initial interest in this area arose from the observation that the orbitals of the commonly accepted planar geometry of the parent nitrile ylide do not correctly account for the cycloaddition regioselectivities observed for these species. Thus, as shown by the examples in Fig. 14, the digonal carbon is the nucleophilic center of the molecules, whereas the HOMO of the planar species has the largest coefficient at the trigonal carbon, which should, therefore, be the more nucleophilic center of the molecule. However, full optimization of the geometry of nitrile ylide using the... 

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