Nitrile ylides, cycloaddition with cycloadduct

Confirmation was provided by the observation that the species produced by the photolysis of two different carbene sources (88 and 89) in acetonitrile and by photolysis of the azirine 92 all had the same strong absorption band at 390 nm and all reacted with acrylonitrile at the same rate (fc=4.6 x 10 Af s" ). Rate constants were also measured for its reaction with a range of substituted alkenes, methanol and ferf-butanol. Laser flash photolysis work on the photolysis of 9-diazothioxan-threne in acetonitrile also produced a new band attributed the nitrile ylide 87 (47). The first alkyl-substituted example, acetonitrilio methylide (95), was produced in a similar way by the photolysis of diazomethane or diazirine in acetonitrile (20,21). This species showed a strong absorption at 280 nm and was trapped with a variety of electron-deficient olefinic and acetylenic dipolarophiles to give the expected cycloadducts (e.g., 96 and 97) in high yields. When diazomethane was used as the precursor, the reaction was carried out at —40 °C to minimize the rate of its cycloaddition to the dipolarophile. In the reactions with unsymmetrical dipolarophiles such as acrylonitrile, methyl acrylate, or methyl propiolate, the ratio of regioisomers was found to be 1 1. 

Exclusive cyclopropanation to give 6 is seen in the cases of R1 = R2 = Me R3 = H or Me, while nitrile ylides with R1 = R2 = H or R3 = C02R give the [3 + 2] cycloadducts.7 It is assumed that the structure of the 1,3-dipole governs the course of the cycloaddition and that angled structures favor the [2 + 1] cycloaddition. 

The formation of azabicyclohexenes 178 and 179 from the irradiation of azirine 177 clearly proceeds via a nitrile ylide intermediate since the formation of these compounds is entirely suppressed when the irradiation is carried out in the presence of an added dipolarophile. For example, when dimethyl acetylenedicarboxylate is used, cycloadduct 183 was the only product isolated. The fact that the photolysis of 177 produces a nitrile ylide intermediate which could be trapped by an added dipolarophile (i.e., as 183) eliminates a [2-f2]cycloaddition of the azirine C=N double bond with the olefin and subsequent rearrangement of a hypothetical azatricyclo[2.1.1.0 ]hexane intermediate (184) as the mechanism for the formation of the azabicyclo[3.1.0]hex-2-ene system. 

Another system which was found to undergo smooth intramolecular 1,1 cycloaddition was 2/jT-azirine 200. The exclusive formation of a 1 1 cycloadduct with this system indicates that the nitrile ylide produced is capable of undergoing carbene type of addition to a vinyl group just as long as there are no considerable bond distortions involved in the transition state for the internal cycloaddition. 

In contrast to the o-allylphenyl substituted 2/f-azirines (197 and 200) which undergo 1,1 cycloaddition, azirine 203 cycloadds exclusively in the 1,3 sense. The formation of the 1,3-dipolar cycloadduct 204 is quite consistent with the principles of frontier MO theory. With this system the rate of internal 1,3-dipolar cycloaddition of the nitrile ylide derived from 203 proceeds much more rapidly than that of the ylides derived from 197 and 200. This is to be expected since electron-withdrawing substituents on the double bond narrow the HO dipole-LU dipolarophile gap. In order for the 1,3-dipolar cycloaddition of 209 to occur, a slight distortion away from the strictly parallel-plane approach of the dipole and dipolarophile will be necessary. The interplay of entropy and... 

Intermolecular [3+2] 1,3-dipolar cycloaddition of a D-glyceraldehyde-derived nitrile oxide to the 4,5-double bond of 2-methylfuran gave a 60 40 diastereomeric ratio of the two furoisozaxoline isomers. This chemistry was employed in the synthesis of L-furanomycin <2005EJ03450>. As depicted in Scheme 43, an intramolecular cycloaddition of a furan with a carbonyl ylide dipole proceeded under rhodium-catalyzed microwave-promoted conditions to provide the cycloadduct in a modest yield <20040L3241>. 

In 2000, it was proposed that the regioselectivity of the [3 + 2] cycloaddition of fullerenes could be modified under microwave irradiation. Under conventional heating, N-methylazomethine ylide and fuUerene-(C7o) gave three different isomeric cycloadducts because of the low symmetry of C70 vs. C6o-Using microwave irradiation and o-dichlorobenzene as a solvent, only two isomers were obtained, the major cycloadduct 114 being kineticaUy favored (Scheme 39) [75]. The same authors had previously reported the 1,3-dipolar cycloaddition of pyrazole nitrile oxides, generated in situ, to Geo imder either conventional heating or microwave irradiation. The electrochemical characteristics of the cycloadduct obtained with this method made this product a candidate for photophysical apphcations [76]. 

---