Azirines stereochemistry

The course of the photochemically mediated isomerization of vinylazirines is dependent on the stereochemistry of the vinyl group, as is illustrated in Scheme 94a (75JA4682). Under thermal conditions the isomerization proceeds through formation of the butadienylnitrene and subsequent pyrrole formation. Analogous conversions of azirines to indoles have also been effected (Scheme 94b). It is possible that some of the vinyl azide cyclizations discussed in Section 3.03.2.1 proceed via the azirine indeed, such an intermediate has been observed... 

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

Photolysis of (Z)-3-phenyl-2-(2-phenylvinyl)-2//-azirine (1) in benzene solution yields 1-phenyl-3//-2-benzazepine (2) in excellent yield.39 However, the stereochemistry of the alkenyl side chain and the solvent used are important in determining the outcome of the reaction. For example, the E-isomer of the 2//-azirine 1 on photolysis in benzene solution yields 2,3-diphenyl-pyrrole as the major product (85 %) the pyrrole is also obtained on heating the Z- or E-isomer in benzene solution. In contrast, irradiation of the Z-isomer in methanol yields only acyclic products. 

Allylaziridines have been prepared in good yield by the action of allylindium reagents on azirines (e.g. 25).63 The C(3) substituent can control stereochemistry hydroxy- (or acetoxy-) -methyl gives d.v-allylalion (via chelation with the indium (g) reagent), whereas R = Me/Ph/C02Et gives a trans result, presumably due to steric repulsion. 

Highly diastereoselective Lewis acid mediated aza-Diels-Alder reactions of chiral auxiliary derivatized 2H-azirines have been studied (02T5983,03JOC9958,03CC1150). The cycloaddition proceeded with high diastereoselectivity (97% de), with the absolute stereochemistry of the major product confirmed by X-ray crystallography. Without the presence of a Lewis acid, no diastereoselectivity was obtained at room temperature. 

Figure 7.42 Successful and unsuccessful photoaffinity labels from carbohydrate di-azirines. The mechanistic details for the observed stereochemistry of reaction of the 2-azi-mannitol in D2O are speculative.

Aryl-27/-azirine-2-(/V-benzyl)carboxamides can be diastereoselectively reduced to the corresponding eu -aziridines using sodium borohydride11. The stereochemistry of the as-aziridines was revealed by H-NMR spectroscopy which showed a cis coupling constant of J2H,3h = 7-8 Hz. 

Inverse electron-demand cycloadditions of N-sulfonyl vinylimines and allenamides, exemplified by the formation of 180 from 181 and 182, have been examined. The synthetic limitations, mechanistic issues, and stereochemistry of the process have been addressed <04T7629>. Fulvenes have been used as dienophiles with N-sulfonyl vinylimines to synthesize the [IJpyrindine system <04OL3453> and in a formal [6+3] cycloaddition with an appropriate 2//-azirine to give the [2]pyrindine system <04TL1663>. 

The above mechanism also accommodates the unusual stereochemical results observed with azirine 185. As was pointed out earlier, the formation of the thermodynamically less favored endo isomer 186 from 185 corresponds to a complete inversion of stereochemistry about the n system in the cycloaddition process. The stereochemical results have been rationalized by assuming that collapse of the trimethylene derivative 189 to the thermodynamically more favored exo isomer 190 results in a severe torsional barrier on ring closure. Collapse of 189 to the thermodynamically less favored endo isomer 186 moves the phenyl and methyl groups increasingly further apart and accounts for the formation of the less stable product. Supporting evidence for this rationale was obtained from the irradiation of the isomeric Z-2-butenyl-2/f-azirine 188. Photolysis of this azirine resulted in the quantitative formation of the same e do-azabicyclohexene (186) and is perfectly consistent with the preferred kinetic closure of intermediate 189. The formation of 186 from 2i/-azirine 188 also provides convincing support for this interpretation. 

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