Azirine azomethine cycloaddition

Scheme 30 Preparation of tricyclic [1-lactam 92 using azirine-azomethine cycloaddition...

Aziridines can also be synthesized from their unsaturated azirine counterparts or existing aziridine rings. The first examples of enantiopure 2-substituted 2Z/-azirine 3-carboxylates 46 were prepared via dehydrochlorination of methyl 2-chloroaziridine-2-carboxylates. Bicyclic and tricyclic aziridines such as 47 were then generated via an aza-Diels-Alder reaction with the corresponding dienes <070L1707>. A related azomethine cycloaddition in the presence of an aziridine has also been reported <07JOC8506>. 

Aziridines, e.g. (91), undergo thermal ring opening in a conrotatory manner to generate azomethine ylides. These azomethine ylides are 47r-components and can participate in [4 + 2] cycloadditions with 1-azirines acting as the 27r-component 73HCA1351). 

Some cycloadditions to azirines have been reviewed by Anderson and Hassner.27 Schmid et al. 28 photolyzed the arylazirine 1 in benzene in the presence of 2 equivalents of DM AD and obtained 40% of the pyrrole 3, a compound prepared previously by Huisgen et al.29 30 from oxazolones and sydnones with DMAD. Padwa and his co-workers have investigated the scope of these photoinduced cycloadditions to arylazirines. Irradiation of 1 in pentane for 3 hours in the presence of DMAD gave 95% of (3)31 the azomethine ylid 2 was postulated as an intermediate. 

Intramolecular azomethine ylide cycloaddition to the C—O double bond of an aldehyde was reported in 197369 and cycloaddition to the C—C double bond was first reported in 1975.70 Competition between 1,1- and 1,3-cycloaddition is observed in intramolecular reactions, although intermolecular reactions give only 1,3-cycloaddition. Photolysis of 2//-azirines is one generation method of nitrile ylides applicable to intramolecular cycloaddition.70 Another method involves the base-catalyzed 1,3-elimination of hydrogen halide from alkenyl imidoyl halides. Still other procedures involve thermolytic and photolytic cycloreversions of oxazolinones and dihydrooxazaphospholes. 

The homologous azirine (143) with a one-atom bridge gave quite different results.70 Photolysis led to the 3,5-fused bicyclic dihydropyrrole (144). The isomeric azirine (145) also led to (144), although the initial products included dihydropyrrole (146) which apparently converted to (144) as photolysis continued. Azirines (143) and (145) were shown to not interconvert and die postulated two discrete azomethine ylides were trapped with methyl trifluoroacetate. Formation of dihydropyrrole (144) was explained based on a two-step cycloaddition process involving a common diradical intermediate. The observation of (146) from photolysis of (145) but not (143) can be explained based on extinction coefficient differences. Azirine (145) has a high extinction coefficient as does (146). The initial product (146) can then be optically pumped to (144) with a low extinction coefficient. Azirine (143) also has a low extinction coefficient and any (146) that formed from it would be optically pumped to (144) before observa-... 

The thermal and photochemical reactions of aziridines and azirines primarily involve opening of the strained three-membered ring. Aziridines produce azomethine ylides, while 2//-azirines produce nitrile ylides or nitrenes. Typically, these intermediates react further in cycloaddition processes or other rearrangements. 

Cycloaddition reactions of the C(3)=N bond of azirines are common (Scheme 45) <71AHC(13)45, B-83MI 101-03,84CHEC-I(7)47>. Azirines can participate in [4 + 2] cycloadditions with dienes including cyclopentadienones, isobenzofurans, triazines, and tetrazines. They also participate in 1,3-dipolar cycloadditions with azomethine ylides, nitrile oxides, mesoionic compounds, and diazomethane. Cycloadditions with heterocumulenes, benzyne, and carbenes are known. Azirines also participate in other pericyclic reactions, such as ene reactions. 

UV Irradiation of an 3-aryl-2-azidoacrylic ester (2-azidocinnamate) results in elimination of nitrogen and formation of a 2/f-azirine, which undergoes spontaneous electrocyclic ring opening to give a reactive intermediate which can react as an azomethine ylide dipole or an alk-oxycarbonyl(benzylidenimino)carbene. In favorable cases, the carbene form can be trapped by intramolecular [l-t-2] cycloaddition to an alkene double bond to give a dihydro-cyclopropa[c]isoquinoline, e.g.l, and 2 (Houben-Weyl, Vol. E19b, pi 166). 

---