Azomethine oxides, cycloaddition alkynes

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

Dipolar cycloaddition reaction of azomethine ylides to alkynes or alkenes followed by oxidation is one of the standard methods for the preparation of pyrroles.54 Recently, this strategy has been used for the preparation of pyrroles with CF3 or Me3Si groups at the (3-positions.55 Addition of azomethine ylides to nitroalkenes followed by elimination of HN02 with base gives pyrroles in 96% yield (Eq. 10.48).56... 

As a part of a program directed toward the synthesis of the potent topisomerase I inhibitors, the lamellarins (e.g., 153 and 154), Porco has reported the silver triflate-catalyzed tandem cycloisomerization-azomethine ylide cycloaddition of 155 (Scheme 2.42).75 The postulated mechanism of this intriguing and highly efficient process is shown in Scheme 2.43. Silver-catalyzed addition of the imine nitrogen to the alkyne results, on subsequent deprotonation, in the formation of an azomethine ylide 160. This ylide participates in [3+2] cycloaddition with the alkyne component leading to formation of a dehydropyrrole 161. Finally, oxidation by adventitious oxygen leads to formation of the product 162. 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

Ag-catalyzed in situ generation of azomethine ylides from alkynyl A-benzylidene glycinates 35 and their reaction with electron-deficient alkynes 36 were demonstrated by Su and Porco (Scheme 16.17) [26]. This reaction is supposed to be initiated by cycloisomerization of alkynyl imines 35 to isoquinolinium species A with the assistance of AgOTf. Subsequent proton transfer would afford azomethine ylides B with regeneration of Ag(I). 1,3-Dipolar cycloaddition with alkynes 36 followed by aerobic oxidation may furnish pyrroloisoquinoline products 37. It is worth noting that various types of electron-deficient alkynes, irrespective of internal and terminal alkynes, are applicable to this reaction. 

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