Azomethine with electron-deficient alkynes

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. 

Domino reactions of imines with difluorocarbene in the presence of electron-deficient alkynes lead to 2-fluoropyrroles. For instance, reaction of A-benzylideneaniline (18) with difluorocarbene yields an intermediate azomethine ylide 19 capable of undergoing 1,3-... 

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... 

Af-(Silylmethyl)thioimidates (34) also undergo water-induced desilylation leading to the N-protonated azomethine ylides (38). These ylides react with a range of electron-deficient alkenes and alkynes, aldehydes, and ketones followed by elimination of methane thiol to give formal nitrile ylide adducts (e.g., 40) (23,24). The reactivity of these species is rather dependent on the nature of R (e.g., good for R = Ph but less so for R=Et or i-Pr), which may be due to competition from tautomerization to give the A -methylthioimidate (39). 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

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