Addition of Azomethine Ylides

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... 

Maggini, M., and Scorrano, G. (1993) Addition of azomethine ylides to CM Synthesis, characterization, and functionalization of fullerene pyrrolidines./. Am. Chem. Soc. 115, 9798-9799. 

Meyers and co-workers (143-146) studied the addition of azomethine ylides to the chiral bicychc half-aminal 97 (Scheme 12.32). The diastereoselectivities of these reactions were highly dependent on the substituents of both 97 and... 

Pyrazolines have also been incorporated as modifying groups by 1,3-addition of azomethine ylides to the carbon-carbon double bond of unsaturated poly(esters) (186 Scheme 89) (68MI11100). Poly(isoxazolines) were prepared in similar fashion by reaction of an unsaturated polymer with a nitrile oxide (75MI11106). 

Figure 8 Tether-directed additions of azomethine ylides to fullerene C60, assisted by a removable anchor.

Prato and coworkers succeeded in the 1,3-dipolar addition of azomethine ylides to CNTs [161], Treatment of pristine SWCNTs with an aldehyde and an N-substi-tuted glycine derivative resulted in the formation of substituted pyrrolidine moieties on the SWCNT surface (Scheme 1.22). The approach works effectively with both SWCNTs, prepared by several different methods, and MWCNTs. The pyrro-lidino-functionalized CNTs were sufficiently soluble in common organic solvents and were characterized by several spectroscopic techniques and TEM [161]. The... 

Scheme 1.22 1,3-Dipolar addition of azomethine ylides to SWCNTs and MWCNTs.

By using the same type of 1,3-dipolar cyclo-addition of azomethine ylides it was possible to anchor ferrocene (Fc) onto the sidewalls of SWCNTs [96]. Accordingly, a nitrogen-functionalized glycine (R-NHCH2COOH, R= CH2CH2OCH2CH2OCH2CH2NHCO-FC) and paraformaldehyde were refluxed in dimethylformamide in the presence of SWCNTs. From differential scanning calorimetry the extent of functionalization was determined as approximately 1 Fc molecule per 100 carbon atoms of the SWNTs. 

Dipolar addition of azomethine ylides to electron-deficient olefins is a versatile route to nitrogen-containing heterocycles. Applying this approach to ( )-ethyl 3-fluoroacrylates utilizing L-menthol as a chiral auxiliary provides a stereoselective and regioselective synthesis of enantiopure-fluorinated prolines 28 and 29. Careful... 

Tagmatarchis, N. and Prato, M. The addition of azomethine ylides to [60]fullerene leading to fuUeropyr-rolidines. Synlett6, 768-779, 2003. 

The synthesis of the 2,5-disubstituted pyrrolidine 43 from D-mannitol by standard chemistry and the synthesis of pyrrolidines 44 by addition of azomethine ylides to vinylene carbonate " as well as the synthesis of the imino-heptitol 45 from 2,3 5,6-di-0-isopropylidene-a-D-mannofuranose have been reported. 

The addition of azomethine ylides 102 formed by heating of the aziridines 77a,b (R=t-Bu) to the trifluoromethylated alkenes 103 led to mixtures of the diastereomeric pyrrolidines 104 and 105. Subsequent elimination of HF by treatment with sodium methoxide in methanol gave predominantly the pyrrole 106 and minor amount of the regioisomer 107 [43]. 3,4-Bis(trifluoromethyl)pyrrole 108 with a free nitrogen atom was obtained using iV-trimethylsilyl aziridine 77c [48],... 

Cycloaddition reactions have a great fascination for many synthetic chemists, as they can produce molecules with considerable stereo- and regio-specificity. Grigg has published extensively over the last few years on the addition of azomethine ylides to activated double bonds, and previously suggested that these additions were stereospecific. A paper from his group now, however, has modified this view, and the work has shown that the extent of stereo- and regio-control varies with the substituents on the or-amino-ester imine, and on the reactivity of the dipolarophile. 

Fulleropyrrolidines are synthesized through the addition of azomethine ylides as 1,3-dipolar compounds to fullerene (Scheme 3.7). This reaction is known as the Prato reaction. There are several methods of generating azomethine ylides. In the Prato reaction, a decarboxylation route is employed with the use of easily available aldehydes and a-amino acid derivatives. Both starting materials undergo dehydrative condensation to give 5-oxazolidinones, which generate azomethine ylides with elimination of CO2. Azomethine ylides react with Cgo and produce fulleropyrrolidines in moderate yields. 

Enantioselective total synthesis of ((47J,5iS)-5-Amino-4-(2,4,5-tri-fluorophenyl) cyclohex- l-enyl)-(3-(trifluoromethyl)-5,6-dihydro-[l, 2,4]tri-azolo[4,3-a]pyrazin-7(877)-yl)methanone ABT-341 (708), a DPP4 (dipeptidyl peptidase IV) inhibitor, has been completed in diphenylprolinol silyl ether (707), in the one-pot, multicomponent, reaction of nitroalkene (704), acetaldehyde (703), vinyl phosphonate (706) and amine (705) (Scheme 178) A novel, catalytic, asymmetric Michael addition of azomethine ylide (710) with p-substituted tetraethyl alkyhdene bisphosphates (709) has been realised in the presence of a chiral copper(I)/TF-Bipham-Phos (712) complex. This system provided enantioenriched unnatural i -amino acid derivatives (711) containing gem-bisphosphonates in high yields with... 

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