Dipolarophiles azomethine ylide generation

Our first entry to the use of porphyrins as dipolarophiles in 1,3-DC reactions involved the reaction of porphyrins with azomethinic ylides, generated in situ from a-amino acids and aldehydes, to yield chlorins and isobacteriochlorins (bisadducts) <99CC1767, 05JOC2306>. 

Although trifluoropropene reacts poorly with the stabilized azomethine ylide generated by thermal ring opening of an aziridine, trifluoromcthyl-substituted alkenes are excellent dipolarophiles with azomethine ylides generated from organosilylated compounds, or with melalloazomethine ylides. 

Better diastereoselectivities were achieved with dipolarophiles such as unsaturated esters that bear a chiral auxiliary297-298. For instance, cycloaddition of the EVE-azomethine ylide, generated from the following imine by metalation, with the chiral alkene (27 )-2-(2-methoxycar-bonylethenyl)-3-phenyl-l,3-diazabicyclo[3.3.0]octane affords the pyrrolidine derivative as a single regio- and stereoisomer297. 

A series of novel dispirooxindolecyclo[pyrrolo[l,2-c]thiazole-6,5 -thiazolidine] derivatives (172) were obtained regioselectively by the 1,3-dipolar cycloaddition reaction of 5-arylidene-2-thioxothiazolidin-4-ones (171) as dipolarophiles with nonstabilized azomethine ylides, generated in situ via decarboxylative condensation of isatin (155) and thiazolidine-4-carboxylic acid (170) in ethanol under both classical refluxing and ultrasound irradiation (Scheme 8.54). Because of the advantages of ultrasonic irradiation of mild reaction conditions, short reaction times, and high efficiency, it is quite profitable to develop the 1,3-dipolar cycloaddition of azomethine ylides under these conditions (Hua et al. 2012). 

Azomethine ylides generated in situ are used in the synthesis of pyrrolidines by trapping with dipolarophiles. 

Gong et al. have confirmed that oxygen-linked bisphosphoric acid (274) provided the highest level of stereoselectivity for the 1,3-dipolar cycloaddition reaction tolerating a wide range of substrates including azomethine ylides, generated in situ from a broad scope of a-amino esters (275), aldehydes (276), and various electron deficient dipolarophiles (277). This reaction actually represents one of the most enantioselective catalytic... 

Azomethine ylides (Section 4.03.6.1.1) have been generated from a wide variety of aziridines using both thermal and photochemical methods. With carbon-carbon unsaturated dipolarophiles, pyrrolines or pyrrolidines are obtained. With hetero double bonds, however, ring systems of interest to this discussion result. 

Azomethine ylides 38 reacted with a variety of dipolarophiles to generate cycloadducts in a highly diastereo- and regioselective manner. The novel shapes, along with the rich array of functionalities displayed by these products, provide opportunities for the creation of chemical diversity (Scheme 12.28). 

Another example of a microwave-assisted 1,3-dipolar cycloaddition using azomethine ylides and a dipolarophile was the intramolecular reaction reported for the synthesis of hexahydrochromeno[4,3-fo]pyrrolidine 105 [70]. It was the first example of a solvent-free microwave-assisted intramoleciflar 1,3-dipolar cycloaddition of azomethine ylides, obtained from aromatic aldehyde 102 and IM-substituted glycinate 103 (Scheme 36). The dipole was generated in situ (independently from the presence of a base like TEA) and reacted directly with the dipolarophile present within the same molecifle. The intramolecu-... 

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