Nitrile ylides synthesis

An elegant procedure for the synthesis of 5//-dibenz[c,e]azepines 14, which is an extension of the procedure outlined at the beginning of this section, has been developed in which the nitrile ylides, generated by the treatment of iV-(2-arylbenzyl)benzimidoyl chlorides 12 with potassium /er/-butoxide, undergo a 1.7-electrocyclization at the adjacent phenyl ring, followed by a hydrogen shift 13 - 14.102... 

The use of thiirene dioxide 292 as a dipolarophile in the synthesis of thiazine 1,1-dioxides was already mentioned in CHEC(1984) <1975CL1153>. The same compound also reacts with nitrile ylide 293 to afford 294 <1984JOC1300> (Equation 97). 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

Variously substituted nitrile imines are easily available and react readily with a wide range of double and triple bonds. Intermolecular cycloaddition is therefore an area of major interest, and a large proportion of the papers on the use of nitrile ylides in synthesis is concerned with the exploitation of this reaction. Space limitation means, regrettably, that work leading to results that were predictable on the basis of known chemistry (19) has generally not been included. 

Thus, N-metalated azomethine ylides of the cyano-stabilized type are important in the stereoselective synthesis of pyrrohnes. These reactive intermediates are regarded as synthetic equivalents of nonstabilized nitrile ylides. 

Over the last 25 years both nitrile ylides and nitrile imines have continued to provide fascinating and synthetically useful chemistry. In both cases, the exploitation of [3 + 2]-cycloaddition chemistry with an increasing range of dipolarophiles has continued as a key route to five-membered heterocycles. The major development of new chemistry, however, has been in the extensive exploration of intramolecular reactions both in cycloaddition chemistry and in the electrocycliza-tion of 1,3-dipoles with extended conjugation. Such chemistry harnesses the unique reactivity of 1,3-dipoles in the synthesis of relatively elaborate structures but does require the design and preparation of quite complex reactants containing both the 1,3-dipole precursor and the dipolarophilic component. However, access to this chemistry is becoming much easier via the application of new synthetic procedures... 

Supercritical carbon dioxide with a minute co-solvent addition is an effective medium for the 1,3-dipolar cycloaddition of azomethine ylides with DMAD to produce substituted pyrroles.67 The 1,3-dipolar cycloaddition of nitrile ylides [e.g. benzonitrile (4-nitrobenzylide) and 4-nitrobenzonitrile(benzylide)] with acrylamides provided a synthesis of 3,4-dihydro-2//-pyrroles with moderate to good yields.68 The Pt(II)-or Au(III)-catalysed 3 + 2-cycloaddition of the transition metal-containing azomethine ylide (63) with electron-rich alkenes provided a carbene complex (64), which yields tricyclic indoles (65) having a substituent at 3-position (Scheme 17).69 The 1,3-dipolar cycloadditions of azomethine ylides with aryl vinyl sulfones are catalysed by Cu(MeCN)4C104-Taniaphos with nearly complete exo- selectivity and enantioselec-tivities up to 85% ee.10 The 3 + 2-cycloaddition of benzol/>]thiophene 1,1-dioxide... 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

Another synthesis based on the combination of these fragments is the 1,3-dipolar cycloaddition of carbonyl compounds to nitrile ylides. The latter are generated by photolysis of 1-azirines when the irradiation is carried out in the presence of an acyl chloride and triethylamine, oxazoles are formed in moderate yields (equation 121). 

The first synthesis of phosphorylated analogues of pyrazinamides such as substituted pyrazines containing two phosphonate groups (2,5-position) (269) and pyrazines containing one phosphonate group (2-position) (270) has been elaborated. The synthesis is based on thermal ring opening of 2H-azirines (271) followed by dimerization of unstable nitrile ylide intermediates (272) (Scheme... 

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