Acetylene derivs azomethines

Cycloaddition of thiazolium azomethine ylides with dialkyl acetylenedicarboxylates 61 provides another approach to pyrrolo[2,1 -bjthiazoles 64 <070L4099>. Quatemization of 2-methylthiothiazole with trimethylsilylmethyl trifluoromethanesulfonate (TMSChkOTf) and subsequent fluoride-induced desilylation of the resulting (trimethylsilyl)methylammonium salt generate the acyclic azomethine ylide 62. This ylide readily participates in 1,3-dipolar cycloadditions with acetylene derivatives 61 to give adducts 63, which undergo spontaneous elimination of methylmercaptan to give the A-fuse cl thiazoles 64. ... 

Stereoselective 1,3-dipolar cycloaddition of the azomethine imine 283, obtained by reacting acetaldehyde and the dihydropyrazolo[4,3-d]-pyridazin-4-one 282, with the acetylenic derivative 284 resulted in the construction of the second fused pyrazole ring of 285. Condensation of 282 with the dialdoglucopyranose 286 instead of acetaldehyde gave the aldose azomethine imine 287, which added 284 to give the C-nucleoside 288 carrying two carbohydrate moieties (93FA231) (Scheme 87). 

A large variety of silylmethylamino derivatives have been shown to be excellent starting materials for the in situ generation of non-stabilized azomethine ylids. Combined with a number of electron-deficient olefinic or acetylenic molecules that have been recognized as good dipolarophiles, ready access to diversely substituted five-membered ring nitrogen heterocycles has consequently been opened. 

Imidates, generated from secondary amides, are treated with trimethylsilyhnethyl triflate to give an azomethine ylid which reacts with electron-poor alkenes and acetylenes, yielding A2-pyrroline and pyrrole derivatives.54 Similar transformations are conducted from thioamides (vide infra). 

The N-unsubstituted azomethine ylides derived from the imines of a-amino nitriles are intramolecularly trapped by acetylenes to give pyrroles... 

Murphy et al. [39] reported the synthesis of pyrrolidine 7 combinatorial libraries. Starting from polystyrene resin-bound amino acids, the a-amino ester was condensed with aromatic and heteroaromatic aldehydes in neat trimethylorthoformate to afford the resin-bound aryl imine. Pyrrolidine and pyrroline derivatives were obtained through cycloaddition of the 1,3-dipoles azomethine ylides to olefin and acetylene dipolarophiles. A library of 500 compounds was reported. The screening of this library for in vivo inhibition of angiotensin-converting enzyme (ACE) led to the identification of l-(3 -mercapto-2 -(S)-methyl-1 -oxopropyl)-5-phenyl-2,4-pyrrolidinedicarboxy-lic acid 4-methyl ester as a potent ACE inhibitor that incorporates the mer-captoisobutyryl side chain (Fig. 3e). 

Stable triazolinedione ylides have been isolated from the reaction of TADs with appropriately substituted diazo derivatives, isobenzofurans, and acetylenes. Reaction of azomethine imines prepared by this way with ethyl-enic dipolarophiles, e.g, vinyl ethers or acetylene dicarboxylates, gives the... 

Several methods for making pyrroles involve in situ generation of azomethine ylides and anions. In the presence of electrophilic acetylenes these can be trapped and converted to pyrroles. One source of azomethine ylides are A -(a-trimethylsilylmethyl) derivatives of imidates and thioimidates. Azomethine ylides are generated by desilylation with fluoride ion. The salts are obtained by N-alkylation of imidate esters <83TL4303> or S-alkylation of thioacetamides <86JOCi997>. The alkoxy or alkylthio groups are eliminated after cycloaddition. Electrophilic alkenes such as dimethyl maleate, dimethyl fumarate, maleonitrile and methyl acrylate give A -pyrrolenines (Scheme 80). 

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