Dimethyl acetylenedicarboxylate azomethine ylide generation

A possibility for azomethine ylide generation from 4-isoxazolines was first suggested by Baldwin, who demonstrated a thermal N—O bond cleavage of 4-isoxazoline systems (68JA5325). Cycloaddition of N-methylene(t-butyl)-amine V-oxide to dimethyl acetylenedicarboxylate takes place at 0°C, rapidly and quantitatively, to give 4-isoxazoline 146 (R = t-Bu, =R = COOMe), which isomerizes at 80°C into 4-oxazoline 148 (R = f-Bu, R = R = COOMe). The nitrone bearing an N-aryl substituent and the same acetylene directly afford 2-acylaziridine 147 (R = 2,4,6-trimethylphenyl, R = R = COOMe). Reaction of the N-t-butylnitrone with 3-methylbutyn-... 

Possibly, the most common protocols used in the generation of azomethine ylides are those based on the in situ, fluorine-mediated desilyation of cyanoami-nosilanes developed by Padwa et al. (2). Typically, treatment of precursor 1 with AgF, in the presence of dimethyl acetylenedicarboxylate (DMAD), led to the formation of the intermediate cycloadduct 2, which was subjected to immediate DDQ oxidation to give pyrrole 3. The mechanistic rationale invokes fluoride-mediated desilyation to form the intermediate anion 4, which then undergoes loss of cyanide furnishing the corresponding azomethine yhde (Scheme 3.1). 

In the dipole cascade reaction, a proton must be removed from the a-carbon atom in order to generate the azomethine ylide. When the a-position of the pyrrolidine ring was blocked by a benzyl group, formation of the azomethine ylide dipole could not occur. In fact, treatment of diazoketone 186 with rhodium(II) acetate in the presence of dimethyl acetylenedicarboxylate afforded only the carbonyl ylide-derived cycloadduct 187 in 95% yield [117]. 

Few examples are known for the generation of C-heterosubstituted azomethine ylides by the aziridine route. Interesting is the thermolysis of 2,2-dichloroaziridine, readily accessible by the reaction of an imine with di-chlorocarbene (81JOC2079). Thermoylsis of 16 in the presence of dimethyl acetylenedicarboxylate gave pyrrole 18 by the cycloaddition of intermediate 1,1-dichlorinated azomethine ylide 17 (84JCR(S)82). None of the usual thermolysis product, 2-chloroacetoimidoyl chloride (19), was obtained (78JOC1346). 

A series of azomethine yUdes have been generated through a rhodium-catalyzed reaction between sulfonyl triazoles and functionalized pyridines (Schane 3.141) [150]. Using this approach, an array of sterically and electronically diverse azomethine ylides were generated by systematic modification of the precursors. In addition to the isolation of these intriguing species, they were also used as intermediates in the preparation of 1,4-diazepines through a one-pot multicomponent reaction involving an internal activated alkyne such as dimethyl acetylenedicarboxylate. 

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