Cycloaddition with dimethylacetylene dicarboxylate

Cyclopropyl imines can be used as five-atom components in intermolecular [5 + 2]-cycloaddition reactions with dimethylacetylene dicarboxylate (DMAD) (Scheme 14).45 In this hetero-[5 + 2]-cycloaddition reaction, dihydroaze-pines are constructed from simple, readily available starting materials. The cyclopropyl imines can be preformed or made in situ by the condensation of cyclopropyl carboxaldehydes and amines. Although, thus far, DMAD is the only... 

Reaction of the nitrilimine derived from C-(2-pyridyl)hydrazonoyl bromide 33 with dimethylacetylene dicarboxylate afforded a mixture of the usual 1,3-dipolar cycloadduct 208 and an unusual cycloaddition product 209 (81H717). 

The aryl-substituted pteridine-5-oxide derivative (32) with dimethylacetylene dicarboxylate (DM AD) in a 1,3-dipolar cycloaddition reaction gave a mixture of the 8-aryldimethylxanthine (33) and the pyrrolopyrimidine (34) (Equation (3)) <85H(23)2317,88MI711-06). 

Irradiation of a solution of 51 in benzene causes an interesting isomerization to 4-phenyl-4-oxazolin-2-one (56), via an epoxy isocyanate141 lEq. (33)1. In the presence of 1,1-dimethoxyethylene, a 2 + 2 cycloaddition occurs in competition with a-cleavage to give 57. Compound 51 is also reported to react with dimethylacetylene dicarboxylate... 

Cycloaddition reactions have been carried out with Vilsmeier bases of pyrroles. Thus reaction of (180) with dimethylacetylene dicarboxylate gave pyrrolizines (181) and 3a-azaazulenes (182) in a non-concerted reaction <74JHC811>. In a closely related reaction, (183) was obtained from the Vilsmeier base with phenyl isocyanate <76H(4)i28i>. 

A recent and succinct approach to 2-aryltetrahydrofuran precursors to lignan natural products involves the cycloaddition of 2-aryM-phenyloxazoles with di-methylacetylene dicarboxylate. For example, 2,4-diphenyloxazole 273 (R = H) reacts with dimethylacetylene dicarboxylate in refluxing xylenes in the presence of sodium carbonate and hydroquinone to provide 2-phenyl-3,4-furandicarboxylic acid dimethyl ester 274 in 98% yield (Fig. 3.82). Not surprisingly, 4,5-diphenylox-azole and 2,4,5-triphenyloxazole gave lower yields of the corresponding furans... 

Experimental support [14] for this notion was further presented by the Diels-Alder cycloadditions of dimethylacetylene dicarboxylate and norbornadiene with the pyrazine derivatives shown in Scheme 6. 

Beyond RCM and CM strategies, Craig has reported cleavage using Diels-Alder reactions (Scheme 1.16). ° [4 + 2] Cycloaddition (with concomitant aromatization) of the o-quinodimethane precursor (52) with dimethylacetylene dicarboxylate (DMAD), trichlor-oacetonitrile, and benzoquinone provided dimethyl naphthalene-2,3-dicarboxylate (53), 3-(trichloromethyl)isoquinoline (54), and 2,3-naphthoquinone (55), respectively. The diverse products from a single polymer-supported intermediate, such as the bismuth linkers discussed previously, make Craig s multifunctional linker unit attractive for approaches toward diversity-oriented synthesis. 

A number of examples of photoaddition to alkynes has been described. Dimethyl acetylenedicarboxylate has been found to add to methyl-substituted 3-benzoylthiophens301 and to thiophen and 2,5-dimethylthiophen302 on irradiation. Benzo[f>]thiophen also undergoes cycloaddition reactions with alkynes,303 and in the case of dimethylacetylene dicarboxylate, product formation has been shown to be wavelength dependent.304 Intramolecular [ 2 -(- 2] cycloaddition has been observed on both direct and triplet-sensitized irradiation of the alkyne (353) and gives the cyclobutene (354)305 the isomer (355) is formed on prolonged irradiation. 

The synthetic reactions of nucleophilic carbenes have been reviewed.11 Isonitriles, dimethoxycarbene, and NHCs are covered. The review focuses on the 1,3-dipolar cycloaddition reactions made possible when the nucleophilic carbene reacts with electrophiles such as dimethylacetylene dicarboxylate. Such reactions were also the subject of research papers during 2005 (see the section on nucleophilic and basic carbenes). 

The more activated TpRe(CO)(MeIm)(r/2-anisole) complex has demonstrated a slightly broader range of reactivity by undergoing cycloadditions with both N-methylmaleimide (Scheme 13) and dimethylacetylene dicarboxylate (DMAD) (Scheme 14). Analysis of these reactions is complicated by the fact that the initial anisole complex exists as a 3 1 mixture of... 

The final class of dipoles discussed here are the carbonyl ylids. Padwa et al. generated these reactive intermediates from a rhodium (Il)-catalyzed reaction with l-diazopentanediones.388 a synthetic example of this reaction is taken from Padwa s synthesis of ribasine,389 where diazo compound 497 was treated with Rh2(tfa)4 [tfa = trifluoroacetic acid ligand] to give carbonyl ylid 498. In the presence of dimethylacetylene dicarboxylate (DMAD), cycloadduct 499 was isolated in 82% yield. Interestingly, formation of the carbonyl ylid and cycloaddition was very dependent on the rhodium catalyst used, and when Rh2(OAc)4 was used, 482 was not produced. 

Fukushima and Ibata reported direct evidence for the formation of an acyl nitrile ylide intermediate during Rh2(OAc)4-catalyzed reactions of a-diazoaceto-phenones 133 with nitriles in the presence of dimethylacetylene dicarboxylate (DMAD). The authors isolated mixtures of both 5-aryl-2-phenyloxazoles 137 and tetrasubstituted pyrroles 138 (Scheme 1.37). They proposed that 137 arose from the acyl nitrile yhde 136 via 1,5-cyclization, whereas 1,3-diploar-cycloaddition of 136 with DMAD followed by a 1,5-hydrogen shift produced 138. The authors showed that 138 did not arise via a Diels-Alder reaction of 137 with DMAD. 

Cycloaddition Reactions.— The use of dimethylacetylene dicarboxylate (DMAD) in cycloaddition reactions with various substrates is illustrated in the Table. 

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