Dimethylacetylene cycloaddition with

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 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 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>. 

Palladium catalysts have been used for cycloaddition of dimethylacetylene di-carboxylate (DMAD) to polycyclic arynes 3, 77 and 79 (Schemes 34-36). All these reactions exhibit the same reactivity pattern as is observed in the [2+2+2] cycloaddition of benzyne to DMAD (see Sect. 3.1) Pd2(dba)3 leads selectively to the cocycloaddition of one molecule of aryne and two molecules of DMAD, while Pd(PPh3)4 induces the reaction of two molecules of aryne with one molecule of DMAD. Both reactions afford the corresponding polycyclic aromatic hydrocarbons in good yields and with high chemoselectivity, constituting a novel and versatile method for the synthesis of functionalized PAHs under mild reaction conditions [70-72] (Scheme 34). 

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). 

Irradiation of phenyl-2//-azirines in the presence of carbon dioxide leads to the formation of the 3-oxazoline-5-one system121-123 and, in some cases, to the isomeric 2-oxazolin-5-one122 [Eq. (24)1. The azirines serve as incipient nitrile ylides, whose 1,3-dipolar structure permits cycloaddition to the dipolarophile C02123 [Eq. (25)1. The reverse reaction, photolytic extrusion of C02 from pseudoxazolones, is synthetically useful, since the dipolar nitrile ylide thus formed can be trapped with a variety of dipolarophiles. Thus, 2,2,4-triphenyl-3-oxazolin-5-one (48) is readily converted into the stabilized ylide (49)124 [Eq. (26)1, and the use of methyl acrylate,122 acrylonitrile,122 and dimethylacetylene dicarboxy-... 

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. 

Scheme 10.64. A cycloaddition (and rearrangement) reaction of trimethylsilylazide with 2-butyne (dimethylacetylene, CHsC CCHs). See Birkofer, L. Wegner, P. Chem. Ber., 1966,99, 2512 Hoffmann, k Hartung, K. I Nguyen,T. H. Mewes, R. Baluzow, W. Zeit Chemie, 1986, 26,105 Rickborn, B. Organic Reactions, Vol. 52, Paquett, L. A., ed. Wiley, Hoboken, NJ, 1998.

When chlorotrimethylsUane [(013)3810] is treated with lithium azide (UN3) in oxacyclopentane (THF), trimethylsilylazide [(CH3)3SiN3] results. Treatment of the latter with 2-butyne (dimethylacetylene, CH3C=CCH3) results in a cycloaddition reaction (Scheme 10.64), and, what is of particular interest, the 1-trimethylsilyl-l,23-triazole that results undergoes a 1,5-sigmatropic rearrangement to generate the more stable 2-trimethylsilyl-l, 2,5-triazole. 

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

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