Cycloadditions, thermal acetylenedicarboxylate

Occasionally, these thermally induced reactions give rise to complex mixtures of products and hence are not of any great preparative value. For example, 1-mcthylindolc with dimethyl acetylenedicarboxylate in acetonitrile yields seven products including the 1-benzazepine 8 (14%), the 1-methyl derivatives of the cis- and /rwK-indolylacrylates 3. a [4 + 2] cycloadduct of the 1-benzazcpinc with the alkyne dicster (see Section 3.2.2.5.3.), and dimethyl l-mcthyl-2-(l-methylindol-3-yl)-2,3-dihydro-l //-l-benzazepinc-3,4-dicarboxylate (9).21 This last product, which is the major product if the cycloaddition is carried out in acetonitrile containing trace amounts of water,21 has been obtained earlier.143 but was incorrectly formulated. 

The [3 -f 2] cycloaddition of aziridines and dipolarophiles, like dimethyl acetylenedicarboxylate or dimethyl fumarate and maleate, was investigated by Gaebert and Mattay. Via C—C and C—bond cleavage five-membered heterocycles are formed in moderate yields. The different product ratios dependent on the reaction conditions (PET/direct excitation/thermal reaction) gave insights to the reaction details and are summarized in the proposed mechanism (Scheme 52) [84],... 

As can be seen in the intramolecular cycloaddition (Section 8.03.5.1), the intermolecular Diels-Alder reactions between functionalized 2(l/f)-pyrazinones 83 and dimethyl acetylenedicarboxylate (DMAD) forming bicyclo adducts 84 has been shown to be significantly rate enhanced and increased in yields by using controlled microwave irradiation compared to the conventional thermal protocols (Scheme 21) <2002JOC7904>. The microwave-assisted Diels-Alder reactions of substituted 2(l//)-pyrazinones with ethene are significantly more effective utilizing prepressurized (up to 10 bar) reaction vessels <20040BC154>. 

Methylnaphtho[l,8-c e][l,2,3]triazine (72) reacts with dimethyl acetylenedicarboxylate in refluxing o-dichlorobenzene via a thermally allowed 1,11-dipolar cycloaddition to give the dihydroacenaphtho[5,6- /e][l,2,3]triazine (73) which was dehydrogenated under the reaction conditions to (74) (72CC1281). 

Coburn and Bhoosan reported the first synthesis of 1,3-disubstituted l,3,5-triazine-4,6-dione (82) and the corresponding thione derivative. The dione (82) is thermally stable, but forms ring-opened products on exposure to moisture. The reaction of (82) with dimethyl acetylenedicarboxylate gives the 1 1 adduct rather than the expected cycloaddition products (Scheme 50) (75JHC187). The fused system (83) reacts with ethylamine to produce the 1,3,5-triazine (84 equation 41) (81JCS(Pl)33l). 

Pyrazolo[l,2- ]pyrazole systems 166 can be obtained by the reaction of hydrazine with acrylic esters (Scheme 99) <2001J(P2)243, CHEC-III(12.10.12.1)406>. The betaines 167 reacts with dimethyl acetylenedicarboxylate to give products 168 which easily undergo thermal fragmentation to 169 followed by another cycloaddition to form 170 (Scheme 100) <1981JA7743>. Criss-cross addition of azines, e.g. 171, also involves two successive 1,3-dipolar cycloadditions to give pyrazolo[l,2-. 

Thermal cycloaddition reactions of benzo[c]cinnoline with butadiene and isoprene are reported to give only small yields of adducts in various solvents. Reactions of 1 and its 3,8-dimethyl derivative with dimethyl acetylenedicarboxylate at room temperature give the 1 2 adducts 56 and 57 via a stepwise process involving dipolar intermediates (see also Sections IV,A and 2.132 corresponding reactions of the diethyl ester in... 

An analogous photo-isomer of A -benzyloxycarbonylmethyl-2(l//)-pyridone has been prepared and various transformations of its cyclobutene ring have been explored. The photodimerization of A -methyl-2(l/ )-pyridone in water gives exclusively the products of [4 + 4] addition the yields of trans-anti- (31), trans-syn-, cis-anti-, and cw-jjfn-dimers were 51, 0.6, 11.2, and 6.8%, respectively. In non-aqueous solvents (ethanol or benzene), only a t/-dimers were formed. The thermal cycloaddition of dimethyl acetylenedicarboxylate to 2(l/f)-pyridones also occurs across positions 3 and 6. Reaction is favoured where steric buttressing of the methyl groups in the starting pyridone occurs for example, the cyclo-adduct (32) is... 

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