Cycloadditions of DMAD

Benzo[g]cycl[3.2.2]azines or pyrrolizino[3,4,5- 3]isoquinolines, for example, 366, are similarly obtained by cycloaddition of DMAD to pyrrolo[2,l- ]isoquinolines <1985CPB3038>, and l-aza-benzo[ ]cycl[3.2.2]azines are prepared by cycloaddition of DMAD to imidazo[2,l- ]iso-quinolines <1985H(23)2531> (Scheme 102). In all of the above cases, as with the simpler cyclazines, the ester functions are removable by hydrolysis in aqueous alkali followed by... 

Similarly, in a 1,3-dipolar cycloaddition of DMAD to the conformationally locked cyclic a-alkoxycarbonylnitrone (727), bicyclic ring systems, containing a nitrogen atom at the bridgehead position have been synthesized. A mechanistic interpretation of the origin of the fused pyrroles (729) includes the intermediate formation of the aziridine ring in (728) (Scheme 2.303) (820). 

After completing his initial intramolecular cycloaddition, Hodgson utilized conditions that had been optimized for the intermolecular cycloaddition of DMAD with simple cyclic carbonyl ylides used by Hashimoto and co-workers (139). Hodgson et al. (140) found that the reaction indeed gave excellent overall chemical yield, but the enantioselectivity dropped to 1%, giving essentially a racemic mixture. It appeared that ee ratios were sensitive to the electronic nature of the dipole. Hodgson chose to screen several binaphthol derived rhodium catalysts of the type developed by McKervey and Pirrung, due in part to the reports of... 

A fairly general route to 1,2-dihydroazocines (64) is provided by the [2+2] cycloaddition of DMAD to 1,2-dihydropyridines (62) (74JCS(Pi)2496,77JOC2903). The reaction gives good yields of the dihydroazocine-6,7-dicarboxylates with N- alkyl, -aryl or functionally substituted removable protective groups. Other substituents can be present at C-3 or -4 in the pyridine, but carboxyl substituents at N-l or C-5 of the pyridine reduce the enamine character, and Diels-Alder addition of the acetylene occurs at the diene system. The [4.2.0] bicyclic intermediates (63) can be detected at -10 to 0°C by NMR warming to 20 °C causes complete conversion to (64). 

Cycloaddition of DMAD to 1,2-dihydropyridines (77JOC2903) is a fairly general route to 1,2-dihydroazocines which proceeds via a bicyclic intermediate as described in Section 3.2.2.3.8. 

Analogous [ 4 + 2] cycloaddition reactions of DMAD with indoles would disrupt the aromatic character of the fused benzene ring. It is not unexpected, therefore, that indole reacts with two molecules of DMAD to give the dihydrocarbazole derivative (234), via an initial Michael addition reaction, followed by cycloaddition of DMAD to the vinylindole. Aromatization of the 1 2 adduct (234) normally yields the carbazoletetracarboxylic ester... 

Tominaga et al.1B0 studied the cycloaddition of DMAD to 3-indoledi-thiocarboxylic acid derivatives (278). A 2-substituent was essential for success, and 278 (R1 = R2 = R3 = Me) gave a 90% yield of 279. Similarly, morpholino- and piperidinothioamides 282 formed cycloadducts 283. Treatment of 279 with methanolic hydrochloric acid gave 281 via the ring-cleaved intermediate 280. 

Methyl- and 2,6-dimethylpyrazines with DMAD in acetonitrile yield the corresponding azaindolizines (249),351 whereas 2,5-dimethyl-pyrazine gives a 1 3-molar adduct less the elements of acetonitrile. This adduct, originally described as an azepine,336 is probably the cyclo-butaindolizine 251,337 and could be formed via 250 by cycloaddition of DMAD across the dihydropyrazine ring and elimination of acetonitrile. 

Kobayashi et a/.392 have studied the 1,4-dipolar cycloadditions of DMAD to enaminodithiocarboxylates derived from dihydroquinolines. Addition of acetylene to 351 gave the spirocycloadduct 352 which did... 

Addition of DMAD to the aminochlorobenzodiazepine 17 gave 18 the addition of EP was also described. Cycloadditions of DMAD and EP to the TV-oxide 19 gave 20 and 21, respectively.468,469... 

The cycloaddition of DMAD and EP to 7-acylamino-3-azidomethyl-3-cephem-4-carboxylic acid derivatives (88) gave the expected 1,2,3-triazole derivatives 89 and 90.813 A similar addition of MP to the diazo compound 91 gave 92,814 and the nitrone 93 gave 94 with DMAD, a rearrangement having taken place.815... 

Potts and Roy555 showed that cycloaddition of DMAD occurs with ease to the mesoionic thiazolones 42 and 43. After 15 hours reflux in... 

The synthesis of aza[ ]adderanes and azahomo[ ]adderanes (n number of fused rings) containing /3-lactams at the terminus has been reported for the first time (see Section 2.04.6.3). Cycloaddition of DMAD to the norborene 7i-bond of 513 in the presence of a ruthenium catalyst yielded [5]homoladderane 514 in 89% yield (Equation 85) <1997SL38>. Other examples of these types of compounds are reported in Section 2.04.6.3. 

Photosensitized [w28+ 2,] cycloaddition of DMAD to benzo[6]furan yields the mixture of adducts (314), (315), (316) and (318) (77JOC2374). Adduct (314) is the primary photoproduct and it rearranges via a diradical to the other products. Irradiation of any of the pure isomers yields the same mixture of products. Thermolysis of the adducts (314) and (318) affords the benzoxepins (317) and (319) which may be reclosed photochemically (Scheme 91). 2-Methylbenzo[6]furan yields similar products but only two adducts are formed from benzo[6]furan and methyl propiolate. 

The fluorine containing 7t-exTTF 550 was obtained in the 1,3-dipolar cycloaddition of DMAD to dithiocarboxylic moiety of the dithiocrotonate 549 and subsequent reaction of the resulting intermediate ylide with the starting 549 as a Michael acceptor in an addition-elimination process followed by ethyl bromide elimination. Formation of the second 1,3-dithiole moiety in 550 was connected with the consecutive cycloaddition followed by ethyl bromide elimination (Equation 71) <2003CEJ4324>. 

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