Dimethyl -1,2,4,5 -tetrazine- 3,6-dicarboxylate Diels-Alder with

Pyrroles, indoles and benzo[ft]thiophene act as good dienophiles in inverse electron demand Diels-Alder reactions with 1,2-diazines, 1,2,4-triazines and sy/n/n-tetrazines. This is examplified by the formation of compounds (189) in excellent yields on interaction of indoles and benzo[c]thiophene with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate (87JOC4610 90JOC3257). There are also many examples of such intramolecular reactions, e.g. (190 — 191). 

A novel formal inverse-electron-demand hetero-Diels-Alder reaction between 2-aryl-a,/3-unsaturated aldehydes and ketones produces dihydropyran derivatives stereo-specifically.161 The inverse-electron-demand Diels-Alder reaction of 3,4-r-butylthio-phene 1-oxide with electron-rich dienophiles shows vyn-jr-face and endo selectivity.162 (g) The inverse-electron-demand Diels-Alder reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate with a variety of dienophiles produces phthalazine-type dihydrodiol and diol epoxides which were synthesized as possible carcinogens.163... 

The spiro compound 106 underwent a Diels-Alder cycloaddition with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate to give the condensed 1,2-diazocine 107, presumably via retrograde deazatization of the initial [4+2] cycloadduct with cleavage of the cyclobutane ring (Scheme 22) <20040L1313>. 

The inverse electron demand Diels-Alder (IDA) reactions of 3-substituted indoles as 2rt-components with 1,2,4-triazines and 1,2,4,5-tetrazines proceeded in excellent yields both inter- and intramolecularly <1996TL5061>. The reaction of iT-BOC-tryptamine (1110, R = BOCNH(CH2)2) and indole 1110 (R =Me) with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate 1111 in refluxing dioxane (3h) provided cycloadducts 1112 (R2 = B0C) and 1113, respectively, in excellent yields (80% and 82%, Scheme 217). Deprotection of compound 1112 produced derivative 1112 (R = H, >99%). 

Diels-Alder Reaction of Dimethyl 1,2,4.5-Tetrazine-3,6-dicarboxylate with C=N Heterodienophiles ... 

The procedure describes the preparation and use of a reactive, electron-deficient heterocyclic azadiene suitable for Diels-Alder reactions with electron-rich, unactivated, and electron-deficient dienophiles. Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate, because of its electron-deficient character, is ideally suited for use in inverse electron demand (LUMOdiene-controlled) Diels-Alder reactions. Table I and Table II detail representative examples of the reaction of dimethyl 1,2,4,5-tetrazine-3.6-... 

Most of the synthetic approaches towards benzoannelated [2.2]paracyclo-phanes use the Diels-Alder reaction to build up the annelated rings [18,22,29]. [2.2]Paracyclophane-l-ene (32) and [2.2]paracyclophane-1,9-diene (42) can be considered as the simplest dienophiles for this purpose. Since the first syntheses of these compounds in 1958 by Cram et al. [32], various attempts have been made to get them to react with dienes in terms of Diels-Alder reactions. However, [2 + 4] cycloadditions were never observed [33], and could not be facilitated either by the application of high pressure, or the presence of Lewis acid catalysts Diels-Alder adducts were not even obtained with dienes such as tetrachloro-thiophene dioxide, known for its high reactivity in [2 + 4] cycloadditions with an inverse electron demand. All the more surprising was the observation that monoene 32 reacts smoothly with dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate at room temperature leading to a dihydropyridazine-annelated paracyclophane 39 in high yield [34a]. As reported for other tetrazine Diels-Alder reactions... 

A review containing 123 references on recent mechanistic and theoretical studies of hetero-Diels-Alder reactions has been presented. The hetero-Diels-Alder reactions of homochiral 1,2-diazabuta-1,3-dienes with diethyl azodicarboxylate are accelerated by microwave irradiation to produce the corresponding functionalized 1,2,3,6-tetrahydro-l,2,3,4-tetrazines. " The transition structures for hetero-Diels-Alder reactions involving the heteroatoms O, S, and N in dienes and also in dienophiles were determined at the MP2 and the hybrid DPT levels of theory. The activation volume of the Diels-Alder reaction between dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate and hex-l-ene indicates the conservation of all four nitrogen atoms in the transition state. " 4-n-Propyl-l,2,4-triazoline-3,5-dione reacts with cyclopentadienes, cyclohexadienes, and cycloheptadienes to yield 4 + 2-cycloadducts. ... 

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