Dimethyl 1,2-diazine-3,6-dicarboxylates

Boger et al. reported the first total synthesis of ningaline D (282) starting from the diphenylacetylene 1092 and dimethyl l,2,3,4-tetrazine-3,6-dicarboxylate (1093) (687). In this synthesis, the key step is the formation of the fully substituted pyrrole core using an inverse electron demand heterocyclic azadiene Diels-Alder reaction followed by a reductive ring contraction of the resultant 1,2-diazine. 

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). 

Preparation and Diels-Alder Reaction of a Reactive, Electron-Deficient Heterocyclic Azadiene Dimethyl 1,2,4,5-Tetrazine-3,S-Dicarboxylate. 1,2-Diazine and Pyrrole Introduction. 

Diels-Alder reactions pyrrolesThis azadiene undergoes [4 + 2] cycloaddi-non with unactivated dienophiles to form dimethyl l,2-diazine-3,6-dicarboxylates, hich are reduced by zinc in acetic acid with ring contraction to dimethyl pyrrole-1.5-dicarboxylates. 

Deuteration of arenes, 206 Deuterium, role in nmr, 243 Dextrorotatory, 70 Diastereomers, 69 conformational, 80 Diastereoselective reactions, 91 Diazine, 458, 460 Diazomethane, 67, 353 Diazonium ions, 409 Diazonium salts, 416 Dicarboxylic acids, 342 Diels-Alder reaction, 154 Dienes, polymerization, 153j summary of chemistry, 154 Dienophile, 154 Dihalides, dehalogenation, 91 Dimethyl sulfoxide (DMSO), 305 Dioxane, 285 Dioxin, 447... 

This approach to 1,2-diazine and pyrrole introduction based on the inverse electron demand Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate complements the [4 + 2] cycloaddition reactions of a range of electron-deficient heterocyclic azadienes which permits the divergent preparation of a range of heterocyclic agents employing a common dienophile precursor, Scheme I. 

Dimethyl 4-phenyl-1,2-diazine-3,6-dicarboxylate 3,6-Pyridazinedicarboxylic acid,... 

PREPARATION AND DIELS-ALDER REACTION OF A REACTIVE, ELECTRON-DEFICIENT HETEROCYCLIC AZADIENE DIMETHYL 1,2,4,5-TETRAZINE-3,6-DICARBOXYLATE. 1,2-DIAZINE AND PYRROLE INTRODUCTION... 

Diels-Alder Reactions of Dimethyl 1,2,4,5-Tetra2ine-3,6-dicarboxylate 1,2-Diazine Introduction6 ... 

Dimethyl 4-phenyl-1,2-diazine-3,6-dicarboxylate 3,6-Pyridazinedicarboxylic acid, 4-phenyl-, dimethyl ester (9) (2166-27-0)... 

Boger DL, Panek JS et al (1992) Preparation and Diels-Alder reaction of a reactive, electron-deficient heterocyclic azadiene dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate. 1,2-Diazine (dimethyl 4-phenyl-l, 2-diazine-3, 6-dicarboxylate) and pyrrole (dimethyl 3-phenylpyrrole-2, 5-dicarboxylate) introduction. Organic Synth 70 335... 

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