Hetero Diels-Alder reaction triazines

Pyridine synthesis via hetero-Diels-Alder reaction of 1,2,4-triazines and dieno-philes (e.g. enamine) followed by extrusion of N2. 

Indian workers described the synthesis of l,3,4-thiadiazolo[3,2-a]-5-triazine-5(//)-thiones (61) by a hetero Diels-Alder reaction between 2-(arylideneamino)-5-ethylthio-l,3,4-thiadiazoles (60) and aromatic isothiocyanates (Equation (2)) <94MI 410-0I>. Thiadiazoles can be reduced with sodium amalgam to the aldehyde thiosemicarbazone while lithium aluminum hydride will reduce mesoionic thiadiazoles all the way to the hydrazine <84CHEC-I(4)545>. 

Sheldrake and co-workers devised an elegant approach to interesting cage compounds based on an intramolecular hetero Diels-Alder reaction (88CC1482) (Scheme 51). The [4 + 2] cycloaddition of triazines 223 to 1,5-cyclooctadiene at M0°C resulted in the formation of 7-azatetracyclo[7.3.0.02 6.05 lo]dodec-7-ene derivatives 225 in 44-66% yield. The initial formation of 224 followed by the intramolecular cycloaddition of the electron-poor 2-azadiene moiety to the second carbon—carbon double bond of the cyclooctadiene system accounts well for the process. The dienophile unit can be placed just over the diene system favoring... 

Intramolecular hetero-Diels-Alder reactions provide a novel approach to polycyclic pyrazines and lumazines if 1,2,4-triazines contain the dienophilic component in a side chain tethered to the... 

Boger and Panek (85JA5754) have also accomplished a formal total synthesis of streptonigrin (63) based on two hetero Diels-Alder reactions (Scheme 8). The initial cycloaddition of the S-methylthioimidate 64 and l,2,4,5-triazine-3,6-dicarboxylate 65 provided 1,2,4-triazine 66 (82%), which was then used as an azadiene component of the second Diels-Alder reaction. The following step will be described in Section III,B,1. 

Hetero-Diels-Alder reactions. A method of pyridine synthesis by catalyzed reaction between a 1,2,3-triazine with an aldehyde enamine is useful for the elaboration of fusaric acid. 

Butyl-2-methylpyridine (29) was made in modest yield by hetero Diels-Alder reaction of enamine (30) with 1,2,3-triazine (31) (Scheme 12) (94H(38)1595). 

Pyrrolidine has been the common organocatalyst used by Boger and coworkers for the synthesis of highly substituted pyridines based on the inverse-electron-demand Diels-Alder reaction of in situ formed enamines and 1,2,4-triazines. Barbas and coworkers have described the amine-catalysed direct self-Diels-Alder reaction of a,p-unsaturated ketones. The inverse-electron-demand hetero-Diels-Alder reaction of nitrosoalkenes and in situ formed enamines as dienophiles was also shown to be possible. ... 

Among the reactions of the 1,2,4-triazines, the hetero-DiELS-ALDER reactions with electron-rich alkenes and alkynes are of general importance in synthetic chemistry [321]. 

The Boger pyridine synthesis involves the reaction of triazine 1 with activated alkene 2 in a hetero-Diels-Alder fashion. The intermediate bicyclic species 3 is unstable and a facile cycloreversion takes place due to the loss of nitrogen gas to afford the appropriately substituted pyridine derivative 4. 

As a rule, the initial hetero-DiELS-ALDER adduct 2 cannot be isolated. It eliminates N2 in a retro-DiELS-Alder reaction and is converted into a 4,5-dihydropyridazine 3. This can be stabilized as a 1,4-dihydropyridazine 7 (especially if X = H) by a 1,5 hydrogen shift or (if X = OR and NR2) as the pyridazines 5 and 6 by dehydrogenation or HX elimination. As a diazadiene, it can also engage in a further Diels-Alder reaction with excess of alkene 3delding the stable 2,3-diazabicyclo[2.2.2]oct-2-ene 4. The initial Diels-Alder product tetraazabicyclo[2.2.2]octatriene 8, which arises from the reaction between alkynes and 1,2,4,5-tetrazines, undergoes a cycloreversion with N2 elimination affording the pyridazine 6. With nitriles, 1,2,4-triazines 9 are obtained. 

Pyridines can be achieved by the [4 + 2] hetero Diels-Alder cycloaddition of i) an alkene dienophile and an 3-azadiene such as 1,2,4-triazine (the Boger reaction), oxazole (Kondrat eva pyridine synthesis), oxazinone, pyrimidine, or ii) an alkene and a 4-azadiene or iii) a butadiene and an azadienophile. 

The Boger pyridine synthesis involves an inverse-electron demand hetero-Diels-Alder [4 + 2] reaction of the electron-deficient 1,2,4-triazine... 

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