Diazines 2 + 4 cycloaddition

Exceptions to this generalization are restricted to the reactions of ynamines with electron-deficient 1,2-diazines, where both C-3/C-6 and C-4/N-l 1,2-diazine cycloaddition have been observed [Eq. (15)].73... 

The number and position of electron-withdrawing substituents on the 1,2-diazine nucleus control the mode and regioselectivity of the ynamine 1,2-diazine cycloaddition, and in each case studied, only one reaction product was detected.73 Much of this work is summarized in Table lO-III. 

Aspects of benzonitrile oxide cycloaddition to all three parent diazines have been investigated <96T6421>, and the stereochemistry of resultant biscycloadducts determined <96JCR(S)220>. 

Similarly, mono- and bicyclic 1,2-diazines tethered to indole dienophiles by only one alkylene chain 14 afford tetra-and pentacyclic condensed carbazoles 15. Unactivated pyridazines undergo these thermally induced [4+2] cycloaddition reactions only very sluggishly. However, the examples with the more activated electron-deficient pyridazines, especially pyridazine diesters and pyridazino[4,5-, pyridazindiones, demonstrate the synthetic usefulness of this strategy for the construction of polycyclic carbazoles (Equation 3) <2004T6495>. 

Figure 13 1,2-Diazines obtained by cycloaddition reactions starting from 1,2,4,5-tetrazines.

The other diazines can also undergo cycloaddition with ynamines an example of a pyridazine addition is shown in equation (94) (72TL1517), and of an addition to a pyrazine in equation (95) (72LA(761)39). Pyrazinediones react with the electron-deficient acetylenedicar-boxylic ester, with subsequent expulsion of isocyanic acid, as shown in equation (96) (73JCS(P1)404). 

The most interesting compounds described in this paragraph are meso-ionic naphtho[reactions with olefinic compounds. For instance, the reaction with acetylenedicarboxylates gives rise to adducts 458, which are dehydrogenated spontaneously to the new heteroaromatic systems 459 with the aromatic 147r-electron contour [75JCS(PI)556]. 

Heterocyclic azadienes like di- and triazines have been used in the synthesis of pyridine rings. In general terms the reaction involves a regiospecific inverse electron demand Diels-Alder cycloaddition between the heterocycle and the enamine 280 followed by elimination of HCN (diazines) or N2 (triazines) and an amine from the primary cycloadduct 281 or 283, respectively, to give pyridines 282 and 284 (equation 61). At least in one case the latter type of intermediate has been isolated and fully characterized148. 

Thus, the electron-deficient 1,2,4,5-tetrazine 7 reacts smoothly with the electron-rich acetylene 8 in an inverse electron-demand Diels-Alder reaction First, the [4+2] cycloaddition of 7 with 8 takes place and then the formed intermediate 9 loses N2 to provide the symmetrical 1,2-diazine 6. 

Weinreb, S. M., Scola, P. M. N-acyl imines and related hetero dienes in [4+2]-cycloaddition reactions. Chem. Rev. 1989, 89,1525-1534. Marcelis, A. T. M., van der Plas, H. C. Diels-Alder reactions of diazines and pyridines. Trends Heterocycl. Chem. 1990, 1,111-123. 

The addition of cyclopropenes to diazines gives seven-membered lactones under very mild conditions, apparently by initial [4 + 2] cycloaddition, loss of nitrogen and then a Cope rearrange-... 

A related approach has been used for the synthesis of 1,2-diazines of type 146 according to Scheme 68 [165]. After cycloaddition to tetrazine 144, nitrogen is... 

Diazines, triazines, and tetrazines react with electron-rich dienophiles as well as with electron-deficient dienophiles by a (4- - 2)-cycloaddition reaction. The reaction between 1,2,4-triazines and JV,N-diethylaminopropyne does not give pyridazines as reported previously/ but the corresponding pyrimidines. 

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. 

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