2,3-Diaza-1,3-butadienes Diels-Alder reactions

Since diazaquinones are among the most powerful dienophiles, they undergo [4+2] cycloaddition (Diels-Alder) reactions with a great variety of dienes to give various heterocyclic systems accessible with difficulty by other methods. Diazaquinone reacts with butadiene and substituted butadienes, carbocyclic and heterocyclic dienes, 1-vinylcycloalkenes, polyaromatic compounds and vinylaromatic compounds to afford bicyclic and polycyclic bridgehead diaza systems, including diazasteroids (Scheme 56). 

Jimenez et al. studied the asymmetric Diels-Alder reactions of 1-aryl-1,2-diaza-l,3-butadienes 114, heterodienes derived from sugars, with diethyl azodicarboxylate (115), a heterodienophile [85]. The reactions were performed without solvent in a focused microwave reactor for periods of a few hours. The reaction is stereoselective... 

The stereoselective normal electron demand Diels-Alder reaction of chiral 13-diaza-13-butadienes 42, derived from acyclic carbohydrates, with diethyl azodicarboxylate 2 yields the corresponding functionalized l,23,6-tetrahydro-133,4-tetrazines 43. The observed stereoselectivity is markedly dependent on the relative stereochemistry at C-1 3 - Reactions proceed slowly in benzene solution at room temperature, but are greatly accelerated by microwave irradiation <99JOC6297>. 

Avalos et al. has reported the microwave-assisted synthesis of tetrazine derivatives by a hetero Diels-Alder reaction of homochiral 1,2-diaza-l,3-butadienes with diethyl azodicarboxylate (Scheme 3.40)65. Under conventional conditions, reactions could be performed in benzene solution at room temperature. However, under microwave heating conditions, the reaction was significantly accelerated (by a factor of 1000) when carried out solvent free. The observed stereoselectivity was identical for the hetero Diels-Alder reaction under both microwave-heated and conventional conditions. 

Avalos, M., Babiano, R., Cintas, P., Clemente, F.R., Jimenz, J.L., Palacios, J.C. and Sanchez, J.B., Hetero-Diels-Alder reactions ofhomochiral 1,2-diaza-1,3-butadienes with diethyl azodicarboxylate under microwave irradiation. Theoretical rationale of the stereochemical outcome, /. Org. Chem., 1999,64, 6297-6305. 

Several other options arise from this approach. Thus, amino-N-heterocycles such as 238 can also be used to form l,3-diaza-l,3-butadiens such as 239 as intermediates which undergo the appropriate hetero-Diels-Alder reaction to give 240 and 241 in a ratio of 11 1 [63]. This approach has so far only been used in a two-component domino reaction (Scheme 5.47). 

Further calculations were performed on 2,3-diaza-1,3-butadiene with different heterodienophiles such as ethene, formaldehyde and formaldimine showing the same exo oxygen or nitrogen lone pair preference [49] as well as on the nitro-soethene/ethene system [50]. Recently, ab initio studies have also been performed for the Lewis acid catalysed hetero Diels-Alder reaction of isoprene and sulfur dioxide by Sordo [51]. 

A plethora of different acyclic and cyclic diaza dienes has been employed in aza Diels-Alder reactions. With regard to acyclic dienes, the main interest has focused on the cycloadditions of 1,3-diaza-1,3-butadienes. A current example of these transformations is the preparation of highly substituted pyrimidine derivatives such as 3-65 by cycloaddition of diaza-1,3-butadienes e.g. 3-64 with electron-deficient acetylenes (Fig. 3-20) [299]. 

The formation of pyridazines from 1,2-diaza-1,3-butadienes and electron-rich dienophiles has been reported [308] on the other hand, tetrazine and triazole derivatives have been prepared from these heterodienes and azo esters [309]. Aza Diels-Alder reactions of 1,4-diaza-1,3-butadienes have been employed for the synthesis of unsymmetrical pyrazine derivatives by Heathcock et al. [310]. 

An investigation concerning intramolecular aza Diels-Alder reactions of 3-(co-alkynyl)-l,2,4-triazines has been published by Taylor et al. [327] and trichloro-1,2,4-triazine has been introduced as novel triazine diene recently [328]. 1,2,4-Triazines are a useful alternative of 1,4-diaza-l,3-butadienes with regard to the aforementioned synthesis of pyrazines since Taylor s group has found them to undergo cycloadditions with nitriles followed by extrusion of nitrogen [329]. This reaction is noteworthy since it is a Diels-Alder reaction of both electron-deficient diene and dienophile. 

Boger et al. have worked out numerous total syntheses of natural products basing on aza Diels-Alder reactions of electron-deficient N-heterocycles which act as diaza-1,3-butadienes [11]. The key steps of these reactions have been highlighted in Sect. 3.5. 

Although Diels-Alder reactions of disilenes to 1,3-dienes rather represent an exception, [2+4]-cycloaddition is the preferred reaction route for the photolysis of 1 in the presence of 1,4-heterodienes. Thus, for example, 1,4-diaza-1,3-butadienes react smoothly to yield the six-membered ring products 15 when the spatial demands of the substituents at nitrogen are not too great. 

A select group of 1,4-diaza-1,3-butadienes have been demonstrated to participate as 4ir components of Diels-Alder reactions (Table 12). Perhaps the most successful system described to date is the LUMOdiene-controlled [4 + 2] cycloaddition reaction of diiminosuccinonitrile, a 1,4-diaza-1,3-butadiene substituted with C-2 and C-3 electron-withdrawing groups, with electron-rich dienophiles (equation 15). A common and competitive reaction of the a-diimines is [2 + 2] cycloaddition to afford azetidine cycloaddition products and many of the early reports of the [4 + 2] cycloaddition reactions are incorrect. 

The examples of 2,3-diaza-1,3-butadienes participating as 4tt components of Diels-Alder reactions are rare, and each successful case constitutes the reaction of a cyclic diene confined to an s-Z (cisoid) diene conformation (Table 12). Typical efforts to promote the Diels-Alder reactions of 2,3-diaza-l,3-buta-dienes provide simple imine addition products, e.g. 2 1 adducts, or [3 + 2] criss-cross products that may be attributed to the strong preference for simple acyclic 2,3-diaza-1,3-butadienes to adopt an s-E (trans-oid) diene conformation. 

Hetero-Diels-Alder reactions of chiral l-aryl-l,2-diaza-l,3-butadienes gave 97 . Condensation of hydrazones with 2-hydrazino-4-methyl quinoline afforded 98. ... 

A select group of 1,3-diaza- 1,3-butadienes has been reported to undergo [4 + 2] cycloadditions, but the lack of extensive efforts with this system reflects the current difficulty encountered in the preparation of stable 1,3-diaza-l,3-butadienes and their reluctance to participate in the Diels-Alder reactions. Successful efforts which have been described include the thermal isomerization of an unsaturated iV-silylurea with the in situ generation and subsequent Diels-Alder reaction of a 2-trimethylsily-loxy-1,3-diaza-1,3-butadiene [Eq. (49)],124... 

In a complementary series of observations the simple azoalkenes, 1,2-diaza-1,3-butadienes, were shown to participate in apparent normal (HO-MOdiene controlled) Diels-Alder reactions with typical electron-deficient dienophiles [Eq. (44)]108... 

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