Diaza-Diels-Alder cycloaddition

A diaza-Diels—Alder cycloaddition generated the adduct 62 which was hydrogenolyzed to form the nine-membered ring in 63. Ring enlargement to a 13-membered system, presumably via 65, was achieved by treating 64 with acid. 

Conjugated dienes possessing the 2,3-diaza-1,3-butadiene system rarely participate in effective [4 + 2] cycloadditions. Typical efforts to promote the Diels-Alder cycloadditions of such systems with representative dienophiles afford 2 1 adducts or [3 + 2] criss-cross products.11... 

Diaza-l, 3-butadienes undergo hetero-Diels-Alder cycloaddition with Cgo to afford fused tetrahydropyridazine derivatives 85. The heterodienes are produced in situ upon heating of 2,5-dihydro-l,3,3-thiadiazole-l,l-dioxide 84 (06TL4129). 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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). 

A very different type of Diels-Alder reaction is that of the Schiff s base (165) with pyrrolidinocyclohexene (equation 19) (76CPB2889) it is a rare example of a cycloaddition to the 1,3-diaza-l,4-diene system. 

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]. 

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. 

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. 

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... 

Only a select group of 1,4-diaza-1,3-butadienes has been shown to function as 4w components of [4 + 2] cycloadditions. Dehydroindigo affords Diels-Alder products on reaction with styrene, vinyl aryls, acrylonitrile, methyl acrylate, and methyl propiolate under forcing conditions [Eq. 

Diels-Alder reaction at higher temperature (around 110-120 °C) to give azaphos-phabarrelenes 38 which finally decompose to yield the expected 2,3,5,6-tetrafunc-tional phosphinines 39. Importantly, the difference of reactivity between diaza and mono aza-phosphinine derivatives allows the successive use of two different alkynes. The general principle of this synthetic approach is presented in Scheme 10. It is important to mention that all these cycloaddition/cycloreversion sequences can be performed in the same flask and there is no need to isolate the 2-zaphosphinine formed after the first Diels-Alder reaction. 

---