Azadienes, in Diels-Alder reactions

The benzoxazoles 59 and 60 can act as azadienes in Diels-Alder reactions with nucleophilic alkenes such as vinyl ethers <98JCS(P1)3389>. ... 

Pyridine annelation.1 1,2,4-Triazine can function as a reactive azadiene in Diels-Alder reactions with enamines, particularly pyrrolidine enamines, to form substituted pyridines. 

Azadienes undergo Diels-Alder reactions to form pyridine, dihydro- and tetrahydropyridine derivatives. N-Vinyl lactim ethers undergo Diels-Alder reactions with a limited set of dienophiles. " Thioketones react with dienes to give Diels-Alder cycloadducts. The carbonyl group of lactams have also been shown to be a dienophile. Certain heterocyclic aromatic rings (among them furans) can also behave as dienes in the Diels-Alder reaction. Some hetero dienes that give the reaction are -C=C-C=0, 0=C-C=0, and N=C-C=N. ... 

Bis-l,2,4-triazole-3,5-diones such as 110 have also been used in Diels-Alder reactions, and give bispyridazines.171 The pyridazine derivative 111 is formed in quantitative yield from PTAD and 2,7-dimethyl-2,3,5,6-octatetraene,172 and the azadiene, 4-aza-l,3,5-triphenylpenta-2,4-diene, also reacts readily with PTAD to give 112.173 There are many other examples of Diels-Alder additions of ADC compounds to simple acyclic dienes which proceed entirely as expected the above selection has been limited to reactions of synthetic potential and with novel features. 

The diastereofacial selectivity of 2-azadienes with a stereogenic center attached to C-l in Diels-Alder reactions has been investigated (Scheme 63). The synthesis of monochloro derivatives 284 was readily achieved in excellent yields by halogenation of 139 with ALchlorosuccinimide. The... 

Five-membered heteroaromatic systems that possess an electron-deficient azadiene substructure, e.g., oxazoles and thiazoles, are suitable for participation in Diels-Alder reactions with inverse electron-demand [49JA3062 59JA4342 62AG(E)329]. The introduction of strongly electron-donating substituents in many cases is sufficient to overcome the electron-deficient nature of the azadiene moiety and permits normal HOMO diene/ LUMO dienophile controlled Diels-Alder reactions (87MI6). 

The preparation or in situ generation of azabutadienes bearing a formal positive charge, i.e. an im-monium cation, provides a substantial enhancement of the electron-deficient character of the azadiene and in many instances such systems have proven to be effective 41 components in Diels-Alder reactions with electron-rich or neutral dienophiles. The most widely recognized class of cationic azadienes shown... 

In many instances, the entropic assistance provided in the intramolecular Diels-Alder reaction is sufficient to promote azadiene participation in Diels-Alder reactions.12 The incorporation of the azadiene system, or dienophile, into a reactive or sensitive system, e.g., heterocumulene or strained olefin, allows a number of specialized azadiene Diels-Alder reactions. Many such examples may represent stepwise, polar [4 + 2] cycloaddition reactions. 

An extensively investigated and useful hetero-2-azadiene system capable of 4it participation in Diels-Alder reactions is the vinylnitroso compounds.75-78 The complementary addition of electron-withdrawing substituents to the 3 position of the vinylnitroso system enhances the rate of diene participation in inverse electron demand Diels-Alder reactions with electron-rich or neutral dienophiles (simple olefins).75,76 Table 9-IV summarizes a series of representative examples of the 47r participation of vinylnitroso compounds in Diels-Alder reactions, and an extensive review has summarized much of this work.5,75... 

Since the early demonstrations of the participation of substituted 1,2,4,5-tetrazines1 and oxazoles2 in Diels-Alder reactions with olefinic and acetylenic dienophiles, the potential utilization of the [4 + 2] cycload dition reactions of heteroaromatic systems possessing a suitable azadiene arrangement has been the focus of extensive investigations.3-8 In general, the heteroaromatic systems which possess an electron-deficient azadiene... 

AAAcylimines, e.g., 4, are the most widely recognized and the most extensively investigated hetero-2-azadiene system capable of participation in Diels-Alder reactions, and comprehensive reviews have been published.7,71 In general, substituents X and Y are strongly electron-withdrawing groups and consequently the AAacylimines participate as electron-deficient partners in cycloaddition reactions with electron-rich dienophiles. Diels-Alder reactions of electron-deficient /V-acylimines with vinyl ethers, enamines, olefins, sulfenes, acetylenes, and the carbon-carbon or carbon-oxygen double bond of ketenes have been detailed.57 71 This 47t participation of electron-deficient AAacylimines does complement the ability of many simple AAacylimines to behave as 2ir dienophile components in Diels-Alder reactions with typical electron-rich dienes.6... 

The additional substitution of the heterocyclic azadiene system with electron-withdrawing groups accents the electron-deficient nature of the heterodiene and permits the use of electron-rich, strained, or even simple olefins as dienophiles.3 415 6 Substitution of the heterocyclic azadiene with strongly electron-donating substituents in many instances is sufficient to overcome the electron-deficient nature of the azadiene and permits the use of conventional electron-deficient dienophiles in normal (HOMCWne controlled) Diels-Alder reactions.4 6 The entropic assistance provided by the intramolecular Diels-Alder reaction is sufficient in most instances to override the reluctant azadiene participation in Diels-Alder reactions.7 The incorporation of the heterocyclic azadiene, or the dienophile, into a reactive system, e.g., heterocumulene, allows a number of specialized [4 + 2] cycloaddition processes which are best characterized as stepwise addition-cyclization [4 + 2] cycloadditions.8... 

Azadienes (amino or amido dienes) constitute another important class of hetero-substituted dienes. There are three major types, amino dienes such as 147, amido dienes such as 148, and carbamoyl dienes such as 149. Both 1- and 2-substituted aminodienes are possible and function as diene partners in Diels-Alder reactions. 

Alternatively, the complementary addition of strong electron-donating substituents to the azadiene system increases the nucleophilic character of the azadiene system and permits the use of conventional electron-deficient dienophiles in Diels-Alder reactions. In such instances, the azadiene systems are participating in normal (HOMOd,ene controlled) Diels-Alder reactions. The appropriate introduction of electron-donating substituents to the azadiene system raises the HOMOazadiene, reduces the magnitude of the HOMOazadiene-LUMOdienophiie energy separation, and accounts for the accelerated participation of nucleophilic azadienes in normal Diels-Alder cycloadditions. 

Alkynes can also undergoes consecntive process under silylformylation conditions. Thus, rhodium catalyzed silylformylation of alkyne 217 in the presence of primary or secondary amines leads directly to the azadiene 221 by silylformylation and enamine formation [ 139]. These azadienes undergoes Diels-Alder reaction with dimethyl acetylendicarboxilate to give dihydropyridiaes 222. 

Considering the Frontier Molecular Orbitals (FMO) involved justifies the unexpected normal Diels-Alder reactivity of 2-azadiene 1 toward diethylfumarate. Compare the reactivities of butadiene and 2-azadiene 1 and discuss the dual reactivity of this compound with respect to both, electron-deficient and electron-rich dienophiles. Justify the observed reactivity of dienes 4, 5 and 6 in Diels-Alder reactions. 

Heterocyclic and acyclic azadiene Diels-Alder reaction in total synthesis of nothapodyine B, alkaloid with antiviral activity 98JHC1003. 

In 1996, the first example of the catalytic enantioselective aza Diels-Alder reactions of azadienes using a chiral lanthanide catalyst was reported [4], In this article, successful examples of such catalytic reactions are surveyed. 

For examples of Diels-Alder reactions involving 2-azadienes, see (a) Boger, D.L. Weinreb, S.M. In Hetero Diels-Alder Methodology in Organic Synthesis, Academic Press San Diego, 1987, p. 255 (b) Boger, D. L. Tetrahedron 1983, 39, 2869. 

Tungsten alkynyl Fischer carbene complexes are excellent dienophile partners in the classical Diels-Alder reaction with 1-azadienes (see Sect. 2.9.2.1). On the contrary, the chromium-derived complexes exhibit a different behaviour and they react through a [4S+3C] heterocyclisation reaction to furnish azepine derivatives [116] (Scheme 68). The reaction is initiated by a 1,2-addition of the nitrogen lone pair to the carbene carbon followed by a [l,2]-Cr(CO)5 shift-pro-... 

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