Diels-Alder reaction Of azadienes

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. 

Intramolecular Diels-Alder reactions of azadienes 76 afforded 6-cyano-2,3,4,8,9,9a-hexahydropyrido[2,l-6][l,3]oxazines 77 (99TL7211, 99TL7215). Cyclization was carried out smoothly at or below room temperature in... 

Bis-silyloxy-3,4-dihydropyridines are stable dienes easily synthesized from glutarimide. The Diels-Alder reaction of azadiene 47 with iV-methylmaleimide in benzene at 60 °C gives predominantly the endo-adduct 48, whereas the selectivity is reversed in reaction with lithium trifluoromethanesulfonimide in ether giving predominantly the < vo-adduct 49 (Scheme 12) <1995SL565>. When methyl acrylate is used as the dienophile, the reaction... 

A synthesis of streptonigrin (5), an antitumor antibiotic, depends on two sequential Diels-Alder reactions of azadienes, reaction of 1 with an S-methyl thioimidate to give the 1,2,4-triazine 2, and reaction of 2 with a morpholinoenamine (3) to afford 4 (Chart I). ... 

Boger DL (1983) Diels-alder reactions of azadienes. Tetrahedron 39 2869-2939... 

Many ring-fused imidazole derivatives have been synthesized by various methods. Domino Michael addition retro-ene reaction of 2-alkoxyiminoimidazolidines and acetylene carboxylates provided a synthesis of 2,3-dihydroimidazo[l,2-a]pyrimidin-5-(l//)-ones <05T5303>. A single step synthesis of 3,5-dialkyl-9-nitroimidazo[l,2-c]quinazolin-2(3//)-ones from simple carbonyl compounds, primary amines or amino acid methyl esters and 2-azido-5-nitrobenzonitrile has been published <05TL5778>. Diels-Alder reaction of azadienes and benzimidazole-4,7-diones afforded imidazo[4,5-g ]quinoline-4,9-dione derivatives <05EJ01903>. Reaction between isocyanides and dialkyl acetylenedicarboxylates in the presence of 4,5-diphenyl-l,3-dihydro-2//-imidazol-2-one provided a one-pot synthesis of 5//-imidazo[2,l-ft][l,3]oxazine derivatives <05T2645>. Microwave irradiation was employed in the synthesis of 1-ary 1-3-acetyl-1,4,5,6-... 

There is a further disadvantage in using simple Diels-Alder reaction of azadienes to make heterocycles. The products, e.g. 2 and 4 are themselves either imines or enamines and are inherently unstable and it is also necessary to stabilise them to make isolation of the heterocycle possible. 

Six-membered heterocycles The Diels-Alder reaction of azadienes with TCNE yielded tetrahydropyridines. Dicyanopyridines 402 have been obtained by cyclization of tetracyanoethylated ketones with hydrochloric (X = Cl) or hydrobromic (X = Br) acid. Yields are between 61 and 84%". ... 

A very selective hetero Diels-Alder reaction of azadiene (32) with maleic anhydride gave tetrahydropyridine (33) in greater than 98% d.e. under mild conditions (Scheme 13) <94T(A)557). 

Cycloadditions continue to be a powerful way to build pyridines. Indeed, a recent review describes the Diels—Alder reaction of azadienes to form pyridines either by the traditional thermocyclic manner or when catalyzed by transition metals (140rganic Chemistry FrontierslOlO). In addition to cycloaddition approaches, the other main route to pyridines continues to be cyclocondensations. 

The Diels-Alder reaction of azadiene 106 prepared from l-methyl-2,4-dihydro-lH-pyrazino[2,l-fo]quinazoline-3,6-dione [255] with 3-methyleneoxindole 107 proceeds smoothly in chloroform at rt to afford exo- (108) and endo-isomer (109) in 55 and 18% yields, respectively. Mild hydrolysis of... 

Fig. 8.80 Imino Diels-Alder reaction of azadiene formed in situ with DHP catalyzed by InCb.

Diels-Alder Reactions of Azadienes Scope and Limitations"... 

Tab. 5.13 Catalytic asymmetric aza Diels-Alder reactions of 2-azadienes...

Diels-Alder reactions of 1-azadienes are less thermodynamically favorable [92] than the all-carbon analogs because of the stronger carbon nitrogen 7r-bond which is broken during the Diels-Alder reaction. 

Ultrasound irradiation is particularly beneficial for Diels Alder reactions of unactivated azadienes because the reaction can be carried out under mild conditions. 

Spanish researchers [32] also noted a considerable improvement upon sonica-tion of Diels-Alder reactions of l-dimethylamino-3-methyl-l-azadiene 44 with a variety of electron-deficient dienophiles by using diene as solvent or in acetonitrile (Scheme 4.9). Ultrasound irradiation which allows mild reaction conditions gave good to excellent yields. 

Lanthanide triflates catalyze the Diels-Alder reaction of imines, generated from anilines and aldehydes, with both dienes and alkenes [26]. Thus N-benzyl-ideneaniline in the presence of Yb(OTf)3 (Scheme 6.16) reacts in organic solvent with open-chain dienes, such as Danishefsky s diene, to give tetrahy-dropyridine derivatives, while with cyclopentadiene and vinylethers and vinylthioethers it works like azadiene in both organic solvent and aqueous medium, affording tetrahydroquinoline derivatives. 

Behforouz M., Ahmadian M. Diels-Alder Reactions of 1-Azadienes Tetrahedron 2000 56 5259-5288... 

Boger D. L. Heterocyclic and Acyclic Azadiene Diels-Alder Reactions Total Synthesis of Nothapodytine B. J. Heterocycl. Chem. 1998 35 1003-1011 Keywords inverse electron-demand Diels-Alder reactions, acyclic azadienes, synthesis of natural products... 

Catalysts such as Fe(BuEtCHC02)3 have been d eloped that are effective for the heteroatom Diels-Alder reaction. Indium trichloride (InCls) is a good catalyst for imino-Diels-Alder reactions. Hetero-Diels-Alder reactions involving carbonyls have been done in water. Ultrasound has been used to promote the Diels-Alder reactions of 1-azadienes. ... 

The Diels-Alder reaction of 1-azadienes suffers from low conversion, because of the low reactivity of these systems. In an attempt to overcome this problem, considerable effort has been focused on both inter- and intramolecular versions of the reaction. 

Similarly, Motorina described the intramolecular hetero-Diels-Alder reaction of N-alkyl-2-cyano-l-azadienes 86 (Scheme 9.26) [76] although the reaction had already been performed by heating the reactants in benzene overnight in a sealed tube at 110 °C, it was found that reaction time could be reduced to 14 min in a microwave oven at 650 W. 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

PREPARATION AND INVERSE ELECTRON DEMAND DIELS-ALDER REACTION OF AN EEECTRON-DEFICIENT HETEROCYCLIC AZADIENE TRIETHYL 1.2,4-TRIAZINE-3,5,6-TRICARBOXYLATE... 

The regiochemistry of the Diels-Alder reaction of l-alkoxy-3-(rm-butyldimethylsilyl)oxy-2-azadienes and naphthoquinones, as a route to 2-azaanthraquinon-3-ones, has been investigated (91H915). 

Preparation and Diels-Alder Reaction of a Reactive, Electron-Deficient Heterocyclic Azadiene Dimethyl 1,2,4,5-Tetrazine-3,S-Dicarboxylate. 1,2-Diazine and Pyrrole Introduction. 

Ab initio and density functional theoretical studies of the 4 + 2-cycloaddition of 2-azabutadiene with formaldehyde predict a concerted reaction that agrees well with experimental evidence.184 The azadiene A-plienyl-l-aza-2-cyanobuta-l,3-diene reacts with electron-rich, electron-poor, and neutral dipolarophiles under mild thermal conditions.185 5,6-Diliydro-4//-1,2-oxazines have been shown to be usefiil as synthon equivalents of 2-cyano-l-azabuta-1,3-dienes.186 The intramolecular Diels-Alder reaction of 1-aza-l,3-butadienes (106) can be activated by a 2-cyano substituent (Scheme 37).187 Stereoselectivity in the hetero-Diels-Alder reactions of heterobutadienes, nitrosoalkenes, and heterodienophiles has been extensively reviewed.188 The azadiene l-(f-butyldimethylsilyloxy)-l-azabuta-1,3 -diene (107) reacts with halobenzo-quinones, naphthoquinones, and A-phcnylmalcimidc to yield low to good yields of various pyridine heterocycles (108) (Scheme 38).189 The 4 + 2-cycloaddition of homophthalic anhydride with A-(cinnamylidcnc)tritylaminc produces the 3,4-adduct whereas with A -(cinnamylidcnc)bcnzylidinc the 1,2-adduct is produced.190... 

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