Diethyl azodicarboxylate, cycloadditions

Treatment of 6-arylidenehydrazino-3-alkyl-5-nitrouracils 510 with etha-nolic KOH caused a benzylic acid type of rearrangement to give 511, which were alkylated to give 512, whose cyclization with diethyl azodicar-boxylate gave (80H1295) 513 by intramolecular cycloaddition through valence isomerization and then aromatization with diethyl azodicarboxylate (Scheme 107). 

The reactivity of compound 113 toward reactive linear and cyclic dienophiles was reported in a study directed to find a model systems for the proposed [4+2] cycloaddition in the biosynthesis of the natural products brevianamides, paraherquamides, and marcfortines. With DMAD and diethyl azodicarboxylate the formation of 114 and 115 was almost quantitative after 48 h at 80 °C (Cbz = Carbobenzyloxygroup). When relatively unreactive dienophiles such as cyclopentene and cyclohexene were used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the formation of 116a and 116b (Scheme 16). In contrast, the analogous intramolecular reaction carried out on compound 117 takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst, to give 118 in 42% yield (Scheme 16) <2000T6345>. 

A similar 1,3-dipolar cycloaddition occurs with diethyl azodicarboxylate, and the intermediate 1,3-cycloadduct was isolated. Amidines (101) and halogenoacetonitriles (XCHjCN) yield 4-amino-1,3-diazolium salts (102) directly. These salts (102) could not be transformed into the corresponding meso-ionic heterocycles (98) with base ... 

Avalos and co-workers (220-228) extensively investigated the 1,3-dipolar cycloaddition chemistry of 2-aminothioisomiinchnones with both acetylenic and olefinic dipolarophiles. For example, sugar derivatives of the mesoionic imi-dazo[2,l-Z7]thiazolium-3-olate system react regioselectively with a variety of acetylenic dipolarophiles [DMAD, diethyl azodicarboxylate (DEAD), methyl propiolate, ethyl phenylpropiolate] to give the corresponding imidazo[l,2-a]pyr-idin-4-ones (e.g., 323) following sulfur extrusion from the not isolable cycloadducts (220). Similarly, these thioisomtinchnones react with diethyl azodicarboxylate and arylisocyanates in the expected fashion (221), and also with aryl aldehydes to form episulfides (222). 

Hydrogenated derivatives of this system have been prepared from acyclic enyne precursors (Scheme 75) by ringclosing metathesis, followed by [4-1-2] cycloaddition of the resulting diene with diethyl azodicarboxylate <2003S2017>. 

A similar 1,3-dipolar cycloaddition occurs with diethyl azodicarboxylate, and the intermediate 1,3-cycloadduct was isolated.60... 

The [4 + 2] cycloaddition reaction of dibenzyl azodicarboxylate and glycals allows the stereoselective introduction of an amino group at the C-2 of a carbohydrate, the key step in the reaction is shown in Equation (1) <89JA2295>. The nature of the products was determined by x-ray crystallography NMR and IR data proved insufficient as the two possible products from [4 4- 2] and [2 + 2] addition are so similar. X-ray analysis confirmed that the reaction of diethyl azodicarboxylate with cyclopropylfuran gives compound (4), by a [4 4- 2] addition, in 94% yield. Further comparison of the NMR and IR data for all the adducts with spectral data of compound (4) confirmed that [4 + 2] adducts were formed consistently. 

The reaction of diethyl azodicarboxylate with cyclopentadiene reported by Diels in 1925 is of historical significance since it is one of the first examples of a Diels-Alder [4 2] cycloaddition (equation... 

Azodicarboxylates and related compounds have been widely used as dienophiles over the last six decades. A thorough description of these reactions is beyond the scope of this review. In a recent representative example of such a cycloaddition, Schmidt and coworkers found that diene (147) adds to diethyl azodicarboxylate to yield (148). This product was used in synthesis of aminoxylose derivative (149) (equation 59). 

In the gas phase, 2 is a thermally very stable compound up to 850 °C. Pyrolysis at 880°C/10 Torr generates styrene (55-62%) and o-xylene (6%) along with small amounts of phenylacetylene, benzene, toluene and unidentified hydrocarbons. Cycloaddition reactions with dienophiles were among the first reactivity studies on 2 they were of course driven by the expectation to generate a cyclobutadiene structure by a twofold (4 + 2) cycloaddition. However, while 2 reacts readily with electron-deficient alkenes such as TCNE, A -phenyhnalermide, 4-phenyl-l,2,4-triazolinedione and diethyl azodicarboxylate to form 1 1 adducts 115, a second Diels-Alder reaction... 

In other examples of the use of azo compounds in pyridazine synthesis, dialkyl azodicarboxylates undergo cycloaddition with dienes to give 1,2,3,6-tetrahydropyridazines. Azobis(formamidine) reacts similarly. Diethyl azodicarboxylate also reacts with furans to give an adduct which is transformed into a pyridazine by acid. In a photochemical synthesis,... 

Both 1,4-dimethoxy- and 1,4-di-/-butyloxy-1,3-butadiene give moderate yields of diethyl 3,6-dialkoxy-l,2,3,6-tetrahydropyridazine-l,2-dicarboxylates by [4 + 2] cycloaddition with diethyl azo-dicarboxylate. The butadienes are formed as mixtures of geometrical isomers, and at least for the t-butyloxy case, it was shown that the (Z,Z) isomer did not react under the conditions used <82JOC5083, 83JOC3096>. 2-Cyanobutadiene, produced in situ from 3-cyano-2,5-dihydrothiophene dioxide, reacts with diethyl azodicarboxylate to give diethyl 4-cyano-l,2,3,6-tetrahydropyridazine-l,2-dicar-boxylate in 95% yield <88T6451>. Bis(trichloroethyl) azodicarboxylate undergoes cycloaddition with... 

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