Dialkyl azodicarboxylates

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

Cycloaddition reactions of aziridines with a wide assortment of dipolarophiles have been studied. The reaction of dialkyl azodicarboxylates with the cf5-aziridine (27) is stereospecific... 

In an indirect amination process, acyl halides are converted to amino acids. Reaction of the acyl halide with a chiral oxazolidinone leads to a chiral amide, which reacts with the N=N unit of a dialkyl azodicarboxylate [R"02C—N=N—CO2R ]. Hydrolysis and catalytic hydrogenation leads to an amino acid with good enantioselectivity. ... 

This class of compound is represented by 2,3-disubstituted-l,2,3-benzoxadiazoles and new caged structures. 2,3-Disubstituted-l,2,3-benzoxadiazoles 128 were prepared in high yield when the Huisgen zwitterion, formed between dialkyl azodicarboxylates 127 and triphenylphosphine, was reacted with 3-methoxy 4,6-disubstituted-l,2-benzoqui-nones 126 (Equation 23 Table 6) <20050L5139>. 

Ley developed an efficient tandem organocatalytic synthesis of chiral dialkyl 3-alkyl-l,2,3,6-tetrahydropyridazine-1,2-dicarboxylates 272 from /3-oxohydrazines 271. Compound 271 was obtained from commercially available achiral aldehydes and dialkyl azodicarboxylates using (6)-pyrrolidinyl tetrazole as the chiral catalyst. This synthesis proceeds with good to excellent yields (58-89%) and enantioselectivities (69-99% ee). The highest ee values are obtained for the most bulky di-/-butyl azodicarboxylate and the shortest branched aldehydes (Scheme 67) <2006SL2548>. 

In an indirect amination process, acyl halides are enantioselectively converted to amino acids.176 The key step involves addition to the N=N bond of a dialkyl azodicarboxylate 22. 

No cycloaddition has been found to occur in the reaction of several indolizines with tetracyanoethylene, substitution occurring instead in the 1- and 3-positions (78JHC1471). Similar products have been formed in the reactions of 2-methylindolizine with nitroethane, yielding (86) (79JPS321), and of indolizines with dialkyl azodicarboxylates, which gave a mixture of (87) and (88) (80TL3673, 79H(12)787>. 

Intermolecular and intramolecular nucleophilic substitution of an alcoholic hydroxy group by the triphenylphosphine/dialkyl azodicarboxylate redox system is widely used in the synthesis and transformation of natural products and is known in organic chemistry as the Mitsunobu reaction.1951 This reaction starts with formation of the zwitterionic phosphonium adduct 19 (Scheme 9) from triphenylphosphine and diethyl (or diisopropyl) azodicarbox-... 

The 4,5-double bond of 2(3//)-oxazolones participates in thermal [4 + 2] cycloaddition reactions. With dialkyl azodicarboxylates the addition occurs at 80 C to give the cycloadducts 430 (Scheme 97). With a chiral substituent attached to N(3), diastereoselectivities as high as 72% can be obtained. Cycloadditions with cyclopentadiene or benzofuran require higher temperatures and longer reaction times, but can yield highly efficient chiral oxazolidin-2-one auxiliaries. 

By a related approach, lithium enolates of chiral carboximides 8 were reacted with various dialkyl azodicarboxylates to form the a-hydrazino adducts 917. 

Direct Asymmetric a-Amination Reaction of 2-Keto Esters. The cir-DiPh-Box copper complex catalyzes highly enantioselective direct a-amination reaction of 2-keto esters with dialkyl azodicarboxylates and thus provides convenient access to optically active jyn-3-amino-a-hydroxy esters (eq 2). This enantioselective, direct a-amination is applicable to a range of 2-keto esters when dibenzyl azodicarboxylate is used as the nitrogen source. The immediate product of the amination reaction is prone to racemization. Stereoselective reduction of the keto functionality by L-selectride enables further synthetic operations to be carried out without loss of enantiopurity. 

Mitsunobu reaction Substitution of primary and secondary alcohols with nucleophiles in the presence of dialkyl azodicarboxylate and trialkyl- or triarylphosphine. 294... 

Model studies for the syntheses of phosphonate analogues of sphingomyelin and ceramide 1-phosphate from pentaco-ordinate phospholene 112 have been reported. Compound 112 undergoes ring opening on reaction with dialkyl azodicarboxylates to give 113 which reacts with sodium borohydride stereoselec-tively to give predominantly trans- 4 (Scheme 6). The preparation has been described, via phosphorus chloride methods, of the potential haptens 115 for the production of phospholipase A2-like catalytic antibodies. ... 

Cycloaddition Reactions of Dialkyl Azodicarboxylates and of 1,2,4-Triazole-3,5-diones... 

Table 5. Bicyclo[2.1.0]pentane Derivatives via Addition of Dialkyl Azodicarboxylate or 4-Substituted-1,3,4-Triazole-3,5-dione to Cyclopentadienes...

The betaine (47), derived from the reaction of tris(dimethylamino)phosphine and dialkyl azodicarboxylate, has been used to prepare monosaccharide... 

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,... 

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