Azodicarboxylic acid synthesis with

The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphosphonium salts and p-quinones. 

The photochemical addition of 2H-azirines to the carbonyl group of aldehydes, ketones and esters is completely regiospecific (77H143). Besides the formation of the isomeric oxazolines 18 from 3 and ethyl cyanoformate, there is also formed the imidazole 19 from addition to the C = N in the expected regioselective manner. Thioesters lead to thiazolines 20, while isocyanates and ketenes produce heterocycles 21 (Scheme 4). The photocycloaddition of arylazirines with a variety of multiple bonds proceeds in high yield and provides a convenient route for the synthesis of five-membered heterocyclic rings. Some of the dipolarophiles include azodicarboxylates, acid chlorides, vinylphospho-nium salts and p-quinones. 

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,... 

Mitsunobu et al. [46] reported an efficient macrolactonization using diethyl azodicarboxylate (DEAD) and Ph3P. In the case of (o-hydroxy acids having a secondary alcohol, this cyclization takes place with inversion of the configuration of the alcohol. In the total synthesis of latrunculin A (82) and B, the Mitsunobu reaction was used for the macrolactonization of the seco-acid 81 with inversion of the secondary alcohol [47]. 

Thioesters.—Mixed anhydrides prepared from 2,4,6-trichlorobenzyl chloride and a carboxylic acid react with various thiols in the presence of 4-dimethyl-aminopyridine to give thioesters in 78—86% isolated yield.Somewhat less impressive yields were obtained in a few of the cases studied when l-fluoro-2,4,6-trinitrobenzene was used to couple the acid and the thiol.Treatment of 1-acylimidazoles with thiols in the presence of a catalytic amount of Mg(OEt)2 furnishes thioesters in good yields. Diphenyl-2-oxo-3-oxazolinylphosphonate brings about effective reaction between acids and thiols. Thiolacetates are efficiently prepared using the reaction of an alcohol with triphenylphosphine and di-isopropyl azodicarboxylate in the presence of thiolacetic acid/ A synthesis of some amino-acid derivatives containing the thioester functional group is achieved by the reaction of a vinyloxyborane with a Schiffs base (Scheme 56). ... 

The Mitsunobu reaction was also applied to the synthesis of [ 1,2,4]triaz-ino[4,5-n]indoles (84AG517). Thus, reaction of the 2-acylindoles 127 with sodium borohydride in methanol or with lithium aluminium hydride in tetrahydrofuran gave the corresponding alcohols 128. Their cyclization with diethyl azodicarboxylate in the presence of triphenyl-phosphine gave the triazinoindoles 129. Acid treatment of the latter afforded 130 (Scheme 30). 

Stoodley developed an asymmetric synthesis of (5A)-2,3,4,5-tetrahydropyridazine-3-carboxylic acid (see Section 8.01.6.4). The ring construction was achieved via cycloaddition of dienes 295 bearing a tetraacetyl /3-D-glucopyranosyl moiety for chiral induction with azodicarboxylates (Equation 73) <1999J(P1)2591>. 

The minor product 86, obtained in the synthesis of vertaline (61) from 84 (Scheme 9), was treated with diethyl azodicarboxylate and triphenylphosphine in the presence of benzoic acid to give the benzoate 87, with inversion of the configuration at C-2, in 77% yield. Hydrolysis of 87 followed by lactonization under Mukaiyama-Corey or Masamune conditions afforded decaline (62) in 57 or 45% yield, respectively. 

S-Hydroxy-l-azetidinones. A biomimetic synthesis of the y3-lactam 4 from BOC-L-serine (1) has been reported. The protected serine derivative is converted into the hydroxamic acid 2 by condensation with O-benzylhydroxylamine mediated by the water-soluble l-ethyl-3(3 -dimethylaminopropyl)carbodiimide (1, 371). The product is cyclized directly in high yield to the / -lactam 3 by treatment with diethyl azodicarboxylate and triphenylphosphine. No racemization is observed. Deprotection by catalytic hydrogenation gives the N-hydroxy-jS-lactam 4. Previous biomimetic syntheses of 2-azetidinones have involved cyclization ot /3-cMoroamides with sodium hydride (e.g., 7, 335). 

In summary, the electrophilic amination of lithium enolates derived from 1 with di-toT-buty] azodicarboxylate (DBAD) provides an excellent approach to the stereoselective synthesis of a-hydrazino and a-amino acids. 

The synthetic potential of a simple method for the direct introduction of nitrogen into the 5-position of the pyrimidine ring is illustrated by the synthesis of 1,3-dimethyluric acid (15) from 1,3-dimethyluracil-6-amine by reaction with diethyl azodicarboxylate, reduction to 5-[(ethoxycarbonyl)amino]-l,3-dimethyluracil-6-amine, and thermal ring closure. "... 

Direct alkylation of hydrazine itself with halides and sulfates usually gives mixtures of mono- and poly-alkylated hydrazines. It is possible to get useful yields of the monoalkylhydrazine by using an excess of hydrazine. Several specific procedures leading to monoalkylhydrazines are based on selective alkylation of hydrazine derivatives with protecting groups attached. So, easily prepared acetone N-(diethoxyphosphoryl)hydrazone (75) can be used. Phase-transfer catalyzed N-alkylation of (75), followed by deprotection with p-toluenesulfonic acid provides monoalkylhydrazine sulfonates (76 Scheme 17). Similarly, N-alkyl-N-arylhydrazines have been prepared by phase-transfer catalyzed N-alkylation of arylhydrazones (Scheme 18). An efficient, one-pot method for the synthesis of a variety of polysilyl-ated hydrazines employs hexamethyldisilane (equation 30). Polysilylated hydrazines were found to react with aldehydes or ketones to give hydrazones under anhydrous conditions. By treatment with triphenylphosphine and diethyl azodicarboxylate primary and secondary alcohols can be converted to hy-dr ine derivatives (equation 31). ... 

Evans, D. A., Britton, T. C., Dellaria, J. F., Jr. The asymmetric synthesis of a-amino and a-hydrazino acid derivatives via the stereoselective amination of chiral enolates with azodicarboxylate esters. Tetrahedron 1988, 44, 5525-5540. 

P-Lactams.1 A biomimetic synthesis of /3-lactams from chiral amino acids such as L-serine has been developed by Mattingly and co-workers. The protected amino acid (1) is first converted into the O-alkyl or O-acyl hydroxamate (2), which undergoes cyclization to derivatives of l-hydroxy-2-azetidinones on treatment with triphenylphosphine-carbon tetrachloride. This cyclization is also possible with triphenylphosphine-diethyl azodicarboxylate.2 The final step involves reduction of the N—OH group with TiClj.3 The advantage of this method over that of Wasserman (9,428), which involves cyclization of /3-haloamides, is that a strong base such as NaH is not required. 

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