Aza-Wittig cyclization

Table 32 Aza-Wittig cyclization of azinoiminophosphorane intermediates with benzaldehydes to give 1,2,4-triazoles derivatives (Scheme 14) ...

For the synthesis of base-sensitive oxazoles (Scheme 52), /3-acyloxyvinyl azides (130) react with triethyl phosphite via an aza-Wittig-cyclization. Phosphorimidate 131 is converted to 1,3-oxazole 132 with spontaneous elimination of triethyl phosphate (89JOC431). Benzoxazoles are also available by this synthetic route (71CC1608). 

A direct aza-Wittig cyclization to triazolotriazine 176 (Scheme 67) takes place when triazinone 174 is treated with diphenylthiourea, the latter being substituted on the nitrogen. Elimination of triphenylphosphane sulfide from 175 makes 1,2,4-triazole accessible [86JCS(P1)2037]. When the nucleophilic attack continues on the sulfur, thiadiazoles are formed [86JCS(P1)2037]. 

Kurita et al. reacted a-azidocinnamate 327 with benzoyl chloride (Scheme 119) to form benzoate 328, which upon conversion of the azide group into an iminophosphorane (329) underwent an aza-Wittig cyclization to yield 1,3-benzoxazepine (330) (92CC81). 

As Scheme 120 shows, more benzoxazepines are available by aza-Wittig cyclization of o-acyloxy-2-azidoacetophenone (331). The benzoyloxy derivatives, however, eliminate triphenylphosphane oxide but afford an acyclic product (332) for steric reasons (90S455). 

The Staudinger-aza-Wittig cyclization methodology for imine formation can also be applied to the synthesis of oxazolines under essentially neutral conditions.Thus, an azido ester such as 281 reacts with triphenylphosphine to give the oxazoline 283 in excellent yield. There was no evidence for cychzation at the benzoate presumably because cyclization to a five-membered ring is faster than... 

The pyrido[2,3- pyrimidinones 380 and 381 were thermally obtained from boiling the ethyl acrylate derivatives 378 and 379, respectively, with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and EtNHPd in THF (Scheme 13) <2001W02001055148, 2004USP2004009993>. The acrylates were obtained from reaction of the corresponding pyrimidine-5-carbaldehyde with (carbethoxymethylene)triphenylphosphorane. On the other hand, acrylate 382 was converted into 383 via aza-Wittig cyclization (Equation 32) <1997LA1619>. 

A new class of compounds (13a-f) has been prepared from (12a-f) by a Staudinger reaction with PhaP followed by an intramolecular aza-Wittig cyclization. Compounds (13) are cruciform 7i-systems with the phenyloxazole arms almost perpendicular to the terphenyl system. ... 

A new approach to indoloquinohne alkaloids from Cryptolepis sanguino-lenta has been reported based on the cyclization of an o-substituted vinyl isocyanate 244 imder microwave irradiation and further additional cyclization based on an Aza-Wittig reaction carried out in the presence of microwaves [159]. The apphcation of this synthetic scheme to the synthesis of Cryptotackienine 247 is reported in Scheme 91. 

Aminoethylidenehydrazones 161 react with triphenyl phosphine to give the azinoiminophosphorane intermediates 162 which cyclize via an aza-Wittig reaction with benzaldehydes to give the corresponding 1,2,4-triazoles 163a-j (Scheme 14 and Table 32) <2002JHC845>. 

With phenyllithium, the iminophosphoranes of benzoic acid hydrazides 157 can be deprotonated, as shown in Scheme 62.0-Acylation of the amide-enolates 158 affords intermediates 159, which are in turn cyclized by an aza-Wittig reaction to 1,3,4-oxadiazoles 160 (68JA5626). 

Access to pyridines from aza-l,3,5-triene units, achieved by an intramolecular aza-Wittig reaction and thermal electrocyclic cyclization with a subsequent 1,3-H shift, was mentioned in Section V,B (cf. Scheme 28) as an... 

Quinazolines have become increasingly important as biologically active principles, e.g., as antiseptics or antimalarials. An interesting approach to this class consists of a combination of the aza-Wittig reaction with photochemical processes, as shown in Scheme 76. o-Azidocinnamates (206) are cyclized with the aid of triethyl phosphite to afford 2-alkoxyquinolines... 

Finally, the synthesis of 4//-3,l-benzoxazines 239 via a tandem aza-Wittig reaction (Scheme 89) should be mentioned. Carbodiimide 238 or isocyanate generated by an intramolecular aza-Wittig reaction bears an o-hydroxymethyl group on the A(-aryl substituent this OH attacks the carbodiimide C intramolecularly with cyclization to give a 3,1-benzoxazine (91S21). 

The pharmacologically important tryptanthrine, a quinazoline alkaloid, is known for its antimycotic activity and is used against skin infections. This alkaloid is obtained from isatin (260) and o-azidobenzoyl chloride (261), as shown in Scheme 96. The adduct formed is cyclized via a Staudinger and an aza-Wittig reaction to afford tryptanthrine (262) (92H153). 

As shown for the aziridines, BETMIP (68) has proved to be useful in the synthesis of azepines (Scheme 118). Treatment with methylenephosphorane leads to a phosphonium salt which in turn is deprotonated with BuLi and cyclized with benzene-l,2-dialdehyde in a Wittig and aza-Wittig step to form benzazepine 326 (93JOC1987). 

Diazepines represent an important class of bicyclic seven-membered heterocycles. They are the basis of several tranquilizers and are accessible from a-amino acid esters and o-azidobenzoyl chloride in the presence of triethylamine. The A/ -(o-azidobenzoyl)amino esters (333) formed in this way (Scheme 121) are cyclized by Staudinger and aza-Wittig reactions to give 2-ethoxy-l,4-benzodiazepin-5-ones (334) (92MI2). 

The quinoline-2-one was then converted into the required 1-methyl-(o-azidophenyl)-quinoline-2-one via known synthetic manipulations. Cyclization of this intermediate to the target Cryptotackieine was performed under microwave irradiation at 180 °C for 30 min, in the presence of trimethyl phosphine. It is noteworthy that the same aza-Wittig reaction, when carried out under classical heating for 24 h, furnished inferior yields. The quinolin-2-one intermediate, when heated at 150 °C in o-xylene under conventional heating conditions, underwent a nitrene insertion at the C-4 position of the pyridinone ring. Subsequent Red-AI reduction of the carbonyl group furnished the Cryptosanguinolentine. 

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