Staudinger-Wittig reaction

A unique tandem Staudinger-Wittig reaction finds application in lactam synthesis ... 

Scheme 7.6. Synthesis of (-)-vasicinone (7-15) by a domino Staudinger-reduction/aza-Wittig reaction.

NaBH(OAc)3 Staudinger reduction followed by aza-Wittig reaction, then reduction... 

An elegant synthesis of the spiroaminal containing domain of azaspiracids 201 makes use of a Staudinger-aza-Wittig reaction in a cascade sequence to generate the spiroaminal 202 <06T5338 06JA15114>. 

The simplest available derivatives of pyrrole in this sense are pyrrolines (97) which are accessible by simple intramolecular aza-Wittig reaction of iminophosphorane 96, the latter being formed by a Staudinger reaction from -y-azidoketones (95), as shown in Scheme 44. The process occurs under neutral conditions, so that once the double bond is formed, it cannot isomerize (86TL1031 87NKK1250). 

Imidazoles are synthesized from A-(2-azidoethyl)phthalimide (136) via the Staudinger reaction to obtain an initial intermediate iminophosphorane 137, which is then converted by an intramolecular aza-Wittig reaction and... 

Another approach to the syntheses of quinazolines involves 3-(o-azido-phenyl)isoxazoles (210) which are accessible from a-chloro-Z-azido benzal-doximes (209) and /3-keto esters (R = Ph, = OEt). As shown in Scheme 78, the iminophosphorane resulting from the Staudinger reaction is transformed without isolation by an aza-Wittig reaction into 3,4-disubstituted isoxazolo[4,3-c]quinolines (211) (92MI1). 

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). 

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). 

Several condensed systems, especially those combined with pyridine rings, show biological activity, e.g., in the field of crop protection and as anti-virus and anti-cancer compounds. Aza-Wittig reactions in particular should make several novel heterocyclic rings available. The aza-Wittig reaction of iminophosphoranes has to be considered as a major principle in modern synthetic chemistry, as was wisely foreseen by Staudinger and Meyer as early as 1919. 

In the first report on this famous reaction, Wittig expressed a clear preference for the cyclic phosphorane intermediate 22 such as had already been formulated by Staudinger and Meyer in their earlier work. This view became generally accepted onlv many years later35). In this respect, the Wittig reaction did indeed still reflect some prominent features of the underlying research program on penta-coordinated molecules, from which it now evolved rapidly to a very active life of its own 36). 

Bravo et al. treated (Ss)-(+)-p-toluenesulfinamide (63), prepared by hydrolysis of 44,23 with triphenylphosphine in the presence of DEAD to give the N-sulfinyl iminophosphorane 64 in 92% yield.45 The Staudinger, aza-Wittig reaction of 64 with methyl or ethyl trifluoropyruvate afforded the unstable sulfinimine 65. Attempts to purify the imino sulfinimines by flash chromatography resulted in hydrolysis. 

Another useful synthetic method for the synthesis of complex heterocyclic compounds is the aza-Wittig reaction, involving carbodiimides as intermediates. This reaction was discovered by Staudinger and Hauser in 1921. Carbodiimides have also found use as agricultural chemicals and pharmaceutical intermediates. For example. 

By Aza-Wittig Reaction. In the reaction of heterocumulenes with iminophos-phoranes, carbodiimides with different substituents on nitrogen are obtained. The reaction of iminophosphoranes 61 with isocyanates (X=0) or isothiocyanates (X=S) to give carbodiimides with two different substituents 62 was discovered by Staudinger and Hauser in 1921.102... 

Treatment of thiol ester azide 212 with PPhs in anhydrous THF (under reflux) provided thiazoline 213 in good yield (Scheme 84). In situ generation of a phosphinimine by Staudinger reaction of the azide with PPh3 allowed an intramolecular aza-Wittig reaction to take place with the thioester under the neutral and anhydrous conditions <2004PNA12067>. 

PhCH2NPPh3 affords the isocyanide derivative [Os3(CO)g(CNCH2Ph)(n3-ri rri iTi -Ceo)]. The Staudinger reaction in combination with an intramolecular aza-Wittig ring closure reaction has been applied in the synthesis of quinazolin-4-ones. Other examples of intramolecular aza-Wittig reactions are reported as parts in multi-step synthetic routes. A theoretical study of the aza-Wittig reaction of HN = PX3(X = H and Cl) with formaldehyde in the gas phase and in solution has been reported. ... 

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