Aza Wittig reaction

In the first step, the triphenylphosphine reacts with an alkyl azide to form an iminophosphorane with loss of nitrogen Staudinger reaction). In the second step, the nucleophilic nitrogen of the iminophosphorane attacks the carbonyl group to form a four-membered intermediate (oxazaphosphetane) from which the product Schiff base and the byproduct triphenylphosphine oxide are released. 

The solid phase synthesis of trisubstituted guanidines was achieved in the research group of D.H. Drewery by utilizing the aza-Wittig reaction. The reaction of solid-supported alkyl iminophosphorane and aryl or alkyl Isothiocyanates afforded carbodiimides, which upon treatment with primary or secondary amines provided the trisubstituted guanidines.  

In the total synthesis of antitumor antibiotic (+)-phloeodictine A1 by B.B. Snider and co-workers, the key step was an aza-Wittig reaction followed by a retro-Dlels-Alder reaction to afford the desired bicyclic amidine. The polystyrene-supported PPhs made it easy to separate the product from by-products with a simple filtration. 

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Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

Two intramolecular aza-Wittig reactions leading to 1,3-benzoxazepines have been described. In the first,19 ethyl (Z)-3-(2-acyloxyphenyl)-2-azidoprop-2-enoates 1 are treated with triphenyl-phosphane under argon at 20°C for 3-4 hours when 2-substituted ethyl 1,3-benzoxazepine-4-carboxylates 2 are obtained in 85-90% yield. 

Alkoxy-3//-l,4-benzodiazepin-5(4//)-ones by Intramolecular Aza-Wittig Reactions... 

An intramolecular aza-Wittig reaction of the imino-A5-phosphancs 4, prepared by the action of triphenylphosphane on the corresponding azido compounds, affords l//-l,2,4-benzo-triazepines 5.346 The reactions were carried out by heating compounds 4 in acetonitrile or 2-hydroxyethyl methyl ether for the time indicated. No further details were reported. 

The ready synthesis of iminophosphorane 767 from 766 and its subsequent conversion to benzylidene derivative 768 and aza-Wittig reaction... 

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. 

The aza-Wittig reaction of phosphazenes 3 with a,P-unsaturated aldehydes gives 3-azatrienes, which on heating are converted to pyridines 4 <96TL(37)6379>. 

The synthesis of pyrrolo[3,4-c]pyridazines 20 is achieved by intramolecular aza-Wittig reactions of the phosphazines 19 <95JHC1457>. 

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

An aza-Wittig reaction-cycloaddition reaction sequence was utilized for the synthesis of pyridotriazines 94. Treatment of iminophosphorane 92 with phenylisocyanate leads to the formation of the corresponding carbodiimide intermediate, which with another molecule of isocyanate affords 94 in [4+2] heterocycloaddition reactions (Equation 13) <1997T16061>. 

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>. 

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>. 

The pentacoordinate oxazaphosphetidines 53 (Tip = tri(isopropyl)phenyl) are related to intermediates in the aza-Wittig reaction. Thermolysis of 53 shows that the compound displays two types of reactivity as an azaphosphetidine to give 51 and 52 and as an oxaphosphetane to yield 54 and 55 <00TL5237>. 

In a similar sense, the intramolecular aza-Wittig reaction of azide 135 resulted in quinazolinone-containing product 136 in good yield <00H1765>. Compound 136 then underwent acid-promoted cleavage through intermediate 137 to yield fused quinazolinones 138 after tautomerization. 

VI. The Aza-Wittig Reaction A Versatile Principle in Heterocyclic Synthesis. 182... 

Within the last decades, the aza-Wittig reaction has assumed increasing importance for the specific construction of many heterocyclic systems. This first comprehensive review provides an overview of the synthetic potential exhibited by an iminophosphorane moiety. 

Although several recent reviews deal with selected aza-Wittig reactions of iminophosphoranes (910PP1 92OPP209,92T1353 94S1197), heretofore no detailed synopsis has appeared on the preparative importance of this synthetic principle for individual heterocycles with different ring size. 

The aza-Wittig reaction offers several strategies for the syntheses of heterocyclic compounds, and in Section VI a broad choice of examples is presented. Aza-Wittig reactions can be divided into an intramolecular and an intermolecular variant, the former starting with a molecule 49 (Scheme 26) that contains both an iminophosphorane group and a carbonyl function in a geometrically favorable orientation. 

Conjugated heterocumulenes generated in situ by an aza-Wittig reaction are also capable of electrocyclic-ring closure with a subsequent 1,3-H shift. This principle, applied for the first time by Saito et al. on butadiene iminophosphorane 51 (Scheme 28) by treatment with isocyanate and isothiocya-... 

Since the electrophilic character of carbonyl groups in acid halides is more pronounced than in carboxylic anhydrides, the former are better suited for aza-Wittig reactions. Zbiral et al. studied the reaction of imino-phosphoranes with acid halides and obtained imidoyl halides (69LA29 72PS35). A -alkyl and A -aryl iminophosphoranes can be set to use in this reaction (72PS35). 

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