Iminophosphoranes synthesis

Fig. 2. Facsimile of the original paper on the first iminophosphorane synthesis by Stau-dinger (19HCA635).

Takahashi, M., Suga, D. Synthesis of 2-aryl-3-(arylsulfonyl)indoles and 2-anilino-3-(arylsulfonyl)indoles from 2-[(arylsulfonyl)methyl]anilines using the aza-Wittig reaction of iminophosphoranes. Synthesis 1998, 986-990. 

Molina P, Alajarin M, Vidal A (1990) New methodology for the preparation of pyrrole and indole derivatives via iminophosphoranes synthesis of pyrrolo[l,2-fl]quinoxalines, indolo[3,2-c] quinolines and indolo[l,2-c]quinazolines. Tetrahedron 46(3) 1063-1078. doi 10.1016/80040-4020(01)81384-3... 

Iminophosphoranes versatile tools in heterocyclic synthesis 95AHC(64)159. 

Another total synthesis used the rich chemistry of iminophosphoranes (95AHC159). The /3-(3-indolyl)vinyl iminophosphorane 354 underwent an aza-Wittig/electrocyclic ring closure reaction to give the carboline 355 which was hydrolyzed with lithium hydroxide (Scheme 106). A selective reduction, deprotection, decarboxylation and diazotation followed by ring closure gave Fascaplysine (353) (94TL8851). 

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

A general synthesis of the secondary amines RNHMe and RNHEt has been developed starting from the iminophosphoranes (181). Alkylation with methyl or ethyl iodides (all other halides gave olefins) gave the salts (182) from which secondary amines were obtained on alkaline hydrolysis. 

Reduction of azides is a classical approach to primary amine synthesis. Treatment of 17 with sodium azide in DMF or in THF/H2O mixtures in the presence of phase transfer catalysts effects a quantitative conversion to the corresponding polymeric azide, 27. Recently the reduction of azides to primary amines via hydrolysis of iminophosphoranes produced by interaction of the azide with triethyl phosphite was reported.30 Application of this technique to the azidomethyl polymer, 27, as shown below, failed to produce a soluble polyamine. 

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>. 

The 2,3-dihydro-6/7-pyrimido[2,l-A]quinazolin-4(177)-ones 201 were obtained in a one-pot synthesis from the iminophosphorane 199 and isocyanate, through the 2-aminoquinazoline 200. Yields were good (R1 = H, Rz = c-hexyl) to excellent (R1 = Rz = Ph) (Equation 21) <1996TL9071>. 

Several interesting 1,2,4-triazole fused-ring systems have been reported. A facile synthesis of 3,5-dihydro-677-imidazo[l,2-fc]-l,2,4-triazol-6-ones 162 was obtained by an iminophosphorane-mediated annulation <06EJ04170>. 8-Trifluoromethyl-l,2,4-triazolo[4,3- >]pyridazines 163 has been prepared from 4-trifluoromethyl-4,5-dihydropyridazin-3-one... 

An efficient solid-phase synthesis of [l,2,4]triazolo[l,5-7]indazoles has been described starting from bis(azide) 367. The coupling of this compound with polymer-bound triphenylphosphine gives compound 368. This unprecedented bis(iminophosphorane) reacts with various isothiacyanates to give the corresponding iminophosphoranes 215 (unreported yields) attached to the resin (Scheme 37) <2000SL1411>. 

As early as 1919 Staudinger and Meyer reported for the first time the synthesis of an iminophosphorane (3) from triphenylphosphane (2) and organic azides (1) with simultaneous nitrogen extrusion (Scheme 1) (19HCA635). A modern graphic representation of the first Staudinger iminophosphorane is shown in Fig. 1. A facsimile of the original paper published in Helvetica Chimica Acta is shown in Fig. 2. 

Since many functional groups react with phosphorus pentachloride, the synthesis of iminophosphoranes (10) from dihalogenophosphoranes and primary amines (Scheme 6) represents one of the most versatile routes to this class of compounds (59LA142 66MI1). 

The smooth hydrolysis of imidoyl chlorides provides access to carbonam-ides from iminophosphoranes via an aza-Wittig reaction, without the occurrence of free acid or amino functions. This is of special advantage in the synthesis (Scheme 32) of sensitive substrates such as )8-lactam antibiotics (60) (77H719, 79JOC4393). 

A recent review on four-membered heterocycles formed from imino-phosphoranes concentrates on the preparation and the reactivity of 2,4-diimino-l,3-diazetidine and related compounds (93JPR305). As an example, the synthesis via bisiminophosphorane 85 is described in Scheme 42. The bisiminophosphorane has both a heteroaryl and a styryl site. From a mechanistic view, the reaction of the bisiminophosphorane proceeds with aryl isocyanate formation via an aza-Wittig mechanism. Intermediate car-bodiimide formation (86) occurs directly on the iminophosphorane moiety... 

An interesting l,3-oxazol-2-one synthesis of 126 starts from propargyl alcohol 125, CO2, and primary amines with n-butylphosphane as a catalyst (Scheme 50). It is not yet clear if the phosphane reacts by formation of an iminophosphorane followed by an aza-Wittig reaction with CO2 (90TL1721). 

The iminophosphorane 177 available from methyl azido(phenylhydrazo-no)acetate by a Staudinger reaction represents an ideal starting material for the synthesis of l//-l,2,4-triazoles (180). Two synthetic routes are possible (Scheme 68). The first is the reaction of iminophosphoranes with halides via isolable A-acylphosphonium salts (178), and imidoyl chlorides (179), leading to triazoles. The other approach involves the less reactive anhy-... 

The synthesis of 4//-pyrano[2,3-d]pyrimidines, a class of compounds important in crop protection, is presented in Scheme 91. Dichlorotriphenyl-phosphorane affords iminophosphorane 247 with ethyl 2-amino-4//-pyran-3-carboxylate (246). Phenyl isocyanate cyclizes under alkoxide migration to afford pyrano[2,3-d]pyrimidines (248) (90LA995). 

Taylor and Patel describe a quinazoline synthesis (Scheme 93) transforming the iminophosphorane of anthranonitrile with isocyanate to car-bodiimide 254. Addition of ammonia in tetrahydrofuran (THF) leads to guanidine 255, which affords with the adjacent nitrile function quinazoline derivatives 256 (91JHC1857). 

A recently developed synthesis (Scheme 94) of pyrido[3, 2 4,5]-thieno[3,2-d]pyrimidines starts with the appropriate iminophosphorane 257, which affords with heterocumulenes the tricyclic pyrimidines 258a-c (94T6705). 

Rossi et al. have used the tandem aza-Wittig principle (88TL3849 89T4263 91T5819, 91TL5379 92JOC6703, 92T4601) in the synthesis of quinazolines (Scheme 98). In the primary step, iminophosphorane 267 is... 

An interesting variation of this quinoxaline synthesis is outlined by the synthesis of sydnoquinoxalines shown in Scheme 103. The starting material is phenylsydnone 288 with an iminophosphorane group in an o-position. With isocyanate or isothiocyanate carbodiimide intermediates 289 are formed by an electrophilic aromatic substitution at the sydnone ring (4 position), the 4-(arylamino)sydno[3,4-a]quinoxalines (290) are obtained (91S745). 

Molina et al. were able to prepare the mesoionic thiadiazole (292) from iminophosphorane 297 and carbon disulfide. As Scheme 106 shows, 298 reacts with a,w-dihalo compounds to form dimer 299 [91JCS(P1)1159]. The synthesis of the mesoionic thiazolo[2,3-6][l,3,4]thiadizole is described in (92T1285). 

This last section underlines once again the great synthetic potential of the iminophosphorane group, as predicted by Staudinger and Meyer after their first successful synthesis of the P = N double bond. Recently, iminophosphoranes have proved to be novel and versatile heteroannulation components in their reaction with two other components heterocumulenes and heteroarenes (C=X double bonds). 

Although this review is by no means exhaustive, it should present an impression of the importance of iminophosphoranes as versatile synthons in heterocyclic synthesis. Much attention was paid to the aza-Wittig reaction, which enables the preparation of a wide range of simple and complex heterocyclic systems. 

A comprehensive overview of the multifaceted use of iminophosphoranes as versatile reagents in heterocyclic synthesis is provided by H. Wamhoff, G. Richardt, and S. Stdiben (Bonn, Germany). 

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