Preparation of iminophosphoranes

A variant of the Kirsanov reaction was developed by Zimmer et al, where the system iodine/base/triphenylphosphane was used for the preparation of iminophosphoranes (68TL3811). 

Iminophosphoranes have also proved to be key intermediates because they react with carbonyl compounds, isocyanates, isothiocyanates, acid chlorides, carbon dioxide, and carbon disulfide to give a wide range of imines and heterocumulenes, which are intermediates to pteridines. The preparation of iminophosphoranes has been investigated... 

The Staudinger reaction of azides with tertiary phosphines is one of the two major routes in the preparation of iminophosphoranes [30]. This reaction proceeds... 

The Staudinger reaction has also been employed for synthetic purposes other than the preparation of iminophosphoranes. Thus, reactions between appropriate k -phosphorus azides and phosphines gave the amine functionalized dendron (68) that could be grafted onto a tetraphosphorus macrocycle with four pendant P-N=P(C6H5)2(p-C6H4-CHO) groups in order to obtain the expected topologicaly amplified compound as a mixture of diastereoisomers. ... 

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. 

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. 

To examine further the possible intermediacy of iminoiodinane 101, a compound having this presumed structure was prepared (Scheme 17.33) [91]. Support for the assignment of 101 was obtained upon treatment with Ph3P, which leads rapidly to the formation of iminophosphorane 102. The putative iodinane 101 also reacts with 2 mol%... 

A phosphine-free procedure has now been developed that avoids the need to prepare the iminophosphoranes altogether. Thus, treatment of benzamidines 831 with aldehydes under microwave conditions results in direct formation of 4-substituted quinazolines 832 and benzoquinazolines <2005T3533>. 

Imines have also been prepared by the reaction of iminophosphoranes with aromatic, heteroaromatic, aliphatic and a, 3-unsaturated aldehydes at reflux in dry benzene. Reactions with ketones were rather sluggish. Acetone was used as the reagent and the solvent and cyclohexanone was reacted at reflux in toluene for a prolonged period of time.235... 

The most common synthetic approaches to both types of pyrimidopyrimidine have been described in CHEC-I and in review articles by Delia . In addition some new strategies in the preparation of pyrimido[4,5-rf]pyrimidines have been developed in the last few years. A new approach is the aza-Wittig-type reaction of iminophosphoranes of 5-aminouracils with aromatic isocyanates which leads to functionalized pyrimido[4,5-rf]pyrimidines. Ethyl 1,3-dimethyl-6-(triphenylphosphoranylideneamino)-uracil-5-carboxylate (105) reacts with isocyanates via adduct (106a) intermediates to afford 7-ethoxypyrimido[4,5-. 

Preparation and reactions of iminophosphoranes and their synthetic applications in the aza-Wittig reaction... 

Nitrogen Heterocycles.- Reactions of iminophosphoranes have been used to prepare a wide range of heterocycles. Examples of compounds prepared by intramolecular aza-Wittig reactions include 3,4-dihydroquinazolines (191) and quinazolines (192), quinazoline derivatives (e.g. 193),pyrrolo( 1,2-a)quinoxalines (194), indolo[3,2-clquinolines (195), and indolo[l,2-c]quinazolines (196),"8 imidazolinones (197),"9 quinazolinones (198),"9, 120 pyrido[2,3-d]pyrimidine derivatives (199), 21 and 4,5-dihydropyrazolo(3,4-d]pyrimidine derivatives (200). 22 Tributyl(cyclohepta-1,3,5-trienylimino)phosphorane (201), prepared by thermal isomerization of the 2,4,6-derivative, reacts with a,p-unsaturated ketones to give 9H-cyclohepta[b]pyridine derivatives (202). 23 a synthesis of (2,4)pyridinophanes (204) by the reaction of N-vinyliminophosphoranes (203) with a,P-unsaturated ketones has been reported. 24... 

Various hetero-, for example (205) 25 and (206), 26 and carbo-(2 07) 25 cycles have been prepared by aza-Wittig reactions of iminophosphoranes with isocyanates and diphenylketene, respectively, followed by cyclization. The reaction of triphenylphosphine with o-azidobenzaldimines (208) followed by hydrolysis has been used to prepare 2,3-diamino-2H-indazole derivatives (209) (Scheme 30). 27... 

Molina, P., Vilaplana, M. J. Iminophosphoranes useful building blocks for the preparation of nitrogen-containing heterocycles. Synthesis 1994,1197-1218. 

Argues, A., Molina, P. Bis(iminophosphoranes) as useful building blocks for the preparation of complex polyaza ring systems. Curr. Org. Chem. 2004, 8, 827-843. 

Other heterocycles prepared using iminophosphoranes include novel py-rimidinone and quinazoline derivatives, obtained from in situ aza-Wittig reactions of N aryl-iV-(triphenylphosphoranylidene)carboxidamides (114) and ketenes, and pyridothienopyridazines and pyrimidothienopyridazines, accessed from aza-Wittig/electrocyclic-ring closure reactions between phos-phoranes (115) and (116) and heterocumulenes. ... 

A variety of cyclic phosphonium ylide structures have been reported. Hetero-cyclic and -bicyclic structures, including the ylide (11) and a variety of iminophosphoranes, are the products of the reaction of the 1,2-dihydro-1,3,2-diazaphosphinine (10) with dimethyl acetylenedicarboxylate. Attempts to prepare a simple adduct of DBN with the (phosphino)(P-chlorophosphonio) carbene (12) led instead to formation of the unsaturated tricyclic adduct (13). The diphosphete structure (14) is the product of a simple two component reaction of dichloro(bis(trimethylsilyl)methylphosphine) with DBU. Details of the synthesis, chemistry and structure of X -phosphetes (15), benzo-X, -phosphetes (16), and naphtho-X -phosphetes (17) have been reported. 2,4-Diphosphoniodihydro-phosphetide cations (19) have been prepared by condensation of the... 

The preparation of furodipyrroles (12 R =C02Et, R = Me, PhCHj) (Table 2) has been accomplished from the appropriate iminophosphoranes (174) which were in turn obtained from the reaction between suitable ethyl azidoheteroacrylates and triphenylphosphine with phenylisocyanate... 

The Wittig-type reactions of iminophosphoranes with isocyanates and related compounds have also been extensively used in heterocyclic synthesis. Examples include the preparations of the mesoionic [l,3,4]thiadiazolo[2,3-c][l,2,4]triazines (210) from (209), 0 bicyclic guanidines, e.g. (212), from (211), naphthypyridines (215), (216), and (217) from (213) and (214), 2 pyrido[l,2-f]pyrimido-[4,5-d)pyrimidines (218), 7H-pyrido-[4,3-c]- (219) and 10H-pyrido[3,4-b]- (220) carbazoles, tricyclic fused 2,4-diimino-l,3-diazetidines (222) from the bisiminophosphorane (221), benzotriazepines (225) from (223) and (224), 6 and mesoionic thiazolo-[2,3-b]-1,3,4-thiadiazoles (227) and N,N-bisheteroarylamines from the iminophosphorane (226), derived from 3-amino-4-phenylthiazole-2(3H)-thione. The carbodiimides (229), prepared from the iminophosphorane (228), can be converted into quinolines or a-carboline derivatives depending on the nature of the isocyanate used in the reaction with (228) and the reactions of iminophosphoranes (230) and (231) with aryl and styryl isocyanates provide one-pot syntheses of quinoline, a-carboline, and quinindoline derivatives. 9... 

In 1992, Molina et al. synthesized partial structures of lavendamycin using the aza-Wittig reaction as the main strategy (68) to form a /3-carboline at the 2-position of a quinoline (Scheme 23) (68). The reactions of the iminophosphorane 194, prepared from 3-formyl-l-methyl indole by treatment with ethyl azidoacetate and triphenylphosphine, with the 2-formyl-quinoline derivatives 195 in toluene at 160°C in a sealed tube gave the corresponding quinoline derivatives 196 and 197. Treatment of iminophosphorane 194 with pyruvaldehyde yielded the key j3-carboline intermediate 198, which was reacted alternatively with the 2-aminobenzaldehyde 199 and JV-(0-formylphenyl)triphenyliminophosphorane 200 to obtain the corresponding partial structures of lavendamycin, 201 and 202, respectively. 

One example of a successful application of solid-phase chemistry constitutes the highly versatile synthesis of quinazolinones 300/301 which efficiently combines an aza.-Wittig reaction with a multidirectional cyclisation cleavage. Iminophosphoranes were shown to be useful intermediates in organic synthesis, particularly for the preparation of different heterocyclic systems containing an endocyclic C,N double bond. In these cases, an aza-Mfrig-mediated anellation reaction was involved as the key step. 27-i29... 

Six-membered heterocyclic systems which have been synthesised by similar methods include l,6-methano[10]annulenopyridines (214) from (213), y-carblines (215), lavendamycin methyl ester,a range of functionalised 2,3-dihydropyrido[3 ,2 4,5]thieno[3,2-d]pyrimidines (216), and the quinazolino[3,4-a]perimidine derivatives (e.g. 218) from 1,2-dihydro-properimidine azide (217). The previously unreported 4-methylene-4H-3,l-benzozazine ring (219) has been prepared from o-azidoacetophenone and the zwitterionic heteropolycyclic uracils (220) have been synthesised by a three-component reaction of iminophosphorane, isocyanate, and substituted pyridine. ... 

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