Heterocyclic synthesis iminophosphoranes

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

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). 

Wamhoff, H., Richardt, G., Stolben, S., Iminophosphoranes Versatile Tools in Heterocyclic Synthesis, 64, 159. 

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

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... 

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... 

Antonio Arques Adame was born in Badajoz in 1952. He studied chemistry at the University of Murcia (Spain), from where he also obtained his Ph.D. in 1980. He joined the group of Prof. P. Molina at the University of Murcia and from 1984 he held a position as an assistant professor at the University of Murcia. The major focus of his research interest relates to heterocyclic chemistry using iminophosphorane methodology. His current research interest is focused on the development of hetero-difunctional ferrocene-coordination ligands and their application to organic synthesis. 

Reports of the use of the Wittig and related methods in synthesis have, if anything, increased and many of these include useful innovations. New results and speculation on the mechanism of the Wittig reaction continue to be published by groups with well established reputations in the area. There has been a substantial increase in the number of reports of the use of iminophosphoranes in synthesis, especially those of heterocycles. 

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... 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

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... 

Aza-Wittig reaction of the iminophosphoranes 41, followed by heterocyclization using amines, provides a novel, one pot, synthesis of functionalized pyrimido[4 ,5 4,5]thieno-[2,3-c]pyridazines 42 <97H(45)1319>. 

The Aza-Wittig reactions of iminophosphoranes have proved to be extremely useful for the synthesis of a variety of AT-heterocycles. The topic has been reviewed [92AHC(55)1291. 

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