Iminophosphorane, synthesis isocyanates

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... 

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>. 

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... 

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). 

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). 

Phenyl isocyanate was used differently by Taylor and Patel (91JHC1857), who synthesized 2-anilinothieno[2,3-d]pyrimidine 76 by the sequence of reactions 48 — 74 — 75 — 76. This synthesis involves (i) adding the o-aminocarbonitrile 48 (R2 = R3 = H) to a mixture of triphenylphosphine and bromine at 0°C to give iminophosphorane 74, (ii) an aza-Wittig reaction on the iminophosphorane with phenyl isocyanate to yield carbodiimide 75, and (iii) cyclization of the latter with ammonia. 

Resin-bound iminophosphoranes 103 derived from the reaction of resin-bound 2-aminobenzimidazole 102 with triphenylphosphine oxide were reacted with aryl isocyanates in an abnormal aza-Wittig reaction with a chemoselectivity that depends on the reaction temperature and the nature of the aryl isocyanate (Scheme 22). The mechanism considered for the solid phase synthesis reaction involves the loss of triphenylphosphin-imide instead of triphenylphosphine oxide, resulting in the formation of isocyanates instead of carbodiimides as intermediates. Optimization studies revealed that employing electron-poor aryl isocyanates at high temperature leads to 95% of the abnormal aza-Wittig products 3-aryl 2,4-dioxo-l,3,5,-triazino[l,2-fl]benzimidazoles 104 [76]. 

The reaction is useful in the synthesis of acycHc imines [122-124] and heterocumulenes [112-117] and in the intramolecular formation of carbon-nitrogen double bonds in heterocycHc synthesis [112-117]. On the other hand aza-Wittig type reactions of iminophosphoranes with carbon dioxides, carbon disulphides, isocyanates, isothiocyanates and ketenes render access to functionalized heterocumulenes as highly reactive intermediates able to undergo a plethora of heterocycUzation reactions [112-117]. 

Reviews on the synthesis and chemistry of carbodiimides are given in [1248-1250]. Carbodiimides are mainly synthesized in one of three ways from ureas or thioureas, from isocyanates, or from isocyanides. Several reagents have been employed in carbodiimide synthesis phosgene [1252, 1253], dimethylphosgenimi-nium chloride [1254], tiiphosgene [561, 562], phosphorus pentoxide [1255], phos-phoryl chloride [1256], triphenylphosphine dibromide [758, 1257-1261], triphenylphosphine/tetrahalomethanes [1262, 1263], iminophosphoranes [1264-1277], Mitsunobu reagent [1278, 1279], p-tosyl chloride [1280, 1281], and CDC [1137] oxidative additions have also been used [1282-1284]. 

N-Vinylcarbodiimides 1732, useful building blocks for the synthesis of N-het-erocycles, are prepared from isocyanates 1730 and vinyl-iminophosphoranes 1731 in yields of about 70% [1268]. N-Vinylcarbodiimides 1732 react with tosyl isocyanate 1733 in a hetero-Diels-Alder reaction to form pyrimidines 1734 in 40-45% yield. 

A-Vinylic phosphazenes, are useful building blocks, that have been used in Aza-Wittig reactions with unsaturated aldehydes to form 3-azatrienes through a [2 -I- 21-cycloaddition-cycloreversion sequence. " The presence of an alkyl substituent in position 3 of A-vinylic phosphazenes increases the steric interactions, and [4 + 2] periselectivity (1,4 addition) is observed." Other Aza-Wittig reactions include the reaction of iminophosphorane (60) with aromatic isocyanates to obtain, inter alia, useful carbodiimides for the selective synthesis of pyrimidones." Also the iminophosphorane (61) was reacted with furan-2-carbaldehyde, thiophene-2-carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde to give, depending on temperature and aldehyde, trans imines or mixtures of trans and cis imines." " The... 

The toxicity of phosgene and thiocarbonyl chloride represents a drawback in the laboratory synthesis of isocyanates and isothiocyanates from amines the use of iminophosphoranes has been shown effectively to circumvent this problem. The key step is the mild reaction of CO2 or CS with the iminophosphoranes (50), which are readily available from the corresponding amines. The reaction appears to be general for both aromatic and aliphatic amines and yields are good (Scheme 60). 

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