Iminophosphorane

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). 

Treatment of resin-bound iminophosphorane 197 with an excess of solid CO2 and CS2 in a sealed glass tube, and with aryl isocyanates afforded I-OXO-, 1-thioxo- 198, and l-arylimino-l//-pyrido[l,2-c]pyrimidine-3-car-boxylates 199 (OlJMClOll). Reaction of iminophosphorane 200, derived from 2-(2-azidophenyl)pyridine with excess PPh3, yielded 6//-pyrido[l,2-c] quinazoline-6-thione (201). 

The conversion of an alcohol to an amine can be achieved in a one-pot reaction the alcohol 1 is treated with hydrazoic azid (HN3), excess triphenylphosphine and diethyl azodicarboxylate (DEAD). The initial Mitsunobu product, the azide 14, further reacts with excess triphenylphosphine to give an iminophosphorane 15. Subsequent hydrolytic cleavage of 15 yields the amine—e.g. as hydrochloride 16 ... 

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). 

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

A Wittig-type reaction of iminophosphorane 995 with benzoyl and ethoxycarbonyl isocyanates gave (91T6747) thiadiazolotriazines 996, whereas reaction of 995 with aromatic isocyanates afforded 997. On the other hand, iminophosphorane 995 reacted with methyl and benzyl isothiocyanates to give 998. Reaction of 995 with acid chlorides gave 999 (88H1935). All these compounds display mesoionic or zwitter ionic character (Scheme 184). 

Reaction of iminophosphorane 1006 with ethoxycarbonyl isocyanate gave (91T6747) regioselectively thiadiazolotriazine derivatives 1007, whereas treatment of 1006 with aromatic isocyanates in ethanol or in the presence of tetrafluoroboric acid afforded 1008 and 1009, respectively. Similarly, 1006 with methyl isocyanate gave 1010 (91T6747) (Scheme 187). 

Imido-bromides yield amidinotriphenylphosphonium salts (73) with iminophosphoranes. The fluxional nature of these salts is shown by the marked temperature dependence of the n.m.r. of the alkyl groups. ... 

A simplified route to penta-arylphosphoranes aryl-lithiums on the iminophosphoranes (1). 

Diphenylcarbodi-imide reacts with ylides to give, in general, the iminophosphorane (86) and the imines (85). The latter usually react with a second mole of ylide to give the stable phosphoranes (87) although the imine (85 R = R = Ph) was isolated. Hydrolysis of the solution... 

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. 

The iminophosphoranes (181) with imide bromides gave the amidino-phosphonium bromides (183) which, it appears from their temperature-variable n.m.r. spectra, are interesting fluxional molecules. The free energy of activation for the interconversion of (183a) and (183b) (R R = Pr R3 = Ph) is 17.2 0.9kcalmol-i. 

Oxazoles (191) are producedwhen triphenylphosphine is treated simultaneously with an a-azidocarbonyl compound and an acyl halide. The intermediate iminophosphoranes (189) react with the acyl halide before they can react with themselves to give pyrazines. Elimination of phosphine oxide from the resulting salts may give the intermediate halo-genoimines (190), or the oxazoles may be formed via the betaines (192). 

Trifluoroacetonitrile and the iminophosphorane (193) gave the adduct (195) presumably via the four-membered intermediate (194). 

For the formation of iminophosphoranes from triphenylphosphine and a-bromo-ct-cyano-succinimides see Chapter 1, Section 2C. 

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. 

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