Polymer-supported triphenylphosphines

Reagents and conditions i) 2-nitrobenzyl bromide, DMF, 70°C ii) a) Na2S20 , EtOH, reflux, b) HBr, MeOH, dioxane Hi) PMB chloride, py, CHsCIs iv) methyl 4-formylbenzoate, NaOMe, MeOH, reflux v) aminomethyl resin, AcOH, MeOH/dioxane vi) NaOMe, MeOH, reflux vii) toluene, DMF, distillation viii) KOtBu, reflux. 

The transformations and cleavage reactions of polymer-supported phosphonium salts of type 6 3 can be considered as nice examples of traceless linker strategies. 

In recent years, the Mitsunobu reaction has been studied extensively in solution and has found many useful applications. In an effort to overcome many of the problems associated with solution synthesis, the use of highly loaded triphenylphosphine polystyrene-derived resin represents a simple solution to the problem of purification. Thus, reaction of a series of alcohols of type 67 with carboxylic acids in the presence of diethyl azodicarboxylate (DEAD) and PS-PPhj in THF between 0°C and room temperature resulted in the clean formation of the expected esters of type 68. 5 Filtration through a plug of AljO, gave the essentially pure products in high yields (70-90%). 

Staudinger reaction of azido nucleosides for the synthesis of amino nucleosides 

In a Staudinger-type reaction, the azido group was converted into the corresponding phosphoryl imine which after hydrolysis gave the desired amino nucleosides. The starting azido nucleosides were used either with protected or unprotected bases with good results. Filtration of the crude mixture led to pure products in in excellent yields (89-100%). 

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Scheme 4 Microwave-assisted Wittig reactions using polymer-supported triphenylphosphine in methanol...

Very recently a novel one-pot three-step Wittig reaction using microwave irradiation and polymer-supported triphenylphosphine has been reported [57]. By use of... 

Scheme 12.15 Microwave-mediated one-pot, three-component Wittig olefinations utilizing polymer-supported triphenylphosphine.

Scheme 2.2 Polymer-supported triphenylphosphine equivalents for use in Wittig reactions.

In this context, it was shown that polymer-supported triphenylphosphine as a ligand for metal-based oxidation is an alternative catalytic system [72]. 

A PEG-star supported triphenylphosphine analog (66) was synthesized and employed in Mitsunobu reactions. Four phenolethers were prepared within 3-18 h reaction time and 68-93% yield. Upon completion of the reactions, the formed polymer supported triphenylphosphine oxide was isolated by precipitation from diethyl ether in > 85% yield. The reagent could be recycled by means of alane reduction (73%). 

The palladium-catalyzed, microwave-assisted conversion of 3-bromopyridine to 3-cyanopyridine using zinc cyanide in dimethylformamide (DMF) has been reported <2000JOC7984>. Substoichiometric quantities of copper or zinc species improve both conversion rate and efficiency of Pd-catalyzed cyanation reactions <1998JOC8224>. A modification of this procedure uses a heterogeneous catalyst prepared from a polymer-supported triphenylphosphine resin and Pd(OAc)2 the nitriles were obtained from halopyridines in high yields <2004TL8895>. The successful cyanation of 3-chloropyridine is observed with potassium cyanide in the presence of palladium catalysts and tetramethylethylenediamine (TMEDA) as a co-catalyst <2001TL6707>. 

In conclusion, we have shown that attachment of transition metal complexes to polymer supported triphenylphosphine leads to air stable, versatile immobilised catalysts that are as active as their homogeneous analogues and have the advantage that they can be re-used numerous times. Work is currently underway to exploit the activity of other polymer-supported organometallic complexes in metal-mediated organic synthesis. 

One of the main drawbacks of the Wittig reaction is the formation of unwanted triphenylphosphine oxide. A new route, which makes use of polymer-supported triphenylphosphine and microwave dielectric heating has been developed (Scheme 13), which yields the required alkene without the triphenylphosphine oxide. An alternative strategy for separation of the product alkene from unwanted phosphine oxide by-product is to carry out the Wittig reaction in a fluorous solvent using a perfluorinated ylide such as (45). One drawback of this... 

Acid amide-triphenylphosphine dihalide adducts (4) have found wide application in organic synthesis. - Synthetic equivalents are adducts (5) from acid amides and triphenylphosphine/CCU, which are prepared in situ from the educts. - With these reagents the following transformations have been performed dehydration of amides or aldoximes to nitriles, preparation of isonitriles from secondary form-amides, preparation of imidoyl halides from amides or acylhydrazines and preparation of ketene imines from amides. Using polymer-supported triphenylphosphine the work-up procedure is much easier to achieve. Triphenylphosphine can be replaced by tris(dialkylamino)phosphines. - Instead of CCI4 hexa-chloroethane, hexabromoethane or l,l,2,2-tetrabromo-l,2-dichloroethane can be used " the adducts thus formed are assumed to be more effective than those from the triphenylphosphine/CCU system. 

Other phosphorus compounds, e.g. PBrs, mixtures of PBrs and Br or PCI3/CI2 and phenyltetra-chlorophosphorane (PhPCU) have been used to convert amides to imidoyl halides. The formation of imidoyl halides proceeds under mild conditions by action of triphenylphosphine/CCU or triphenylphos-phine dihalides on secondary amides or ketoximes. The work-up procedure can be facilitated by use of polymer-supported triphenylphosphine/CCU. By the action of POCI3, phenyl- or methyl-phos-phonic acid dichloride on aminocarboxylic acid thiol esters in the presence of triethylamine the imidoyl chlorides (205 equation 114) are formed in moderate to good yields. The mechanism of this reaction has not been established. The methylene dialkylchlorophosphorane (206 equation 115) allows the conversion of secondary aromatic amides to imidoyl chlorides under very mild conditions. ... 

Polymer-supported triphenylphosphine has not only been used for the preparation of polymer-supported Wittig reagents, but also as a reagent for Mitsu-... 

The l,2,4-triazolo[4,3-fl]pyridine nuclens can be accessed by cyclocondensation of 2-hydrazino-pyridines the synthesis of the antidepressant trazodone, shown below, is an example. Condensation of 2-hydrazinopyridines with carboxylic acids, promoted by polymer-supported triphenylphosphine with tri-chloroacetonitiile and heated with microwave irradiation, is also efficient. °... 

Polymer-supported triphenylphosphine ditriflate (37) has been prepared by treatment of polymer bound (polystyrene-2% divinylbenzene copolymer resin) triphenylphosphine oxide (36) with triflic anhydride in dichloromethane, the structure being confirmed by gel-phase 31P NMR [54, 55] (Scheme 7.12). This reagent is effective in various dehydration reactions such as ester (from primary and secondary alcohols) and amide formation in the presence of diisopropylethylamine as base, the polymer-supported triphenylphosphine oxide being recovered after the coupling reaction and reused. Interestingly, with amide formation, the reactive acyloxyphosphonium salt was preformed by addition of the carboxylic acid to 37 prior to addition of the corresponding amine. This order of addition ensured that the amine did not react competitively with 37 to form the unreactive polymer-sup-ported aminophosphonium triflate. 

Scheme 7.12 Preparation of polymer-supported triphenylphosphine ditriflate (37).

Polymeric reagent. Hodge and Richardson have prepared a polymer-supported triphenylphosphine by bromination of a polystyrene cross-linked with divinylbenzene followed by reaction with lithium diphenylphosphide (4, 303). A similar reagent has been described by Regen and Lee. Polymeric material is available from Strem. 

Polymer-supported triphenylphosphine (Ps-PPh2) has attracted much attention as a ligand for immobilization of metal complexes, as it is the supported analog of the ubiquitous simple tertiary phosphine ligand PPhs- Also, it is commercially available from a range of suppliers. 

In medicinal chemistry nitriles are very useful because they can be transformed into biologically important structures such as tetrazoles, triazoles, oxazoles, thia-zoles, oxazolidinones. .. A variety of aryl nitriles has been prepared in excellent yields by Pd-catalyzed coupling of aryl halides with Zn(CN)2 using polymer-supported triphenylphosphine as the ligand and DMF as the solvent under micro-wave irradiation conditions (Scheme 10.34) [76], Products were obtained in high yields and excellent purity without the need for purification. 

Use of phosphoranes as polymer-bound acylation equivalents has also been reported [66]. Initial alkylation of the polymer-supported triphenylphosphine reagent was achieved with bromoacetonitrUe under microwave irradiation conditions (Scheme 16.44). Simple treatment with triethylamine transformed the polymer-bound phosphonium salt into the corresponding stable phosphorane, which could be efficiently coupled with a variety of protected amino acids. After Fmoc deprotection and subsequent acylation the resulting acyl cyano phosphoranes could be released from the polymer support by ozonolysis at —78 °C. The released highly activated electrophiles can be converted in situ with appropriate nucleophiles [66]. 

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