Triphenylphosphine supported reagents

Weik and Rademann have described the use of phosphoranes as polymer-bound acylation equivalents [65]. The authors chose a norstatine isostere as a synthetic target and employed classical polymer-bound triphenylphosphine in their studies (Scheme 7.54). Initial alkylation of the polymer-supported reagent was achieved with bromoacetonitrile under microwave irradiation. Simple treatment with triethyl-amine transformed the polymer-bound phosphonium salt into the corresponding stable phosphorane, which could be efficiently coupled with various protected amino acids. In this acylation step, the exclusion of water was crucial. 

Supported reagent. Trost and Keinan have prepared two supported forms of this palladium(O) species one supported on silica gel, named ( )—Pd, and the other supported on polystyrene and named Pd. Both are fairly stable to air, in contrast to tetrakis(triphenylphosphine)palladium. 

The renaissance of solid supported reagents and parallel synthesis during the last fifteen years found numerous applications in the Mitsunobu reaction. Solid-supported triphenylphosphine and azadicarboxylate reagents were developed to aid in the purification of Mitsunobu reactions or help with difficult reactions. These reagents have become commercially available. In addition, important yield-limiting reactants were tethered to solid supports... 

If the conversion of the alcohol to the chloride is attempted in refluxing MeCN, dehydration to form the alkene occurs (eqs 7 and 8). Occasionally the separation of the product from the triphenylphosphine oxide produced in the reaction can be problematic. This can be overcome by using a polymer-supported phosphine. Simple filtration and evaporation of the solvent are all that is required under these conditions. Not only is the workup facilitated, but the rate of the reaction is also increased by employing the supported reagent. ... 

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%). 

Polymer-supported Wittig reagents have recently been developed as an extension to the traditional reagents.29 For example, polystyryldiphenylphosphine has been developed in an attempt to replace the use of triphenylphosphine in the preparation of phosphoranes (see Protocol 1). The hope is that these polymer-bound regents will overcome the practical problem of removing the triphenylphosphine oxide by-product formed in Wittig reactions. Polymer supported phosphonates and Wittig substrates have also been prepared for use in solid phase synthesis and combinatorial chemistry.30... 

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. 

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

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. 

There have been many attempts to develop alternative phosphines as well as various solid-phase methods in order to avoid the issue of the removal of the triphenylphosphine oxide byproduct.16-18 The advantage of a solid-supported phosphine reagent is that a simple filtration would remove the oxide and thus simplify the workup. One example of this approach is the... 

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. 

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