Triphenylphosphine, reaction with alkyl halides

Triphenylphosphine. reaction with alkyl halides, 721 Triple bond, electronic structure... 

Triphenylphosphine reacts with alkyl halides to form alkyltriphenylphosphonium salts. Upon reaction with strong bases, the salts release a proton to form an ylide (alkylidenetriphenylphosphorane), which is capable of reacting with aldehydes or ketones providing an unambiguous route to olefins. Since there are virtually no... 

Competitive lithiation cannot occur with monocyclic compounds, and clean a-lithiation was observed with the rhenium bis-(triphenylphosphine) dihydro complex at -78°C (Scheme 13) [89JOM(362)C31 90H(31)383]. So far, only reaction with alkyl halides has been reported, but presumably other electrophiles would react similarly. 

Triphenylphosphine reacts with alkyl halides to form phospho-nium salts. Organolithium bases react with alkyltriphenylphos-phonium salts to give phosphorus ylids, which react with aldehydes and ketones to give alkenes in what is known as the Wittig reaction. 

Various alkyl and acyl halides have been reported (39, 40, 41, 42, 43, 44) to undergo addition to terakis(triphenylphosphine)palladium(0). In addition, the analogous reaction with the halides listed in Table III has been carried out. 

The reaction of triphenylphosphine and an alkyl halides is facilitated by the use of microwave irradiation. Indeed, the Wittig reaction itself is assisted by micro-wave irradiation. Phosphonium salts are also prepared by addition of phosphines to Michael alkenes (like 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as... 

Recently Blum reported that chlorotris(triphenylphosphine) rhodium (XI) is an active catalyst for the decarbonylation of aroyl halides and showed several examples (2). But in this case too, the real catalyst seems to be chlorocarbonylbis(triphenylphosphine)rhodium (XII), which is formed in situ from XI by the stoichiometric reaction with acyl halides. Formation of alkyl halides by decarbonylation of acyl halides can be carried out by the Hunsdiecker reaction, but the reaction is unsatisfactory when applied to aroyl halides. Therefore, the decarbonylation reaction of aroyl halides by the rhodium complex is a new and useful means of introducing halogen onto the aromatic ring. 

Phosphorus ylides are prepared from a nucleophilic substitution reaction between alkyl halides and triphenylphosphine (PPh3). The resulting alkyltriphenylphosphonium salt is then deprotonated by reaction with a strong base (e.g. BuLi) to form the ylide. 

The phosphonium ylide needed for a particular synthesis is obtained by an Sn2 reaction between triphenylphosphine and an alkyl halide with the appropriate number of carbon atoms. A proton on the carbon adjacent to the positively charged phosphorus atom is sufficiently acidic (p/fa = 35) to be removed by a strong base such as butyl-lithium (Section 12.11). 

In fact, lithium diphenylphosphide can be reacted in situ with alkyl halides to give phosphines. Obviously, this reaction could be a serious side reaction in mixtures obtained from lithium reagents and phosphorus trichloride in which residual lithium was present. It should be noted also that metalation of triphenylphosphine with butyllithium occurred at the meta position on one ring to a small extent (58). Consequently, in the condensation of phosphorus halides with lithium reagents prepared by an exchange reaction employing butyllithium, an excess of the latter could result in mixtures. 

The iV-propargylaminophosphines (78) readily rearrange to give the azabuta-dienylphosphine (79) via intramolecular nucleophilic attack of phosphorus at the terminal acetylenic carbon. Full details have now appeared of the reactions of 2 -1,2,3-diazaphosphole derivatives (80) with alkyl halides, giving 2,3-disub-stituted indoles as the major product. Several examples of the attack of phosphines at carbon of a, -unsaturated carbonyl compounds have been described. The betaine (81) is the active intermediate in the triphenylphosphine-induced polymerization of maleic anhydride. Phosphines also catalyse the... 

Preparation.—Conventional quaternization reactions of phosphines with alkyl halides have been used for the preparation of chiral P-hydroxyalkylphosphonium salts for use in prostaglandin synthesis and of the salts (111), (112), and (113). This approach has also been used for the preparation of polymer-bound phosphonium salts for use in subsequent Wittig reactions and of a range of co-dialkylaminoalkylphosphonium salts. The salt (114), of limited thermal stability, is formed on treatment of the parent phenylphosphaferrocenophane (67, R = Ph) with iodomethane. The oxonium salt (115) is converted into the mixed onium salt (116) on treatment with triphenylphosphine. A range of... 

The reaction of trialkylphosphines, especially triphenylphosphine, with alkyl halides is particularly useful since the resultant phosphonium salts are easily converted to the phosphonium ylid on treatment with a suitable base (sec. 8.8r kk Ylids are, of course, the reactive species in the well-known Wittig olefination reaction, which will be discussed in section 8.8.A.i. A related Sn2 process involves reaction of a trialkylphosphite with an alkyl halide, the Arbuzov reaction (sometimes called the Michaelis-Arbuzov reaction). Triethylphos-phite (70) reacts with iodomethane to give the phosphonium salt, 71. Heating generates the monoalkyl phos-phonic ester (72). This type of phosphonic ester can be converted to an ylid and used in the well-known Horner-Wadsworth-Emmons oiefination (sec. 8.8.A.iii). 

Nucleophilic substitution of the halogen end group of ATRP-prepared polymers has also been used to synthesize phosphonium-functionalized polymers. ° Model studies of the reaction of triphenylphosphine and tri-n-butylphosphine with alkyl halides revealed that the tri-n-butylphosphine reacted 20 times faster than the triphenylphosphine (eqn [51]). PMMA-Br was reacted with tri-n-butylphosphine (10 molar excess) for 48 h at 30 °C. The resulting polymer was analyzed by MALDI-TOF MS and NMR. It was observed that the bromine end group was completely converted to the phosphonium end group. Similar results were observed for PSBr. 

Alkylphosphines (PR3) are analogs of the parent phosphine (PH3) in the same ways that alkylamines (NR3) are analogs of the parent ammonia (NHg). Phosphorus is directly beneath nitrogen in group 15 of the periodic table, so it is reasonable to expect that phosphines (PR3) should react similarly to amines (NR3). In most cases, this is a correct assumption, and phosphines react with alkyl halides by an mechanism in the same way as amines. In one example, benzyltriphenylphosphonium bromide (50) is formed by reaction of benzyl bromide with triphenylphosphine (49). This Sn2 reaction with phosphine and alkyl halides is sometimes called the Arbuzov reaction, named after Alexander Arbuzov (Russia 1877-1968). 

A useful apphcation of phosphines for replacing a carbonyl function with a carbon—carbon double bond is the Wittig reaction (91). A tertiary phosphine, usually triphenylphosphine, treated with the appropriate alkyl halide which must include at least one a-hydrogen, yields the quaternary salt [1779A9-3] which is then dehydrohalogenated to form the Wittig reagent, methylenetriphenylphosphorane [19943-09-5] an yhde. 

Phosphorus ylides like 1 can be prepared by various routes. The most common route is the reaction of triphenylphosphine 5 with an alkyl halide 6 to give a triphenylphosphonium salt 7, and treatment of that salt with a base to give the corresponding ylide 1 ... 

An aldehyde or ketone reacts with a phosphorus ylide to yield an alkene in which the oxygen atom of the carbonyl reactant is replaced by the =0 2 of the ylide. Preparation of the phosphorus ylide itself usually involves reaction of a primary alkyl halide with triphenylphosphine, so the ylide is typically primary, RCH = P Ph)3-This means that the disubstituted alkene carbon in the product comes from the carbonyl reactant, while the monosubstituted alkene carbon comes from the ylicle. 

It is possible to replace one isocyanide by triphenylphosphine, or to replace two isocyanides with diphos, giving phosphine analogues of these complexes. These species are not available from analogous reactions of phosphine-palladium(O) and (II) complexes. Reactions with active alkyl halides proceeds with oxidation nitric oxide also oxidizes these complexes. [Eqs. (31, 32)]. 

Wittig reactions are versatile and useful for preparing alkenes, under mild conditions, where the position of the double bond is known unambiguously. The reaction involves the facile formation of a phosphonium salt from an alkyl halide and a phosphine. In the presence of base this loses HX to form an ylide (Scheme 1.15). This highly polar ylide reacts with a carbonyl compound to give an alkene and a stoichiometric amount of a phosphine oxide, usually triphenylphosphine oxide. 

Halogenations with dihalotriphenylphosphoranes have been reviewed briefly by Fieser and Fieser.4 Dibromotriphenylphos-phorane appears to have been studied somewhat more than the dichloro compound, but both reagents effectively convert alcohols to alkyl halides, carboxylic acids and esters to acid halides, etc. The reaction of 1,2-epoxycyclohexane with dibromotriphenylphos-phorane under conditions similar to those described here gives a mixture of cis- and trans-1,2-dibromocyclohexanes. A reagent prepared from triphenylphosphine and carbon tetrachloride has been used for similar transformations.5... 

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