Phosphines with alkyl halides

The Wittig reagent is prepared by the treatment of phosphonium salt with a strong base (such as PhLi, n-BuLi or lithium diisopropylamide). The phosphonium salts are prepared by the reaction of phosphines with alkyl halides. 

Unsymmetrical ligands, e.g., Ph2PCH2PH2 (25), can be prepared from chloromethyl-diphenyl-phosphine, phosphine, and potassium hydroxide in a two-phase system (toluene/water) using nBu4NCl as a phase-transfer catalyst.35 This general procedure can be extended to the synthesis of the primary phosphine (26) by selective alkylation of phosphine with alkyl halides in the presence of concentrated aqueous potassium hydroxide in DMSO, or in a two-phase system involving a phase-transfer catalyst.36... 

Pertinent to this review is the study by Henderson and Buckler (130) on the kinetics of the reactions of variously substituted phosphines with alkyl halides. These authors point out that while attack by phosphine on an alkyl halide is almost certainly SN2, it does not follow that reaction proceeds by attack from the rear with inversion. For nucleophiles capable of expanding their valence shells, including esters of phosphorous... 

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... 

Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

CLASSIFICATION OF REACTIONS BY TYPE OF COMPOUND SYNTHESIZED 16-47 Reaction of phosphines with Michael alkenes or with alkyl halides... 

B. By Hydrolysis Reactions.—Details have appeared of the synthesis of dibenzophosphorin oxides (15) from 5-alkyldibenzophospholes, by reaction with methyl propiolate in the presence of water, and of confirmatory syntheses from phosphinic acid chlorides, as shown below. Evidence for the suggested mechanism of the ring-expansion reaction is presented. The hydrolysis of enamine phosphine oxides is an efficient, although somewhat indirect, method for the preparation of j8-ketoalkylphosphine oxides (16) [see Section 3(iii), for the preparation of enamine oxides]. Reasonable yields (48—66%) of trialkylphosphine oxides (17) have been obtained by the alkaline hydrolysis of the products from the pyrolysis at 220 °C of red phosphorus with alkyl halides, in the presence of iodine. 

A. Nucleophilic Reactions of the P=0 Group.—Tris(trifluoromethyl)-phosphine oxide (33) reacts with hexamethyldisiloxane to give a phos-phorane, whose n.m.r. spectrum at — 140 °C shows non-equivalent trifluoromethyl groups. Although this unusual reaction clearly involves nucleophilic attack of the phosphoryl oxygen on silicon at some stage of the reaction, a full study of the mechanism has not been published. Tertiary phosphine oxides can be converted cleanly into dichlorophos-phoranes (34) by treatment with two moles of phosphorus pentachloride. Alkylation of the sodium salt of tetraphenylmethylenediphosphine dioxide (35) with alkyl halides, in dimethyl sulphoxide, has been reported to... 

These reactions may be considered to be a method of obtaining 1,3,2,5-dioxaborataphosphoniarinanes with different substituents at carbon and phosphorus atoms of the ring. Comparing the properties of cyclic oxyalkyl-phosphines and boryloxyalkylphosphines, it should be noted that in both cases the reaction with alkyl halides results in the formation of a tertiary phosphonium salt. The reaction with electrophilic reagents such as diphe-nylchlorophosphine and diphenylchloroborane proceeded quite differently [Eq. (100)]. 

The reaction of phosphines and alkyl halides presents an alternative way to generate phosphonium electrophiles (Scheme 3.8). In particular, the combination of a phosphine and carbon tetrabromide (the Appel reaction) allows for in situ formation of a phosphonium dibromide salt (48, X = Br). Treatment of a hemiacetal donor 1 with the phosphonium halide 48 initially provides the oxophosphonium intermediate 38 (X = Br). However, the oxophosphonium intermediate 38 can react with bromide ion to form the anomeric bromide intermediate 49 (X = Br) with concomitant generation of phosphine oxide. With the aid of bromide ion catalysis (i.e. reversible, catalytic formation of the more reactive P-anomeric bromide 50) [98], the nucleophile displaces the anomeric bromide to form the desired glycoside product 3. The hydrobromic add by-product is typically buffered by the presence of tetramethyl urea (TMU). 

An efficient resolntion of the racemic lithinm tert-bntylphosphine-borane complex 203 dnring deprotonation by n-BnLi/(—)-sparteine (11) and alkylation was reported by Liv-inghonse and Wolfe (eqnation 47) . One of the epimers 204/cp/-204 on warming to 0 °C crystallizes during a dynamic thermodynamic resolntion, and reaction with alkyl halides fnmishes the alkylation prodncts 205 with high ee values. Applying dihalides, essentially enantiomerically pure diphosphines snch as 206, besides few of the mcio-diastereomer, were obtained. Borane is removed by treatment with diethylamine to yield the free tertiary phosphines 207. 

Phenols attached to insoluble supports can be etherified either by treatment with alkyl halides and a base (Williamson ether synthesis) or by treatment with primary or secondary aliphatic alcohols, a phosphine, and an oxidant (typically DEAD Mitsu-nobu reaction). The second methodology is generally preferred, because more alcohols than alkyl halides are commercially available, and because Mitsunobu etherifications proceed quickly at room temperature with high chemoselectivity, as illustrated by Entry 3 in Table 7.11. Thus, neither amines nor C,H-acidic compounds are usually alkylated under Mitsunobu conditions as efficiently as phenols. The reaction proceeds smoothly with both electron-rich and electron-poor phenols. Both primary and secondary aliphatic alcohols can be used to O-alkylate phenols, but variable results have been reported with 2-(Boc-amino)ethanols [146,147]. 

Many diorganogold(III) compounds with tertiary phosphines and arsines are now known. It has been shown previously (Section 1II,B) that the reactions of [AuRL] complexes with alkyl halides usually produced [AuXL] and a triorganogold(lll) species. In certain instances, however, the expected [AuXR2L] compounds were formed (46, 194, 195), notably in the reactions of [AuMeL] (L = PMe3, PMe2Ph, or AsPh3) with methyl iodide. 

Rh(CO)2 2(Por) complexes undergo addition reactions with carbonyl compounds and with alkyl halides to give acyl or alkyl Rhul(Por) similar to Rh1(CO)(phosphine)3 (Scheme 33).1.34... 

The Co(II) compounds react with alkyl halides according to Equation 1. The initial and rate-determining step is halogen abstraction (14). For L = phosphines... 

The selective preparation of various chlorophosphines used as building blocks for the preparation of polyfunctional phosphines is achieved using dichloro (diethylamino)phosphine (Et2NPCl2). Alkylation of this phosphine with organozinc halides furnishes, after borane treatment, protected aminodi-organophosphines. These in turn can be converted to the corresponding... 

Other preparative methods of bis(trialkylsiIyl)phosphines involve reaction of RPLi2 with Me,SiCl (equation 8)28 and reaction of (Me3Si)2PLi with alkyl halides (equation 9)29. 

Primary and secondary phosphines may be readily alkylated with alkyl halides simply by nucleophilic displacement of halide by a phosphine anion (equation 50)84,392. With primary phosphines, dialkylation is readily achieved if excess base is used. Alkyl halides will also react with phosphine oxide and other phosphorous anions, especially if the reaction is performed under PTC392"395. 

Thiocarbonyl derivatives of 1,3-dioxolanes and 1,3-oxathiolanes are readily isomerized to the 2-carbonyl compounds as shown in Scheme 20. Alkylation of the sulfur atom with alkyl halides usually leads to ring-opened products (Scheme 21) (69JOC3011). Most of the other chemistry of the sulfur derivatives has focused on desulfurization and subsequent generation of alkenes. The reaction is shown in equation (20) and proceeds with cis elimination via carbene intermediate (see Section 4.30.2.2.5) and is usually carried out with a phosphine (73JA7161) or a zero-valent nickel complex (73TL2667). 

Diaminophosphoninm salts, [R2P(NR2)2] X, can be prepared by reactions of bis(dialkylamino)phosphines, RP(NR2)2, with alkyl halides. Diphosphines are cleaved by chloramine to form diaminophosphoninm salts (eqna-tion 7). ... 

Tris(amino)phosphines, P(NR2)3, react with alkyl halides and with halogens to form triaminophosphonium salts (Scheme 24). 

Ethylene oxide or 1,2-epoxybutane may also be used for the synthesis of ylides. The resulting ylide is in equilibrium with its conjugated salt (equation 15). The use of ethylene oxide offers some advantages over more conventional bases used in Wittig reactions. The application is simple since ylides and most often also phosphonium salts (from phosphine and alkyl halide) need not to be prepared separately. The reaction medium is neutral, so that base-induced side reactions fail to appear. The method is however less applicable to weakly acid phosphonium salts, since deprotonation requires high temperatures (150 C). 

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