Organophosphorus Chemistry Volume 8

A Review of the Literature Published between July 1975 and June 1976

By S. Trippett

The Royal Society of Chemistry

Copyright © 1977 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-076-3

Contents

Chapter 1 Phosphines and Phosphonium Salts By D. W. Allen, 1,
Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett, 31,
Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller, 50,
Chapter 4 Phosphine Oxides and Sulphides By J. A. Miller, 71,
Chapter 5 Tervalent Phosphorus Acids By B. J. Walker, 84,
Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson, 102,
Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson, 133,
Chapter 8 Nucleotides and Nucleic Acids By J. B. Hobbs, 151,
Chapter 9 Ylides and Related Compounds By D. J. H. Smith, 177,
Chapter 10 Phosphazenes By R. Keat, 204,
Chapter 11 Photochemical, Radical, and Deoxygenation Reactions By R. S. Davidson, 232,
Chapter 12 Physical Methods By J. C. Tebby, 248,
Author Index, 276,

CHAPTER 1

Phosphines and Phosphonium Salts

BY D. W. ALLEN

1 Phosphines

Preparation. — From Halogenophosphine and Organometallic Reagents. The cyclopentadienylphosphines (1) have been obtained from the reaction of cyclopentadienylthallium with chlorophosphines in ether. Diphenyl(4-pyridyl)phosphine (2) is prepared from 4-pyridyl-lithium and chlorodiphenylphosphine, and an improved procedure for the synthesis of tri-(2-pyridyl)phosphine (3) from 2-pyridyl-lithium and phosphorus trichloride has been reported.

Treatment of phosphorus trichloride with an excess of the Grignard reagent (4) leads to the sterically hindered phosphine (5). A sample of 14C-labelled triethylphosphine has been synthesized from 14C-labelled ethylmagnesium iodide and phosphorus trichloride. The reaction of chlorodiphenylphosphine with the Grignard reagent derived from 2,2′-dibromobibenzyl in THF solution leads to the diphosphine (6), which is dehydrogenated by various rhodium complexes to form trans-2,2′-diphenylphosphinostilbene (7).

The reaction of halogenophosphines with esters of trialkylstannylacetic acids gives a general route to compounds containing the — P(CH2CO2R)n grouping. Diphosphinoacetic acid esters (8) can be prepared from the monophosphino-esters by treatment with sodium and dialkylchlorophosphines.

From Metallated Phosphines. The synthesis of polymeric tertiary phosphines based on the reaction of lithium diphenylphosphide with chloromethylated polystyrenes continues to attract interest. Considerable breakdown of the carbon–carbon back-bone of PVC occurs on reaction with lithium diphenylphosphide in THF, and only oligomers of low molecular weight result. The potassium salt (9) reacts with chloromethylated polystyrene to form the polymeric diphosphine (10).

The ω-chloroalkyldiphenylphosphines (11) have been prepared by the reaction of equimolar quantities of sodium diphenylphosphide with αω-dichloroalkanes. Whereas the phosphine (11; n = 3) can be converted into the Grignard reagent (12), which reacts with dimethylchlorophosphine to form the unsymmetrical diphosphine (13), the Grignard reagent (14) undergoes a β-elimination reaction to regenerate diphenylphosphide ion.

Similarly, the chloroalkylarsine (15) (obtained from lithium diphenylarsenide and 1,2-dichloroethane) reacts with lithium diphenylphosphide to form the mixed phosphine-arsine (16).

Organosilylphosphines are conveniently prepared by cleavage of alkyldiarylphosphines with lithium in THF, followed by treatment with chlorotrimethylsilane, and tris(trimethylsilyl)phosphine has been prepared from the reaction of chlorotrimethylsilane with a mixture of sodium and potassium phosphides.

The product of the reaction between lithium diphenylphosphide (or trimethylsilyldiphenylphosphine) and dimethyl 2,3-dichloromaleate has been shown to be the fumarate (17) and not (as previously supposed) the expected maleate (18). Nucleophilic displacement of halide ion from a saturated carbon atom by alkalimetal diphenylphosphide reagents occurs with inversion of configuration at carbon, as is found in normal SN2 displacements. Thus menthyl chloride or bromide gives the neo-menthyldiphenylphosphine (19).

An improved procedure has been reported for the synthesis of the C-functionalized tertiary phosphine (20), based on the reaction of potassium diphenylphosphide with ethyl chloroacetate.

Two reports of the hitherto little documented attack of organophosphide anions on halogen have appeared. Addition of 1,2-dibromoalkenes to lithium diphenylphosphide in THF gives an acetylene and tetraphenyldiphosphine (Scheme 1).

In the corresponding reactions of o-dihalogenobenzenes, attack on halogen, leading to the generation of benzyne, competes with attack at carbon, leading to the o-halogenophenyldiphenylphosphine (21). Further attack of phosphide on the halogen of the latter gives the anion (22), which on treatment with D2O gives the ortho-deuterated phosphine (23) (Scheme 2). Lithium diphenylphosphide reacts with the benzyne-furan adduct (24) to give, after dehydration, a mixture of 1- and 2-diphenylphosphinonaphthalenes.

By Addition of P — H to Unsaturated Compounds. This route continues to be exploited for the synthesis of polydentate tertiary phosphine ligands. Thus base-catalysed addition of diphenylvinylphosphine to the secondary phosphine (25) affords (26). Neopentylpolytertiaryphosphines, e.g. (27), have been similarly prepared by addition of primary or secondary phosphines to vinylphosphines (or the related phosphine sulphides, followed by a desulphurization step).

Free-radical-catalysed additions have also been reported, and provide a genuine alternative to the more familiar base-catalysed addition routes. Thus the secondary diphosphine (28) readily adds to diphenylvinylphosphine in the presence of AIBN to give (29). Similarly, addition of di(pentafluorophenyl)phosphine to diphenylvinylphosphine affords the diphosphine (30). Sequential addition of silanes and secondary phosphines to terminal αω-dienes under the influence of u.v. light affords the silylalkylphosphines (31), which may be anchored via silicon to the surface of inorganic oxides and used as polymeric catalysts.

Addition of P — H bonds to unsaturated systems also continues to be used as a route to heterocyclic systems. Thus base-catalysed cyclization of the phosphine (32) [prepared by the addition of methyl methacrylate (2 moles) to phenylphosphine], followed by subsequent hydrolysis and decarboxylation, affords the phosphorinanone (33). The phosphorinanone system is also directly accessible by the addition of phenylphosphine to divinyl ketones. The radical-initiated addition of phenylphosphine to dialkynyl systems (34) gives the heterocyclohexadienes (35). The stereochemistry of the addition of phenylphosphine to cyclo-octa-2,7-dienone to give the phosphinone (36) has been studied. Contrary to an earlier report, both syn– and anti-isomers are formed.

By Reduction. The first known compounds containing a tervalent phosphorus function and an epoxide ring [(37) and (38)] have been prepared by reduction with phenylsilane of the corresponding phosphine oxides; they are quite stable, showing no tendency to undergo oxygen transfer to phosphorus, and can be distilled in vacuo. The phosphinylacetonitriles (39) undergo selective reduction to the corresponding phosphinoacetonitriles (40) on treatment with diphenylsilane.

The isomeric bicyclic phosphines (41) have been obtained by reduction with trichlorosilane of the related isomeric phosphine oxides, the reaction proceeding with retention of configuration. In contrast, reduction with trichlorosilane of the pure cis– or trans-diazaphospholine oxides (42) gives mixtures of the cis– and trans-phosphines (43). The lack of stereospecificity is attributed to pseudorotation of phosphorane intermediates.

The Δ3-phospholen sulphides (44), bearing reactive functional groups, may be reduced to the phosphine using nickelocene in the presence of allyl iodide. The intermediate nickel complex is decomposed with cyanide to free the functionalized Δ3-phospholen (45).

A cautionary note has appeared concerning the use of sodium bis(2-methoxyethoxy)aluminium hydride as a reducing agent in phosphorus chemistry. The use of this reagent is severely limited by the enhanced alkylating ability of the ether groups. Thus the reduction of chlorodiphenylphosphine gives a mixture of diphenylphosphine, methyldiphenylphosphine, and 2-hydroxyethyldiphenylphosphine. Lithium aluminium hydride has been employed in the reduction of the ω-phosphinylalkyldiorganostannanes (46) to the phosphines (47), which are useful precursors for the synthesis of heterocyclic compounds containing both tin and phosphorus as ring members.

Miscellaneous. A number of reports of the synthesis of unusual heterocyclic phosphines have appeared. Improved procedures for the synthesis of 1,3,5-triaza-7-phospha-adamantane (48) have been reported, and the triazaphosphahomoadamantane (49) has also been prepared. Routes to the large ring phosphacycloalkanes (50) have been described, and the bicyclic diphosphine (51) has been isolated from the reaction of white phosphorus with o-dichlorobenzene in the presence of transition-metal halides.

The heterocyclic acylphosphines (52) and (53) have been prepared by the reaction of phenylbis(trimethylsilyl)phosphine with the acid chlorides derived from phthalic and diphenic acids. The reaction of 2,3-dichloromaleic anhydride or thioanhydride with phenylbis(trimethylsilyl)phosphine gives derivatives of the 1,4-dihydro-p-diphosphorin system (54).

cis-Addition of alkyl cuprate reagents to alkynyl-phosphines occurs to give the vinylphosphines (55).

The alkynylphosphine (56) reacts with Wilkinson’s catalyst to give an intermediate rhodium complex, which, when treated with diphenylacetylene followed by cyanide ion, yields the diphosphine (57), of interest as a rigid chelating ligand of fixed geometry.

Convenient routes to several new sterically crowded chelating diphosphines have been described. Thus, e.g., m-xylylene dibromide, on treatment with di-t-butylphosphine, affords a bisphosphonium salt, which on treatment with a weak base affords the diphosphine (58).

Rhodium and iridium complexes effect the dehydrogenation of the alkane chain in 1,6-bisdiphenylphosphinohexane to form (after treatment with cyanide ion) 1,6-(bisdiphenylphosphino)-trans-hex-3-ene.

A new route to compounds claimed to contain the phosphyl P [equivalent to] C linkage has been described. Thus, e.g., cyanogen bromide reacts with phosphine to give (59), which on treatment with isoamyl nitrite gives (60).

Reactions. — Nucleophilic Attack at Carbon, (i) Carbonyls. Methyl arylglyoxylates react with trisdimethylaminophosphine (TDAP) to form cis-αβ-dimethoxycarbonylstilbene oxides. The initially formed zwitterion (61) reacts with a second molecule of the ester to form a trans-diphenyl-1,4,2-dioxaphospholan intermediate, which undergoes a concerted symmetry-allowed retrograde π2S + π4S cycloaddition to give a carbonyl ylide, conrotatory cyclization of which leads to the cis-oxirans (62) (Scheme 3).

The ‘K-region’-oxirans (63) and (64), of interest in studies of chemical carcinogenesis, have been prepared by cyclization with TDAP of the dialdehydes obtained by oxidative cleavage of the parent hydrocarbons.

The reaction of the phospholen (65) with aromatic acid chlorides in the presence of triethylamine, followed by addition of D2O, gives a ready route to aromatic [1-2H]-aldehydes with 100% incorporation of deuterium.

(ii) Miscellaneous. Nucleophilic attack of dimethylphosphine (or tetramethyldiphosphine) occurs at the terminal olefinic carbon of hexafluoropropene to give a mixture of cis– and trans-dimethylpentafluoropropenylphosphines (66) in proportions which depend on the reaction conditions. The products do not arise by dehydrofluorination of a 1:1 adduct.

Further evidence of anchimeric assistance between the oxygen 2p orbitals of the o-methoxyphenyl group and the 3d orbitals of the developing phosphonium centre has been obtained in studies of the rate of quaternization of the phosphine (67). However, the presence at phosphorus of ferrocenyl substituents which are capable of conjugative stabilization of the developing phosphonium centre does not lead to a marked increase in the rate of quaternization of tertiary phosphines [e.g. (68)], supporting the concept that the transition state for the SN2 reaction of a tertiary phosphine with an alkyl halide lies closer to the reactants rather than to the products in the energy profile diagram.

Ring opening of diphenylthiiren 1,1-dioxide and diphenylcyclopropenone occurs on reaction with tertiary phosphines to form the betaines (69) and the keten phosphoranes (70), respectively. Tertiary phosphines react with the thione (71) to form mainly the betaine (72).

Nucleophilic Attack at Halogen. The reactions of tertiary phosphines, in particular triphenylphosphine and TDAP, with tetrahalogenomethanes continue to attract much interest. Recent progress in understanding the course of the reactions occurring between triphenylphosphine, carbon tetrachloride, and a substrate, and the preparative applications of tertiary phosphine-carbon tetrachloride ‘reagents’, have been reviewed. In reactions employing these reagents, the reactions of the substrate compete with the ‘internal’ reactions of the two-component system, so that the overall course is much more complex than previously assumed.

The first isolable product in the reaction of triphenylphosphine and carbon tetrachloride is the salt (73), which reacts rapidly with further phosphine to give the stable phosphorane (74). In contrast, tris-t-butylphosphine reacts with germanium and tin tetrahalides to form the salts (75); compounds of the latter type have long been postulated as arising from the reactions of phosphines with carbon tetrahalides but so far have defied detection.

Two routes for the reaction of substrate with the triphenylphosphine–carbon tetrachloride reagent are now recognized. Direct interaction (76) of the substrate with the initially formed dipolar associate leads to the formation of chloroform and the intermediate phosphonium salt (77).

Direct chlorination of the substrate by the dichlorotriphenylphosphorane present in the reaction mixture competes with the above route. The HCl liberated is taken up by the dichloromethylenetriphenylphosphorane also present to form dichloromethyltriphenylphosphonium chloride (78), which reacts further with triphenylphosphine with the eventual formation of chloromethyltriphenylphosphonium chloride (79) (Scheme 4). This route, which does not lead to the formation of chloroform appears to be followed to the extent of 95 % in the reactions of enolizable ketones with the triphenylphosphine–carbon tetrachloride reagent. The phosphonium salts (78) and (79) precipitate from the reaction mixtures. Such precipitates observed earlier in other reactions have been referred to as triphenylphosphine oxide and/or triphenylphosphine hydrochloride without characterization.

In spite of the above complexity, exploitation of these reagents in synthesis continues. Thus the triphenylphosphine–carbon tetrachloride combination has been employed as a condensing agent in peptide synthesis, and the TDAP–carbon tetrachloride combination for the synthesis of halogenated and sulphonated carbohydrates. Other reactions reported include the use of triphenylphosphine-carbon tetrachloride to chlorinate poly(hydroxyethyl methacrylate) and poly(2-hydroxypropyl methacrylate), and to convert S-alkylthiocarbamates or dithiocarbamates into N-phenylchlorothioformimidates. Arylhydroxylamines are converted by the triphenylphosphine–carbon tetrachloride reagent into a mixture of the azobenzene and corresponding azoxybenzene. A full report of the reactions of the TDAP–carbon tetrachloride reagent with vicinal diols, to give either trans-epoxides or spirophosphoranes, has appeared. The reactions of αω-diols with TDAP–carbon tetrachloride have also been studied and conditions defined for the exclusive formation of monoalkoxyphosphonium salts (80), which may then be subjected to a range of nucleophilic displacement reactions. Alkylphosphinates (81) are formed in good yield by the simultaneous action of alcohols and carbon tetrachloride on chlorophosphines in the presence of an auxiliary base.

Applications of the combination of polymer-supported triarylphosphines (82) with carbon tetrachloride for the synthesis of peptides and acid chlorides, involving a simple filtration and evaporation process for product isolation, have been reported.

The reactions between PP-diphosphines, carbon tetrachloride, and primary or secondary amines have been studied. In general, diaminophosphonium salts (83) are formed, except for reactions involving sterically hindered amines, when chloromethylphosphonium salts [e.g. (84)] or methylenebisphosphonium salts [e.g. (85)] result. The corresponding reactions of the cyclic diphosphine (86) occur either with ring opening to give (87) or with ring expansion to give (88), depending on the nature of the amine. The reactions of cyclopolyphosphines with carbon tetrachloride and with amine–carbon tetrachloride combinations have also been investigated.

The rates of dehalogenation of α-bromo- and α-iodo-m-cyanobenzylphenyl-sulphones (89) by a number of sterically hindered phosphines in aqueous DMF have been studied. Variation in the rate data for tri-o-tolylphosphine and tri-o-anisyl-phosphine is best explained in terms of a steric effect rather than a special electronic effect arising from interactions of the methoxy-group with the phosphonium centre (cf. ref. 57). The use of diphosphines (e.g. 1,2-bisdiphenylphosphinoethane), in which a second phosphorus atom might assist in the transition state, produces no special effects.

Nucleophilic Attack at Other Atoms. The adduct (90) from triphenylphosphine and diethyl azodicarboxylate (DAD) catalyses transesterification under neutral and mild conditions (Scheme 5).

Unsaturated monosaccharides [e.g. (91)] react with the Ph3P–DAD combination in the presence of phthalimide, with inversion of configuration of C-4, to form the phthalimido-derivatives (92). Treatment of carbohydrates having a free anomeric OH group with 6-chloropurine, DAD, and methyldiphenylphosphine gives the purine nucleosides (93).

(Continues…)Excerpted from Organophosphorus Chemistry Volume 8 by S. Trippett. Copyright © 1977 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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