Organophosphorus Chemistry Volume 7

A Review of the Literature Published between July 1974 and June 1975

By S. Trippett

The Royal Society of Chemistry

Copyright © 1976 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-066-4

Contents

Chapter 1 Phosphines and Phosphonium Salts By D. J. H. Smith, 1,
Chapter 2 Quinquecovalent Phosphorus Compounds By S. Trippett, 29,
Chapter 3 Halogenophosphines and Related Compounds By J. A. Miller, 45,
Chapter 4 Phosphine Oxides, Sulphides, and Selenides By J. A. Miller, 66,
Chapter 5 Tervalent Phosphorus Acids By B. J. Walker, 78,
Chapter 6 Quinquevalent Phosphorus Acids By R. S. Edmundson, 105,
Chapter 7 Phosphates and Phosphonates of Biochemical Interest By D. W. Hutchinson, 131,
Chapter 8 Nucleotides and Nucleic Acids By J. B. Hobbs, 146,
Chapter 9 Ylides and Related Compounds By S. Trippett, 166,
Chapter 10 Phosphazenes By R. Keat, 188,
Chapter 11 Photochemical, Radical, and Deoxygenation Reactions By R. S. Davidson, 212,
Chapter 12 Physical Methods By J. C. Tebby, 228,
Author Index, 271,

CHAPTER 1

Phosphines and Phosphonium Salts

BY D. J. H. SMITH

1 Phosphines

Preparation. — From Halogenophosphine and Organometallic Reagents. 1,2-Phosphaboretens, e.g. (1), have been obtained from the reaction of sodium trialkyl-1-alkynylborates with chloro-phosphines; with acetic acid they give (E)-alkenylphosphines. Lithium amino-acetylides react with chlorodiphenylphosphine to form (phosphino-ethynyl)amines (2).

Condensation of dimethyl methylphosphinite with chlorodiphenylphosphine at room temperature gave (3), which with an excess of chlorodiphenylphosphine gave tetraphenyldiphosphine.

The diphosphine (4) can be synthesized by reaction of an excess of chloro(phenyl)-t-butylphosphine with chlorotrimethylsilane in the presence of magnesium.

A wide range of 1,3-diphosphorinans and 1,3-diphospholans has been obtained from the reaction of alkali-metal diphosphides (5) and a variety of halides.

Optically active diphenylmenthylphosphine can be conveniently prepared from chlorodiphenylphosphine and the configurationally stable Grignard reagent derived from menthyl chloride.

Optically active ferrocenylphosphines are readily obtained by selective lithiation of (6) followed by treatment with a chloro-phosphine. A second phosphino-group may be introduced into the other cyclopentadienyl ring by stepwise lithiation (Scheme 1).

From Metallated Phosphines. The red solutions formed by cleavage of phenyl from alkyldiphenyl- and dialkylphenyl-phosphines with excess lithium in THF show detectable e.s.r. spectra (see Chapter 12). The resulting alkylphenyl- or dialkylphosphides can be added to diphenylvinylphosphine to produce unsymmetrical bis-(tertiary phosphines) and react with alkyl halides to form dissymmetric tertiary phosphines. The corresponding silylphosphine dilithio-derivatives (7) are also alkylated on treatment with methyl chloride.

The compound (8), which can be obtained in solution from the reaction of lithium dimethylphosphide with aluminium chloride, forms silyl-phosphines, e.g. (9), when treated with silicon halides.

Trifluorosilylphosphine has been prepared by the reaction of trifluorosilyl bromide with (10).

The cyclothiatetraphosphine (11) is obtained in good yield from the reaction of pentaphenylcyclopentaphosphine and sulphur. This phosphine is also obtained from the reaction of dipotassium triphenylcyclotriphosphine and sulphur dichloride, whereas reaction with dichloro-trisulphane produces the novel heterocycle (12).

Addition of dilithium ethylphosphide or phenylphosphine to phthaloyl chloride leads to the cyclic phosphines (13).

The preparation of a chiral biphosphine ligand (14) from a dioxole ditosylate has been described.

Derivatives of 2,3-bis(diphenylphosphino)maleic anhydride (15) have been prepared from the 2,3-dichloro-compounds with the aid of diphenyl(trimethylsilyl)-phosphine. Similarly, ethylene diphosphines, e.g. (16), can be obtained by treatment of the corresponding dichloro-compound with a lithium phosphide.

The reaction of sodium methylphenylphosphide with (+)-(R)-1-chloroethylbenzene gave (Sp)-(Sc)-methyl-(α-methylbenzyl)phenylphosphine oxide (17) after oxidation. Determination of optical purity showed that some induced asymmetry had occurred at the phosphorus atom in the initial reaction.

By Addition of P — H to Olefins. A detailed study of base-catalysed additions of phosphines, containing two P — H bonds, to vinylic phosphorus compounds has appeared. Treatment of primary phosphines with di-isopropyl vinylphosphonate in a 1 : 1 ratio, followed by reduction, gave (18) ; in the corresponding reaction with methylphosphine only (19) was isolated (Scheme 2). Full experimental details are now available for the preparation of methylated poly(tertiary phosphines) by the conversion of a P — H bond into a PCH2CH2PMe2 unit using dimethylvinylphosphine sulphide. Two isomers of (20) with widely differing physical properties are obtained from the base-catalysed addition of (21) to diphenylvinylphosphine.

The sexidentate ligand (22) has been prepared by reduction of the ester (23) followed by condensation with diphenylvinylphosphine in THF, and synthesis of poly(tertiary phosphines) with 5, 7, 8, and 10 P atoms has been described.

Secondary phosphines have been added to formaldehyde t-butylimine to give aminomethyl-phosphines.

Bicyclic phosphines such as (24) or (25) have been prepared by treating alkylphosphines with equimolar amounts of cyclo-octadienes in the presence of a free-radical catalyst.

By Reduction. Chiral amino-alanes have been used in the asymmetric reduction of racemic 3-methyl-1-phenyl-Δ2-phospholen 1-oxide (26) and methylphenyl-n-propylphosphine oxide. The sign of rotation of the phosphine from reduction of (26) varies, depending upon the reaction conditions.

Trichlorosilane can be used to reduce selectively the phosphine oxide bond in the presence of a keto-group (27) or an ester group (28).

The chiral diphosphine (29), an excellent ligand for use in asymmetric hydrogenation with rhodium catalysts, has been made by reduction of the corresponding diphosphine dioxide. Higher yields and less meso-(29) were obtained using tributylamine with trichlorosilane rather than the more commonly used triethylamine. Reoxidation with hydrogen peroxide established that inversion had occurred at both phosphorus atoms during the silane reduction.

Miscellaneous. A monophosphorus analogue (30) of HMT has been isolated from the reaction of tris(hydroxymethyl)phosphine with HMT in the presence of formalin. Similar treatment of tris(hydroxymethyl)phosphine with cyanamide in the presence of formalin gives (31).

The reaction of di-isopropyl polymethylenediphosphinates with polymethylene dibromides in the presence of Red-al at high dilution gives cis– and trans– macrocyclic diphosphine oxides, which can be reduced to the corresponding cyclic diphosphines (32) using trichlorosilane in benzene.

Primary and secondary phosphines react with dialkylaminomethyl-phosphines, causing P — C bond cleavage and resulting in the formation of P — P bonds. Thus (33) and diphenylphosphine yield tetraphenyldiphosphine, whereas phenylphosphine gives pentaphenylcyclopentaphosphine and (34).

Phosphine, when passed through an electric discharge, yields as much as 50% of diphosphine. Methylphosphine gave a mixture of products, among which methyldiphosphine and 1,2-dimethyldiphosphine could be identified. A discharge through a mixture of acetylene and phosphine produces reasonable quantities of ethynylphosphine.

Reactions. — Nucleophilic Attack at Carbon. Carbonyls. The condensation of o-aminobenzylphosphine with aldehydes and ketones gives substituted tetrahydro-1,3-benzazaphosphorines (35). Substituted perhydro-1,3,5-oxazaphosphorines (36) have been prepared by cyclization of phenylphosphine with benzaldehyde and imines. However, the interaction of diphosphines of the type (37) with benzaldehyde does not give cyclic products but leads to (hydroxyalkyl)-phosphines, which rearrange to phosphine oxides.

The reaction of diphenylphosphine with carbonyl compounds has been reexamined. The products of these reactions, the α-hydroxyalkyldiphenylphosphines (38), arise from nucleophilic attack at carbonyl carbon followed by proton transfer. The corresponding reaction with tertiary phosphines leads to products containing a P — O — C bond, which are thought to arise from rearrangement of the initial P — C — O adducts. Tertiary phosphines have been shown to catalyse the isomerization of α-hydroxy-phosphines Pentafluorobenzaldehyde reacts rapidly with tris(dimethylamino)phosphine (TDAP), giving a mixture of diastereomeric stilbene oxides (39).

Miscellaneous. Edge participation of the cyclobutene ring of the non-classical ion (40) is indicated in its reaction with triphenylphosphine, which yields only a product with the substituent in the anti-position to the cyclobutene moiety.

1,4-Thiaphosphorins (41) have been obtained by addition of phenylphosphine to di-l-alkynyl sulphides in the presence of lithium amide in liquid ammonia.

Alkylbis(hydroxymethyl)phosphines (42) can be converted into (hydroxyethyl)-phosphine derivatives by treatment with ethylene oxide.

Nucleophilic Attack at Halogen. A review of the reactions of tervalent phosphorus compounds with tetrahalogenomethanes and the reactions of the compounds obtained has appeared. A detailed examination of the influence of the nature of the phosphine, solvent, temperature, and of excess phosphine on the course of the reaction of phosphines with carbon tetrachloride in the presence of acidic nucleophiles has been carried out. Several reports of the isolation of phosphonium salts from such reactions have been published this year.

The aminophosphonium salts (43), formed from the reaction of optically active methylphenyl-n-propylphosphine, carbon tetrachloride, and amines, are optically inactive. Racemization does not occur via amine exchange but probably arises from permutational isomerization of a pentaco-ordinate intermediate. These amino-phosphonium salts can be used for the conversion of alcohols into secondary and tertiary amines under mild conditions.

(Aryloxy)- and (arylthio)-phosphonium salts (44) can be obtained by the simultaneous action of phosphines and carbon tetrachloride on phenols or thiophenols.

Alkoxyphosphonium salts derived from the action of TDAP and carbon tetrachloride on diols and secondary alcohols have been isolated. N-Chlorodi-iso-propylamine can be substituted for carbon tetrachloride in these reactions. The action of TDAP and carbon tetrachloride on the hydroxybenzotriazole (45) leads to an alkoxyphosphonium salt which is a very effective agent for peptide-coupling reactions, in which there is little racemization.

The use of the phosphine–carbon tetrachloride system for the conversion of alcohols into alkyl chlorides has been modified by the use of a polystyryl-diphenyl-phosphine resin as the phosphorus reagent, enabling a simple filtration and evaporation process for product isolation.

Oximes give imidoyl chlorides (46) or amides via Beckmann rearrangements, and N‘-benzoyl-N-arylhydrazines (47) are converted into hydrazonyl chlorides, using triphenylphosphine with carbon tetrachloride.

Diphosphines (48) are cleaved by carbon tetrachloride, in a reaction which is reversible at temperatures of up to 100 °C, leading to mixtures of chlorophosphines and (trichloromethyl)phosphines. Isocyanates and dihalogenophosphines can be obtained from the reaction of carbamoyl halides (49) with triphenylphosphine–carbon tetrachloride. Fluorophosphoranes have been synthesized by the reaction of phosphines and chlorophosphines with carbon tetrachloride and HF donors (see Chapter 2).

Phosphinic acids react with triphenylphosphine–carbon tetrachloride to give the corresponding acid chloride or anhydride. Only the anhydrides are formed in the presence of triethylamine but in the presence of primary or secondary amines the acids are converted directly into the corresponding amides (50). Primary amides can react further with triphenylphosphine–carbon tetrachloride, yielding imides (51). In some cases phosphazenes are produced as dehydration products (see Chapter 9).

The use of TDAP and carbon tetrachloride as an activating system for the nucleophilic substitution of alcohols continues to be developed. The intermediate alkoxyphosphonium chlorides (Scheme 3) are usually converted into a more stable salt such as hexafluorophosphate and then treated with a nucleophile. Activation of a single hydroxy-group of propane-1,3-diols is possible. Selective activation of various positions in carbohydrate derivatives has been achieved, and the ability of the system to activate alcohols and then enable substitution without rearrangement has been exploited in the synthesis of aryl alkyl ethers and thioethers free from isomers. (See also Ref. 76.)

A new route to 2,3-dialkylthiiren 1,1-dioxides is provided by the reaction of the tetrabromosulphones (52) with triphenylphosphine in dichloromethane at -40 °C. However, phosphines open the 2,3-diphenyl analogues at room temperature to give quantitative yields of the betaines (53).

The reaction of phosphines with α-cyano-α-halogeno-imides of the type (54), and further reactions of the betaine products, continue to be studied.

The mechanism of the rapid reduction of a-nitro-bromo-esters to the phosphonium salts (55) with 3 moles of triphenylphosphine has been discussed in some detail.

Nucleophilic Attack at Other Atoms. The reaction of the acyl glycerol (56) with carboxylic acids in the presence of the triphenylphosphine–diethyl azodicarboxylate complex causes substitution of the hydroxy-group without concomitant acyloxy-group migration.

A simple synthesis of alkyl aryl ethers has been described involving the reaction between an alcohol and a phenol in the presence of triphenylphosphine-diethyl azodicarboxylate. These reactions occur with inversion of configuration of the alcohol carbon, as shown by the conversion of cholestan-3β-ol into the ether (57). However, the reaction of cholesterol with benzoic acid in the presence of the same reagents gives a complex mixture of benzoates which are, at least partially, derived from an intermediate (58) involving C=C participation.

Triphenylphosphine appears to be the phosphine of choice for reactions of this type. When monosaccharide derivatives containing isolated hydroxy-groups are treated with equal amounts of TDAP and a dialkyl azodicarboxylate, mixed carbonates (59) are obtained. Substituted carbohydrates can be converted into the expected phthalimide derivatives by diethyl azodicarboxylate–triphenylphosphine in the presence of phthalimide, but when TDAP is used the main products are (59; R2 = Et) and (60; R2 = Et).

The combination of triphenylphosphine and 2,2′-dipyridyl disulphide as a condensing agent has been shown to be very effective under neutral aprotic conditions. The use of these reagents has been extended to the intramolecular synthesis of macrocyclic lactones from ω-hydroxy-alkanoic acids, the synthesis of lactones, e.g (61), in the prostaglandin series, and of complex naturally occurring macrocyclic compounds from hydroxy-acids. Their use as condensing agents in solid-phase peptide synthesis has also been investigated.

A stopped-flow kinetic study of the reaction of triphenylphosphine with aryl disulphides in aqueous dioxan, which affords the corresponding benzenethiol and triphenylphosphine oxide in quantitative yield, has been reported. The authors propose a two-step mechanism for these reactions (Scheme 4).

Selective formation of 5′-S-alkylthio-5′-deoxyribonucleosides (62) can be achieved by the reaction of nucleosides with dialkyl disulphides and tri-n-butylphosphine, even when excess amounts of the phosphine and dialkyl disulphides are used. The combination of diphenyl disulphide and tri-n-butylphosphine is useful for the introduction of the phenylthio-group onto phosphate residues of nucleotides.

Dimethylphosphinous acid esters of thio- or seleno-sugars (63) have been prepared by the reaction of tetramethyldiphosphine with the carbohydrate disulphide or diselenide.

The o-nitrophenylsulphenyl group can be used for protecting amino-groups of peptides. This group is selectively removed in the presence of benzyloxycarbonyl, benzyl ester, and t-butyl groups, by the use of triphenylphosphine and an active-hydrogen compound such as a phenol (Scheme 5).

Miscellaneous. The treatment of tertiary phosphines with alkyl-lithium reagents may lead to nucleophilic substitution at phosphorus, which can be very competitive with deprotonation depending upon the medium used. Thus methyldiphenylphosphine gives 1.7 times more substitution of phenyl than deprotonation with n-butyl-lithium in THF. Investigation of the stereochemistry of the substitution reaction shows that, when the phosphine (64) is treated with n-butyl-lithium, substitution of benzyl occurs with complete inversion of configuration, presumably through an intermediate or transition state (65).

The ring size of cyclopolyphosphines in solution may be determined by the multiplicity of the proton-decoupled 31P n.m.r. signal (see Chapter 12). Using reassigned ring sizes, it has been shown that tetra- and pentacyclopolyphosphines have electrochemical reduction potentials which are solely dependent upon the pendant organic group and are not affected by ring size.

Acylphosphines (66) can be decarbonylated by heating with Wilkinson’s catalyst in xylene.

The P — C bond of phosphines can be cleaved in acidic media if a β-carbonyl group is present, e.g. as in (67).

The absolute configuration of the phosphine (68) has been determined by chemical correlation with (+)-(S)-benzylmethylphenylpropylphosphonium bromide.

2 Phosphonium Salts

Preparation. — Treatment of a variety of tertiary phosphines with allylic halides yields phosphonium salts, which can be cyclized to heterocyclic systems with 115% polyphosphoric acid (PPA), e.g. as in Scheme 6.

(Continues…)Excerpted from Organophosphorus Chemistry Volume 7 by S. Trippett. Copyright © 1976 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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