Triphenylbismuth diacetate, phenylation

Selective protection of the primary hydroxy group in polyols by the trityl group can generally be accomplished by the reaction with trityl chloride in pyridine. TTie use of DMAP (0.04 equiv.) and EtsN (1.5 equiv.) facilitates the reaction. " Selective phenylation of one hydroxy group of diols can be carried out by the reaction with triphenylbismuth diacetate. While regioselectivity for primary-secondary vicinal diols is poor, only secondary alcoholic functions are converted to the phenyl ether in secondary-tertiary vicinal diols. Although phenylation of glycols occurs smoothly, monohy oxy alcohols are left essentially intact. ... 

Various 3-(3 - and 4 -substituted phenyl)-4-hydroxycoumarins were easily accessible by reaction of 4-hydroxycoumarins with triarylbismuth dichloride and triarylbismuth dinitrate under basic conditions or with triphenylbismuth diacetate (47) under neutral conditions. In the latter reaction, the best yields were obtained when the reaction was performed in methylene dichloride in the dark.40... 

Phenylation of 3,5-di-rerr-butylphenol (13) was also obtained by reaction with triphenylbismuth diacetate (47) in methylene dichloride under reflux, under neutral conditions.27 However, as this reaction is greatly improved by copper catalysis (see section 6.7), the scope of the non-catalysed system was not studied. 

These two systems of phenol 0-phenylation [0-phenylation with tetraphenylbismuthonium trifluoroacetate (6) or with triphenylbismuth diacetate (47)] may be ligand coupling reactions involving hexavalent transient intermediates, but no proof of such structures was ever detected. The former reaction does not involve free radicals, as addition of 1,1-diphenylethylene (72) (DPE), did not affect the overall yield. These reactions were explained by a direct aromatic Sn2 displacement, facilitated by the partial charge on the carbon bonded to the bismuth atom.24 (see section 6.6)... 

O-Phenylation of tertiary alcohols can be realized through reaction with pentaphenylbismuth (4), a benzyne intermediate being involved. r rf-Butyl phenyl ether (80) was also obtained in rather low yields in the reaction of triphenylbismuth diacetate with rerr-butyl alcohol used as solvent in the presence of potassium carbonate or by reaction of triphenylbismuth dichloride with lithium ten-... 

The reaction of triphenylbismuth diacetate (47) with secondary alcohols under neutral conditions resulted in poor to moderate yields of the corresponding 0-phenyl ethers 2-propanol gave about 20% of the 0-phenyl ether with a large excess of the dcohol, cyclohexanol less than 3% and 3p-cholestanol gave 36% of the 0-phenyl ether. Moreover, no reaction was observed between triphenylbismuth diacetate and primary alcohols.53-55... 

Selected examples ofmono O phenylation of glycols with triphenylbismuth diacetate (47)... 

It was subsequently found that this reaction is not restricted to glycols. Ether-alcohols, amino-alcohols and benzoin were also prone to the phenylation reaction with triphenylbismuth diacetate (47). 5 In the case of the amino-alcohol, the amino group is preferentially phenylated to afford the -phenyl derivative, which can undergo subsequently a second arylation. This second arylation occurs both on the nitrogen and oxygen atoms, preferentially on the oxygen rather than on the aniline-type nitrogen. 

In the reaction of alcohols with the various types of pentavalent organobismuth compounds, 0-phenylation is usually disfavoured, oxidation taking place preferentially. However, in the case of the reaction of glycols with triphenylbismuth diacetate, an apical-equatorial chelation (93) was suggested to explain the facile mono-O-phenylation which is observed. By contrast, diapical chelation (94) takes place with monofiinctional alcohols, and the ensuing reductive process leads to oxidation. 

The arylation of lower aliphatic alcohols was observed when the copper-catalysed decomposition of triarylbismuth diacetate was carried out in simple alcohols, used as solvent (20 mL per mmole of bismuth reagent). The yields of alkyl aryl ethers (based on the bismuth reagent) ranged from 60 to 95% for primary and secondary alcohols, but only 9% were obtained in the case of t rt-butyl alcohol.Under stoichiometric conditions, the 0-phenylation of 3-p-cholestanol by triphenylbismuth diacetate (1 equiv.) was not significantly improved upon addition of copper diacetate. 5 Different copper compounds, such as Cu(OAc)2, CuCl2, CuCl or metallic copper, can be used as effective catalysts. 

This copper-catalysed phenylation reaction with triphenylbismuth diacetate is not limited to glycols as it has been extended to the arylation of other hydroxylic substrates such as phenols and enols.27 Variously substituted phenolic substrates have been selectively 0-phenylated under very mild neutral conditions (1 to 24 hours at room temperature in methylene dichloiide). The best yields were obtained with metallic copper used as the catalyst. The electronic nature of the substituents of the phenol did not influence the yields (4-nitro, 97% 3,5-dimethoxy, 90%). Only steric hindrance of the 2- and 6-substituents interfered with the reactivity. Thus only 26% of the 0-phenyl ether was obtained in the phenylation of 2,4-di-rerr-butylphenol, and no phenylation took place in the case of 2,4,6-tri-rer/-... 

These reactions of d-phenylation are preferably performed with the copper catalysed-triphenylbismuth diacetate system which is more general and gives higher yields, particularly in the case of phenol (9-phenylation. ... 

The reaction of simple aliphatic amines with triphenylbismuth diacetate and copper diacetate (the ratio used being 5-20 1 0.01-0.02) in tetrahydrofuran led to good yields of the derived arylamine (60-85% based on the bismuth reagent). In the case of the phenylation of iVJV-diphenylamine, a very poor yield was (< 3%) of triphenylamine was realized.99... 

However, when the reaction is performed in methylene dichloride in the presence of catalytic amounts of metallic copper, the iV-monophenylated amine derivatives are obtained in preparatively useful yields. Phenylation of aliphatic and aromatic amines with triphenylbismuth diacetate and metallic copper (ratio 1 1.1 0.1) in methylene dichloride at room temperature led to good to high yields of the derived anilines (up to 96% based on the amine). In the case of less reactive substrates, use of copper diacetate instead of metallic copper as catalyst constitutes a more reactive system which allows the preparation of the A -phenyl derivatives in moderate yields. These yields can also be improved by performing the reaction at a higher temperature. 

In the phenylation reaction of substituted anilines, the electronic nature of the substituents plays a role only on the reaction rate, not on the overall yield (4-methoxyphenyl 91% after 15 minutes and 4-nitrophenyl 90% after 16 hours). The steric hindrance is also a factor which influences the reaction in slowing down the reaction rate. To obtain good to excellent yields, an excess of bismuth reagent is then required with hindered substrates. For example, mesitylamine required 2.2 equivalents of triphenylbismuth diacetate to afford the AT-phenyl derivative in 92% after 24 hours. Moreover, triphenylamine was obtained in 23% yield after 48 hours by arylation of, iV-diphenylamine. A variety of aliphatic, alicyclic, heterocyclic and aromatic amines as well as hydrazines were N-arylated by this system. No reaction took place with a-amino acids but their esters were mono-iV-phenylated under... 

By contrast with the reaction of lithium rert-butoxide with triphenylbismuth diacetate, which gave ferf-butyl phenyl ether (r-BuOPh) in 66% yield, the same reaction with triphenylantimony diacetate appeared to stop at the stage of the formation of (/err-butoxy)acetoxytriphenylantimony. The ligand coupling did not proceed, and re/t-butanol was recovered after hydrolysis of the mixture. ... 

DAVID-THIEFFRY Monophenylation of Diols Selective phenylation of one hydroxyl group of glycols by triphenylbismuth diacetate. 

Triphenylbismuth diacetate in ethanol containing some cupric chloride afforded phenyl ethyl ether (ref.68). 

The selective formation of phenyl ethers from one hydroxy-group of a diol has been achieved with triphenylbismuth diacetate, Ph3Bi(OAc)2. Two new protecting groups suitable for 1,2- and 1,3-diols are shown in the ketal (39) and the t-butylsilylene derivative (40). ... 

Triphenylbismuth(V) diacetate acts as O-phenylating agent of alcohols. The reaction of ci s-l, 2-cyclopentanediol catalyzed by a Cu(II) acetate-chiral pyridinyloxazoline combined system gives the mono-phenylation product in up to 50% ee (Scheme 127) (307). 

Triphenylbismuth carbonate generally does not react with amines, although phenyl transfer to the amino functionality was first observed during an attempt of oxidation of the hydroxyl function of an aminoalcohol by triphenylbismuth carbonate in chloroform. It also reacted with iV-phenylhydro-xylamine under neutral or basic conditions to give diphenylnitroxyl and iV,iV-diphenylacetamide after reductive acetylation (29-33%). No reaction was noted between triphenylbismuth carbonate and nitrosobenzene. High-yielding -arylation was found in the reaction of amino-alcohols with triarylbismuth diacetate in methylene dichloride under reflux. 5... 

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