Phenols reductive elimination

By-products from capture of nucleophilic anions may be observed.53 Phenols can be formed under milder conditions by an alternative redox mechanism.98 The reaction is initiated by cuprous oxide, which effects reduction and decomposition to an aryl radical, and is run in the presence of Cu(II) salts. The radical is captured by Cu(II) and converted to the phenol by reductive elimination. This procedure is very rapid and gives good yields of phenols over a range of structural types. 

Oxidative addition of a silyl-protected 4-(bromomethyl)phenol precursor to (tme-da)Pd(II)Me2 (tmeda = tetramethylethylenediamine), followed by ethane reductive elimination, resulted in formation of the benzylic complex 16 (Scheme 3.10). Exchange of tmeda for a diphosphine ligand (which is better suited for stabilizing the ultimate Pd(0) QM complex), followed by removal of the protecting silyl group with fluoride anion, resulted in the expected p-QM Pd(0) complex, 17, via intermediacy of the zwitterionic Pd(II) benzyl complex. In this way a stable complex of p-BHT-QM, 17b, the very important metabolite of the widely used food antioxidant BHT20 (BHT = butylated hydroxytoluene) was prepared. Similarly, a Pd(0) complex of the elusive, simplest /)-QM, 17a, was obtained (Scheme 3.10). 

These compounds contain a furan ring fused to a benzene moiety in the 2,3-position. This synthesis was also described by Flynn et al. [73] and is shown in Scheme 25 involved the coupling of 2-iodo-5-methoxyphenol 104, 4-methoxyphenylethyne 105 to form the intermediate o-alkynylphenolate 106. Aryl iodide 107 was added to the phenolate in DMSO with heat. Oxidative addition, palladium(II)-induced cyclization and reductive elimination resulted in the product 108 with an 88% yield. 

The reaction involves a key transesterification of the phenol with the phosphinite ligand. Orthometallation of the resulting phosphinite leads to a metallacycle. After reductive elimination, the biaryl product is formed and undergoes a transesterification to afford the phenol product (Scheme 27).123... 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

These results led to the proposal of the following mechanism. Decomplex-ation of the central C2 fragment allows coordination of the alkyne (intermediate 119), which then inserts to form the metallacycle 120. Deinsertion (reductive eliminate of the cobalt moiety allows ring closure to give the cyclohexadienone complex 121, which upon decomplexation yields the desired phenol. The regiochemistry of the alkyne insertion determines the ratio of 116 117 (for simplicity, only the sequence leading to 116 has been shown). 

The proposed mechanism is given in Scheme 15. Initially the dissociation of water, maybe trapped by the molecular sieve, initiates the catalytic cycle. The substrate binds to the palladium followed by intramolecular deprotonation of the alcohol. The alkoxide then reacts by /i-hydride elimination and sets the carbonyl product free. Reductive elimination of HOAc from the hydride species followed by reoxidation of the intermediate with dioxygen reforms the catalytically active species. The structure of 13 could be confirmed by a solid-state structure [90]. A similar system was used in the cyclization reaction of suitable phenols to dihydrobenzofuranes [92]. The mechanism of the aerobic alcohol oxidation with palladium catalyst systems was also studied theoretically [93-96]. 

Cleavage of the Resin-Bound Phenols Using Catalytic Reductive Elimination... 

General Procedure for Cleavage of Phenols by a Reductive Elimination Reaction Preparation of Compounds 20 and 22... 

Land EJ, Ebert M (1967) Pulse radiolysis studies of aqueous phenol. Water elimination from dihy-droxycyclohexadienyl radicals to form phenoxyl. Trans Faraday Soc 63 1181-1190 Lind J, Shen X, Eriksen TE, Merenyi G (1990) The one-electron reduction potential of 4-substituted phenoxyl radicals in water. J Am Chem Soc 112 479-482 Loft S, Poulsen HE (1999) Markers of oxidative damage to DNA antioxidants and molecular damage. Methods Enzymol 300 166-184... 

Aryl-A3-iodanes bearing an electron-deficient alkyl ligand such as aryl(sul-fonylmethyl)-A3-iodanes (Section 3.2.7) and aryl(perfluoroalkyl)-A3-iodanes are relatively stable. A series of (perfluoroalkyl)phenyl-A3-iodanes 96 were synthesized in good yields by treating bis(trifluoroacetoxy)-A3-iodanes with benzene in the presence of triflic acid [47]. The AModanes 96 transfer the perfluoroalkyl groups to a variety of nucleophiles with reductive elimination of iodobenzene. The nucleophiles involve Grignard reagents, alkyllithiums, enolate anions, alkenes, alkynes, trimethylsilyl enol ethers, arenes, phenols, and thiols. In these reactions, the AModane 96 serves as a source of the perfluoroalkyl cation and, in... 

Phenol itself can be arylated multiply around the oxygen up to five times by use of excess bromobenzene (Eq. 4) [8]. The use of a less polar solvent such as o-xylene is important no reaction of phenol occurs in DMF. The lack of hexa-arylated product may be attributed to steric reasons. When the 2- and 6-positions of phenol are masked by fert-butyl groups, the 4-position is arylated (Eq. (5) and path b in Scheme 3) [10]. It is worth noting that a diaryl ether is formed by reductive elimination of the alkoxyarylpalladium intermediate when a bulky phosphine ligand is used (path d) [11]. 

Phenoxy-substituted 2H, 8 -naphtha [l,2,3-de]-benz[/j]-2,8-quinolinedione (IIIC, R2 = hydrogen, R3 = CH3) was synthesized by cyclization of TV-chloro-acetyl-6-aminonaphthacenequinone in pyridine to the corresponding naphthacenepyrido-nyl-3-pyridinium chloride, with the subsequent reductive elimination of the pyridi-nium residue.39 The 3-acetyl derivative was obtained by the interaction of 6-amino-ll-chloro-5,12,naphthacenequinone with acetic anhydride in phenol in the presence of anhydrous sodium carbonate.39... 

The reaction is considered to involve two mechanistic patterns i.e.,the reactions of arylpalladium intermediates with (a) phenolates at the ortho-positions, this being similar to the a-arylation of ketones (see Sect. 2.2 and Scheme 4), and with (b) thus formed biphenyl-2-ols as in Eq. (56). While the latter proceeds in both DME and xylene, the use of the less polar solvent is essential for the former to occur effectively. However, the intramolecular cyclization of halophenyl-linked phenols is known to occur in DMA [ 122]. It is worth noting that 0-arylation of phenols to give diaryl ethers occurs when bulky phosphine ligands are used (Eq. 60) [26-28]. This may imply that in the aryl(aryloxy)palladium intermediates, reductive elimination to give the ethers is enhanced by the ligands (Scheme 4). 

The compound R2Bi-O BiR2 has been found as an intermediate in the oxidation of trialkylbismuth compounds. Unlike BiPhs, the compound Bi(Rf)3 [Rf = 2,4,6-(Cp3)3C6H2] is air sensitive and slowly evolves RfORf and Rf OH upon standing in air. These findings are consistent with the intermediacy of an 0=Bi(Rf)3 complex followed by the insertion of O into a Bi C bond. Reductive elimination from such an intermediate would generate the ether, while hydrolysis would produce the phenol. 

The coupling reaction between phenol and ethylene to give ortho-ethylphenol is catalyzed by (triphenylphosphite)ruthenium complex [20]. In this reaction, the ortho C-H bond of triphenylphosphite is cleaved by orthometallation, and then insertion of ethylene followed by reductive elimination lead to the formation of triarylphos-phite having an ortho-ethylphenoxo group. Transesterification between the phosphite and phenol then releases (ortho)-ethylphenol by reproducing triphenylphosphite (Scheme 14.8). 

Numerous aryl bromides, iodides [203], borates [204] and triflates [205, 206] have been successfully carbonylated. Triflates could serve as a route for the synthesis of arenecarboxylic acid derivatives from phenols. This carbonylation using dppf in a catalytic mixture generally shows higher efficiency than PPhj or P(o-Tol)3 [207]. Poor performance is also noted for PPhj in a Pd-catalyzed vinyl substitution of aryl bromides [208]. Side-reactions involving the formation of [PPhjAr]Br and ArH are responsible. A system which is catalyzed effectively by PdCljfdppf) under 10 atm CO is the desulfonylation of 1-naphthalenesulfonyl chloride 58 in the presence of Ti(OiPr)4. Formation of isopropyl 1-naphthoate 59 can be explained in a sequence of oxidative addition, SOj extrusion, carbonylation and reductive elimination (Fig. 1-27) [209]. A notable side-product is di-l-naphthyl disulfide. 

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