Anisole oxidative coupling

Finally, the oxidative coupling with CuCla has also been used for the chemical synthesis of various polythiophenes. Thus the reaction of the bifunctional Li—Tj—Li 26, obtained in 92% yield by deprotonation of H-Tj-H 2, with two equivalents of n-BuLi, with cuprous chloride in anisole lead to poly(bithiophene) P2, an insoluble brown precipitate [Eq. (10)]. After extraction, the polymer was obtained in yields ranging from 25 to 50%. Its doping with AsFs afforded a polymer with a conductivity of 5 Scm which is somewhat lower than that determined for films grown electrooxidatively [53]. 

The oxidative carbonylation of arenes to aromatic acids is a useful reaction which can be performed in the presence of Wacker-type palladium catalysts (equation 176). The stoichiometric reaction of Pd(OAc)2 with various aromatic compounds such as benzene, toluene or anisole at 100 °C in the presence of CO gives aromatic acids in low to fair yields.446 This reaction is thought to proceed via CO insertion between a palladium-carbon (arene) allyl chloride, but substantial amounts of phenol and coupling by-products are formed.447... 

The combination of ortho metallation and meta nucleophilic acylation was used to prepare a key intermediate in a synthesis of deoxyfrenolicin (42), as outlined in Scheme 11. The complex of anisole is orf/io-metallated with n-butyllithium and quenched with chlorotrimethylsilane the resulting [(o-(tri-methylsilyl)anisole)Cr(CO)3] (43) is then metallated again, converted to the arylcuprate, and coupled with ( )-2-hexenyl bromide to give the complex of l-trimethylsilyl-2-methoxy-3-(2-hexenyl)benzene (44). Addition of the carbanion from the cyanohydrin acetal of 4-pentenal, followed by the standard iodine oxidation and subsequent hydrolysis of the cyanohydrin acetal to regenerate the carbonyl group... 

The benzene derivatives containing the fluorinated sulfone have been prepared either by nucleophilic substitution of the 4-fluorophenyl derivative (e.g. 1) or by starting with the appropriately substituted sodium thiophenoxide and reacting with perfluoroalkyl iodide follow by oxidation with either MCPBA or chromium oxide (12. li.) The biphenyl derivatives have been prepared by palladium catalyzed cross coupling chemistry of the 4-bromophenyl derivative (e.g. 2) with substituted phenyl boronic acid (yields 37-84%) (JLH, .). Compound 16 has been prepared by palladium catalyzed cross coupling of (4-bromophenyl)perfluorohexyl sulfone with vinyl anisole in 37 % yield (JJL). The vinyl sulfones, 7 and 9, have been prepared by condensation of CH3S02Rf (JJL) with the appropriate aldehyde (yields 70,and 73%) following a literature procedure (1 ). Yields were not optimized. 

The radical cations derived from anodic oxidation of simple aryl ethers have been found to be quite stable, especially in trifluoroacetic acid or trifluoroacetic acid-dichloromethane mixtures [68-71]. Thus, aryl ethers with unsubstituted pr/ra-positions may be coupled anodically to form the corresponding biphenyls, as in the anodic dimerization of anisole derivatives [Eq. (29)]. Yields are on the order of 90-100% on a preparative scale. The biphenyl products are ultimately obtained by reversing the cell polarity in order to reduce the product radical cations, which are more readily formed than those of the starting ethers [69]. 

The anodic oxidation of benzene produces a mixture of polyphenylene compounds. This oligomerization can be performed in acetonitrile [21] or in liquid sulfur dioxide [22]. Mixed coupling between naphthalene and alkyl benzenes has also been demonstrated (Table 1, numbers 12-16). The relative yield of mixed coupling products increases with the basicity of the alkyl benzene with mesitylene 19%, with tetramethylbenzene 42%, and with pentamethylbenzene 64% of mixed coupling products are obtained. This suggests an electrophilic reaction between naphthalene cation radicals and alkylbenzenes. The mixed coupling reaction of phenanthrene with anisole has been studied kinetically. The results indicate that initially a complex PA is formed between the phenanthrene radical cation and anisole, followed by an electron transfer from the complex. The resulting PA" -anisole complex then decomposes to the product [23]. 

In neutral or acidic medium, phenols are oxidized to phenoxonium ions, which can undergo an electrophilic aromatic substitution, for example with anisole to para-meih-oxyphenylcyclohexadienones (Table 2, number 14). In the oxidation of X [Eq. (5a)], the intermediate phenoxonium ion disproportionates to phenoxy radicals, which couple in 95% yield to the quinhydrone XIa [47a] ... 

The intermolecular examples of synthetic value are self-couplings, e.g. formation of the dimer (43) from benzylsesamol, in 85% yield using vanadium oxytrifluoride preparation of the biaryl (44 95%), from 4-methylveratrole, employing iron(III) chloride supported on silica and synthesis of 4,4 -dimeth-oxybiphenyl (69%) fr om anisole by oxidation with thallium(III) trifluoroacetate in the presence of catalytic palladium(II) acetate. This approach has been used in a natural product synthesis. The dimers (45) and (46) were prepared from appropriate derivatives of gallic acid, and transformed into schizandrin C (47) and an isomer respectively. ... 

Probably the best modem method for introduction of OF by electrophilic aromatic substitution is lithiation, reaction with a boronate ester, and oxidation.4 These are the same boron compounds that are used in Suzuki coupling (chapter 18) and are made the same way. In this example, selective mono-lithiation by Br/Li exchange on available tribromoanisole 39 (easily prepared by bromination of anisole or phenol) occurs ortho to the MeO group and reaction of aryl-lithium 39 with trimethyl borate gives the boronic ester 40. Peroxyacids such as peracetic acid are usually used for the final oxidation. 

Meanwhile, Nicholas succeeded in the development of catalytic variants of work by Yu and Chatani in Eqs. (1) and (2). The key to the success is a careful choice of the solvent an anisole/DMSO cosolvent system is essential for the good conversion (Eq. 27) [52]. Li and coworkers also reported the catalytic system with tert-butyl peroxide (TBP) as an oxidant (Eq. 28) [53]. In the latter case, an aminyl radical species might be involved in the C-N forming step [54], although the details are not clear. Additionally, the sulfoximine is also a promising coupling partner for 2-phenylpyridine, albeit with a stoichiometric amount of Cu(OAc)2 (Eq. 29) [55]. 

In the second mechanism proposed as an alternative to the previous one, radical-cations are involved as active intermediate species [11]. In this case it is postulated that a Lewis acid (A), considered as an electron acceptor, reacts with the aromatic hydrocarbon and its derivatives to give a radical-cation species (9), which couples with another aromatic substrate to produce a dimer (10). Such a mechanism was proposed in order to interpret the oxidative dimerization of anisole by Lewis acids, involving addition of a radical-cation to the substrate (Scheme 6.3) [12,13]. 

DeBoef and co-workers described the aerobic oxidative inter- and intra-molecular coupling of benzoxazole (120) with benzene derivatives in the presence of catalytic amounts of Pd(OAc)2 and heteropolymolybdovanadic acid (HPMV) (Scheme 10.40). Under these conditions, the monoarylated C2 products 121-123 were obtained in moderate to good yields in less than 2 hours extended reaction times led to formation of the undesired 2,3-diarylated products. Problematic coupling partners included anisole (which afforded regiomeric mixtures of the C2 product) and electron-poor or acidic arenes which led to no product formation. Palladation is thought to occur at the more nucleophilic C3 position before migration to the C2 position and biaryl product formation. 

Figure 3a is a typical cyclic voltammogram (0 - 0.5 V, 5 mV/s) obtained for the graphite-ferrocene electrode in the 0.1 M phosphate buffer solution containing either cytochrome m or anisole. Only ferrocene oxidation and ferricinium ion reduction is indicated. Neither anisole nor cytchrome m alone has any affect on the response of this redox couple. 

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