Aromatic ether coupling

J.-F. Marcoux etal, US Patent 6,395,939 (May 28, 2002) Assignee Massachusetts Institute of Technology Utility Aromatic Ether Coupling Reagent... 

The Ullman reaction has long been known as a method for the synthesis of aromatic ethers by the reaction of a phenol with an aromatic halide in the presence of a copper compound as a catalyst. It is a variation on the nucleophilic substitution reaction since a phenolic salt reacts with the halide. Nonactivated aromatic halides can be used in the synthesis of poly(arylene edier)s, dius providing a way of obtaining structures not available by the conventional nucleophilic route. The ease of halogen displacement was found to be the reverse of that observed for activated nucleophilic substitution reaction, that is, I > Br > Cl F. The polymerizations are conducted in benzophenone with a cuprous chloride-pyridine complex as a catalyst. Bromine compounds are the favored reactants.53,124 127 Poly(arylene ether)s have been prepared by Ullman coupling of bisphenols and... 

Substitution reactions at aromatic carbon (see also Reduction reactions, Ullmann ether coupling, specific reactions such as Nitration) Arene(tricarbonyl)chromium complexes, 19... 

The reaction of pentafluoroiodobenzene with aromatic compounds such as anilines, pyrroles, indoles, imidazoles, aromatic ethers and phenols leads to aryl—aryl coupling477. The reactions proceed via pentafluorophenyl radicals which are generated by photoin-duced electron transfer (PET) and loss of iodide ion. Coupling between the pentafluorophenyl radical and the radical cation of the donor gives biaryl cations (138,139) which lose a proton. The reaction is illustrated for N, A-dimethylaniline (equation 125). 

Intramolecular coupling of aromatic systems based on this principle has been particularly fruitful. Phenols or aromatic ethers are usually involved If the activation of the aromatic system is sufficient, the reactions do not require especially nonnucleophilic solvents. In the simplest case anisole may be anodically coupled in CH2CI2-CF3COOH to give, after workup in the presence of Zn dust, 4,4 -dimethoxybiphenyl in 60% yield [247]. 

Birch reduction of aromatic ethers is well known to afford alicyclic compounds such as cyclohexadienes and cyclohexenones, from which a number of natural products have been synthesized. Oxidation of phenols also affords alicyclic cyclohexadienones and masked quinones in addition to C—C and/or C—O coupled products. All of them are regarded as promising synthetic intermediates for a variety of bioactive compounds including natural products. However, in contrast to Birch reduction, systematic reviews on phenolic oxidation have not hitherto appeared from the viewpoint of synthetic organic chemistry, particularly natural products synthesis. In the case of phenolic oxidation, difficulties involving radical polymerization should be overcome. This chapter demonstrates that phenolic oxidation is satisfactorily used as a key step for the synthesis of bioactive compounds and their building blocks. 

Silica-bound FeCls can act as a one-electron-transfer oxidant, which is very effective for oxidative coupling reactions of aromatic ethers and phenols. 1,2-Diarylethane 691 was oxidized with FeCF supported on silica gel in CH2CI2 to give the corresponding para-para coupled product 692 in almost quantitative yield (98%). Similar oxidation of 2-methoxy-p-hydroquinone (693) provided a dibenzofuran 694 (35%) (Scheme 136). ... 

Recent efforts in the synthesis of sulfonated aromatic polymers are directed to the polymerization of sulfonated monomers (such as (b), (d), (g), (j), (k), and (1) shown in Scheme 3) [14,15,53,54,96-102] or coupling reactions of sulfonated compoimds with fimctional groups attached to a polymer backbone [ 103,104]. In post-sulfonation, attachment of the sulfonic acid group is restricted to the activated position ortho to the aromatic ether bond, as indicated in Scheme 4a, while in direct polymerization of sulfonated monomers, the sulfonic acid groups are attached to the deactivated site on the ring (Scheme 4b). An enhancement of stabUity toward desulfonation and a modestly higher acidity are expected for the structure shown in Scheme 4b. Recently, polymerization of sulfonated monomers was also used to obtain sulfonated polysulfone (m) via oxidation of a sulfonated polysulfide-polysulfone copolymer [105]. 

The unique cataljdic oxidative coupling polymerization to high-molecular-weight, linear aromatic ethers is typically carried out at room temperature by bubbling oxygen through a solution of 2,6-xylenol monomer in the presence of a copper-based catalyst [1, 2, 4]. 

There are, however, certain types of natural reactions that occur in many situations, that are probably brought about by similar enzymes, and that may profit from an electrochemical study. Three of these that we have worked on for many years have been phenol oxidation, oxidative decarboxylation, and indole oxidation. The coupling of aromatic ethers electrochemically is unlikely to be a natural reaction, but the results have been so interesting and so analogous to phenol coupling, that this topic will be discussed briefly also. 

Figure 5. Oxidatively Coupled Products from Aromatic Ethers...

In 1989, Fr chet and co-workers first reported the convergent growth approach [8,9]. In contrast to the divergent growth approach, dendrimer construction is initiated at what will eventually become the outer surface shell of the ideally branched macromolecule and proceeds inward, by a stepwise addition of branching monomers, followed by the final attachment of each branched dendritic sub-unit (or dendron ) to a poly-functional core. This synthesis generated a poly(aromatic ether) dendrimer and a repetitive sequence of Williamson ether coupling and bromination reactions were employed as shown in Scheme 8.1. 

Poly(aryl ethers) have been prepared by Ullman coupling of bisphenols and dibromoarylenes in the presence of a copper catalyst (111). This methodology does not require the presence of an activating group for halo-displacement hence aromatic ether polymers can be prepared without polar functionahty. 

Chemical Shifts and Coupling Constants of Aromatic Ethers (d in ppm, J in Hz)... 

Ullman reaction The synthesis of diaryls by the condensation of aromatic halides with themselves or other aromatic halides, with the concomitant removal of halogens by a metal, e.g. copper powder thus bromobenzene gives diphenyl. The reaction may be extended to the preparation of diaryl ethers and diaryl thio-ethers by coupling a metal phenolate with an aryl halide. 

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