Preparation of Biaryls

The arylation of support-bound arenes has mainly been performed using the Suzuki and Stille coupling reactions. Both reactions proceed smoothly with arenes and het-eroarenes such as furans, thiophenes, or pyridines. Examples of the arylation of het-eroarenes are presented in Chapter 15. 

The examples reported to date do not allow a clear ranking of palladium catalysts with regard to their ability to catalyze the Suzuki reaction. It should also be kept in mind that palladium(O) complexes are air-sensitive, and the quality of commercially available catalysts of this type can vary substantially. Some successful Suzuki couplings are listed in Table 5.12. Further examples have been reported [184,186-196], 

Experimental Procedure 5.2 Suzuki couplinu with a polwvrene-hound arvl bromide [185] 

The Stille coupling is closely related to the Suzuki coupling. The only difference is that a stannane is used instead of a boronic acid derivative, and that a base is not generally required. Additional functional groups tolerated in the reactants include hydroxyl, azide, nitro, oxirane, and carbamate groups, but neither primary aliphatic 

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In the presence of a precious metal catalyst, aryl halides can undergo dehalo-dimerization to give biaryl products, with varying degrees of selectivity. The major byproduct of this reaction is usually the dehalogenated aryl compound. This type of chemistry is currently one of the very few viable means for the large scale preparation of biaryl compounds. 

The focus of this paper is on the preparation of biaryl moieties which are commonly present in a wide variety of pharmaceutically active compounds. Two different and practical approaches to synthesize the biaryl substructure will... 

Mechanistic studies carried out by the Buchwald group97,98 on the key C-O bond formation step in these reactions have reinforced the importance of the properties of the ligand, and have led to the adoption of a variety of more sterically hindered ligands (e.g., 23, 24, 27, 29, and 30), which have given improved results for the preparation of biaryl ethers (Equation (15)),89 /-butyl aryl ethers,99 and aryl ethers of primary alcohols.100... 

The most prominent application of the Ru-arene chemistry has been for the preparation of biaryl ethers in the syntheses of portions of vancomycin,467 ristocetin (Equation (127)),462,468-473 and teicoplanin (see also Section 10.14.1.2).474-476 Additional applications477-479 have included the syntheses of the macrocyclic biaryl ether-containing compounds K-13480,481 and OF4949-III,481,482 several macrocyclic depsipeptides,483,484 and poly(phenylene oxide) polymers.485... 

Solid-phase Suzuki reaction was first used in the preparation of biaryls [248]. One recent example is given by Baudoin et al. for the synthesis of biologically active biaryl compounds (Scheme 3.13) [249]. 

Scheme 21. Preparation of biaryl derivatives of type 83 with potential liquid crystalline properties from 2-chloro-2-cyclopropylideneacetic acid. Conditions A DCC, CH2CI2, 0°C, 5 h. B DEAD, Ph3P, Et20,20°C, 14 h [25]...

PREPARATION OF BIARYLS BY THE Ni- OR Pd-CATALYZED REACTION OE ARYLMETALS WITH ARYL HALIDES ... 

Ortho- and para-rearrangement and phenol formation on uv-irradiation of aryl esters are accompanied in several cases by decarboxylation,37,60,62,64,80,81 represented for 3,5-di-t-butylphenyl benzoate by the equation 118 -> 119-122. It was shown that this reaction cannot be sensitized,64 but the dramatic differences in product distribution could be observed by changing of the solvent.60,84 The results in Table VI indicate that in polar solvents the decarboxylation process is minimized while the formation of the photo-Fries rearrangement 119 is enhanced. The reverse appears to be true when nonpolar ethereal solvents are used. A considerable amount of biaryls are formed, and hence this reaction may prove useful for the preparation of biaryls and alkylary Is. 

Bcugclmans Bois-Choussy Tang Tetrahedron Lett. 1988, 29, 1705. For other preparations of biaryls via SrnI processes, sec A lam. Amatorc Combcllas Thilbault Vcrpcaux Tetrahedron Lett. 1987, 28. 6171 Picrini Baum gartner Rossi Tetrahedron Lett. 1988, 29. 3429. 

Han, Y. Walker, S. D. Young, R. N. Silicon Directed ipso-Substitution of Polymer Bound Arylsilanes Preparation of Biaryls via the Suzuki Cross-Coupling Reaction, Tetrahedron Lett. 1996, 37, 2703—2706. 

Preparation of Biaryls via Pd(0) Catalyzed Cross-Coupling of Boronic Acids with Aryl Halides ... 

Table 5.12. Preparation of biaryls by the Suzuki reaction on insoluble supports.

Preparation of biaryls via microwave-mediated Suzuki coupling... 

Coupling of an aryl triflate with an arylstannane is a good mediod for the preparation of biaryls and other bis-aromatic species of all types. Coupling of vinyl groups takes place with retention of stereochemistry. Furdiermore transfer of die allyl group occurs smoothly. 

In 2005, the group of Alcaide has reported the regiocontrolled preparation of biaryl-2-azetidinones (I and II, Fig. 17), via aryl-aryl radical cyclization and/or rearrangement of (3-lactam-tethered haloarenes [286]. 

Preparation of biaryls by the coupling of arenes with aryl halides... 

The Pschorr Reaction allows the preparation of biaryl tricyclics by intramolecular substitution of one arene by an aryl radical. This radical is generated in situ from an aryl diazonium salt by copper catalysis. Although excess copper salts are used, the yield is normally moderate. 

Gomberg and Pemert4 recommended the use of the sodium diazotates for the preparation of biaryls from aniline and from p-toluidine and the normal diazo method for negatively substituted amines such as the bromo- and nitro-anilines. Grieve and Hey 7 found little difference in the yields of biaryls obtained by the two procedures when they coupled diazotized aniline with six different components benzene, toluene, m-xylene, chlorobenzene, nitrobenzene, and ethyl benzoate. Where it is applicable, this modification offers the advantage that the dropwise addition of alkali is eliminated. 

TPDS can be also used for the preparation of biaryl through the intramolecular free radical // -substitution of A-(2-bromoaryl)arenesulfonamide (9) and radical ring expansion of a-haloalkyl cyclic (3-keto ester (11) (eqs. 12.5a and 12.5b). 

Han Y, Walker SD, Young RN, Silicon directed ipso-substitution of polymer bound arylsilanes preparation of biaryls via the Suzuki cross-coupling reaction, Tetrahedron Lett., 37 2703-2706, 1996. 

The first observation concerning the preparation of biaryls was reported in 1981 [4]. Thus, the palladium-catalyzed cross-coupling reaction of phenylboronic acid with a number of haloarenes was found to proceed smoothly in the presence of base to selectively afford the corresponding biaryls in high yields (Eq. (1) and Table 1). 

Ullmann reaction (4, 33 6, 654). The nickel species generated from NiBri and zinc in HMPT is an effective catalyst for the preparation of biaryls from aryl iodides. An excess of zinc is generally helpful potassium iodide exerts a favorable effect. The reaction is conducted at 40-70° for 3-30 hours. Yields are >90% for iodobenzene itself and are also similar for para- and me/a-substituted derivatives. Yields are lowered by the presence of ort/io-substituents. 

The two coupling reactions appear to have a common free-radical intermediate. Functional groups already in the aromatic compound, Axil, orient ortbo-para regardless of their nature. The reactions are most valuable for the preparation of biaryls of unequivocal structure when the hydrocarbon, Ar H, is unsubstituted. Good directions are given for the synthesis of p-bromobiphenyl (35%), and the literature of the reaction has been reviewed. Among the hydrocarbons prepared in this way are a- and yS-phenylnaphthalenes, o-, m-, and p-methylbiphenyls and m- and p-terphenyls. Thiophene and pyridine nuclei also have been aryl-ated. ... 

Aryl coupling reactions Preparation of biaryl compounds... 

Pd-catalyzed C-C-coupling reactions of the Heck type, e. g., Suzuki [48c] and Stille [49c] cross-coupling, are excellent tools for the preparation of biaryls (see also Section 3.1.9). The activity and stability of the catalyst is highly dependent on the steric and electronic properties of the ligands. Sterically demanding basic alkylphosphines e. g., tri(/-butyl)phosphine, have proven to be very effective ligands in the Heck reaction [50] as well as in the Suzuki cross-coupling [51]. NHCs resemble those basic phosphines (see above) and therefore were tested... 

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