Biaryl thioethers

Palomo, C., Oiarbide, M., Lopez, R., Gomez-Bengoa, E. Phosphazene bases for the preparation of biaryl thioethers from aryl iodides and arenethiols. Tetrahedron Lett. 2000,41, 1283-1286. 

In the presence of the phosphazene Et-P2 base as well as DBU the coupling of aryl iodides with arenethiols only requires catalytic amounts of copper(I) bromide (CuBr). Under these conditions, the reaction can be performed in refluxing toluene to give biaryl thioethers in excellent yields [40] (Scheme 5.22). 

Uses of bases of this type, such as DBU and DBN have been reviewed [15] and more recently they have been used as stoichiometric bases in the synthesis of 2H-isoindoles [ 16],biaryl thioethers [17],phthalocyanines [18] and the related macrocyclic compounds [18], 2,4-dioxo-l,2,3,4-tetrahydroquinazolines [19], dihydro alanine-containing peptides [20] and [[pyrazolylmethyl)amino]-propyl azepinones and -pyrrolidinones [21]. Chiral DBU/DBN-related molecules have also been synthesized which were fovmd to be useful as catalysts in an asymmetric Michael reaction [22]. 

In 2004-2005, we reported direct thioetherification of tautomerizable heterocycles with sulfur nucleophiles via phosphonium coupling to produce biaryl thioethers or alkyl aryl thioethers. Thiophenols are... 

Alternatively, boronic acids react under the influence of Cu-catalysis with electrophilic iV-thioimides under mild conditions and in the absence of base (Eqn. 1-7). Various copper carboxylates can be used (e.g., CuMeSal, CuTC, and CuOAc) but not salts such as CuCl, CuCN, or CU2O. A presumed Cu(I)/Cu(III) cycle is put forth, where the thioimide is oxidatively added to the Cu(I) catalyst, and the RB(0H)2 supplies the R group on the metal (with loss of imide-B(OH)2) prior to reductive elimination. Several biaryl thioethers were made in this way (e.g., 85,86) in THF (or dioxane), along with aryl alkenyl derivative 87. All bases examined (K2CO3, NaOH, TBAF, pyridine, EtsN) inhibited the reaction. 

Modified Ullmann biaryl ether / thioether and biaryl amine synthesis ... 

Liebeskind reported a new method for cross-coupling heteroaromatic thioethers with boronic acids [56]. This required the use of copper(I) thiophene-2-carboxyhc acid (CuTC) but allowed the reaction to be conducted under mild and neutral reaction conditions from readily available starting material. As an example, thiomethylpyridine 161 was cross-coupled to boronic acid 162 to afford the biaryl 163. 

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