C-S coupling

Calculations indicate that the unpaired electron density in the cation-radical of tetrathiafulvalene resides principally on sulfur, hut with the internal carbon being the site of second highest density. The product of coupling of an a-carbonyl radical to sulfur, an a-carbonyl-sulfonium salt would be destabilized by the adjacent dipoles. The transition state would be expected to mirror this, thus slowing down the C-S coupling and permitting the observed coupling to the carbon of tetrathiafulvalene. 

K. Kunz, U. Scholz, D. Ganzer, Renaissance of Ullmann and Goldberg Reactions - Progress in Copper Catalyzed C-N-, C-O- and C-S-Coupling, Synlett 2003, 2428-2439. 

In contrast to the observed reactivity of phenoxide and aryl alkoxide ions, arene and heteroarene thiolate ions typically couple with aryl radical to generate C—S bonds. The only exception to this regioselective reaction is the addition of 1-naphthalene thiolate ion to p-anisyl radical to render both C- and S-substitutions in 14% and 65% yields, respectively, while with 1-naphthyl radical, 95% of C—S coupling is obtained. In general, PhS- ions react with Arl in liquid ammonia under photostimulation to afford good yields of ArSPh or heteroaryl-SAr (70-100%). Substitution of the less-reactive ArBr can be achieved under photochemical initiation in DMF, MeCN, or DM SO [1],... 

The carbon-coupled products 66 were duly characterized. No C-S coupling was observed for these radicals, and this suggested that their electrophilic nature might control their reactivity. This could be rationalized by suggesting a slower combination between these radicals and the S. The retardation could result from an unfavorable transition state (67) where the buildup of positive charge on two adjacent carbons is seen. Calculations by Zaharadnik et al. have shown that the spin density on TTP is distributed as shown in Scheme 12, and so support the involvement of the internal carbons of TTF, rather than the peripheral carbons, in radical coupling. 

Synthesis and arylation of heterocycles using copper catalyzed C-N-, C-O- and C-S-coupling reactions 03SL2428. 

Renaissance of Ullmann and Goldberg reactions — progress in copper catalyzed C—N-, C-O- and C—S-coupling , Kunz, K., Scholz, U. and Ganzer,... 

A facile and selective palladium-catalyzed carbonylative domino synthesis of benzothiophenes was developed by Alper and Zeng in 2011 [273]. 2-Carbon-ylbenzo[Z ] thiophene derivatives were produced from 2-gem-dihalovinylthiophe-nols in 24-73 % yields (Scheme 2.39). This protocol involved an intramolecular C-S coupling/intermolecular carbonylation cascade sequence and allowed for access to various highly functionalized benzo[h]thiophenes. 

Copper-catalyzed C-O, C-N, and C-S Coupling. While there is an extensive variety of palladium catalysts for C(aryl)-X bond formation (X = 0, N, and S), copper corrqtlexes have recently gained renewed popularity in these coupling processes. Use of the (CuOTf)2. benzene complex allows the formation of diaryl ethers from aryl bromides or iodides and phenols in very good yields (76-93%) (eq 121). The reaction occurs in toluene in the presence of cesium carbonate as the base and a catal)4ic quantity of ethyl acetate whose role is probably to increase the solubility of the copper species. In the case of less reactive phenols, yields can be increased by the addition of a stoichiometric amount of carboxylic acid. A slight modification of these conditions has been used in the key diaryl ether formation in the synthesis of verbenachalcone. ... 

In 2009, Patel and co-workers developed two ligand-assisted Cu(i)-cata-lyzed sequential intra- and intermolecular S-arylations for the synthesis of arylthiobenzothiazoles in a one-pot manner without an inert atmosphere (Scheme 2.140). Low catalyst loading, inexpensive metal catalyst and ligand, lower reaction temperature, and shorter reaction times make this method superior to all reported methods for the synthesis of aiylthio-benzothiazole. In detail, the reaction started with an intramolecular S-aiy-lation of a dithiocarbamate salt and yielded benzothiazol-2-thiol or MBT (2-mercaptobenzothiazole), which was then followed by an intermolecular C-S coupling giving 2-atylthiobenzothiazoles directly. In the communication, the authors found the following order of reactivity in aryl iodides P-NO2 > 0-NO2 > o-COOMe > m-Cl > H > p-Me > p-OMe. 

Further invention of pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI) ligands has led to a remarkable improvement in palladium-catalyzed C—S coupling [159, 160]. This catalyst effectively couples the less reactive aryl chlorides even at room tempauture [161]. Recently, NHC-based catalyst, [Pd(IPr )(cin)Cl] 18, has been developed for the coupling of aryl halides with aliphatic or aromatic thiols (Scheme 20.53) [162]. 

The first copper-mediated C—S coupling of aiyl boronic acids with alkyl thiols was reported in the presence of an organic base, pyridine (Scheme 20.54) [163]. Copper complexes, Cul-neocuproine [164], Cul-ethylene glycol [165], Cul-bipyridine/air [166], and CuSO -l,10-phenanthroUne/O, [167], have been subsequently explored for the coupling of aryl halides and boronic acids with... 

Although the data (mostly from neutrino experiments) on the c—s coupling are not conclusive, the evidence suggests that it is also left-handed. The apparent connection between quarks and leptons is fascinating. Both sets of doublets are point-like s = 5 fermions their electric charges are quantized in a related way (Q, Q — 1 with Q = 0 for leptons and Q = for quarks) furthermore, the sum of the electric charges of all fermions (in a colour scheme) vanishes as required to cancel triangle anomalies (see Section 9.5.3). It should be noted, however, that serious questions arise if one tries to put the above quark-lepton connection on a quantitative... 

Scheme 24 Oxidative C-S coupling during makaluvamine F total synthesis...

Synthetic strategy Metal-free direct C-S coupling from thiols and diaryhodonium salts Catalyst Cesium carbonate (CS2CO3)... 

Wang, D., Yu, X., Zhao, K., Li, L., and Ding, Y. (2014). Rapid synthesis of aryl sulfides through metal-free C-S coupling of thioalcohols with diaryliodonium salts. Tetrahedron Lett., 55, 5739-5741. 

Scheme 4.12 Synthesis of sugar-based benzothiazoles through C-S coupling.

Cu-catalyzed C—S coupling reaction with 2-haloaniline, followed by intramolecular condensation to produce benzothiazoles 113. 

In 2007, Zhang and co-workers reported the first example of C-S coupling (also called arylthiolation) induced by a NHC-Ni complex, including the reactions of some eleetron-poor aryl chlorides or bromides. Surprisingly, the best NHC for this reaetion was IBn, which was found to be far more reactive than IPr [eqn (10.12)]. It is worth noting that bis-carbenic complexes derived from IBn were found to be slightly more effective but less synthetically accessible. 

C S cross-coupling reactions, where benzothiazole intermediates were further transformed to arylsulfides 139 under intermolecular C—S cross-coupling reaction conditions. In 2010, Pan et al. selectively synthesized 2-(phenylihio)phe-nols 142 via a tandem C S coupling and C H functionalization employing a copper catalyst system. The reaction mechanism, based on an isotope labeled strategy, revealed that dimethyl sulfoxide served as a main oxidant in the C H oxidation step 143. 

---