Thiols, aryl coupling reactions

Microwave and fluorous technologies have been combined in the solution phase parallel synthesis of 3-aminoimidazo[l,2-a]pyridines and -pyrazines [63]. The three-component condensation of a perfluorooctane-sulfonyl (Rfs = CgFiy) substituted benzaldehyde by microwave irradiation in a single-mode instrument at 150 °C for 10 min in CH2CI2 - MeOH in the presence of Sc(OTf)3 gave the imidazo-annulated heterocycles that could be purified by fluorous solid phase extraction (Scheme 9). Subsequent Pd-catalyzed cross-coupling reactions of the fluorous sulfonates with arylboronic acids or thiols gave biaryls or aryl sulfides, respectively, albeit it in relatively low yields. 

The cross-coupling reaction proceeds through the initial oxidation of the more reactive thiol, followed by the gradual thiolysis of the formed disulphide by the less reactive thiol. The method is therefore useful for the cross-coupling of the reactive aryl and n-alkyl thiols with the less reactive f-alkylthiols. 

In 2002, Venkataraman published the synthesis of bisaryl- and arylalkyl-thioethers catalyzed by the Cul/neocuproine system [74]. At the same time, using excess ethylene glycol as a ligand, Cul-catalyzed coupUng of aryl iodides with thiols was found to take place at 80 °C [75]. Soon after, N,N-dimethylglycine (L2) (Table 9.15, entry 1) [76] and L-proline (LI) (entry 2) [77] were revealed to be effective for the same transformation. Recently, CuBr/ 3-keto ester (L19) was reported to be able to promote this cross-coupling reaction to afford the corresponding diaryl thioethers at 60-75 °C (entry 3) [27]. 

Arylation of a wide range of NH/OH/SH substrates by oxidative cross-coupling with boronic acids in the presence of catalytic cupric acetate and either triethyl-amine or pyridine at room temperature in air. The reaction works for amides, amines, anilines, azides, hydantoins, hydrazines, imides, imines, nitroso, pyrazi-nones, pyridones, purines, pyrimidines, sulfonamides, sulfinates, sulfoximines, ureas, alcohols, phenols, and thiols. It is also the mildest method for NIO-vinylation. The boronic acids can be replaced with siloxanes or starmanes. The mild condition of this reaction is an advantage over Buchwald-Hartwig s Pd-catalyzed cross-coupling. The Chan-Lam C-X bond cross-coupling reaction is complementary to Suzuki-Miyaura s C-C bond cross-coupling reaction. 

Catalytic cross-coupling reactions were shown to be of much help in preparing several important compounds. For example, thiazene-substituted thioglycosides were readily synthesized via the reaction of the corresponding thiols with aryl iodides in the Cul/Py catalytic system in MeCN (Scheme 3.39) [69]. 

The products of the oxidative addition of aryl halides have an important use in coupling reactions, as shown in the following general reaction, where HYR may be an amine, alcohol or thiol and a strong base is added to remove the protons ... 

In combination with catalytic amounts of Pd, CuTC has given rise to novel cross-coupling reactions under mild and neutral con-ditions that have furnished a number of very useful organic building blocks. Thus, an unprecedented cross-coupling of thiol esters with aryl and alkenylboronic acids in the presence of a catalytic amount of Pd(0) and 1.6 equiv of CuTC furnished a wide variety of aryl ketones under baseless conditions (eq 7). ... 

Over a century ago, Ullmann reported coupling reactions catalysed by metallic copper. ° ° The harsh conditions typically involved limited its applicability, but Ullmann s work ultimately stimulated the search for milder conditions using copper catalysis. Both copper(I) and copper(II) salts can catalyse the coupling of aryl halides with a range of heteroatom nucleophiles, including phenols (Scheme 2.168, 2.169), ° alcohols (Scheme 2.170),thiols (Scheme 2.171, 2.172), amines (Scheme 2.173), anilines (Scheme 2.174)2" and A/ -heterocycles (Scheme 2.175,2.176).2i2.2i3... 

Thiols have been employed as nucleophiles in palladium-catalysed coupling reactions (Scheme 2.181). An aryl thioether could be formed from an aryl triflate using a strong base, a bidentate ligand and a nonpolar solvent to suppress competitive triflate decomposition. An intramolecular thiol coupling with an iodoindole was a key step in a synthesis of chuangxinmycin (Scheme 2.182). ... 

Palladium-catalyzed Cross-coupling Reactions. The Pd -catalyzed cross-coupling of vinyl and aryl halides with KSTIPS affords the corresponding silyl sulfides, which can be used either to prepare thiols or sulfides. The reaction proceeds with corr5>lete retention of configuration in the case of vinyl derivatives (eq 8). The yields are good to excellent (61-93%) when the reaction is earned out on a small scale (2 mmol). 

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