Palladium thioethers, reactions with

Both 6-alkanesulfanyl- and 6-alkanesulfonylpurines proved competent coupling partners in the palladium-catalyzed Suzuki reaction with boronic acids when an imidazolium carbene ligand was used <20050L1149>. The sulfones were found to be significantly more reactive (60 °C, THF) than the thioethers (90 °C, toluene) (Scheme 44). 

The relative kinetic cis effects of halide ligands on substitution at palladium(ii) have been established by monitoring the reactions of trans-[Pd(4-Cl-py)2Xa] and of rra j-[Pd(py)2Xa], where X = Cl, Br, or I, with amines or with thioethers in 1,2-dimethoxyethane solution at 25 °C. The usual two-term rate law [equation (4)] applies to these reactions, but as the ky terms were all small, the c r-effect trends have been reported only for the k, terms. The cis effects on substrate discrimination are in the order I>Br> Cl for reaction with amines, and Cl>Br>I for reaction with thioethers. This pattern is the same as that established for platinum(n) complexes, ... 

In addition to the success just described with the well-known named processes, a number of other macrocyclization reactions mediated by palladium complexes have been reported. The first of these approaches exploits the established chemistry of palladium Jt-allyl complexes for use in activation towards reaction with nucleophiles. This reaction was employed by Harran et al. as a critical step in the construction of a series of macrocycles such as 116 via 115) designed to significantly reduce the peptidic character of known active peptides (Scheme 11.14). " The approach tolerates a variety of functionality, including alcohols, amides, thioethers and selected heteroaromatics, and was also successfully conducted on solid support. 

In some cases the use of homoleptic solvento-complexes as starting materials in non-aqueous solvents involves a diversion fiom the common reaction pathway. The interaction between platinum(II) and palladium(II) complexes with potentially tetradentate thioether ligands,8-n Figure 4.2, has been studied. The reactions of the tetrahalide complexes [MX4P-, where M = Pt, Pd X = Cl, Br, I, with the thioether ligands in an ethanol-dichloromethane... 

Thiols add to alkenes under photochemical conditions to form thioethers, and the reaction can be done intramolecularly to give cyclic thioethers. Thiols also add to alkynes and with a palladium catalyst, vinyl sulfides can be formed. " Selenium compounds (RSeH) add in a similar manner. ... 

Regarding the use of other metals for this transformation, Shirai and co-workers reported that a system constituted by palladium(II) complex [Pd(p-Cl)(r -aUyl)]2 and thioether-imidazolium chloride 19 achieved the arylation of aldehydes with boronic acids [33] and potassium trifluoroborates in good to excellent yields (Scheme 7.5) [34], More recently, Buffard and Itami showed that a NKcod) / IPr-HCl system could catalyse the reaction of arylboronate esters and inactivated aldehydes and ketones (Scheme 7.5) [35]. 

Several Pd11 complexes with thiolate or thioether derivative ligands have been studied to be applied in the hydroxycarbonylation reaction.394 Aminothiolate complexes of palladium with PPh3 catalyze the conversion of styrene to 2-phenylpropionic acid in high yield and excellent regioselectivity.644 Under mild conditions and in the presence of a catalytic amount of an S, TV-chelated palladium or//zo-amino-arenethiolate complex, styrene reacts with CO and oxalic acid or water to selectively give 2-phenylpropanic aid in high yield.645... 

Pyrimidine thioethers may also be synthesized via direct Pd-catalyzed C—S bond formation between halopyrimidines and thiolate anions. For very unreactive thiol nucleophiles such as 2-thiopyrimidine, both a strong base and a palladium catalyst are essential. Without a palladium catalyst or replacing f-BuONa with K2C03, the reaction failed to furnish the desired pyrimidine thioether [49]. 

These reactions are convenient methods for incorporating a sulfur-containing group onto an aromatic ring. With Ar S, diazosulfides Ar—N=N—S—Ar are intermediates/° which can in some cases be isolated. ° Thiophenols can be made as shown above, but more often the diazonium ion is treated with EtO-CSS or 82, which give the expected products, and these are easily convertible to thiophenols. Aryldiazonium salts are prepared by the reaction of an aniline derivative with an alkyl nitrite (RONO), and when formed in the presence of dimethyl disulfide (MeS-SMe), the product is the thioether, Ar-S-Me. ° Aryl triflates have been converted to the aryl thiol using NaST(P5) and a palladium catalyst, followed by treatment with tetrabutylammonium fluoride ° (see also, 14-22). 

---