A Well-Defined (POCOP)Rh Catalyst for the Coupling of Aryl Halides with Thiols

Abstract

This article describes a well-defined pincer-Rh catalyst for C-S cross-coupling reactions. (POCOP)Rh(H)(Cl) serves as an active precatalyst for the coupling of aryl chlorides and bromides with aryl and alkyl thiols under reasonable conditions (3% mol cat., 110 °C, 2-24 h, >90% yield). For select substrates, >90% yields were obtained with catalyst loading as low as 0.1%. Key mechanistic intermediates have been isolated and fully characterized, including (POCOP)Rh(Ph)(SPh) (6a) and (POCOP)Rh(SPh2) (6b). The aryl/bis(phosphinite) (POCOP)Rh system has been shown to favor aryl thiolate reductive elimination at elevated temperatures and in some cases at room temperature, compared with the analogous diarylamido/bis(phosphine) (PNP)Rh pincer system. Concerted reductive elimination has been studied with 6a directly and in the presence of aryl bromide and aryl chloride traps. This investigation demonstrates a clear rate dependence on aryl chloride concentration during catalysis, a dependence that is absent when using aryl bromides. The rate of catalysis is dramatically reduced or brought to zero for ortho-tolyl halides, which can be traced to slower C-S coupling and slower carbon-halogen oxidative addition for ortho-substituted aryls. The influence of the sterics in the thiol component is less straightforward. The S-H oxidative addition product (POCOP)Rh(H)(SPh) (16) has been fully characterized and its reactivity has been examined, resulting in the isolation of the sodium-thiolate adduct (POCOP)Rh(NaSPh) (19). The solid-state structure of 19 shows Na interactions not only with sulfur, but also with a neighboring Rh and the chelating aryl carbon of the pincer framework. The reactivity of 16 and 19 indicates that these potential side products should not hinder catalysis.

Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry

“…Recently, a well-defined (POCOP)Rh system for the catalytic coupling of aryl bromides and chlorides with aryl and alkyl thiols was reported by Ozerov et al [34]. (POCOP)Rh(H)(Cl) was demonstrated to be an active precatalyst for the coupling of aryl chlorides and bromides with aryl and alkyl thiols under reasonable conditions (Fig.…”

Concerted aryl-sulfur reductive elimination from PNP pincer-supported Co(iii) and subsequent Co(i)/Co(iii) comproportionation

“…In the event, formation of four diarylsuldes was instead observed, along with the four expected Co II products: 2a, 2b, 3a, and 3b (Scheme 6). 19 F NMR analysis during the course of the reaction at 80 C revealed the formation of the Co(III) crossover product 6c (Fig. S5 †).…”

“…[32][33][34][35][36][37][38][39][40][41][42] In 2018, we reported on the reactivity of (POCOP) Co(Ph)(SPh). 43 In contrast to (PNP)Rh(Ph)(SPh) 18 or (POCOP) Rh(Ph)(SPh), 19 it did not undergo C-S RE but instead a RE of the phenyl with the pincer aryl (Scheme 1). Because of this, the POCOP system did not allow for the investigation of the C-S RE.…”

“…[13][14][15][16][17][18] This approach with Rh proved especially fruitful in catalytic C-S coupling. 19 Catalytic C-S coupling with Pd has received a considerable amount of attention. 20,21 It is easy to envisage the steps of the analogous pincersupported Co I/III cycle (Fig.…”

Carbon–sulfur bond formation by reductive elimination of gold(iii) thiolates

“…1,2 Reductive elimination leading to carbon-heteroatom bonds are comparatively rare but have also been observed, such as the formation of C(sp 3 )-X and C(sp 2 )-X carbon-halide bonds, [3][4][5] as well as C(sp 2 )-E bonds through reactions with P-, 6 O-and N-nucleophiles 7 including phosphine ligands, via three-coordinate intermediates (Scheme 1 A -E). The formation of C-S bonds by reductive elimination of metal thiolates has been studied extensively for palladium 8,9 and has also been observed for rhodium pincer complexes 10 and applied to the rhodium-catalysed formation of diaryl thioethers. 11 By 2 contrast, we are aware of only one example for C-S bond formation involving gold(III), the reaction of cyclometallated gold(III) C^N chelate complexes with -SH containing peptides, which allowed the transfer of the C^N moiety to the peptide via C-S linkages (Scheme 1 F).…”