Mono-Oxidation of Bidentate Bis-phosphines in Catalyst Activation: Kinetic and Mechanistic Studies of a Pd/Xantphos-Catalyzed C–H Functionalization

Abstract

Kinetic, spectroscopic, crystallographic, and computational studies probing a Pd-catalyzed C-H arylation reaction reveal that mono-oxidation of the bis-phosphine ligand is critical for the formation of the active catalyst. The bis-phosphine mono-oxide is shown to be a hemilabile, bidentate ligand for palladium. Isolation of the oxidative addition adduct, with structural elucidation by X-ray analysis, showed that the mono-oxide was catalytically competent, giving the same reaction rate in the productive reaction as the Pd(II)/xantphos precursor. A dual role for the carboxylate base in both catalyst activation and reaction turnover was demonstrated, along with the inhibiting effect of excess phosphine ligand. The generality of the role of phosphine mono-oxide complexes in Pd-catalyzed coupling processes is discussed.

Chiral Catalysts for Pd0‐Catalyzed Enantioselective C−H Activation

“…In 2015, in the contexto f am echanistic investigation of Pd 0 -catalyzed CÀHa rylations mediated by Xantphos, Blackmond and co-workers revealed that the monooxidation of the P, P-ligand, which leads to corresponding bis-phosphine mono-oxide (BPMO), is crucial for the formationo ft he active catalyst. [86] As ar esult,X antphos monooxide performs as ah emilabile P, O-ligand, which affords additional coordinationf or an internal CMD base (Figure 4). As a consequence, andk nowing that the reduction of Pd II precatalysts such as Pd(OAc) 2 is accompanied by the oxidation of a phosphine in the corresponding monooxide, [87] chiral P, P-ligands reported thereafter in conjunction with ap alladium(II) source should not likely be considered as the actual ligands that participate in the catalytic cycle.…”

“…Despite the fact that diphosphine ligands were employed in various Pd‐catalyzed C−H activation reactions, their exact role remained unknown for a long time. In 2015, in the context of a mechanistic investigation of Pd 0 ‐catalyzed C−H arylations mediated by Xantphos, Blackmond and co‐workers revealed that the monooxidation of the P,P‐ligand, which leads to corresponding bis‐phosphine mono‐oxide (BPMO), is crucial for the formation of the active catalyst [86] . As a result, Xantphos mono‐oxide performs as a hemilabile P,O‐ligand, which affords additional coordination for an internal CMD base (Figure 4).…”

Umpolung Synthesis of Diarylmethylamines via Palladium‐ Catalyzed Arylation of N‐Benzyl Aldimines

“…Finally, given Eastgate and Blackmond’s recent report of reactions catalyzed by mono-oxidized bidentate XANTPHOS and palladium, [9] we wanted to determine if such species might be involved in the arylation reactions outlined herein. To address this issue, we employed the Buchwald precatalyst [10] with NIXANTPHOS ligand, which generates Pd(0) by reductive elimination (Scheme 6).…”

Selective Palladium(II)‐Catalyzed Carbonylation of Methylene β‐C−H Bonds in Aliphatic Amines

“…The successful use of phosphines in oxidative C−H carbonylation is surprising given their propensity towards oxidation to phosphine oxides; the unique effect of xantphos, compared to other phosphines, is also striking. Accordingly, we found that a reaction using xantphos monooxide gave almost the same yield as the use of xantphos (entry 10);, however, the yield dropped dramatically when xantphos dioxide was used (entry 11) . While we are unsure of its precise role, we believe that xantphos (or its monooxide) most likely stabilizes Pd 0 at the end of the catalytic cycle prior to oxidation to the Pd II species required for the reaction …”