Palladium‐Catalyzed Rapid Methoxylation and Deuteriomethoxylation of Bromo–chalcones: Uncovering the Catalytic Activity of the Pd/tBuXPhos Catalyst System

Abstract

We report an unprecedented tBuXPhos ligand (L3) supported Pd‐catalyzed rapid methoxylation and deuteriomethoxylation of bromo‐chalcones (5 to 40 min.) with excellent yields. Pd/RockPhos (L2) catalytic system also facilitates the coupling reaction, but the reaction time is fairly longer than Pd/tBuXPhos (L3) catalytic system. The coupling of MeOH/MeOH‐d4 with 4‐bromo‐chalcones is so rapid than that of 3‐bromo‐chalcones, which clearly indicates that the former proceeds through a pure electronic pathway of reductive elimination. These catalyst systems facilitate the coupling of 4‐bromo‐chalcones even with higher alkyl alcohols relatively long reaction time that implies the efficiency and rate of coupling relays on the nucleophilicity of the alcohols. This methodology may be adopted for the 11C‐radiolabeling of organic compounds for PET imaging applications.

Total Synthesis and Anti-Inflammatory Activity of Velutone F

“…The reaction conditions were optimized by the use of MeOH, Cs 2 CO 3 , bis(allylchloropalladium) [(allylPdCl) 2 ], and ligand (tBuXPhos) yielding 1 in 63% yield. 10 The structure of synthetic compound 1 was confirmed by spectral analysis and was identical to the literature data (Table 1).…”

“…A mixture of 7 (3.2 g, 19.5 mmol) and DDQ (4.98 g, 21.9 mmol) in dry toluene (50 mL) was heated under reflux for 3 h. After the reaction was completed (detected by TLC), the resulting mixture was cooled in an ice bath and solids were removed by filtration through Celite. Synthesis of 7-bromo-4-methoxybenzofuran-5-carbaldehyde (10).…”

Synthesis of Fluorinated Alkyl Aryl Ethers by Palladium-Catalyzed C–O Cross-Coupling

“…Under conditions similar to those reported by Singh, using BrettPhos, Pd 2 (dba) 3 , and Cs 2 CO 3 in toluene, no coupled product was formed after 1 h (entry 1) . Switching the ligand to either XPhos or t BuXPhos also resulted in no product formation (entries 2 and 3). , Using t BuBrettPhos as ligand, the coupled product was observed in 51% yield (entry 4). An increase to 70% yield was observed using Buchwald’s t BuBrettPhos Pd G3 precatalyst (entry 5).…”

“… 6 Switching the ligand to either XPhos or t BuXPhos also resulted in no product formation (entries 2 and 3). 15 , 16 Using t BuBrettPhos as ligand, the coupled product was observed in 51% yield (entry 4). An increase to 70% yield was observed using Buchwald’s t BuBrettPhos Pd G3 precatalyst (entry 5).…”

Synthesis and Evaluation of Antiplasmodial Activity of 2,2,2-Trifluoroethoxychalcones and 2-Fluoroethoxy Chalcones against Plasmodium falciparum in Culture

“…Moreover, biological evaluations of fluorochalcones have not been fully explored, except for some fluorochalcone derivatives, which have been reported for their anti-inflammatory [ 38 , 39 ], or anti-proliferative activity [ 40 ], or as inhibitors of monoamine oxidase-B [ 41 , 42 ]. Recently, we have reported a novel methodology for the coupling of bromochalcones with alcohols and fluoroalcohols by Pd/ t BuXPhos catalyst systems [ 43 , 44 , 45 , 46 , 47 ]. Taking into consideration of the importance of fluoroethoxy groups and chalcones in biological activity, we pleased to synthesize fluoroethoxy chalcones and assess their antiplasmodial activity.…”