Ligand Free Palladium‐Catalyzed Synthesis of α‐Trifluoromethylacrylic Acids and Related Acrylates by Three‐Component Reaction

Abstract

Aryl iodides and 2‐(trifluoromethyl)acrylic acid reacted together in ligand‐free Mizoroki‐Heck reaction furnishing a quick and efficient access to highly valuable α‐trifluoromethylacrylic acids. The useful transformation was independent with regard to the electronic nature of the aryl group substituent. A three‐component one‐pot version was also developed to give diverse substituted acrylates. The versatility of α‐trifluoromethylacrylic acids was demonstrated by quick access to 3‐CF3‐coumarins as well as fluorinated analogues of therapeutic or cosmetic agents. Finally, we proposed a catalytic cycle based on the silver carboxylate salt, identified as a key intermediate in the reaction.

Stereoselective Palladium-Catalyzed Arylation of Exo-Glycals with Aryl Iodides

“…The exclusion of either Pd­(OAc) 2 or AgOAc showed that their presence is essential for the formation of the product in high yields (Table , entries 1,2). Based on this result and previous reports, we propose that the silver salt acts as an iodide scavenger, which converts the Pd–I complex to the active catalyst. ,− …”

Palladium-Catalyzed Three-Component 1,4-Alkoxyarylation Reaction of [60]Fullerene

“…Finally, reductive elimination of D results in 1,4-alkoxyarylation adduct 3 , where the aryl group is exclusively located at the para position of the alkoxy group due to less steric hindrance, − along with the regeneration of a Pd­(II) species. The reversal of the above-discussed alkoxyarylation processes, that is, the initial oxidative addition of ArI to a Pd­(II) species affording an ArPd­(IV) species, subsequent arylpalladation to C 60 , and final alkoxylation, may also operate in the present reaction …”

Heck Reaction of 2-Oxyacrylates with Aryl Bromides: A Common Route to Monoaryl Pyruvates and Ortho Ester-Protected Monoaryl Pyruvates

“…Each acrylate type often necessitates the design of a suitable catalytic system. In this context, there are only a handful examples of α-substituted acrylates giving good reactivities and selectivities. , In one of our route scouting program for a clinical drug candidate, we were challenged with the task of converting a densely functionalized electron-deficient aryl bromide 1 to the respective α-monoaryl pyruvate 4 for downstream use. The direct arylation of ethyl pyruvate with aryl bromide 1 would be the most straightforward method to access 4 (Scheme ).…”