Palladium‐Catalyzed Intramolecular CH Difluoroalkylation: Synthesis of Substituted 3,3‐Difluoro‐2‐oxindoles

Abstract

The synthesis of 3,3-difluoro-2-oxindoles through a robust and efficient palladium-catalyzed C–H difluoroalkylation is described. This process generates a broad range of difluorooxindoles from readily prepared starting materials. The use of BrettPhos as the ligand was crucial for high efficiency. Preliminary mechanistic studies suggest that oxidative addition is the rate-determining step for this process.

Difluoromethylation of (hetero)aryl chlorides with chlorodifluoromethane catalyzed by nickel

“…For both the practical application and the fundamental research, replacing the palladium catalyst by a first-row-based transition metal catalyst would pave a new and more cost-efficient way for applications of ClCF 2 H in organic synthesis and medicinal chemistry. Instead of ClCF 2 H activation, only rare examples of nickel catalyzed difluoroalkylation have been reported for the cross-coupling of difluoroalkyl chloride (ClCF 2 CO 2 Et) with nucleophilic arylboronic acids, in which the C–Cl bond is activated by an ester group (CO 2 Et) adjacent to the difluorocarbon 18 – 20 . As an inert substrate, the direct cleavage of C–Cl bond in ClCF 2 H remains a great challenge.…”

Optimized synthesis of a pentafluoro- gem -diol and conversion to a CF2Br -glucopyranose through trifluoroacetate-release and halogenation

“…Although there are many methods to introduce fluorine 3 and trifluoromethyl groups, 4 there are substantially fewer strategies to install a difluoromethylene group. 5–7 The most common synthetic protocols for installing a difluoromethylene group are through the use of a difluoroenol 8 or a difluoroenolate. 9–11 Difluoroenolates are typically derived from bromodifluoroacetate with a Reformatsky reaction.…”

Solvent-, and Catalyst-free Acylation of Anilines with Meldrum's Acids: ANeat Access to Anilides

“…of 1 j led to the complete consumption of 2 b and 2 h . Notably, these amides can readily be converted to oxindoles based on the C−H activation strategy . To our disappointment, 5‐disubstituted Meldrum's acid failed in this reaction, with the starting materials intact.…”