Fluoride‐Catalyzed Nucleophilic Addition of PhSCF₂SiMe₃ to Isatins: Synthesis of 3‐(1′,1′‐Difluoroalkyl)‐3‐hydroxyindolin‐2‐ones

Abstract

The synthesis of 3‐(1′,1′‐difluoroalkyl)‐3‐hydroxyindolin‐2‐ones by employing α,α‐difluoro‐α‐phenylsulfanyl‐α‐trimethylsilylmethane (PhSCF2SiMe3) as a gem‐difluoromethylene building block is described. The reaction involves a fluoride‐catalyzed nucleophilic addition of PhSCF2SiMe3 to various isatin derivatives followed by the reductive cleavage of the phenylsulfanyl group to lead to 3‐(difluoromethyl)‐3‐hydroxyindolin‐2‐ones in good yields. Under similar reduction conditions but in the presence of activated olefins, an intermolecular radical trapping reaction took place to yield 3‐(1′,1′‐difluoroalkyl)‐3‐hydroxyindolin‐2‐one derivatives.

Stereoselective Construction of 3-(Aminoalkylidene)oxindoles in One Pot: Development of a Novel, Robust, and Scalable Process for the Multigram-Scale Preparation of Nintedanib

“…Before the selection of a protecting group, their deprotection technique should be taken into consideration. We hypothesized that PMB ( p -methoxy benzyl) would be a better choice as a protecting group since deprotection of the corresponding group is easier than a benzyl group . Then, the optimization for better reaction conditions was performed for PMB protection of 13 (Table ).…”

Recent Progress on the Synthesis of CF2H-Containing Derivatives

“…A somewhat similar but indirect difluoromethylation method was developed by Pohmakotr and co-workers for the difluoromethylation of isatin derivatives by fluoride (TBAT) catalyzed nucleophilic addition of PhSCF 2 SiMe 3 . 46 The difluoromethyl moiety was obtained through reductive cleavage of the phenylsulfanyl group with Bu 3 SnH involving hydrogen radical abstraction with catalytic amounts of AIBN (Scheme 2, C). This difluoromethylation reaction exhibited compatibility with various derivatives of isatin, including N-methyl, allyl, and benzyl, as well as with electron-donating and electron-withdrawing groups, with yields ranging between 73-97%.…”

Diastereoselective Addition of PhSCF2SiMe3 to Chiral N-tert-Butanesulfinyl Ketimines Derived from Isatins: Synthesis of Enantioenriched gem-Difluoromethylenated Spiro-pyrrolidinyl and Spiro-piperidinyl Oxindoles

“…Our group has long been interested in the synthesis of fluorine-containing organic molecules. For example, we have developed the synthetic utilities of PhSCF 2 SiMe 3 ( 1 ) as a gem -difluoromethylene radical anion building block ( • CF 2 – ) for the preparation of gem -difluoromethylenated linear and angular triquinane scaffolds, , polyhydroxypyrrolizidines and -indolizidines, propanoylbicyclo[3.3.0]­octanes, polycyclic cage compounds, cis -fused bicyclic γ-butyrolactones, and α,β-unsaturated γ-butyrolactones . The reactions of 1 with isatins and cyclic imides were also reported .…”