Related Experiment Video
Updated: Apr 19, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Asymmetric synthesis of gem-difluoromethylenated linear triquinanes via cascade gem-difluoroalkyl radical cyclization
Watcharaporn Thaharn1, Darunee Soorukram, Chutima Kuhakarn
1Center of Excellence for Innovation in Chemistry (PERCH-CIC) and Department of Chemistry Faculty of Science, Mahidol University , Rama VI Road, Bangkok 10400, Thailand.
Abstract:
An asymmetric synthesis of gem-difluoromethylenated linear triquinanes is described exploiting the synthetic utilities of PhSCF2TMS (5) as a "(•)CF2(-)'' building block. The strategy involves fluoride-catalyzed nucleophilic addition of PhSCF2TMS (5) to chiral ketocyclopentenes 6 to provide silylated adducts 9 or alcohol derivatives 10 and 11. Subsequent cascade radical cyclization of the gem-difluoroalkyl radical generated from silylated adducts 9 or alcohols 10 and 11 afforded gem-difluoromethylenated linear triquinanes 16 as an approximate 1:1 mixture of two diastereomers (16A and 16B). Alternatively, a convenient asymmetric synthesis of gem-difluoromethylenated linear triquinanes 16A can be accomplished by oxidation of 16a (R = H) to provide ketotriquinane 17 followed by a highly stereoselective nucleophilic addition to 17 employing DIBAL, NaBH4, and various Grignard reagents.
Related Concept Videos
Radical Chain-Growth Polymerization: Overview
Radical Reactivity: Intramolecular vs Intermolecular
Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
Radical Substitution: Allylic Bromination
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation...

