title: Asymmetric synthesis of both mirror images of 3'-fluorothalidomide by enantiodivergent fluorination using a single, cinchona alkaloid.
abstract: Enantiomerically pure 3'-fluorothalidomide (2) was successfully synthesized by enantiodivergent electrophilic fluorination using a combination of cinchona alkaloids and N-fluorobenzenesulfonimide (NFSI) as the key reaction. Importantly, a single chiral molecule, dihydroquinine (DHQ), allowed access to the mirror image form of 3'-fluorothalidimide by the choice of additives. While the use of TMEDA gave fluorinated (S)-4, the precursor of 2, with 78% ee, Cu(acac)(2)/bipy, afforded the antipode, (R)-4, in 77% ee.
authors.affiliation: Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Norio
authors.initials: N
authors.lastname: Shibata
mesh_terms: D002384:Catalysis; D002930:Cinchona Alkaloids / Q000737:chemistry*; D054879:Halogenation; D015394:Molecular Structure; D013237:Stereoisomerism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D013792:Thalidomide / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D000096926:Benzenesulfonamides
chemical_list: D002930:Cinchona Alkaloids; D013449:Sulfonamides; D013792:Thalidomide; C523711:N-fluorobenzenesulfonimide; D000096926:Benzenesulfonamides