title: Stereoselective Synthesis of Chiral β-Fluoro α-Amino Acids via Pd(II)-Catalyzed Fluorination of Unactivated Methylene C(sp(3))-H Bonds: Scope and Mechanistic Studies.
abstract: The synthesis of fluorinated complex molecules via direct C(sp(3))-H fluorination is attractive yet remains challenging. Here we describe the Pd(II)-catalyzed fluorination of unactivated methylene C(sp(3))-H bonds by an inner-sphere mechanism. This method allows the site- and diastereoselective fluorination of β-methylene C(sp(3))-H bonds of α-amino acid derivatives. A range of substrates containing both aliphatic and benzylic C(sp(3))-H bonds were compatible with this protocol, leading to an array of β-fluorinated α-amino acids. Stoichiometric fluorination of an isolated palladacycle intermediate takes place rapidly under very mild reaction conditions (room temperature, 5-10 min). Data from preliminary mechanistic studies are consistent with direct C-F reductive elimination from a high-valent intermediate.
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Yin
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Shuo-Qing
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Department of Chemistry, Zhejiang University, Hangzhou 310027, China.
authors.forename: Bing-Feng
authors.initials: BF
authors.lastname: Shi
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D054879:Halogenation; D008697:Methane / Q000737:chemistry; D008958:Models, Molecular; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D010165:Palladium; D008697:Methane