Beilstein J. Org. Chem.2018,14, 576–582, doi:10.3762/bjoc.14.44
Kohsuke Aikawa Kohei Yabuuchi Kota Torii Koichi Mikami Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo 152-8552, Japan 10.3762/bjoc.14.44 Abstract The catalytic asymmetricmethylation of
fluoroalkylated pyruvates is shown with dimethylzinc as a methylating reagent in the presence of a copper catalyst bearing a chiral phosphine ligand. This is the first catalytic asymmetricmethylation to synthesize various α-fluoroalkylated tertiary alcohols with CF3, CF2H, CF2Br, and n-CnF2n+1 (n = 2, 3, 8
copper.
Keywords: asymmetricmethylation; chiral phosphine ligand; copper catalyst; dimethylzinc; trifluoropyruvate; Introduction
The introduction of fluorine atoms into organic compounds plays an important role in the discovery of lead candidates with unique biological and physicochemical properties
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Graphical Abstract
Scheme 1:
Synthesis of chiral α-fluoroalkylated tertiary alcohols.
Beilstein J. Org. Chem.2013,9, 2113–2119, doi:10.3762/bjoc.9.248
investigated. As shown in Table 3, benzyl bromide, allyl iodide and methyl iodide reacted very well to give the alkylated products 7 in moderate to good yields and excellent de values of >99% (Supporting Information File 1). Especially, the diastereocontrol of asymmetricmethylation in this case was better
acids 8a, 8b, and 8c in excellent ee values (Table 4, entries 1–3). To our surprise, although the asymmetricmethylation proceeded very well with excellent diastereocontrol (>99 de), epimerization occurred under NaOH cleavage condition. Consequently, chiral acid 8d was obtained in only 89% ee (Table 4
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Graphical Abstract
Scheme 1:
Synthesis of NCPS-supported 2-imidazolidinone chiral auxiliary 3 through direct copolymerization of...