TY - JOUR
T1 - Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne-Dicobalt Complex (Nicholas Reaction) Catalyzed by Chiral Brønsted Acid
AU - Terada, Masahiro
AU - Ota, Yusuke
AU - Li, Feng
AU - Toda, Yasunori
AU - Kondoh, Azusa
N1 - Funding Information:
This work was partially supported by a Grant-in-Aid for Scientific Research on Innovative Areas Advanced Molecular Transformations by Organocatalysts from MEXT, Japan. We greatly appreciate Takasago International Corporation for supplying the enantioenriched propargylic alcohols, and Daicel Corporation CPI Company for conducting chiral stationary phase HPLC analysis of 4h. We also thank JSPS for a research fellowship for Young Scientists (Y.T. and F.L.).
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/8/31
Y1 - 2016/8/31
N2 - Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp2-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp3-hybridized carbon atom. In particular, substitution at the chiral sp3-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid.
AB - Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp2-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp3-hybridized carbon atom. In particular, substitution at the chiral sp3-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid.
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U2 - 10.1021/jacs.6b05948
DO - 10.1021/jacs.6b05948
M3 - Article
AN - SCOPUS:84984900691
VL - 138
SP - 11038
EP - 11043
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 34
ER -