TY - JOUR
T1 - C(sp2)-H Borylation of Fluorinated Arenes Using an Air-Stable Cobalt Precatalyst
T2 - Electronically Enhanced Site Selectivity Enables Synthetic Opportunities
AU - Obligacion, Jennifer V.
AU - Bezdek, Máté J.
AU - Chirik, Paul J.
N1 - Funding Information:
J.V.O. acknowledges the 2015 Howard Hughes Medical Institute International Student Research Fellowship and the 2016 Harold W. Dodds Honorific Fellowship (awarded by the Graduate School at Princeton University). M.J.B. thanks the Natural Sciences and Engineering Research Council of Canada for a predoctoral fellowship (PGS-D). We also thank AllyChem for the generous gift of B2Pin2. Financial support was provided by NIH (R01 GM121441).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/2/22
Y1 - 2017/2/22
N2 - Cobalt catalysts with electronically enhanced site selectivity have been developed, as evidenced by the high ortho-to-fluorine selectivity observed in the C(sp2)-H borylation of fluorinated arenes. Both the air-sensitive cobalt(III) dihydride boryl 4-Me-(iPrPNP)Co(H)2BPin (1) and the air-stable cobalt(II) bis(pivalate) 4-Me-(iPrPNP)Co(O2CtBu)2 (2) compounds were effective and exhibited broad functional group tolerance across a wide range of fluoroarenes containing electronically diverse functional groups, regardless of the substitution pattern on the arene. The electronically enhanced ortho-to-fluorine selectivity observed with the cobalt catalysts was maintained in the presence of a benzylic dimethylamine and hydrosilanes, overriding the established directing-group effects observed with precious-metal catalysts. The synthetically useful selectivity observed with cobalt was applied to an efficient synthesis of the anti-inflammatory drug flurbiprofen.
AB - Cobalt catalysts with electronically enhanced site selectivity have been developed, as evidenced by the high ortho-to-fluorine selectivity observed in the C(sp2)-H borylation of fluorinated arenes. Both the air-sensitive cobalt(III) dihydride boryl 4-Me-(iPrPNP)Co(H)2BPin (1) and the air-stable cobalt(II) bis(pivalate) 4-Me-(iPrPNP)Co(O2CtBu)2 (2) compounds were effective and exhibited broad functional group tolerance across a wide range of fluoroarenes containing electronically diverse functional groups, regardless of the substitution pattern on the arene. The electronically enhanced ortho-to-fluorine selectivity observed with the cobalt catalysts was maintained in the presence of a benzylic dimethylamine and hydrosilanes, overriding the established directing-group effects observed with precious-metal catalysts. The synthetically useful selectivity observed with cobalt was applied to an efficient synthesis of the anti-inflammatory drug flurbiprofen.
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U2 - 10.1021/jacs.6b13346
DO - 10.1021/jacs.6b13346
M3 - Article
C2 - 28139907
AN - SCOPUS:85013861712
SN - 0002-7863
VL - 139
SP - 2825
EP - 2832
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 7
ER -