Organic Letters
Letter
rarely changes the attractive noncovalent interactions in TSL3-
o. In sharp contrast, the coordination geometry of L3
significantly changed in TSL3-m. The pyridine moiety of
TSL3-m is located relatively far from the C(sp2)−H group of
1a compared with TSL1-m. The lack of an electron-donating
tert-butyl group weakens the CH/π interactions between the
pyridine ring and the C(sp2)−H group of 1a and destabilizes
TSL3-m. Therefore, the CH−O hydrogen bond between the
SCH3 and Beg moieties plays a crucial role in stabilizing TSL3-
o (e in Figure 1b). Indeed, because 3r bears a SCF3 group, it
was not suitable for ortho-selective C−H borylation due to the
lack of a stabilizing CH−O hydrogen bond in the TS at the
ortho position (Scheme 2A).
Yoichiro Kuninobu − Institute for Materials Chemistry and
Engineering and Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Fukuoka 816-8580, Japan;
Authors
Jialin Zeng − Department of Molecular and Material Sciences,
Interdisciplinary Graduate School of Engineering Sciences,
Kyushu University, Fukuoka 816-8580, Japan
On the contrary, 5 preferentially afforded the ortho-
borylated product, 6, even using L1. The TS models for the
L1-Ir(Beg)3-mediated C−H oxidative addition of 5 at the ortho
and meta positions (TSL1-o-5 and TSL1-m-5) indicate that
TSL1-o-5 is more stable than TSL1-m-5, in good agreement
with the experimentally observed ortho selectivity of 5 (Figure
1c). This is because the two-point hydrogen bond between the
CH2SCH3 and Beg moieties enhances the stability of TSL1-o-5
(e and f in Figure 1c). The distortion/interaction analysis15
indicates that the interaction energy between the catalyst [L1-
Ir(Beg)3 or L3-Ir(Beg)3] and substrate moieties (1a or 5) has
a significant impact on the relative stabilities of TS-o and TS-m
(Figure S2). Most importantly, the difference in interaction
energies between TS-o and TS-m increases in both TSL3 and
TSL1-5 relative to TSL1. This is mainly caused by a CH−O
hydrogen bond between the sulfide and Beg moieties at the
ortho position in the TS model, as previously described. These
computational results clarify both the importance of the CH−
O hydrogen bond between the sulfide and Beg moieties for
ortho-selective borylation and the origin of changes in
regioselectivity with bipyridine-type ligands (L1 and L3).
In summary, we have developed a simple catalytic system for
the ortho-selective C−H borylation of thioanisoles using
phenylbipyridine as a ligand. The regioselectivity was in
sharp contrast with the Ir-dtbpy-promoted C−H borylation, in
which the reaction occurred at the meta and para positions. In
comparison, the ortho-selective C−H borylation proceeded in
moderate to good yields with high regioselectivity and good
functional group tolerance. Both the boryl and the methylthio
groups of ortho-borylated thioanisole derivatives were success-
fully converted via palladium-catalyzed transformations. DFT
calculations helped to elucidate the origin of the ligand effect
for regioselectivity and revealed the importance of hydrogen
bonding between the C−H bond of the substrate SCH3 group
and an oxygen atom from the boryl ligand as well as the CH/π
interaction between the C−H bond of the aromatic ring of the
substrate and the pyridyl ring.
Morio Naito − Department of Chemistry and Research Center
for Smart Molecules, Faculty of Science, Rikkyo University,
Tokyo 171-8501, Japan
Takeru Torigoe − Institute for Materials Chemistry and
Engineering and Department of Molecular and Material
Sciences, Interdisciplinary Graduate School of Engineering
Sciences, Kyushu University, Fukuoka 816-8580, Japan;
Complete contact information is available at:
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partially supported by JSPS KAKENHI grant
numbers JP 17H03016, 18H04656, and 18H04660 and the
Yamada Science Foundation.
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ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
1
Experimental procedures, characterization data, and H
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and 13C NMR spectra for new compounds (PDF)
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AUTHOR INFORMATION
Corresponding Authors
■
Masahiro Yamanaka − Department of Chemistry and Research
Center for Smart Molecules, Faculty of Science, Rikkyo
D
Org. Lett. XXXX, XXX, XXX−XXX