Journal of the American Chemical Society
Communication
a
Chart 5. Substrate Scope for Substituted Arenes
Chart 6. Synthetic Transformations
a
Conditions: (i) 1.2 equiv of oxone, (3/1) acetone/water, 0 °C to rt,
2 h. (ii) 1.0 mol % [Ir(cyclooctadiene)OMe]2, (4/1) (tetrahydrofur-
an/D2O), 80 °C, 12 h. (iii) 2.5 mol % Pd(PPh3)4. 2.0 equiv of K2CO3,
1.1 equiv of 5-bromo-m-xylene, (1/1) dimethoxyethane/H2O, 100
°C, 12 h. (iv) 10 mol % Cu(OAc)2, 1.5 equiv of NaN3, MeOH, 55 °C,
under air, 24 h. (v) 1.2 equiv of phenylacetylene, 3.0 mol % sodium
ascorbate, H2 O, MeOH, rt, 24 h. (vi) 1.0 mol
%
Pd2(dibenzylideneacetone)3.CHCl3, 4.0 mol % PPh3, 4.0 equiv of
K2CO3, 1.2 equiv of BnBr, (10/1) tetrahydrofuran/H2O, 100 °C, 24
h. (vii) 4.0 equiv of TFA, 2.0 equiv of Cu(OTf)2, CH3CN, 60 °C, 20
h. (viii) 3.0 equiv of CuCl2, (1/1) MeOH/H2O, 80 °C, 12 h. (ix) 3.0
equiv of CuBr2, (1/1) MeOH/H2O, 80 °C, 12 h.
hypothesis. Interestingly, we also found that the heterocyclic
substrate (5a-IX) proceeded with the C−H borylation
affording a high meta borylation.
To demonstrate the synthetic utility, we showed that the
borylated compound (2a) can be transformed to many useful
synthons employing known transformations, such as hydrox-
ylation,17 fluorination,49 chlorination,50 bromination,50 deut-
eration,51 arylation,21 benzylation,52 and azidation followed
by cycloaddition53 (Chart 6).
The standard reaction mechanism of the C−H borylation
of arene was reported54 earlier, and the present meta
borylation possibly follows the same mechanism. But, to get
an understanding of the proposed electrostatic model (Chart
7A, TS-2), we first analyzed the electronic effects of ligands.
Earlier it has been demonstrated that, for electrostatically
directed ortho borylation (TS-1),44 an electronic alteration of
the ligand framework affects the ortho selectivity.
Analyzing the electronic effects of the various 1,10-
phenanthroline ligands,47 we observed that the meta
borylation follows the same trend (Chart 7B) that is
consistent with the previous electrostatic model. For a
further understanding, several control experiments were
performed. As per our hypothesis, the lone-pair electrons of
the nitrogen atom will be delocalized through the
trifluoromethanesulfonyl group rather than the arene ring
(Chart 7A) due to its strong electron-withdrawing nature,
and thus the substrate (1) will develop a partial negative
charge at the oxygen atom (1A) instead of the arene ring
(1B), which would interact with the partial positive charge of
the ligand. We envision that, if this hypothesis is correct, then
a functional group alteration of the nitrogen atom should
affect the meta selectivity. Following this hypothesis, we
performed a borylation with substrates bearing several
functional groups (Chart 7C) and found that substrates
without suitable functional groups (9, 10, & 11) resulted in
either no reaction or a nonselective borylation. Next,
borylation was performed with the substrates (12a, R =
triflate (Tf)) having a free NH unit, and it was found that the
conversion was poor indicating that protection is necessary to
augment the electron delocalization into the −SO2CF3 group
by restricting the chelation with the catalyst. Moreover, when
the R group is altered from Tf to either acetyl (Ac) (12b) or
trifluoroacetic acid (TFA) (12c), almost the same trend is
observed. Moreover, protection of both the H atoms of
aniline (13) with the −SO2CF3 group afforded a regioiso-
meric mixture of the meta and para borylation products in
statistical ratios with a moderate conversion. Thus, this
finding indicates the necessity of an alkyl group as the lone
pairs of N atom are delocalized over two −SO2CF3 groups
and diminish the negative charge density on the carbonyl O
atom. Collectively, all these control experiments are
suggestive of an electrostatic model for the meta borylation.55
In conclusion, we have developed a method for the meta
borylation of arenes via an electrostatic model. The method
shows a broad substrate scope, especially for those substrates
bearing a substituent adjacent to the borylation site, which
was an utmost challenge. While the most iridium-catalyzed
remote C−H borylations require minimum 1.0 equiv of
diborane (B2pin2), our method requires only half of the
B2pin2 (0.5 equiv), demonstrating the practicality of the
7608
J. Am. Chem. Soc. 2021, 143, 7604−7611