Catalytic Electrophilic C?H Borylation Using NHC?Boranes and Iodine Forms C2-, not C3-, Borylated Indoles

Article abstract of DOI:10.1002/chem.201702060

Activation of N-heterocyclic carbene boranes (NHC?BH₃) by I₂ enables the metal-free catalytic C?H borylation of heteroarenes with formation of H₂ as the by-product in a process that uses only bench stable precursors. The borylation of indoles using NHC?BH₃/I₂ produces C2-borylated indoles exclusively in contrast to other catalytic electrophilic C?H borylation methods. Mechanistic studies indicate that this is due to C3 to C2 boron migration facilitated by the absence of exogenous Br?nsted bases. Thus this C?H borylation methodology proceeds under sufficiently Br?nsted acidic conditions to enable the thermodynamic C2-borylated indole isomer to be formed instead of the C3 borylated-isomer. This demonstrates that electrophilic C?H borylation can be used to access a wider range of borylated regioisomers than reported to date.

Full text of DOI:10.1002/chem.201702060

A Journal of
Accepted Article
Title: Catalytic Electrophilic C-H Borylation using NHC·Boranes and
Iodine Forms C2-, not C3-, Borylated Indoles.
Authors: Michael Ingleson, John McGough, and Jessica Cid
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201702060
Link to VoR: http://dx.doi.org/10.1002/chem.201702060
Supported by

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COMMUNICATION
Catalytic Electrophilic C-H Borylation using NHC·Boranes and
Iodine Forms C2-, not C3-, Borylated Indoles.**
[a]
[a]
[a]
John S. McGough , Jessica Cid and Michael J. Ingleson*
Abstract: Activation of N-heterocyclic carbene boranes (NHC·BH
by I enables the metal free catalytic C-H borylation of heteroarenes
with formation of H as the by-product in a process that uses only
bench stable precursors. The borylation of indoles using NHC⋅BH /I
3
)
2
2
3
2
produces C2-borylated indoles exclusively in contrast to other
catalytic electrophilic C-H borylation methods. Mechanistic studies
indicate that this is due to C3 to C2 boron migration facilitated by the
absence of exogenous Brønsted bases. Thus this C-H borylation
methodology proceeds under sufficiently Brønsted acidic conditions
to enable the thermodynamic C2-borylated indole isomer to be
formed instead of the C3 borylated-isomer. This demonstrates that
electrophilic C-H borylation can be used to access a wider range of
borylated regioisomers than reported to date.
Due to the considerable utility of organo-boronic acid derivatives
in modern synthesis the development of new methods to
1
Figure 1: Top, previous main group catalysed electrophilic borylation, middle
stoichiometric C2 borylation in the absence of base, bottom this work C2
borylation using NHC-boranes and sub-stoichiometric I as catalyst.
2
construct C-B bonds, in particular directly from C-H precursors,
1
b, 2
is a field of significant topical interest.
Transition metal
3
catalysis has achieved considerable advances in this area,
most notably using iridium catalysis which now represents a
mechanism involving initial palladation at the indole C3 position
is still proposed to proceed, but deprotonation of the arenium
cation is relatively slow or reversible. This enables migration of
1b, 2
powerful synthetic tool.
One alternative to iridium catalysed
C-H borylation is transition metal free electrophilic C-H
4
borylation, with early methods using stoichiometric main group
7
Pd from C3 to C2 prior to irreversible deprotonation. In contrast,
Lewis acid activators to generate the requisite strong boron
in the catalytic electrophilic C-H borylation of indoles moderate
Brønsted bases are present (or are evolved during borylation by
amine dissociation from borenium cations, or by indole reduction
producing indolines). This generally results in (i) rapid
deprotonation of C3-borylated arenium cations, and/or (ii) rapid
electrophile, thus producing stoichiometric by-products (e.g.
5
[
amineH][Anion]). Recent advances have utilised main group
catalysts (Figure 1, top) to enable the intermolecular electrophilic
6
2
C-H borylation of (hetero)arenes with H the only by-product.
Whilst notable, to date all these electrophilic C-H borylation
procedures functionalise heteroarenes under electronic control
4-6
quenching of any other strong Brønsted acids. Therefore, only
functionalization at the indole C3 position has been observed in
all the catalytic electrophilic borylation processes reported to
date. One route to developing a C2 selective electrophilic C-H
borylation of indoles requires slow (relative to C3 to C2 boron
migration) or reversible deprotonation of the C3-borylated
arenium cation, a process facilitated by the absence of an
exogenous base and / or the presence of a strong Brønsted
4
- 6
and exclusively produce C3 borylated indoles.
The inability of
catalytic electrophilic C-H borylation to access other borylated
heteroarene regioisomers, e.g. C2-borylated indoles, is a current
limitation of this approach.
In contrast to the electrophilic C-H borylation of indoles,
the electrophilic C-H palladation of indoles gives either C2 or C3
functionalised indoles depending on whether the reaction
operates in the presence of a base (for C3-regioisomers) or the
8
acid. Precedence for this hypothesis is provided by the reaction
6 5 3
of B(C F ) with N-Me-indole which over 10 days affords the C2-
presence of
a
moderate/strong Brønsted acid (for C2-
9
borylated arenium species (Figure 1 middle), indicating that
migration of boron from C3 to C2 can occur in indoles in the
absence of an effective exogenous Brønsted base.
7
regioisomers). In the presence of a suitable Brønsted acid a
Building on the seminal studies by Vedejs, Curran and
[
*]
J. S. McGough, Dr J. Cid and Dr. M. J. Ingleson*
School of Chemistry, University of Manchester,
Oxford Road, Manchester, UK, M13 9PL
1
0
Lacôte, we recently reported that NHC-boranes (NHC = N-
heterocyclic carbene) activated with sub-stoichiometric iodine
effect alkyne C-H borylation in the absence of exogenous
E-mail: michael.ingleson@manchester.ac.uk
1
1
base. The turnover enabling step was proposed to involve the
expected by-product from C-H borylation, HI, reacting with
[**]
We acknowledge the ERC under framework 7 (Grant number
305868), and the Royal Society (M.J.I.) for financial support. We
also acknowledge the EPSRC (grant number EP/K039547/1) for
financial support. Additional research data supporting this
publication are available as supplementary information
accompanying this publication.
another equivalent of NHC⋅BR
2
(H) to regenerate the active
. Therefore this C-H
boron electrophile, NHC⋅BR (I), and H
2
2
borylation system operates under strongly Brønsted acidic
conditions, thus potentially enabling formation of C2 borylated
indoles. In addition, the C-H borylation of heteroarenes with
Supporting information for this article is given via a link at the end of
the document.
3 2
NHC⋅BH /I represents an attractive and relatively simple route
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COMMUNICATION
1
2
to access (heteraryl)BH
2
(NHC) compounds, as iodine is an
double indole S
E
Ar product 4. Upon optimisation, 1.25 eq. of
inexpensive activator, and NHC-boranes are readily synthesized
indole : 1 proved to be the best ratio for maximising conversion
to 3a while minimising formation of 4. Using 1.25 eq. of a
substituted indole and 5 mol% of I revealed that a range of
2
1
3
(
and commercially available) with both being bench stable.
Furthermore, the products from C-H borylation using I /NHC⋅BH
are NHC⋅BH (Aryl), which are bench stable boranes useful in
Suzuki-Miyaura coupling reactions, and as masked boronic
2
3
2
indoles underwent borylation at C2 (Figure 3) indicating this is a
general method for achieving C2-borylation under electrophilic
conditions. Under these conditions, no indoline was observed
during C-H borylation. Notably the borylated indoles 3a-d are
stable to column chromatography and even to boiling water
(used to remove unreacted 1) highlighting their suitability as
stabilised masked boronic acids. This protocol was also viable
for the borylation of 2-methylthiophene. However, the yields of
all the borylated products were moderate at best, with the major
1
4
14
acids. Herein we report the development of, and mechanistic
studies into, a catalytic in I C-H borylation methodology to form
NHC⋅BH (indole) exclusively as the C2-borylated isomers in
contrast to other catalytic electrophilic C-H borylation reactions.
,2-dimethyl imidazolylidene borohydride (IMe ⋅BH , 1) was
synthesized on multigram scale from NaBH and the
imidazolium iodide using the route of Curran and co-workers.
Consistent with previous reports, the addition of 0.5 equivalents
of I to 1 in ortho-dichlorobenzene (o-DCB) results in evolution of
and formation of IMe ⋅BH I, 2, as indicated by a triplet in the
B NMR spectrum at -31.7 ppm ( JBH = 112 Hz). To determine
if 2 is an effective electrophile for S Ar compound 1 was
combined with 5 mol% I and N-Me-indole (2 equiv.) was added.
2
2
1
2
3
4
12
mass
balance
being
1,
with
minor
amounts
of
2
(heteroaryl)
2
B(H)(IMe
2
) species analogous to 4 also observed.
H
2
1
2
2
1
1
15
E
2
o
No borylation was observed at ambient temperature or at 60 C
but heating at 130 C led to the production of one major new
o
1
1
1
product at -30.8 ppm in the B NMR spectrum (triplet, JBH = 84
Hz); a number of minor resonances also were observed
including a doublet at -23.9 ppm. The identity of the major
product was shown to be the C2-borylated N-Me-indole by
multinuclear NMR spectroscopy and X-ray crystallography.
Therefore borylation under these base free conditions yields the
1
Figure 3. C-H borylation using 1 / 5 mol% I
NMR spectroscopy relative to mestiylene as an internal standard.
2
. Conversions are in-situ by
H
2 2
C2 isomer, N-Me-2-(BH {IMe })-indole, 3a (Figure 2, inset), and
not the C3 isomer. With its identity in hand the in-situ conversion
to 3a was determined to be 47 % (based on 1).
Attempts to improve the conversion using other NHC·BH
3
activators were performed. The addition of Brønsted acids
-
containing more coordinating (relative to I ) anions, including
3 2
HOTs, HCl and CF COOH, formed the desired NHC⋅BH X
1
5
compound as previously reported. However, these species did
o
not result in any borylation of N-Me-indole at 130 C in o-DCB.
-
Activators that contain/form less nucleophilic anions (than I ),
such as HNTf
2 6 5 3 3 6 5 4
, B(C F ) and Ph C[B(C F ) ] were also explored.
The use of sub-stoichiometric quantities of these three activators
+
with 1 led to the hydride bridged diborane {[IMe
termed [6] (Scheme 1),
2
⋅BH
2 2
] (µ-H)} ,
+
10, 17
as expected (and also confirmed
+
crystallographically). Notably, on heating mixtures of 1 / [6] in
+
the presence of heteroarenes led to the boronium cation, [7]
1
(
δ
11B = -33.1, t JBH = 89 Hz), being formed, with no significant
borylation of N-Me-indole or 2-Me-thiophene (< 10% conversion
in all cases) observed over a range of catalyst loadings. The
identity of [7] was confirmed by independent synthesis, NMR
and mass spectroscopy.
Figure 2. Top, C2-borylation of N-Me-indole, inset top right, solid state
structure of 3a (ellipsoids at 50% probability, hydrogens omitted except on
boron). Bottom, effect of catalyst and reagent ratio of conversion to 3a / 4.
+
2
-methylthiophene
catalytic
activator
or
H
N
N
H
H
H
N
N
N
N
N
N
Attempts using higher loadings of I
conversion, but there was also an increase in the by-product
2
, did lead to a greater
H
N-Me-indole
1
B
B
B
H
H
1
1
[6]+
7]+
[
corresponding to the -23.9 ppm doublet in the B NMR
spectrum. Surmising that this was due to double S Ar by a
single boron centre as observed in the catalytic sila-Friedel
activator = B(C6F5)3,
HNTf2, [Ph3C][B(C6F5)4]
E
+
16
Scheme 1. Activation of 1 leading to the boronium cation [7] on heating.
Crafts reaction of indoles, the amount of N-Me-indole was
increased to 7 equivalents. This led to the formation of a 3:2
mixture of 3a and compound 4 (Figure 2, bottom) which could be
separated by chromatography. Multinuclear NMR and mass
spectroscopy confirmed that this by-product was indeed the
The addition of weak exogenous bases 2,6-dichloropyridine
Cl -py) and NPh , whose conjugate acids are strongly Brønsted
2 3
(
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COMMUNICATION
acidic, also was explored to facilitate borylation. However, with 1
/
N-Me-indole (or 2-Me-thiophene) and I
borylation occurred in the presence of these two bases.
Furthemore, with Cl -py boronium salts [IMe ⋅BH (Cl -py)][Anion]
were observed. Combined the above results indicate that iodide
is essential in NHC·BH X presumably as it provides an optimal
nucleophilicity (more than NHC⋅BH thus preventing formation of
6] and thus [7] , but low enough to be displaced by a
2 6 5 3
or B(C F ) no C-H
2
2
2
2
2
3
Scheme 2. The syntheis of 11C3 via stoichiometric electrophilic borylation.
+
+
[
heteroarene), low Brønsted basicity (thus deprotonation is
relatively slow or reversible under these conditions) and the
generated acid (HI or a protonated indole) is able to react with
further equivalents of 1 to regenerate 2 enabling turnover.
As the regioisomer (C2 or C3) produced by C-H borylation
can be sensitive to steric effects it was important to confirm
which borylated regioisomer is formed with the bulkier NHC-
boranes. Multinuclear NMR spectroscopy was consistent with
indole C2 borylation and for the product derived from 9, 11C2, an
X-ray diffraction study also confirmed C2-borylation (inset Figure
4). Furthermore, the C3-borylated isomer, 11C3, was synthesized
for comparison using an ambient temperature stoichiometric (in
activator) electrophilic C-H borylation route commencing from
As modifying the activator
/ reaction conditions (i.e.
temperature or duration) failed to improve C-H borylation yields
variation in the NHC was explored next. It was hypothesized that
increasing the NHC steric bulk would help prevent deactivation
reactions and the formation of double borylation products (such
as 4). Therefore IPr
imidazolylidene), IPr Me ⋅BH
dimethyl imidazolylidene) and IMes⋅BH
2
⋅BH
3
(8, IPr
(9, IPr Me
2
=
N,N’-diisopropyl
= N,N’-diisopropyl-3,4-
(10, IMes = N,N’-
20
t
2
2
3
2
2
[IPr Me ⋅BCl ][AlCl ]
2
2
2
4
and using tri- Bu-pyridine (TBP) as
3
exogenous base (Scheme 2). The dichloroborane initial product
was converted to the dihydroborane 11C3 by treatment with
excess LiAlH . While the δ for 11C3 and 11C2 are comparable,
bis(2,4,6-trimethylphenyl) imidazolylidene) were synthesised
using established routes, and utilised in the borylation of N-Me-
indole using the conditions optimised with 1 (Figure 4).
4
11B
1
the
H NMR spectra are diagnostic as the indole C2-H
resonance for 11C3 is observed at 6.39 ppm, whereas 11C2 has a
C3-H resonance at 5.56 ppm (a comparable δ1H to that observed
in 3a). It is particularly noteworthy that borylation using
o
[
IPr
2
2
Me ⋅BCl
2
][AlCl
4
] in the presence of a base at 20 C leads to
C3 borylation exclusively whilst that using NHC⋅BH
3 2
/I at higher
temperatures and in the absence of base leads to the C2 isomer.
Figure 4. Borylation of N-Me-indole with NHC-boranes containing NHCs of
varying steric demand. Inset solid state structure of 11C2 (hydrogens omited for
clarity and themal ellipsoids at 50 % probabaility).
C-H borylation is effective with 8 and 9 with an increase in
yield using these two NHC-boranes. The in-situ NMR spectra for
o
Figure 5. Reaction conditions: 9, 10 mol% I
2
, 1.25 equivalents arene, 170 C,
borylation using
analogous to 4 and significantly fewer minor products in the
9
revealed no doubly borylated product
24 hours. In-situ yields versus Me Si as an internal standard. Isolated yields
are given in parentheses. ^ 0.5 equivalents of heteroarene.
4
11
B
NMR spectrum, and again there was no evidence for indoline
1
formation (by H NMR spectroscopy). The much lower yield
A range of indoles were amenable to catalytic borylation
using 9/I and the products were readily isolated in moderate
2
yields. The use of the benzyl protecting group was viable with 9
with only C2 regioisomers again observed. Notably, stabilising
and destabilising (towards the C2-borylated arenium cation that
using 10 is notable as based on percentage buried volume
1
8
(
%Vbur
)
values derived from transition metal NHC complexes
the four NHCs used herein appear to have comparable steric
demand. To determine the NHC steric impact in NHCBH
complexes the previously reported solid structures of 1, 8, 9 and
3
is formally cationic at the three coordinate C3 position) F and Cl
1
0 were used to calculate modified %Vbur values, termed %Vbur(B-
+
1
2, 19
substituents (σ
p
values -0.07 and +0.11) at the C6 position both
C) values using a B-C distance of 1.59 Å.
The %Vbur(B-C) is
led to C2 borylated products (Figure 5). The forcing conditions
and reactive boron electrophiles present in this methodology do
now significantly greater for IMes relative to those for transition
metal complexes, and also greater for IMes in 10 than that for
the NHCs in 1, 8 and 9 (Figure 4, bottom). Thus the slower C-H
borylation reaction with 10 is attributed to the considerably larger
steric demand of IMes increasing kinetic barriers during the
borylation reaction.
however result in functional group incompatibilities (i.e. with CF
3
,
NO and OMe). In contrast, other activated heteroarenes
2
including pyrroles and thiophenes were compatible, as were C3
substituted indoles.
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Chemistry - A European Journal
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COMMUNICATION
The mechanism leading to (indole)BH
2
(NHC) could proceed
In conclusion, herein we demonstrate that catalytic
via (i) electrophile addition at C3, C3 to C2 migration and then
deprotonation, or (ii) direct insertion of the boron electrophile at
electrophilic C-H borylation using NHCBH
3 2
/I represents a
simple route to form (heteroaryl)BH (NHC) complexes that
2
C2-H (with concomitant H
transfer from NHC⋅BH to (indole)BH(I)(NHC). The latter
mechanism is observed for intramolecular C-H borylations with
2
evolution) followed by hydride
previously have been shown to be useful synthetic intermediates.
Furthermore, this method furnishes C2-borylated indoles instead
3
of the C3 regioisomers normally formed via S
key to accessing C2-regioisomer products is the use of
NHC⋅BH /I which enables C-H borylation to be performed in the
E
Ar borylation. The
+
21
[
(amine)BH
mechanism (ii) based on the absence of a KIE during N-Me-
indole borylation using 1 or IMe ⋅BD (1D3) activated with I . The
2
]
species.
With NHC⋅BH
3
/I
2
we disfavour
3
2
2
3
2
absence of an effective Brønsted base, and instead borylation is
operating in the presence of a competent Brønsted acid. These
conditions therefore are distinct to other catalytic electrophilic C-
H borylation methodologies and indicate that it is possible to
access a wider range of borylated products via boron-Freidel-
Crafts approaches than has been reported to date.
transition state for the C-H insertion mechanism involves
considerable B-H elongation, thus the absence of a KIE using 1
(
1
D3)/I
2
disfavours an analogous mechanism. Furthermore, the
borylation of N-Me-indole and its isotopomer deuterated at C2
with 1 / I resulted in a KIE of 2.2. For S Ar proceeding in the
2
E
presence of a strong Brønsted acid a KIE > 1 has been
observed previously as deprotonation of the arenium cation
becomes rate limiting (instead of formation of the σ complex
Keywords: boranes • C-H activation • borylation • electrophilic
substitution • Lewis acids
22
E
being rate limiting which is more common in S Ar reactions).
The KIE value using 1 is also consistent with those for
electrophilic palladations in the presence of Brønsted acids.
Furthermore, in indole borylation C3 to C2 migration leads to the
thermodynamic product based on the relative electronic
energies of the two isomers (calculated at the M06-2X/6-
[
1]
2]
a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457-2483; b) D. Hall,
Ed. Boronic Acids: Preparation and Applications, Wiley-VCH, 2011. c)
N. Schneider, D. M. Lowe, R. A. Sayle, M. A. Tarselli, G. A. Landrum, J.
Med. Chem., 2016, 59, 4385-4402.
7
[
For reviews of Ir catalysed borylation see: a) I. A. I. Mkhalid, J. H.
Barnard, T. B. Marder, J. M. Murphy, J. F. Hartwig, Chem. Rev., 2010,
110, 890-931; b) J. F. Hartwig, Acc. Chem. Res. 2012, 45, 864–873;
For directed C-H borylation see c) A. Ros, R. Fernandez, J. M.
Lassaletta, Chem. Soc. Rev., 2014, 43, 3229-3243.
3
11G(d,p) level, with PCM DCM) showing that 3a is lower in
-1
energy than the C3-isomer by 3.9 kcal mol .
With the above observations supporting a S
E
Ar mechanism it
is notable that 1,2-dimethylindole and 2-phenyl-N-methyl-indole
result in no C3 borylated product using 1 or 9 / I . C3-borylated
indoles are more prone to protodeboronation than the C2
[
3]
For examples of C-H borylation using other transition metal catalysts
see: a) J. V. Obligacion, M. J. Bezdek, P. J. Chirik, J. Am. Chem. Soc.,
2017, 139, 2825-2832 (and references therein). b) T. Stahl, K. Mgther,
Y. Ohki, K. Tatsumi, M. Oestreich, J. Am.Chem. Soc. 2013, 135,
2
23
regioisomers under acidic conditions, thus it is feasible that C3
borylated isomers are formed reversibly under these conditions
but only the C2-isomer is sufficiently robust towards
protodeboronation to accumulate. To test this 11C3 was heated
1
0978–10981.
For a review on electrophilic C-H borylation see: M. J. Ingleson, Synlett
012, 1411–1415.
[
4]
5]
2
+
[
For early studies with Al as a stoichiometric H scavenger see: a) E. L.
o
for 24 h at 130 C which resulted in minimal consumption of 11C3
.
Muetterties, J. Am. Chem. Soc. 1959, 81, 2597. For subsequent studies
However, adding 11C3 to a mixture of 9 / I
2
/ N-Me-Indole and
heating to 130 C for 24 h (conditions that generate HI or
another Brønsted acid as the by-product from S Ar) led to the
+
using amines as stoichiometric H scavengers see: b) A. Prokofjevs, J.
o
W. Kampf, E. Vedejs, Angew. Chem. Int. Ed. 2011, 50, 2098–2101; c)
A. Del Grosso, P. J. Singleton, C. A. Muryn, M. J. Ingleson, Angew.
Chem. Int. Ed. 2011, 50, 2102–2106; d) A. Del Grosso, M. D. Helm, S.
A. Solomon, D. Caras-Quintero, M. J. Ingleson, Chem. Commun. 2011,
E
complete consumption of 11C3 (and formation of 11C2). This
confirms the presence of a strong Brønsted acid during catalytic
indole C-H borylation and that protodeboronation (or protonation
and migration of boron to C2) of 11C3 does occur. A mechanism
consistent with these observations is provided in Scheme 3.
47, 12459–12461.
[6]
a) A. Del Grosso, R. G. Pritchard, C. A. Muryn, M. J. Ingleson,
Organometallics 2010, 29, 241–249; b) M.-A. Légaré, M.-A.
Courtemanche, P. Rochette, F.-G. Fontaine, Science 2015, 349, 513–
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[
7]
8]
2
14681; c) Y. Li, W.-H. Wang, K.-H. He, Z.-J. Zhi, Organometallics, 2012,
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[
In the high temperature electrophilic C-H borylation of polyaromatics
using hindered pyridines isomerisation to the thermodynamic borylation
products was reported: V. Bagutski, A. Del Grosso, J. Ayuso Carrillo, I.
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Scheme 3. Proposed cycle for C2 indole borylation. The Brønsted acid is
shown as HI, it is also feasible to be a protonated indole. Furthermore,
24
deprotonation could be of other indole arenium tautomers after H migration.
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Chemistry - A European Journal
10.1002/chem.201702060
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3
[10] For early studies the activation of NHCBH for reaction with alkene
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2
[
2
(NHC) are more complex e.g., require
2
D.-E. Murr, D. P. Curran, L. Fensterbank, E. Lacôte, M. Malacria, J. Org.
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3
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[
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24] The borylation of 2-D-N-Me-indole led to an approximately 70:30 ratio
of H/D at the C3 position in 3a, indicating degree of hydride
deuteride) migration prior to the irreversible deprotonation step.
[
a
(
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Entry for the Table of Contents
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John S. McGough, Jessica Cid and
Previously: Conventional C-H Borylation
This work: C-H borylation under acidic condition
Michael J. Ingleson*
H
H
by S
E
Ar
B(OR)2
main group
catalyst
NHC:BH3
/ cat. I2
∆
H
BH
2
(NHC)
Catalytic Electrophilic C-H Borylation
using NHC·Boranes and Iodine Forms
C2-, not C3-, Borylated Indoles.**
H
(
RO) BH
N
R2
N
R2
N
2
R1
R
1
R
1
R2
C3-Borylated Indoles
C2-Borylated Indoles
Borylated indoles: I’ll C2 it. Activation of N-Heterocyclic carbene boranes by I
enables the metal free catalytic C-H borylation of heteroarenes with formation of H
as the by-product in a process that requires only bench stable precursors. The C-H
borylation of indoles using NHC⋅BH /I produces C2-borylated indoles exclusively in
contrast to other catalytic electrophilic C-H borylation methods.
2
2
3
2
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