Formal Ir-Catalyzed Ligand-Enabled Ortho and Meta Borylation of Aromatic Aldehydes via in Situ-Generated Imines

Article abstract of DOI:10.1021/jacs.5b11683

The ligand-enabled development of ortho and meta C-H borylation of aromatic aldehydes is reported. It was envisaged that while ortho borylation could be achieved using tert-butylamine as the traceless protecting/directing group, meta borylation proceeds via an electrostatic interaction and a secondary interaction between the ligand of the catalyst and the substrate. These ligand-substrate electrostatic interactions and secondary B-N interactions provide an unprecedented controlling factor for meta-selective C-H activation/borylation.

Full text of DOI:10.1021/jacs.5b11683

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Communication
Formal Ir-Catalyzed Ligand-Enabled ortho- and meta-
Borylation of Aromatic Aldehydes via in situ Generated Imines
Ranjana Bisht, and Buddhadeb Chattopadhyay
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b11683 • Publication Date (Web): 21 Dec 2015
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Formal Ir-Catalyzed Ligand-Enabled ortho- and meta-Borylation of
Aromatic Aldehydes via in situ Generated Imines
Ranjana Bisht† and Buddhadeb Chattopadhyay†,*
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†Center of Bio-Medical Research, Division of Molecular Synthesis & Drug Discovery, SGPGIMS Campus, Raebareli Road,
Lucknow 226014, Uttar Pradesh, India
Supporting Information Placeholder
preparation, a paper describing a novel concept of a meta sel-
ABSTRACT: Ligand-enabled development of ortho and meta
C–H borylation of aromatic aldehydes is reported. It was envi-
saged that while ortho-borylation could be achieved using tert-
butylamine as the traceless protecting/directing group, meta-
ective C–H borylation by a secondary interaction between
ligand and substrate has appeared.10 Unarguably, this method
is one of the most efficient approaches towards meta borylati-
on. However, there are many unsolved problems for the meta
borylation proceeds via an electrostatic interaction and a sec-
borylation. Thus, a critical challenge in developing these cata-
ondary interaction between the ligand of the catalyst and the
lytic processes is the selective ortho and meta borylation of
substrate. These ligand/substrate electrostatic interaction and
benzaldehydes. Traditionally, ortho and meta borylated benza-
secondary B–N interaction provide an unprecedented control-
ldehydes were prepared via a combined halogenation of ben-
ling factor for meta selective C–H activation/borylation.
zaldehydes followed by a Miyaura cross-coupling reaction
with bis(pinacolato)diborane (eq. 1 & eq. 2).11,12 Herein, we
Over the past decade, C–H bond functionalizations have at-
tracted extensive attention as competent and ideal reactions.1
report the discovery of a one-pot unified strategy for the ortho
and meta selective C–H borylation of benzaldehydes using
ligand enabled iridium-catalyzed C–H activation (eq. 3).
In this perspective, the C–H bond borylation has shown poten-
tial because of the synthetic versatility for which B–C bonds
are well-known. A major challenge in C–H borylations is how
to control the selectivity. Generally, steric effects often govern
the regioselectivity of aromatics,2 which makes the C–H bo-
rylations complementary to widely used directed ortho metala-
tions (DoMs).3 However, the inherent functional group restric-
tion and practical limitations of DoMs, (for example, groups
like esters are incompatible with DoM and require low tempe-
rature) have strengthened efforts to develop efficient method
for ortho C–H borylations. In this context, few methods for the
functional group4 directed ortho borylations5 have been deve-
loped.
Table 1. Evaluation and Optimization of Reaction Conditionsa
CHO
CHO
i) 4.0 equiv. R–NH2, DCM, rt, 4 h,
then evaporated solvent
Bpin
ii) 1.5 mol% [Ir(cod)(OMe)]2, 3.0 mol% L,
5.0 mol% HBpin, B-source, THF, 90 oC, 12 h
1a
2a
#
R
Ligand (L)
B-source
Ratio (o/m/p)[b] Yield (%)
B2pin2 (0.7 eq.)
B2pin2 (0.7 eq.)
HBpin (1.5 eq.)
B2pin2 (0.7 eq.)
HBpin (1.5 eq.)
B2pin2 (0.7 eq.)
B2pin2 (0.7 eq.)
B2pin2 (0.7 eq.)
B2pin2 (0.7 eq.)
B2pin2 (0.7 eq.)
L1
1
Me
iPr
0
–
L1
2
0
–
L1
3
tBu
tBu
tBu
tBu
Me
tBu
tBu
tBu
53
33/37/30
86/8/6
–
L1
4
57[c]
0
CHO
CHO
CHO
8-AQ
8-AQ
8-AQ
L2
5
halogenation
Pd-cat.,
B2pin2
(1)
R
R
hal
R
Bpin
6
87[d]
7
100/0/0
100/0/0
100/0/0
95/3/2
97/2/1
ortho-, meta-
ortho-, meta-
CHO
7
Me
i) NBS, CCl4,
(Bz2O)2, hν
Me
8
66[e]
72[f]
62[g]
B(OH)2
B(OH)2
hal
H
Pd-cat.
B2pin2
L3
9
R
R
R
R
ii) aq. KOH
(2)
L4
10
CHO
H
CHO
CHO
NH2
Amine
Ir-Cat., TMP
Amine
Ir-Cat., 8-AQ
Ph
N
N Ph
N
L3
Bpin
H
NH2
N
L1
N NBn2
N
L4
N
8-AQ
(3)
L2
R
R
NH
2
B2pin2
B2pin2
H
This work
Bpin
meta-C–H borylation
aReactions were run with 1.0 mmol substrate, yields are for iso-
ortho-C–H borylation
b
lated ortho-isomer after column chromatography. Ratios are cal-
culated by GC-FID analysis from crude reaction mixture; in
GC/MS no imine borylated products were found, only aldehyde
On the other hand, meta selective C–H bond borylation of
arenes remains a great challenge. Development of strategy for
meta selective C–H bond borylation is very difficult. Litera-
ture reports revealed that only one type of meta C–H borylati-
on is available by Smith-Maleczka6 and Hartwig7 from 1,3-
disubstituted arenes. The regiochemistry of this meta borylati-
on results mainly from sterics.8 Despite the broad utility of this
sterically-controlled meta borylation, the chemistry is limited
mostly to 1,3-disubstituted arenes. Moreover, the arenes bea-
ring reactive functional groups such as aldehydes, ketones etc.
are not well tolerated.9 Notably, when this manuscript was in
borylated products were observed. cMono/o,o-di
= 90/10.
dMono/o,o-di = 89/11. eMono/o,o-di = 80/20. fMono/o,o-di =
87/13. gMono/o,o-di = 85/15.
Recently, Fernández-Lassaletta13 Sawamura,14 and Ishiyama15
disclosed an elegant nitrogen-directed ortho borylation of 2-
phenylpyridines and hydrazones. Inspired by these results, we
hypothesized that imines may serve as an easily removable
directing groups16 for ortho borylation of benzaldehydes. To
test this hypothesis, benzaldehyde-derived imines were treated
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with B2pin2 under the standard borylation conditions using went C–H borylations to afford the ortho-directed products in
hydrazone-derived ligand (L1) developed13a by Fernández and
Lassaletta (entry 1, Table 1). While no borylation was obser-
ved for methyl and isopropyl imines, the tert-butyl imine gave
good ortho selectivity (86%, entry 4).17 Notably, when the
crude reaction mixtures were monitored by GC/MS, the pro-
ducts appeared as aldehyde borylated products.18 Gratifyingly,
the combination of tert-butylamine, 8-AQ and B2pin2 was
found to be the best borylation conditions having 100% ortho
selectivity with excellent isolated yield (87%, entry 6). No-
tably, methylamine provided only 7% yield using 8-AQ as
ligand system (entry 7), presumably methylimine is incapable
to open a vacant coordination site in order to undergo the or-
tho borylation due to the less sterics compared to the tert-
butylimine.19 Other ligand systems such as L2, L3 and L4
were less effective than 8-AQ ligand system and the results are
summarized in Table 1 (entries 8-10).
good to excellent yields without any diborylations (entries 2b–
2d & 2f-2i), except entry 2d, which resulted 7% meta isomer.
However, 4-cyanobenzaldehyde failed to undergo C–H
borylation (entry 2e). Employment of other ligand systems
such as L1, L2, L3 and L4 were also unsuccessful (see SI for
details). Remarkably, for 4-phenylbenzaldehyde borylation,
the Ph C–H bonds are unperturbed under borylation conditions
producing exclusively ortho directed product (entry 2i). Nota-
bly, meta-substituted benzaldehydes (entries 2j-2m) reacted
regioselectively at the sterically less impeded C–H site. In the
case of 3-fluorobenzaldehyde, though the expected borylation
position is the most acidic proton flanked in between CHO and
F, didn’t undergo borylation exclusively (25% borylation)
under these reaction conditions (entry 2k), instead it under-
went ortho borylation, which is less acidic compared to the
another ortho proton. Next, we studied the scope of 2-
substituted substrates. It was found that both electron-rich and
electron-poor substituents are very efficient in these C–H
borylations giving exclusively ortho products (entries 2n, 2p &
2q). However, 2-bromobenzaldehyde borylation was not good
(21% conversion, entry 2o). Furthermore, we have shown that
these borylations could be successfully employed to a range of
highly electron-rich and differently substituted benzaldehydes
(entries 2r-2u).
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Table 2. Ortho-Borylation of Substituted Benzaldehydesa
i) 4.0 equiv. tBuNH2, DCM, rt, 4 h
evaporated under reduced pressure
CHO
CHO
Bpin
Bpin
R
R
ii) 1.5 mol% [Ir(cod)(OMe)]2, 3.0 mol%
8-AQ, 0.7 equiv. B2pin2, 5.0 mol%
HBpin, THF, 90 oC, 12 h
1
2
CHO
CHO
CHO
CHO
Bpin
Bpin
Bpin
Next, we focused on the ligand screening for the meta selecti-
ve C–H activation/borylation. We chose benzaldehyde as our
model system and borylation was performed with bipyridines
L5-L7. As shown in Table 3, there is a clear indication for
increasing meta selectivity as the bipyridine ligand is made
more electron rich (entries 1-3). Encouraged by these initial
results, we next attempted borylation using TMP ligand (L8).
To our delight, improved meta selectivity (66% meta-
borylated aldehyde product) was observed with excellent con-
version (entry 4). To find out the origin of the increased selec-
tivity, we hypothesized that two important factors might be
playing significant role, such as i) an electrostatic interaction,20
which is arising due to the encapsulation21 between the iridium
trisboryl complex attached with electron rich ligand and imine
substrate, and ii) the secondary interaction of the substrate via
either H-bonding22 between the imine hydrogen atom and bo-
ryl oxygen atom of the catalyst (Chart 1, TS-1), or the interac-
tion between the imine N atom and boryl B atom of the cata-
lyst (TS-2).
F
Cl
2b, 78%
CN
CF3
2c, 86%
2d, 79%[b]
2e, 0%[c]
CHO
CHO
CHO
CHO
Bpin
Bpin
Bpin
Bpin
CO2Me
2f, 74%
Et
2g, 80%
Ph
2i, 70%
OMe
2h, 60%
CHO
CHO
CHO
CHO
Bpin
Bpin
Bpin
Bpin
Br
2j, 87%
F
Me
MeO
2k, 72%[d]
2l, 81%
2m, 88%
CHO
CHO
CHO
CHO
Bpin
Bpin
Me
MeO
Bpin
Bpin
Bpin
Br
2n, 80%[e]
CHO
2o, 21%[f]
2q, 79%
2p, 52%
CHO
CHO
CHO
Bpin
Bpin
Bpin
Bpin
MeO
MeO
2s, 64%
MeO
Table 3. Ligand Screening for meta-Borylationa
MeO
Me
OMe
CHO
CHO
i) 4.0 equiv. tBuNH2, DCM, rt, 4 h
evaporated under reduced pressure
OMe
2r, 84%[e]
Me
2u, 56%
2t, 61%[e]
Bpin
ii) 1.5 mol% [Ir(cod)(OMe)]2 3.0 mol%
L, 0.7 equiv. B2pin2, 5.0 mol%
HBpin, THF, 90 oC, 12 h
aReactions were run with 1.0 mmol substrate, yields are for iso-
lated aldehyde borylated products after column chromatography.
1a
3a
bOrtho/meta = 93/07. No reaction occurred even with ligand L1.
c
L
(meta/para/ortho)b mono/di
Conversion (%)c
#
do-o di = 75/25. eReactions were conducted using L1 ligand. f21%
63
83
1
2
3
4
L5
L6
L7
L8
11/61/28
33/46/21
47/37/16
66/23/11
89/11
82/18
88/12
97/03
Me
conversion, failed to isolate due to rapid protodeborylation.
88
With these promising results in hand, borylations for a range
of aldehydes were executed and the results are shown in Table
2. The reactions were conducted under identical conditions,
and the reaction times were not optimized. It was found that
diverse substituents such as halogens (Cl, F, Br), alkyl groups
(Me, Et, CF3), phenyl, methoxy were tolerated well under the-
se borylation conditions. Irrespective of the substituent present
in the aryl ring, 4-substituted benzaldehydes smoothly under-
93 (67)d
Me
R
R
L5, R = CF3
L6, R = H
L7, R = tBu
TMP
Me
(L8)
Me
N
N
N
N
b
c
aReactions were run with 1.0 mmol substrate. GC ratios. GC
conversion was measured using dodecane as internal standard. dIn
parentheses isolated yield for aldehyde meta-borylated product.
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As the electrostatic interaction is present in both cases (TS-1 ry 3d-3g). It deserves mentioning that even use of very bulky
1
2
3
4
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8
& TS-2) which is enhancing the meta selectivity, question
remains which TS (TS-1 or TS-2) is actually controlling the
meta selectivity? In case of H-bond directed approach (TS-1),
the imine substituent (R) is far away from the reaction centre
and thus, the outcome of the meta borylation should not be
dependent on the size of the R group. On the other hand, in
case of TS-2, the outcome should be affected by the size of the
R group, because of the close proximity of the R group and the
boryl group of the catalyst. Thus, we hypothesized that steric
substituents at the 4-position of the benzaldehyde such as
OBoc23 and OBn group (entries 3h & 3i) afforded complete
meta selectivity. Thus, these observations are consistent with
the notion that an electrostatic interaction and secondary inter-
action between the imine N atom and the boryl B atom of the
catalyst.
Table 5. Meta-Borylation of Substituted Benzaldehydesa
CHO
CHO
i) 4.0-10.0 equiv. R–NH2, DCM, rt, 4 h
evaporated under reduced pressure
9
t
alteration of the imine substituent (R) from Bu→iPr→Me,
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R
R
ii) 1.5 mol% [Ir(cod)(OMe)]2 3.0 mol%
L8 (TMP), 0.7 equiv. B2pin2, 5.0 mol%
HBpin, THF, 90 oC, 12 h
meta selectivity should be enhanced further.
Bpin
1
3
Chart 1. Hypothesis for the Origin of meta-Selectivity
CHO
CHO
CHO
Me
Me
Me
Me
Me
Bpin
Ir
Bpin
Ir
N
Bpin
N
Bpin
B
Bpin
Bpin
Bpin
O
OMe
CN
O
O
Cl
3b
B
3d
O
3c
m/o: 81/19 (tBu), 76%
N
m/o: 81/19 (tBu), 74%
m/o: 100/0 (Me), 70%
N
m/o: 100/0 (tBu), 96%
H
H
H
m/o: 100/0 (Me), 66%
N
Me
R
CHO
CHO
CHO
R
N
Me
Me
steric crowding
Ts-2: B–N Bond Directed
TS-1: H Bond Directed
Bpin
Bpin
Bpin
To test this hypothesis, borylations were performed with isop-
ropyl imine and methyl imine of the benzaldehyde. Remarkab-
ly, a clear trend for the enhancement of the meta selectivity
was observed as the imine substituent (R) is made small (Tab-
le 4). We reasoned that the enhanced meta selectivity (100%
for R = Me) results at the expense of reduced steric crowding,
which facilitates the seconday interaction through the imine N
atom and boryl B atom of the catalyst (TS-2). However, the
question of mechanism is open to debate and the detailed me-
chanism of each step remains to be ascertained.
F
Et
OH
3e
3f
3g
m/o: 100/0 (tBu), 80%b
m/o: 100/0 (Me), 82%
m/o: 100/0 (Me), 79%
CHO
CHO
Cl
CHO
Bpin
Bpin
Bpin
OBn
OBoc
3j
3i
3h
m/o: 100/0 (Me), 99%c
m/p+o: 70/30 (tBu), 65%
m/o: 100/0 (Me), 89%
m/p+o: 100/0 (Me), 73%
CHO
Br
CHO
Bpin
CHO
Me
Bpin
Table 4. Effect of Imine Substituent: Proof of Hypothesis for
meta-Borylationa
Bpin
Bpin
3k
3l
3m
m/p+o: 85/15 (tBu), 69%
m/p+o: 100/0 (Me), 63%
m/p+o: 100/0 (Me), 71%
m/p+o: 100/0 (Me), 77%
CHO
CHO
i) 4.0-10.0 equiv. R–NH2, DCM, rt, 4 h
evaporated under reduced pressure
CHO
CHO
CHO
Bpin
ii) 1.5 mol% [Ir(cod)(OMe)]2 3.0 mol%
L8, 0.7 equiv. B2pin2, 5.0 mol%
HBpin, THF, 90 oC, 12 h
Br
Cl
Bpin
MeO
Bpin
Bpin
3a
1a
3p
3n
3o
m/p+o: 100/0 (tBu), 98%
m/p+o: 100/0 (tBu), 89%
m/p+o: 100/0 (tBu), 93%
R
meta/(para+ortho)b mono/di
Conversion (%)c
#
1
2
3
CHO
MeO
CHO
CHO
tBu
iPr
66/34
84/16
97/03
93/07
90/10
97/03
78 (57)
73
Me
Bpin
NC
MeO
Bpin
Bpin
80 (73)d
Me
3s
3q
3r
m/p+o: 100/0 (tBu), 92%
m/p+o: 100/0 (tBu), 91%
m/p+o: 100/0 (tBu), 79%
aReactions were run with 1.0 mmol substrate, see SI for details.
bGC ratios. GC conversion; in GC/MS no imine borylated prod-
c
aReactions were run with 1.0 mmol substrate, for details see SI,
yields are for isolated aldehyde meta-borylated products after
column chromatography. b2.0 mmol substrate was used. c99%
conversion.
ucts were found, only aldehyde borylated products were observed.
dIn parentheses isolated yield of the aldehyde borylated product.
Next, we explored the substrates scope for the meta borylati-
ons and the results are summarized in Table 5. A wide range
of substituents were well tolerated under the borylation condi-
tions affording excellent meta selectivity with excellent isola-
ted yields. For example, while 4-chlorobenzaldehyde gave
81/19 meta/ortho selectivity (entry 3b) using tert-butylamine,
it afforded 100% meta selectivity with methylamine as the
protecting/directing group. 4-Methoxybenzaldehyde gave
81/19 and 100/0 meta/ortho selectivity by the employment of
tert-butylamine and methylamine respectively. (entry 3c).
Likewise, 4-cyano-, 4-fluoro-, 4-ethyl-, 4-hydroxy-
benzaldehydes, resulted meta isomer as the sole products (ent-
On the other hand, 2-substituted substrates proved to be chal-
lenging because of several open reactive sites for C–H activa-
tion/borylation. For example, 2-Bpin-, 2-bromo-, 2-chloro-,
and 2-methyl-benzaldehydes could give mixture of isomers.
To our delight, they resulted complete meta selectivity (entry
3j-3m). For meta-substituted benzaldehydes, as expected bo-
rylations occurred at the meta position and no other borylati-
ons were observed (entries 3n-3r). Moreover, highly electron-
rich 2,3-dimethoxybenzaldehyde proved to be an excellent
meta borylating substrate giving excellent yield (entry 3s).
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2010, 46, 159. (g) Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc. 2012, 134,
134.
(6) Maleczka, R. E., Jr.; Shi, F.; Holmes, D.; Smith, M. R., III J.
Am. Chem. Soc. 2003, 125, 7792.
(7) Murphy, J. M.; Liao, X.; Hartwig, J. F. J. Am. Chem. Soc. 2007,
129, 15434.
(8) (a) Iverson, C. N.; Smith, M. R., III J. Am. Chem. Soc. 1999,
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Chem. Soc. 2000, 122, 12868. (c) Cho, J. Y.; Tse, M. K.; Holmes, D.;
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Chotana, G. A.; Rak, M. A.; Smith, M. R., III J. Am. Chem. Soc.
2005, 127, 10539.
(9) For aromatic ketones borylation, see: Itoh, H.; Kikuchi, T.;
Ishiyama, T.; Miyaura, N. Chem. Lett. 2011, 40, 1007.
(10) For secondary interaction directed meta selective C–H boryla-
tion, see: Kuninobu, Y.; Ida, H.; Nishi, M., Kanai, M. Nat. Chem.
2015, 7, 712.
(11) (a) Tomohiro, K.; Hideto, F.; Katsumi, K.; Shigeru, K. PCT
Int. Appl. WO 2010110400, 2010. (b) Takeshi, K.; Hiroshi, N.;
Tomoko, I.; Mitsukane, Y.; Kensei, Y. Jpn. Kokai Tokkyo Koho, JP
2010173974, 2010.
(12) Matterson, D. S.; Talbot, M. L. J. Am. Chem. Soc. 1967, 89,
1123.
(13) For Ir-catalyzed nitrogen directed ortho borylation, see: (a)
Ros, A.; Estepa, B.; Lopáez-Rodríguez, R.; Alvarez, E.; Fernández,
R.; Lassaletta, J. M. Angew. Chem., Int. Ed. 2011, 50, 11724. (b)
Lopáez-Rodríguez, R.; Ros, A.; Fernández, R.; Lassaletta, J. M. J.
Org. Chem. 2012, 77, 9915. (c) Ros, A.; Lopáez-Rodríguez, R.;
Estepa, B.; Àlvarez, E.; Fernández, R.; Lassaletta, J. M. J. Am. Chem.
Soc. 2012, 134, 4573.
(14) For Rh-catalyzed nitrogen directed ortho borylation, see: Ka-
wamorita, S.; Miyazaki, T.; Ohmiya, H.; Iwai, T.; Sawamura, M. J.
Am. Chem. Soc. 2011, 133, 19310.
In summary, we have developed two complementary methods
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for the ortho and meta selective C–H bond activati-
on/borylation of aromatic aldehydes that cannot be obtained
with DoM, or any other methodology. While the ortho boryla-
tion proceeds through directed C–H activation/borylation u-
sing tert-butylamine as the traceless protecting/directing
group, the meta borylation undergoes through an electrostatic
interaction and a secondary interaction between the ligand of
the catalyst and the substrate. Both methods have shown very
broad substrate scope and functional group tolerance. How-
ever, at this stage, we are not entirely certain about the work-
ing hypothesis for meta selective C–H activation/borylation
and further studies are underway, which will be reported in
due course.
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ASSOCIATED CONTENT
Supporting Information Available: Full characterization, copies
of all spectral data, experimental procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
buddhadeb.c@cbmr.res.in, buddhachem12@gmail.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(15) For aromatic imine-directed ortho-borylation, see: Sasaki, I.;
Amou, T.; Ito, H.; Ishiyama, T. Org. Biomol. Chem. 2014, 12, 2041.
(16) For imine-directed ortho silylation, see: (a) Choi, G.; Tsurugi,
H.; Mashima, K. J. Am. Chem. Soc. 2013, 135, 13149. (b) Williams,
N. A.; Uchimaru, Y.; Tanaka, M. Dalton Trans., 2003, 236.
(17) The o-BpinC6H4CHO can easily be distinguished by the ~ 0.6
Thanks to Professor Milton R. Smith III (Michigan State Univer-
sity, USA) for helpful suggestions. BC thanks DST, New Delhi
for Ramanujan Faculty Award and RB for JRF (Sanction No:
SB/S2/RJN-45/2013). We are thankful to Dr. Bikash Baishya and
Mr. Ajay Verma for helpful discussion on NMR analysis and Mr.
Durga Prasad and Mr. Prasant for HRMS. We are also thankful to
the reviewers for helpful suggestions. We thank the Director,
CBMR for research facilities.
1
ppm downfield shift of its CHO resonance in H NMR spectra due to
hydrogen bonding to a Bpin O.
(18) The imine borylated products can be seen in the crude proton
NMR (see SI for details). We assumed that in the GC/MS, the imine
borylated products are hydrolyzed. Likewise, during silica gel column
chromatography, the products are hydrolyzed.
(19) The mechanism of the ortho C–H bond activation/borylation
of aldehydes via in situ generated imines is related to the analogous
ortho borylation of hydrazones as reported by Fernández-Lassaletta.13a
(20) (a) Das, S.; Incarito, C. D.; Crabtree, R. H.; Brudvig, G. W.
Science 2006, 312, 1941. (b) Leung, D. H.; Bergman, R. G.; Ray-
mond, K. N. J. Am. Chem. Soc. 2006, 128, 9781. (c) Breslow, R.;
Zhang, X.; Huang, Y. J. Am. Chem. Soc. 1997, 119, 4535.
(21) For encapsulation of iridium species, which is facilitated via
an electrostatic interaction, see: ref. 20b.
(22) (a) For example of H-bonding of imine, see: Ligtenbarg, A.
G.; Hage, R.; Meetsma, A.; Feringa, B. L. J. Chem. Soc., Perkin
Trans. 2, 1999, 807. (b) For H-bond directed ortho borylation, see:
Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.;
Maleczka, Jr., R. E.; Smith, M. R., III J. Am. Chem. Soc. 2012, 134,
11350.
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(2) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
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(3) (a) Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew.
Chem., Int. Ed. 2004, 43, 2206. (b) Hurst, T. E.; Macklin, T. K.;
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8155.
(4) For a recent review of functional group directed borylation, see:
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3229.
(5) (a) Boebel, T. A.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130,
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wamorita, S.; Ohmiya, H.; Hara, K.; Fukuoka, A.; Sawamura, M. J.
Am. Chem. Soc. 2009, 131, 5058. (d) Kawamorita, S.; Ohmiya, H.;
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(f) Ishiyama, T.; Isou, H.; Kikuchi, T.; Miyaura, N. Chem. Commun.
(23) Isolation of the 3h was failed due to the elimination of the Boc
group during silica gel column chromatography, it was isolated as 3g.
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TOC Graphic
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meta-C–H borylation
ortho-C–H borylation
Amine
CHO
Ir-Cat., TMP,
Amine
Ir-Cat., 8-AQ,
B2pin2
CHO
CHO
H
H
H
Bpin
H
B2pin2
R
R
R
Bpin
19 examples
66-98%
21 examples
56-88%
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