Iridium-catalyzed ortho-C-H borylation of aromatic aldimines derived from pentafluoroaniline with bis(pinacolate)diboron

Article abstract of DOI:10.1039/c3ob42497a

The development of an Ir-catalyzed ortho-C-H borylation of aromatic aldimines derived from pentafluoroaniline is reported. This reaction proceeded at 120 °C to afford the corresponding borylated products in high yield with good regioselectivity using an I

Full text of DOI:10.1039/c3ob42497a

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Iridium-catalyzed ortho-C–H borylation of
aromatic aldimines derived from
pentafluoroaniline with bis(pinacolate)diboron†
Cite this: Org. Biomol. Chem., 2014,
12, 2041
Received 13th December 2013,
Accepted 28th January 2014
Ikuo Sasaki, Tatsunosuke Amou, Hajime Ito* and Tatsuo Ishiyama*
DOI: 10.1039/c3ob42497a
www.rsc.org/obc
The development of an Ir-catalyzed ortho-C–H borylation of aro-
matic aldimines derived from pentafluoroaniline is reported. This
reaction proceeded at 120 °C to afford the corresponding bory-
lated products in high yield with good regioselectivity using an Ir
complex formed in situ from [Ir(OMe)(cod)]2/2(C6F5)3P in the pre-
sence of 2-norbornene.
Scheme 1 ortho-C–H borylation of aromatic aldimines 1 with B2pin2.
Arylboronic acids and their derivatives are versatile synthetic
intermediates.1 The most straightforward and attractive
method for the synthesis of arylboronic acid derivatives is the
direct C–H borylation of arenes.2 Recently, we have developed
the regioselective ortho-C–H borylation of various benzoates
or aryl ketones using the complex [Ir(OMe)(cod)]2/[3,5-
(CF3)2C6H3]3P or (C6H5)3As.3 At the same time, several groups
have also reported similar borylations of functionalized
arenes.4 The regioselectivity of these reactions is probably
derived from the interaction between the coordinating O
atoms in the directing group and the transition metal center.
However, benzaldehyde derivatives are not amenable to these
directed borylations due to the poor chemical stability of the
formyl group.5 Very recently, Sawamura’s and Lassaletta’s
groups reported directed ortho borylations using imidazoli-
dines6 or N,N-dimethylhydrazones7 as the coordinating groups
which are the synthetic equivalent of an aldehyde. Although
these reactions produced the desired products in high yields
with excellent regioselectivities, the formation of diborylated
side products and the use of hazardous hydrazine might
hamper the industrial application of these reactions.
compounds 2 in high yields without the formation of dibory-
lated side products (Scheme 1). The synthetic utility of this
procedure is demonstrated by the subsequent formation of
biphenyl carbaldehyde.
To find an aldimine moiety suitable for the ortho-C–H
borylation, the borylation of various aromatic aldimines
(5.0 equiv.) was examined using [Ir(OMe)(cod)]2 (1.5 mol%)
and a number of ligands (Table 1, entries 1–11). Consequently,
the pentafluorophenyl-substituted aldimine 1a, which is very
stable towards air and moisture, reacted smoothly with B2pin2
using tris(pentafluorophenyl)phosphine (C6F5)3P8 (6.0 mol%)
as the ligand to produce the desired product 2a in 120% yield
as judged by 1H NMR based on B2pin2 (entry 1). No dibory-
lated side products were observed under these reaction con-
ditions; however, a reduction side product 3a was obtained in
25% yield. The borylation of N-aryl (1b–1d), alkyl 1e, sulfonyl
1f or hydroxyl 1g aldimines did not proceed (entries 2–7). We
then screened possible ligands (entries 8–11). No reaction
occurred when using [3,5-(CF3)2C6H3]3P or (C6H5)3As, which
can weakly coordinate to the Ir metal center like (C6F5)3P
(entries 8 and 9).
Other phosphine ligands also did not result in borylation
(entries 10 and 11). The reaction did not produce 2a without
(C6F5)3P (entry 12). The use of 3 mol% and 9 mol% of (C6F5)3P
did not improve the yield of borylated product 2a (entries 13
and 14). The yield of 2a significantly decreased using one equi-
valent of 1a, indicating that the excess use (5 equiv.) of 1a is
necessary to obtain the products in high yield (entry 15).
Although the desired borylated product could be obtained
in high yield, separation of the imine 2a from the reduction
side product 3a was very difficult. We thus screened various
Herein, we describe the ortho-C–H borylation of stable aro-
matic aldimines 1 with B2pin2, catalyzed by in situ-generated Ir
complexes consisting of readily available [Ir(OMe)(cod)]2 and
(C6F5)3P in mesitylene as the solvent. The reaction proceeds
regioselectively at 120 °C in the presence of 2-norbornene
(1.0 equiv.) to give the corresponding aromatic boron
Division of Chemical Process Engineering, Frontier Chemistry Center (FCC),
Graduate School of Engineering, Hokkaido University, Sapporo, 060-8628, Japan.
E-mail: ishiyama@eng.hokudai.ac.jp; Fax: +81 11 706 6562; Tel: +81 11 706 6562
†Electronic supplementary information (ESI) available: Experimental procedures
and spectral analyses. See DOI: 10.1039/c3ob42497a
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maintaining the high catalytic activity (entries 3–7).9 For
acyclic alkenes such as 1-octene, 1,7-octadiene and 3,3-
dimethyl-1-butene, the undesired formation of 3a was partially
inhibited to less than 11% (entries 3–5). Use of 2-norbornene
successfully inhibited the reduction of 2a to 3a, providing 2a
Table 1 Optimization of the N-substitution of the imine and reaction
conditions using various aromatic aldiminesa
1
in the highest yield of 131% by H NMR and in 90% isolated
yield (entry 6). A trace amount of 3a was detected with a
reduced yield of 2a (126%) when 0.5 equivalent of 2-norbor-
nene was used (entry 7).
Yieldb (%)
Entry
R
Ligand
Time (h)
2
3
The Ir catalyst system [Ir/(C6F5)3P/2-norbornene] was
applied to various aromatic aldimines derived from non-hazar-
dous C6F5NH2 and aromatic aldehydes with electron-donating
or electron-withdrawing groups. The results are listed in
Table 3. The para-substituted aldimines bearing an electron-
donating group such as methyl (1h), methoxy (1i) and di-
methylamino (1j) reacted smoothly with B2pin2 to afford the
desired products in high yields without the formation of
diborylated side products (2h: 138%, 2i: 142%, 2j: 168%).
1
2
3
4
5
6
7
8
C6F5 (1a)
4-CF3C6H4 (1b)
4-MeOC6H4 (1c) (C6F5)3P
C6H5 (1d)
t-Bu (1e)
Ts (1f)
OH (1 g)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
C6F5 (1a)
(C6F5)3P
(C6F5)3P
3
24
24
24
24
24
24
120 25
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
(C6F5)3P
(C6F5)3P
(C6F5)3P
(C6F5)3P
[3,5-(CF3)2C6H3]3P 24
9
(C6H5)3As
(C6H5)3P
(C6H5O)3P
—
(C6F5)3P
(C6F5)3P
(C6F5)3P
24
24
24
24
3
3
24
10
11
12
13c
14d
15e
112 23
91 11
29 n.d.
a
Table 3 ortho-C–H borylation of various aldimines with B2(pin)2
a The reactions were carried out using aldimines (1a–g) (1.625 mmol),
B2pin2 (0.325 mmol), [Ir(OMe)(cod)]2 (0.0049 mmol), and (C6F5)3P
(0.0196 mmol). b 1H NMR yields based on B2pin2 using 1,1,2,2-
tetrachloroethane as an internal standard. c [Ir(OMe)(cod)]2
(0.0049 mmol) and (C6F5)3P (0.0098 mmol) were used. d [Ir(OMe)-
(cod)]2 (0.0049 mmol) and (C6F5)3P (0.0294 mmol) were used. e 1.0
equiv. of 1a was used.
additives to suppress the reduction (Table 2). Addition of
1-hexanol or H2O, which can consume HBpin via hydrolysis, to
the standard conditions described above (Table 1, entry 1)
resulted in disappointing yields (Table 2, entries 1 and 2).
Alkene derivatives were good inhibitors for the reduction while
Table 2 Optimized reaction conditions using various additivesa
Yieldb (%)
Entry
Additive (equiv.)
Time (h)
2a
3a
1
2
3
4
5
6
7
1-Hexanol (1.0)
H2O (1.0)
1-Octene (1.0)
1,7-Octadiene (1.0)
3,3-Dimethyl-1-butene (1.0)
2-Norbornene (1.0)
2-Norbornene (0.5)
3
3
3
3
3
4
3
Trace
20
108
Trace
Trace
11
11
<5
102
106
131(90)c
126
0
a The reactions were carried out by using aldimines 1h–t (1.625 mmol),
B2pin2 (0.325 mmol), [Ir(OMe)(cod)]2 (0.0049 mmol), and (C6F5)3P
Trace
a The reactions were carried out by using aldimine 1a (1.625 mmol), (0.0196 mmol). b 1H NMR yields based on B2pin2 using 1,1,2,2-
B2pin2 (0.325 mmol), [Ir(OMe)(cod)]2 (0.0049 mmol), and (C6F5)3P tetrachloroethane as an internal standard. c Isolated yield. d [Ir(OMe)-
(0.0196 mmol). b 1H NMR yields based on B2pin2 using 1,1,2,2- (cod)]2 (2.5 mol%) and (C6F5)3P (10 mol%) were used. e The reaction
tetrachloroethane as an internal standard. c Isolated yield.
was conducted in the absence of 2-norbornene.
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Although transition-metal catalysis often exhibit high reactivity
toward C–X bonds (X: F, Cl, Br), the halogenated aldimines 1k,
1l and 1m underwent chemo- and regio-selective borylation at
the ortho-C–H bond, in moderate to high yields, without any
evidence of side reactions involving the C–X bonds (2k: 109%,
2l: 89%, 2m: 69%). The reaction of CF3-containing aldimine
1n also afforded the corresponding 2n in 77% yield. The reac-
tion of meta-substituted aldimine derivatives (1o–1q) pro-
ceeded, whereas the corresponding products were obtained in
low yields (2o: 63%, 2p: 51%, 2q: 51%). Steric hindrance
around the reaction site generated by the meta-substituent
most probably caused the low yields for 2o–2q. The borylated
products were also obtained in low yields when ortho-substi-
tuted aldimines (1r–1t) were used (2r: 59%, 2s: 66%, 2t: >5%).
The utility of these borylated aldimines was demonstrated
by the transformation to 2-formylbiphenyl compound
5
(Scheme 2).10 The cross-coupling reaction of arylboronate 2a
with methyl 4-bromobenzoate (1.0 equiv.) in the presence of
PdCl2(dppf) (3 mol%) and K3PO4 (3.0 equiv.) in mesitylene at
120 °C for 24 h afforded the desired product 4 in 85% isolated
yield. The product 4 was then treated with TsOH·H2O (5.0
equiv.) in acetone–H2O (1 : 1) at 50 °C for 1.5 h, to give the
hydrolyzed product 5 in >99% isolated yield. This procedure
should be applicable for other borylated products as a useful
method to obtain these potentially bioactive compounds.
A plausible mechanism for this reaction is shown in
Scheme 3. The mono- (n = 1) or tris- (n = 3) boryliridium com-
plexes A are first produced by reaction of the Ir(I) precursor
with B2pin2.11 Next, the electron-donating nitrogen atom in
the imino group coordinates to the Ir metal center (Path I, B).
Oxidative addition of the ortho-C–H bond to B then produces
the pseudo metallacycle C (Path II). After reductive elimi-
nation, the Ir–hydride complexes D and the product 2a are pro-
duced (Path III). Finally, subsequent oxidative addition of
B2pin2 (Path IV) or HBpin (Path V) to D, followed by reductive
elimination of HBpin or H2, regenerates A. 2-Norbornene acts
as a H2 scavenger in this reaction (Path VII), inhibiting the
reduction pathway (Path VIII) so that 3a is not produced.
Scheme 3
borylation.
A
plausible mechanism for the ortho-selective C–H
presence of 2-norbornene. The borylation produced the corres-
ponding arylboronates in high yields with regioselectivity
without the formation of diborylated side products. This
report is the first example using 2-norbornene in C–H boryla-
tion as a H2 scavenger. The borylation of substrates containing
halogens such as F, Cl and Br afforded the corresponding pro-
ducts in high yields with good chemoselectivity. Additionally,
we demonstrated the utility of 2a by the transformation to the
biphenyl carbaldehyde 5.
This work was supported by a Grant-in-Aid for Scientific
Research (B) (no. 21350049) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, and the
Funding Program for Next Generation World-Leading
Researchers (NEXT Program, GR002).
In summary, an iridium complex formed from [Ir(OMe)
(cod)]2 and (C6F5)3P was found to be an efficient catalyst with
B2pin2 for the ortho-C–H borylation of stable aromatic aldi-
mines derived from non-hazardous pentafluoroaniline in the
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