Ortho-C-H borylation of benzoate esters with bis(pinacolato)diboron catalyzed by iridium-phosphine complexes

Article abstract of DOI:10.1039/b910298a

Iridium complexes generated from [Ir(OMe)(COD)]₂ and tris[3,5-bis(trifluoromethyl)phenyl]phosphine efficiently catalyzed the ortho-C-H borylation of benzoate esters with bis(pinacolato)diboron in octane at 80 °C to produce the corresponding ary

Full text of DOI:10.1039/b910298a

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Ortho-C–H borylation of benzoate esters with bis(pinacolato)diboron
catalyzed by iridium–phosphine complexesw
Tatsuo Ishiyama,* Hironori Isou, Takao Kikuchi and Norio Miyaura*
Received (in Cambridge, UK) 26th May 2009, Accepted 3rd November 2009
First published as an Advance Article on the web 17th November 2009
DOI: 10.1039/b910298a
Iridium complexes generated from [Ir(OMe)(COD)]2 and
tris[3,5-bis(trifluoromethyl)phenyl]phosphine efficiently catalyzed
the ortho-C–H borylation of benzoate esters with bis(pinacolato)-
diboron in octane at 80 1C to produce the corresponding
arylboronates in high yields with excellent regioselectivities.
Increasing attention has been focused on transition metal-
catalyzed activation and the functionalization of unreactive
C–H bonds of hydrocarbons.1 An extension of this methodology
to aromatic C–H borylation of arenes with bis(pinacolato)-
Scheme 1 Ortho-selective C–H borylation of benzoate esters.
diboron (B2pin2, pin = Me4C2O2) or pinacolborane (HBpin)
is of significant value for the preparation of synthetically
Table 1 Reaction conditions for methyl benzoatea
useful aromatic boron compounds2 from the viewpoint of
economy, efficiency, and environmental benignity.3–6 The
most efficient catalyst for this type of transformation is
the combination of [IrCl(COD)]2 or [Ir(OMe)(COD)]2 with
2,20-bipyridine or 4,40-di-tert-butyl-2,20-bipyridine (dtbpy).6
The high level of catalytic activity of 1/2[Ir(OMe)(COD)]2–
dtbpy allows room temperature borylation of arenes with a
stoichiometric amount of substrate to produce the corresponding
arylboron compounds in high yields. The functional group
tolerance of the borylation is quite high. The reaction occurs
selectively at the aromatic C–H bond for arenes bearing MeO,
Me, I, Br, Cl, F3C, MeO2C, and NC. The regioselectivity of
this C–H borylation of arenes is primarily controlled by steric
effects; the functionalization occurs at the least hindered
aromatic C–H bond. Thus, 1,2-disubstituted arenes having
identical substituents and 1,3-disubstituted arenes even having
distinct substituents produce borylated products as single
isomers. A drawback of this method is therefore difficulty in
achieving ortho-C–H borylation. One of the most reliable
protocols would be a process involving the use of chelation-
assisted C–H bond cleavage.1
Entry
Ligand
Yield (%)b
o- : m- : p- (%)c
1
2
3
4
5
6
7
8
9
dtbpy
None
2 pyridine
2 P(C6H5)3
2 As(C6H5)3
2 P(4-MeO–(C6H4)3
2 P(4-F3C–C6H4)3
2 P(C6F5)3
145
13
7
11
9
0 : 58 : 42
38 : 38 : 24
14 : 58 : 28
64 : 18 : 18
67 : 22 : 11
34 : 33 : 33
96 : 2 : 2
3
45
82
95
90 : 7 : 3
98 : 2 : 0
2 P(3,5-2F3C–C6H3)3
a
Reactions were carried out at 80 1C for 16 h by using methyl
benzoate (5.0 mmol), 2 (1.0 mmol), [Ir(OMe)(COD)]2 (0.015 mmol),
b
ligand (0.03 or 0.06 mmol), and octane (6 ml). GC yields based
on 2. Isomer ratios were determined by 1H NMR.
c
reaction of methyl benzoate (5.0 mmol) with B2pin22
(1.0 mmol) by using [Ir(OMe)(COD)]2 (0.015 mmol) as a
catalyst precursor in octane (6 ml) at 80 1C for 16 h
(Table 1). Iridium complexes bearing dtbpy effectively
catalyzed the aromatic C–H borylation, but they did not give
any ortho-borylated products at all (Entry 1). Probably, the
high coordinating ability of dtbpy retards the coordination of
a carbonyl oxygen in the substrate to the iridium centre. The
reaction afforded an ortho-borylated product in the absence of
ligands; however, catalytic activity and regioselectivity were
low (Entry 2). These results prompted us to examine mono-
dentate ligands. Among iridium complexes having pyridine
(Entry 3), triphenylphosphine (Entry 4), and triphenylarsine
(Entry 5), the latter two complexes exhibited moderate
ortho-selectivities but displayed low catalytic activities. Since
We disclose herein the ortho-C–H borylation of benzoate
ester derivatives (1) with bis(pinacolato)diboron (B2pin2) (2)
catalyzed by iridium complexes comprised of easily available
[Ir(OMe)(COD)]2 and commercial tris[3,5-bis(trifluoromethyl)-
phenyl]phosphine in octane at 80 1C to give the corresponding
aromatic boron compounds (3) in high yields with excellent
regioselectivities (Scheme 1).7,8
To achieve the ortho-C–H borylation of benzoate esters 1,
effects of ligands (0.03 or 0.06 mmol) were investigated for the
Division of Chemical Process Engineering, 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
w Electronic supplementary information (ESI) available: Experimental
procedures and spectral analyses. See DOI: 10.1039/b910298a
a
wide variety of triarylphosphines are commercially
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Table 2 Ortho-selective aromatic C–H borylation of 1 with 2a
Entry
Productb
Yield (%)c
Entry
Productb
Yield (%)c
1
2
3
4
R = Me
R = Et
R = i-Pr
R = t-Bu
95
92
89
83
9
Y = Me2N
Y = Me
Y = Br
99
98
64
94
10
11
12
Y = F3C
5
6
7
8
Y = Me2N
Y = Me
Y = Br
97
92
60
98
13
14
15
16
Y = Me2N
Y = Me
Y = Br
93
99
57d
98
Y = F3C
Y = F3C
a
All reactions were carried out at 80 1C for 16 h by using 1 (5.0 mmol), 2 (1.0 mmol), [Ir(OMe)(COD)]2 (0.015 mmol), tris[3,5-bis(trifluoro-
methyl)phenyl]phosphine (0.06 mmol), and octane (6 ml). Isomeric purities over 98% were determined by 1H NMR. GC yields based on 2.
d
b
c
The reaction was conducted in a mixture of octane and mesitylene (1 : 1).
available, we decided to investigate them as ligands of iridium.
Although catalysts having electron-rich phosphines such as
tris(4-methoxyphenyl)phosphine exhibited low activity and
regioselectivity (Entry 6), those having electron-poor phosphines
such as tris(4-trifluoromethylphenyl)phosphine displayed high
ortho-selectivity and moderate catalytic activity (Entry 7).
Complexes bearing more electron-poor tris(pentafluorophenyl)-
phosphine improved the catalytic activity while maintaining
high regioselectivity (Entry 8). Finally, high yield (95%) and
highest ortho-selectivity (98%) were achieved when tris-
[3,5-bis(trifluoromethyl)phenyl]phosphine (P(3,5-2F3C–C6H3)3)
was used as a ligand of iridium (Entry 9).
In summary, ortho-borylated products were obtained
with excellent regioselectivities by the reaction of benzoate
esters with bis(pinacolato)diboron in the presence of a
catalytic amount of iridium complexes generated from
[Ir(OMe)(COD)]2 and commercial tris[3,5-bis(trifluoromethyl)-
phenyl]phosphine in octane at 80 1C. Further investigations to
survey the scope and limitations of this C–H borylation,
including C–H borylation of other aromatic carbonyl
compounds such as ketones and amides, as well as to elucidate
the reaction mechanisms are in progress.
This work was partially supported by Grant-in-Aid
for Scientific Research on Priority Areas (No. 17065001,
‘‘Advanced Molecular Transformations of Carbon Resources’’)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
The choice of iridium precursor was crucial for the
borylation. Although the combination of [IrCl(COD)]2 and
P(3,5-2F3C–C6H3)3 gave borylated products in good yield
(62%), ortho-selectivity was low (55%). No borylated product
was obtained when the combination of [Ir(COD)2]BF4 and the
phosphine was used. The choice of inert solvent was
also important for efficient borylation. The reactions using
1/2[Ir(OMe)(COD)]2–2P(3,5-2F3C–C6H3)3 were faster in
non-polar solvents such as octane than in more polar and
coordinating solvents. The order of reactivity in different
solvents was octane (95%) > mesitylene (3%) > diglyme
(0%) = DMF (0%).
Notes and references
1 (a) J. A. Labinger and J. E. Bercaw, Nature, 2002, 417, 507;
(b) F. Kakiuchi and N. Chatani, Adv. Synth. Catal., 2003, 345,
1077; (c) Handbook of C–H Transformations, ed. G. Dyker,
Wiley-VCH, Weinheim, 2005; K. Godula and D. Sames, Science,
2006, 312, 67; (d) A. L. Dick and S. Stanford, Tetrahedron, 2006,
62, 2439; (e) I. V. Seregin and V. Gevorgyan, Chem. Soc. Rev.,
2007, 36, 1173; (f) R. G. Bergman, Nature, 2007, 446, 391.
2 (a) M. Vaultier and B. Carboni, in Comprehensive Organometallic
Chemistry II, ed. E. W. Abel, F. G. A. Stone and G. Wilkinson,
Pergamon Press, Oxford, 1995, vol. 11, p. 191; (b) K. Ishihara and
H. Yamamoto, Eur. J. Org. Chem., 1999, 527; (c) S. Shinkai,
M. Ikeda, A. Sugasaki and M. Takeuchi, Acc. Chem. Res., 2001,
34, 494; (d) C. D. Entwistle and T. B. Marder, Angew. Chem., Int.
Ed., 2002, 41, 2927; (e) A. H. Soloway, W. Tjarks, B. A. Barnum,
F.-G. Rong, R. F. Barth, I. M. Codogni and J. G. Wilson, Chem.
Rev., 1998, 98, 1515; (f) W. Yang, X. Gao and B. Wang, Med. Res.
Rev., 2003, 23, 346; (g) Boronic Acids, ed. D. G. Hall, Wiley,
Weinheim, 2005.
3 (a) C. N. Iverson and M. R. Smith, III, J. Am. Chem. Soc., 1999,
121, 7696; (b) J.-Y. Cho, C. N. Iverson and M. R. Smith, III,
J. Am. Chem. Soc., 2000, 122, 12868; (c) M. K. Tse, J.-Y. Cho and
M. R. Smith, III, Org. Lett., 2001, 3, 2831; (d) J.-Y. Cho,
M. K. Tse, D. Holmes, R. E. Maleczka, Jr and M. R. Smith, III,
Science, 2002, 295, 305; (e) R. E. Meleczka, Jr, F. Shi, D. Holmes
and M. R. Smith, III, J. Am. Chem. Soc., 2003, 125, 7792;
(f) G. A. Chotana, M. A. Rak and M. R. Smith, III, J. Am. Chem.
Soc., 2005, 127, 10539; (g) S. Paul, G. A. Chotana, D. Holmes,
R. C. Reichle, R. E. Maleczka, Jr and M. R. Smith, III, J. Am.
Chem. Soc., 2006, 128, 15552; (h) G. A. Chotana, V. A. Kallepalli,
R. E. Maleczka, Jr and M. R. Smith, III, Tetrahedron, 2008, 64,
6103.
Representative results of ortho-C–H borylation of benzoate
esters 1 with B2pin22 catalyzed by the combination of
1/2[Ir(OMe)(COD)]2 and 2P(3,5-2F3C–C6H3)3 in octane at
80 1C for 16 h are shown in Table 2. Not only methyl but
also ethyl, isopropyl and tert-butyl benzoates were all viable
substrates for producing the corresponding ortho-borylated
products in high yields with excellent regioselectivities,
whilst their reactivity slightly decreased in the above order
(Entries 1–4). The reactions were suitable for substrates
possessing various functional groups, such as Me2N, Br, and
F3C as well as for substrates with potentially more reactive
benzylic C–H bonds (Entries 5–16).9 Although some transition
metal complexes exhibit high reactivity toward oxidative
addition of Ar–Br bonds,10 methyl 2-, 3-, and 4-bromobenzoates
underwent borylation at the C–H bond (Entries 7, 11, and 15).
Reactions of substrates having a substituent at the 3-position
only occurred at the 6-position, presumably due to steric
reasons (Entries 9–12).
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4 (a) H. Chen and J. F. Hartwig, Angew. Chem., Int. Ed., 1999, 38,
3391; (b) H. Chen, S. Schlecht, T. C. Semple and J. F. Hartwig,
Science, 2000, 287, 1995; (c) T. M. Boller, J. M. Murphy,
M. Hapke, T. Ishiyama, N. Miyaura and J. F. Hartwig, J. Am.
Chem. Soc., 2005, 127, 14263; (d) J. M. Murphy, C. C. Tzschucke
and J. F. Hartwig, Org. Lett., 2007, 9, 757; (e) C. C. Tzschucke,
J. M. Murphy and J. F. Hartwig, Org. Lett., 2007, 9, 761;
(f) J. M. Murphy, X. Liao and J. F. Hartwig, J. Am. Chem.
Soc., 2007, 129, 15434.
N. Miyaura, Angew. Chem. Int. Ed., 2002, 41, 3056; (d) T. Ishiyama,
J. Takagi, Y. Yonekawa, J. F. Hartwig and N. Miyaura, Adv. Synth.
Catal., 2003, 345, 1103; (e) T. Ishiyama, Y. Nobuta, J. F. Hartwig and
N. Miyaura, Chem. Commun., 2003, 2924; (f) T. Ishiyama and
N. Miyaura, J. Organomet. Chem., 2003, 680, 3; (g) T. Ishiyama
and N. Miyaura, Chem. Rec., 2004, 3, 271; (h) T. Ishiyama, J. Takagi,
Y. Nobuta and N. Miyaura, Org. Synth., 2005, 82, 126;
(i) T. Ishiyama and N. Miyaura, Pure Appl. Chem., 2006, 78, 1369.
7 For ortho-borylation directed by
a Me2HSi group, see:
5 (a) S. Shimada, A. S. Batsanov, J. A. K. Howard and
T. B. Marder, Angew. Chem. Int. Ed., 2001, 40, 2168;
(b) D. N. Coventry, A. S. Batsanov, A. E. Goeta, J. A. K.
Howard, T. B. Marder and R. N. Perutz, Chem. Commun., 2005,
2172; (c) I. A. I. Mkhalid, D. N. Coventry, D. Albesa-Jove,
A. S. Batsanov, J. A. K. Howard, R. N. Perutz and T. B. Marder,
Angew. Chem. Int. Ed., 2006, 45, 489; (d) P. Harrisson, J. Morris,
P. G. Steel and T. B. Marder, Synlett, 2009, 247.
6 (a) T. Ishiyama, J. Takagi, K. Ishida, N. Miyaura, N. R. Anastasi
and J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 390; (b) J. Takagi,
K. Sato, J. F. Hartwig, T. Ishiyama and N. Miyaura, Tetrahedron
Lett., 2002, 43, 5649; (c) T. Ishiyama, J. Takagi, J. F. Hartwig and
T. A. Boebel and J. F. Hartwig, J. Am. Chem. Soc., 2008, 130,
7534.
8 For ortho-borylation of benzoate esters catalyzed by Silica-SMAP-Ir,
see: S. Kawamorita, H. Ohmiya, K. Hara, A. Fukuoka and
M. Sawamura, J. Am. Chem. Soc., 2009, 131, 5058.
9 S. J. Blanksby and G. B. Ellison, Acc. Chem. Res., 2003, 36, 255.
10 (a) G. J. Leigh, R. L. Richards, in Comprehensive Organometallic
Chemistry, ed. G. Wilkinson, F. G. A. Stone and E. W. Abel,
Pergamon Press, Oxford, 1982, vol. 5, p. 541; (b) J. D. Atwood, in
Comprehensive Organometallic Chemistry II, ed. E. W. Abel,
F. G. A. Stone and G. Wilkinson, Pergamon Press, Oxford,
1995, vol. 8, p. 303.
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