Iridium-catalyzed ortho-CH borylation of aryl ketones with bis(pinacolato)diboron

Article abstract of DOI:10.1246/cl.2011.1007

ortho-Selective CH borylation of aryl ketones with bis(pinacolato)diboron proceeded at 120 °C in octane in the presence of a catalytic amount of iridium(I) complexes comprising 1/2[Ir(OMe)(cod)]₂ and AsPh ₃.

Full text of DOI:10.1246/cl.2011.1007

doi:10.1246/cl.2011.1007
Published on the web September 5, 2011
1007
Iridium-catalyzed ortho-C-H Borylation of Aryl Ketones with Bis(pinacolato)diboron
Hiroshi Itoh, Takao Kikuchi, Tatsuo Ishiyama,* and Norio Miyaura*
Division of Chemical Process Engineering, Graduate School of Engineering, Hokkaido University,
Sapporo, Hokkaido 060-8628
(Received June 13, 2011; CL-110489; E-mail: ishiyama@eng.hokudai.ac.jp)
O
O
ortho-Selective C-H borylation of aryl ketones with
bis(pinacolato)diboron proceeded at 120 °C in octane in the
1/2[Ir(OMe)(cod)]2-
2AsPh3 (3 mol%)
R
R
B2pin2
+
presence of
a
catalytic amount of iridium(I) complexes
octane/120 °C
Bpin
comprising 1/2[Ir(OMe)(cod)]2 and AsPh3.
FG
FG
1
2
3
O
O
O
O
B
B
B2pin2
=
Arylboronic acids and esters are an important class of
intermediates for the synthesis of natural products, medicinal
compounds, and functional materials.1 Traditional methods for
their synthesis are reactions of trialkylborates with aryllithium or
-magnesium compounds.2 Pd-Catalyzed cross-coupling of aryl
halides with bis(pinacolato)diboron (B2pin2) or pinacolborane
(HBpin) is a milder variant for most functional groups.3,4
Rhodium- or iridium-catalyzed C-H borylation of arenes with
HBpin or B2pin2, studied extensively by Hartwig,5 Marder,6 and
Smith,7 is highly attractive as a direct, economical, and
environmentally benign process to synthesize organoboronic
esters without using any halogenated starting materials. We have
reported unusually high efficiency of a 1/2[Ir(OMe)(cod)]2-
dtbpy catalyst, which allowed stoichiometric borylation of
arenes and heteroarenes at room temperature.8 The regioselec-
tivity of this C-H borylation of arenes is primarily controlled by
steric effects; 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.9,10 One of the most reliable
protocols would be a process involving use of chelation-assisted
C-H bond cleavage. Recently, we developed a new catalyst
system (1/2[Ir(OMe)(cod)]2-2P(3,5-(CF3)2C6H3)3) for ortho-
C-H borylation of benzoate esters with B2pin2.11 We report
here analogous reaction of aryl ketones 1 with B2pin2 (2) for
synthesis of ortho-borylated products 3 (Scheme 1). The
reaction selectively took place at the ortho-carbon when
Scheme 1.
Table 1. Reaction conditions for acetophenonea
O
O
IrI Precursor-Ligand
Me
Me
Bpin
B2pin2
+
octane/120 °C/16 h
(5.0 mmol)
(1.0 mmol)
Yield Sel
/%b /%c
Entry Ir(I) Precursor
Ligand
Solvent
1
2
3
4
5
6
7
8
9
1/2[Ir(OMe)(cod)]2 2AsPh3
octane
octane
octane
octane
octane
octane
octane
124
134
96
32
38
16
4
98
98
98
75
79
92
13
1/2[IrCl(cod)]2
[Ir(cod)2]BF4
2AsPh3
2AsPh3
1/2[Ir(OMe)(cod)]2 none
1/2[Ir(OMe)(cod)]2 2Pr
1/2[Ir(OMe)(cod)]2 2PPh3
1/2[Ir(OMe)(cod)]2 2SbPh3
1/2[Ir(OMe)(cod)]2 2P((CF3)2C6H3)3 octane
56 100
Me3C6H3 126 98
1/2[Ir(OMe)(cod)]2 2AsPh3
1/2[Ir(OMe)(cod)]2 2AsPh3
1/2[Ir(OMe)(cod)]2 2AsPh3
10
11
diglyme
DMF
12 100
0
®
aA mixture of acetophenone (5.0 mmol), B2pin2 (1.0 mmol),
Ir(I) precursor (0.03 mmol/Ir), ligand (0.06 mmol), and solvent
(6 mL) were stirred at 120 °C for 16 h. bGC yields based on the
c
number of equivalents of B2pin2. ortho-Selectivities.
catalyst having P(3,5-(CF3)2C6H3)3, which has been efficiently
utilized in the ortho-C-H borylation of benzoate esters with 2,
displayed the best selectivities (100%), but catalytic activity was
moderate (56%) (Entry 8). The choice of inert solvent was
also important for efficient borylation. The reactions using
1/2[Ir(OMe)(cod)]2-2AsPh3 were faster in nonpolar solvents
such as octane than in more polar and coordinating solvents. The
order of reactivity in different solvents was octane (124%)
(Entry 1) = mesitylene (126%) (Entry 9) > diglyme (12%)
(Entry 10) > DMF (0%) (Entry 11).
Yields over 100% observed in the above borylation indicate
that both boryl groups in diboron 2 participated in the reaction.
Because the catalytic reaction shows a two-step process, fast
borylation by 2 followed by slow borylation by HBpin, the
borylation of acetophenone with HBpin may occur after
consumption of 2. Indeed, reaction of acetophenone with HBpin
under the conditions used for the borylation with 2 gave the
12
iridium(I) complexes comprising [Ir(OMe)(cod)]2 and AsPh3
was used as a catalyst at 120 °C in octane.
To achieve the ortho-C-H borylation of aryl ketones 1,
effects of iridium(I) precursors (0.03 mmol/Ir), ligands (0.06
mmol), and solvents (6 mL) were investigated for the reaction of
acetophenone (5.0 mmol) with B2pin2 (2) (1.0 mmol) at 120 °C
for 16 h (Table 1). Among the conditions screened, a combina-
tion of [Ir(OMe)(cod)]2 or [IrCl(cod)]2, AsPh3, and octane gave
the best yields (124-134%) and excellent ortho-selectivities
(98%) (Entries 1 and 2). A cationic iridium(I) precursor,
[Ir(cod)2]BF4, also worked well (Entry 3). The choice of ligand
was crucial for the borylation. In the absence of ligands, the
reaction afforded the borylated product in low yield with
moderate selectivity (Entry 4). Iridium complexes bearing other
monodentate ligands such as pyridine (Entry 5), PPh3 (Entry 6),
and SbPh3 (Entry 7) also displayed low catalytic activities. The
Chem. Lett. 2011, 40, 1007-1008
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1008
1/2[Ir(OMe)(cod)]2-
2AsPh3 (3 mol%)
O
O
only occurred at the 6-position, presumably due to steric reasons
(Entry 10).16
Me
Me
Bpin
HBpin
+
octane/120 °C/16 h
In summary, ortho-borylated products were obtained with
excellent regioselectivities by the reaction of aryl ketones with
bis(pinacolato)diboron in the presence of a catalytic amount of
iridium complexes generated from [Ir(OMe)(cod)]2 and AsPh3 in
octane at 120 °C. Further investigations to survey the scope and
limitations of this C-H borylation, including C-H borylation of
other aromatic carbonyl compounds such as amides, as well as to
elucidate the reaction mechanisms are in progress.
(1.0 mmol)
(1.0 mmol)
30%
Scheme 2.
Table 2. ortho-C-H borylation of aryl ketonesa
Entry
Product
Yield/%b
O
1
2
3
4
R = Me
R = Et
124
This work was supported by Grant-in-Aid for Scientific
Research (B) (No. 21350049) from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
126
R
R = i-Pr
R = t-Bu
132 (83)
130 (73)
Bpin
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
5
6
7
8
9
FG = MeO
FG = Me
FG = Cl
114 (50)
122
O
Me
154
FG
Me
Bpin
References and Notes
FG = F3C
FG = O2N
48
1
A review, see: Boronic Acids: Preparation, Applications in
Organic Synthesis and Medicine, ed. by D. G. Hall, Wiley,
Weinheim, 2005.
NR
O
2
A review, see: A. N. Nesmeyanov, R. A. Sokolik, Methods of
Elemento-Organic Chemistry, North-Holland, Amsterdam,
1967, Vol. 1.
Me
10
80
Bpin
3
4
5
6
7
8
T. Ishiyama, M. Murata, N. Miyaura, J. Org. Chem. 1995, 60,
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MeO
O
Me
Bpin
11
108
aAll reactions were carried out at 120 °C for 16 h by using an
aryl ketone (5.0 mmol), B2pin2 (1.0 mmol), [Ir(OMe)(cod)]2
(0.015 mmol), AsPh3 (0.06 mmol), and octane (6 mL). bGC
yields based on the number of equivalents of B2pin2 and
isolated yields are in paretheses.
J.-Y. Cho, M. K. Tse, D. Holmes, R. E. Maleczka, Jr., M. R.
Smith, III, Science 2002, 295, 305.
a) T. Ishiyama, J. Takagi, J. F. Hartwig, N. Miyaura, Angew.
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borylated product in 30% yield (Scheme 2). To improve the
yield, the reaction with 2 was carried out in the presence of
various alkenes that have frequently been used as hydrogen
acceptors in C-H silylation with hydrosilanes;13 however,
addition of such reagents retarded the present borylation.
9
For ortho-C-H borylation directed by a Me2HSi group, see:
T. A. Boebel, J. F. Hartwig, J. Am. Chem. Soc. 2008, 130, 7534.
10 ortho-C-H borylation catalyzed by Silica-SMAP-Ir, see: a) S.
Kawamorita, H. Ohmiya, K. Hara, A. Fukuoka, M. Sawamura,
J. Am. Chem. Soc. 2009, 131, 5058. b) S. Kawamorita, H.
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Yamazaki, S. Kawamorita, H. Ohmiya, M. Sawamura, Org.
Lett. 2010, 12, 3978.
Representative results of ortho-C-H borylation of aryl
ketones 1 with B2pin2 (2) catalyzed by the combination of
1/2[Ir(OMe)(cod)]2, 2AsPh3, and octane at 120 °C for 16 h are
shown in Table 2. Not only methyl but also ethyl, isopropyl, and
tert-butyl ketones were all viable substrates for producing the
corresponding ortho-borylated products 3 in high yields with
excellent regioselectivities (Entries 1-4). The reactions were
suitable for substrates possessing various functional groups,
such as MeO, Cl, and F3C, as well as for substrates with
potentially more reactive benzylic C-H bonds (Entries 5-8, 10,
and 11).14 Although some transition-metal complexes exhibit
reactivity toward oxidative addition of Ar-Cl bonds,15
4-chloroacetophenone underwent borylation at the C-H bond
(Entry 7). The low reactivities in the borylation of acetophenone
having an F3C or a O2N group may be attributable to the low
coordinating ability of carbonyl oxygen (Entries 8 and 9).
Reaction of a substrate bearing a substituent at the 3-position
11 T. Ishiyama, H. Isou, T. Kikuchi, N. Miyaura, Chem. Commun.
2010, 46, 159.
12 Utility of AsPh3, see: V. Farina, B. Krishnan, J. Am. Chem. Soc.
1991, 113, 9585.
13 A review, see: F. Kakiuchi, N. Chatani, Adv. Synth. Catal.
2003, 345, 1077.
14 A review, see: S. J. Blanksby, G. B. Ellison, Acc. Chem. Res.
2003, 36, 255.
15 A review, see: J. D. Atwood, in Comprehensive Organometallic
Chemistry II, ed. by E. W. Abel, F. G. A. Stone, G. Wilkinson,
Pergamon Press, Oxford, 1995, Vol. 8, p. 303. doi:10.1016/
B978-008046519-7.00074-5.
16 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.
html.
Chem. Lett. 2011, 40, 1007-1008
© 2011 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/