Mild iridium-catalyzed borylation of arenes. High turnover numbers, room temperature reactions, and isolation of a potential intermediate

Article abstract of DOI:10.1021/ja0173019

The borylation of arenes leads to the formation of synthetically versatile products from unactivated arene reagents. We report that Ir(I) precursors in conjunction with bipyridine ligands catalyze in high yields the borylation of arenes under mild conditions. These reactions encompase arenes bearing both electron-withdrawing and electron-donating substituents. The temperatures required for the transformation are much lower than those previously reported for direct arene borylation. The combination of [Ir(COE)₂Cl]₂ and (4,4-di-t-butyl)bipyridine even allows for reaction at room temperature. The same catalyst system at 100 °C provides remarkably high turnover numbers for a hydrocarbon functionalization process. Mechanistic studies show that the reactions involve uncommon, Ir(II) tris-boryl complexes. An example of this type of complex ligated by di-t-butylbipyridine was isolated and structurally characterized. It reacted rapidly at room temperature to produce aryl boronate esters in high yields. Copyright

Full text of DOI:10.1021/ja0173019

Published on Web 12/28/2001
Mild Iridium-Catalyzed Borylation of Arenes. High Turnover Numbers, Room
Temperature Reactions, and Isolation of a Potential Intermediate
Tatsuo Ishiyama,* Jun Takagi, Kousaku Ishida, and Norio Miyaura*
DiVision of Molecular Chemistry, Graduate School of Engineering, Hokkaido UniVersity, Sapporo 060-8628, Japan
Natia R. Anastasi and John F. Hartwig*
Department of Chemistry, Yale UniVersity, P.O. Box 208107, New HaVen, Connecticut 06520-8107
Received October 15, 2001; Revised Manuscript Received November 26, 2001
Table 1. Ir-Catalyzed Direct Borylation of Arenes with 1 (eq 1)a
The simultaneous activation and functionalization of hydrocar-
bons allows abundant, inert hydrocarbons to serve as direct
feedstocks for functionalized compounds.1-6 The versatility of
organoboron compounds in organic synthesis7,8 makes the borylation
of hydrocarbons an attractive goal. One of our groups has developed
novel preparations9 and reactions10 of arylboronate esters, while
the other has developed catalytic conversions of arenes and alkanes
to aryl- and alkylboronates.11,12
The borylation of both alkanes and benzene by bis(pinacolato)-
diboron (B2pin2, pin ) O2C2Me4) catalyzed by Cp*Re(CO)3 under
photochemical conditions11 and by Cp*Rh(η4-C6Me6) under thermal
conditions12 was reported recently. Cp*Rh(η4-C6Me6),12,13 Cp*Ir-
(PMe3)(H)(Bpin),14,15 RhCl[P(i-Pr)3]2(N2),16 and (Cp*RhCl2)2 have
also been shown to catalyze with variable efficiency the borylation
of aromatic substrates by pinacolborane (HBpin). RhCl[P(i-Pr)3]2-
a All reactions conducted at 80 °C for 16 h with 1 (1.0 equiv), an arene
(N2)16 and Pd/C17 catalyze the borylation of benzylic C-H bonds.
(60 equiv), and 1/2[IrCl(COD)]2/bpy (3 mol %) without solvent. b GLC
In all cases, reactions were conducted at elevated temperatures and
with limited turnovers. Iridium systems required temperatures between
1
yields based on boron atom in 1. c Isomer ratios determined by H NMR.
borylation products in statistical ratios (ca. 2:1) (entries 2-4). The
ortho isomer was not detected in most cases probably due to the
steric effect of the substituents.21 The borylation of benzene in the
presence of o-, m-, or p-borylanisole resulted in neither formation
of anisole nor isomerization of the borylanisoles. This result
indicates that the ratio of isomers was kinetically determined. The
nearly statistical ratio of meta and para isomers is inconsistent with
a mechanism involving electrophilic C-H activation. Although
toluene has weaker benzylic C-H bonds, the reaction occurred only
at the aromatic C-H bonds (entry 3).
150 and 200 °C for both catalytic and stoichiometric18 borylations.
We disclose that air-stable, commercially available iridium(I)
precursors in conjunction with simple 2,2′-bipyridine (bpy) ligands
form complexes that catalyze the direct borylation of arenes by
B2pin2 (1) to produce pinacol arylboronate esters under mild
conditions, including room temperature. All reaction components
are air stable and commercially available. The reaction appears to
proceed through Ir(III) tris-boryl complexes, which have been
isolated and which react rapidly at room temperature to yield the
organoboron products (eq 1).
In contrast, regioselective borylation occurred with disubstituted
arenes because the substituents block ortho activation. Both 1,2-
and 1,4-disubstituted arenes bearing identical substituents yielded
the corresponding boronate ester as a single regioisomer (entries
5-8), although yields for reaction of 1,4-isomers were lower than
those for 1,2-isomers due to steric hindrance. The borylation of
1,3-disubstituted arenes occurred only at the common meta posi-
tion;13 therefore, regioisomerically pure ester products were obtained
even with two distinct substituents on the arene (entries 9-11).
Aromatic C-H bonds were selectively borylated in the presence
of C-Cl and C-Br bonds, despite the thermodynamic driving force
for formation of haloboranes22 (entries 7 and 11).
The reactions in an equimolar mixture of trifluoromethylbenzene
and toluene, trifluoromethylbenzene and anisole, and toluene and
anisole afforded the corresponding arylboronate esters in ratios of
90:10, 85:15, and 40:60, respectively. These data indicate that
electron-poor arenes are more reactive than electron-rich ones.
Inductive effects or coordination of substituents may be influencing
the reactivity of arenes because the borylation of anisole was faster
than that of toluene.
Ir(I)/bpy cat
+ 2ArH room temperature to 80 °C8 2ArBpin + H2
(1)
B2pin2
1
The direct borylation of benzene (60 mmol) by 1 (1.0 mmol)
was initially conducted at 80 °C for 16 h while modifying reaction
conditions. Iridium(I) complexes comprised of [IrCl(COD)]2 (0.015
mmol) and bpy (0.03 mmol) proved to be active catalysts. Both
boryl groups in diboron 1 participated in the reaction to give PhBpin
in 95% yield, along with a trace amount of C6H4(Bpin)2. Complexes
generated from 1,10-phenanthroline also exhibited high catalytic
activity and generated the boronate product in 89% yield. Catalysts
containing pyridine, TMEDA, PPh3, and dppe were ineffective.
Despite the utility of rhodium(I) or platinum(0) complexes in the
related direct metalations of arenes by 1,12 disilanes19 and silanes,20
the combination of Pt(dba)2 and bpy did not catalyze the reaction,
and the combination of [RhCl(COD)]2 and bpy led to formation of
PhBpin in only 20% yield and required 150 °C.
Representative results of the direct borylation of arenes by 1
under these conditions are summarized in Table 1. Both electron-
rich and electron-poor monosubstituted arenes underwent smooth
reaction to produce regioisomeric mixtures of the meta and para
Monitoring of the reaction of 1 with benzene showed that 1 was
completely consumed after 40 min to form PhBpin and HBpin in
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390 VOL. 124, NO. 3, 2002 J. AM. CHEM. SOC.
10.1021/ja0173019 CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
96% yield based on the quantity of 1. After 4 h, the HBpin was
also consumed to form PhBpin in an overall 88% yield based on
the number of equivalents of the Bpin unit in 1. Reaction of HBpin
with benzene under the conditions used for the borylation by 1
gave PhBpin in 80% yield (eq 2).
HBpin + PhH
(60 equiv)
1/2[IrCl(COD)] /bpy (3 mol %)8
+ H (2)
2
2
PhBpin
80%
80 °C/16 h
1
Careful monitoring by H NMR and GC/mass spectroscopy of
the early stages of the reaction between benzene-d6 and 1 at 60 °C
revealed an induction period during which the cyclooctadiene ligand
was reduced to cyclooctene-d2. Thus, we evaluated reactions con-
ducted with [IrCl(COE)2]2 as precursor. These reactions showed
no induction period even when we employed lower reaction temper-
atures. In fact, the reaction between 1 and benzene in the presence
of [IrCl(COE)2]2 and 4,4′-di-tert-butyl-2,2′-bipyridine (dtbpy), which
generates more soluble iridium complexes, produced PhBpin in 83%
yield after 4.5 h at room temperature (eq 3). This reaction of 1
with benzene constitutes the first catalytic C-H borylation at room
temperature. Moreover, this catalyst system provides remarkably
high turnover numbers for a hydrocarbon functionalization process.
Reaction of 1 at 100 °C in benzene catalyzed by 0.02 mol % of
iridium formed 2 equiv of PhBpin for each diboron reagent in 80%
yield (8000 turnovers) (eq 4). This value surpasses previously
published catalyst efficiencies by more than an order of magnitude.
Dissolution of tris-boryl 4 in C6D6 generated 3 equiv of C6D5-
Bpin in 80% yield within minutes at room temperature. Thus, 4 is
chemically and kinetically competent to be an intermediate in the
catalytic process. Reaction of 4 with a mixture of C6H6 and C6D6
revealed a kinetic isotope effect of 3.6 ( 0.2. Catalytic reactions
conducted in this solvent mixture showed an essentially identical
kH/kD ) 3.8 ( 0.4. Reaction of 4 in a mixture of toluene and
trifluoromethylbenzene showed selectivity that was also identical
with that of the catalytic reactions. These similar selectivities further
substantiated the involvement of 4 in the catalytic process.
In conclusion, Ir(I) complexes containing readily available and
air-stable 2,2′-bipyridine catalyze the borylation of arenes by bis-
(pinacolato)diboron even at room temperature. The method provides
a simple and direct route for the synthesis of arylboronates that
traditionally have been prepared by transmetalation between aryl-
lithium or arylmagnesium reagents and trialkyl borates.
1/2[IrCl(COE) ] /dtbpy (5 mol %)8
+ H
(3)
2
2
B2pin2 +
B2pin2 +
2PhH
(60 equiv)
2PhBpin
83%
2
room temperature/4.5 h
1/2[IrCl(COE) ] /dtbpy (0.02 mol %)8
+ H (4)
2
2
2PhH
(60 equiv)
2PhBpin
80%
2
100 °C/16 h
Acknowledgment. J.F.H. and N.R.A. thank the National Sci-
ence Foundation (CHE-9986236 for J.F.H.) for support of this work.
Supporting Information Available: Experimental procedures and
spectral analyses of all reaction products (PDF). This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
Our studies subsequently focused on isolating likely Ir-boryl
intermediates. To do so, we generated the dtbpy- and COD-ligated
Ir(I) complexes [IrCl(dtbpy)(COD)] and [Ir(dtbpy)(COD)]OTf (2).
Addition of 1.1 equiv of diboron 1 to the triflate formed the Ir(III)
bis-boryl complex cis-[Ir(dtbpy)(COD)(Bpin)2]OTf (3) (eq 5).23
Reaction of the chloride did not generate an isolable boryl complex.
Although bis-boryl 3 catalyzed the reaction between C6D6 and B2-
pin2 to form PhBpin in 80% yield after 5 h at 80 °C, thermolysis
of 3 in C6D6 in the absence of added diboron regent, a reaction
that would complete the catalytic cycle, did not form PhBpin.
Instead it simply extruded B2pin2 in 75% yield and generated the
starting [Ir(dtbpy)(COD)]OTf.24
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1
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