Pushing the Ir-catalyzed C-H polyborylation of aromatic compounds to maximum capacity by exploiting reversibility

Article abstract of DOI:10.1021/ja307547j

Small amounts of base (e.g., 10% potassium t-butoxide or sodium methoxide) have been found to promote equilibration of the kinetically favored products from Ir-catalyzed C-H polyborylations of aromatic compounds. In the presence of excess borylating agent, bis(pinacolato)diborane (B₂pin₂), repetitive deborylation/reborylations reposition the Bpin substituents until a pattern that accommodates the maximum number of Bpin substituents is achieved. A high-yield, one-step synthesis of 1,3,5,7,9-pentakis(Bpin)corannulene is reported that illustrates this useful extension of the Ir-catalyzed borylation reaction.

Full text of DOI:10.1021/ja307547j

Communication
pubs.acs.org/JACS
Pushing the Ir-Catalyzed C−H Polyborylation of Aromatic
Compounds to Maximum Capacity by Exploiting Reversibility
Maria N. Eliseeva and Lawrence T. Scott*
Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467-3860, United States
S
* Supporting Information
ortho/peri-prohibition is the one embodied in the 1,3,5,7-
ABSTRACT: Small amounts of base (e.g., 10% potassium
t-butoxide or sodium methoxide) have been found to
promote equilibration of the kinetically favored products
from Ir-catalyzed C−H polyborylations of aromatic
compounds. In the presence of excess borylating agent,
bis(pinacolato)diborane (B2pin2), repetitive deborylation/
reborylations reposition the Bpin substituents until a
pattern that accommodates the maximum number of Bpin
substituents is achieved. A high-yield, one-step synthesis of
1,3,5,7,9-pentakis(Bpin)corannulene is reported that illus-
trates this useful extension of the Ir-catalyzed borylation
reaction.
isomer (4). This isomer never accumulates to any significant
extent, because it borylates easily at the one remaining open
position under the reaction conditions to yield the desired
1,3,5,7,9-pentakis(Bpin)corannulene (1).
oronic acids and their derivatives have rapidly risen to a
B
position of preeminence as versatile synthetic precursors
to a wide range of functionalized and C−C coupled arenes.1 It
is only natural, therefore, that the direct borylation of aromatic
compounds by Ir-catalyzed C−H activation at unsubstituted
sites has drawn considerable attention.2 For several projects in
our own research on geodesic polyarenes, we foresee numerous
potential uses for 1,3,5,7,9-pentakis(Bpin)corannulene (1).3−5
Herein we report the gratifying results of our investigations on
the direct borylation of corannulene.6
The low yield of 1 obtained from these experiments impelled
us to tinker with the reaction conditions, in an effort to increase
the relative amount of 1 produced. Our efforts were rewarded
by the discovery of conditions that yield 1 virtually
quantitatively, producing almost none of the two tetrakis-
1
(Bpin)corannulenes 2 and 3. A comparison of the H NMR
spectrum of the crude product mixture obtained under standard
reaction conditions (Figure 1 top) with that of the crude
product mixture obtained under these modified reaction
conditions (Figure 1 bottom) dramatically underscores the
success of our new borylation procedure.
The polyborylation of corannulene can be driven essentially
completely to 1 by running the reaction at high concentration
with excess B2pin2 and a catalytic amount of base (e.g., 10%
potassium t-butoxide or sodium methoxide) for 4 days in THF
at 85 °C in a pressure vessel, along with a high loading (20%)
of the standard [Ir(OMe)COD]2 catalyst in a 1:2 molar ratio
with 4,4′-dimethylbipyridyl (see the Supporting Information for
details). The reaction is slow but reliable.
Under standard conditions,7 the direct borylation of
corannulene with B2pin2, catalyzed by [Ir(OMe)COD]2 in
the presence of various bipyridyl ligands, does indeed produce
1,3,5,7,9-pentakis(Bpin)corannulene (1), albeit always as a
mixture with the two tetrakis(Bpin)corannulenes 2 and 3, in a
1/2/3 ratio of approximately 1:3:1. As expected, the large steric
demand of each Bpin substituent precludes borylation not only
in the ortho position on the same ring but also in the peri
position on the adjacent ring.7 The peri-Bpin substituents that
flank the fifth rings in compounds 2 and 3 block both C−H
sites in those rings, so the reactions that lead to these undesired
products (multiple pathways) all stop after the fourth
borylation. The only other substitution pattern that accom-
modates four Bpin groups on corannulene without violating the
Monitoring the reaction verifies that a mixture of 1, 2, and 3
is formed relatively rapidly in the first day and that the
concentration of the pentasubstituted product (1) then slowly
Received: April 27, 2012
© XXXX American Chemical Society
A
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Figure 2. The complete conversion of 1,4-bis(Bpin)benzene (5) to
1,3,5-tris(Bpin)benzene (6) under our new borylation conditions
clearly confirms the operation of a deborylation/reborylation “self-
correction” process that repositions the Bpin substituents until a
pattern that accommodates the maximum number of Bpin substituents
is achieved.
mixture chromatographically, which is not trivial, we have
found it convenient simply to concentrate the filtrate to dryness
and heat the residue with acetic acid and HCl to deborylate any
2 or 3 that had formed, along with the remaining 1, back to
corannulene, which can easily be isolated and recycled. From
this very simple workup, hardly any corannulene is lost that is
not converted to pure 1.
No more than five Bpin substituents can be accommodated
on corannulene without violating the ortho/peri-prohibition,
and this level of substitution can be achieved only in the
1,3,5,7,9-isomer (1). Thus, 1,3,5,7,9-pentakis(Bpin)-
corannulene (1) can be considered “saturated” with Bpin
substituents; by the new procedure, the polyborylation has
been pushed all the way to the maximum capacity of the
corannulene. The buildup and subsequent disappearance of the
“wrong” tetrakis(Bpin)corannulenes 2 and 3 clearly indicates
that these new conditions provide a kinetically accessible pathway
for deborylation of these isomers back temporarily to the
tris(Bpin)corannulene stage, thus, imparting a self-correction
aspect to the synthesis of 1.9 A net rearrangement of 2 or 3 to
isomer 4 puts the compound on the pathway to 1. Only one
Bpin group must be moved to isomerize 2 into 4. Isomer 3
must rearrange first to 2 to be transformed into 4.
To demonstrate this deborylation/reborylation unambigu-
ously in a simpler system, we exposed 1,4-bis(Bpin)benzene
(5) to our new borylation conditions and observed its complete
conversion to 1,3,5-tris(Bpin)benzene (6) over a period of 4
days (Figure 2). In light of this result, it is not surprising that
the direct borylation of benzene likewise proceeds all the way
to 1,3,5-tris(Bpin)benzene (6) under these conditions.
To learn more about this new “exhaustive borylation”
method, we have examined biphenyl and have found that it
behaves in exactly the same manner as corannulene. Thus,
borylation of biphenyl under standard conditions produces a
complicated mixture of di-, tri-, and tetraborylated derivatives
(see the Supporting Information). Under our exhaustive
borylation conditions, on the other hand, all of these products
are efficiently converted to 3,5,3′,5′-tetrakis(Bpin)biphenyl (7,
Figure 3). The majority of the product can be isolated in pure
form simply by precipitation with methanol (87% isolated
yield). Symmetrical polyborylated aromatic hydrocarbons such
as 1, 6, and 7 represent attractive platforms from which to build
dendrimers and other potentially useful materials.
The geodesic curvature of corannulene expands the exocyclic
CCC bond angle at each of the five quaternary carbon atoms
on the rim to nearly 130°, and this widening reduces the steric
repulsion from the peri-hydrogen atoms enough for the
molecule to accommodate Bpin groups adjacent to every ring
junction. In planar polycyclic aromatic hydrocarbons, the
corresponding exocyclic CCC bond angles are smaller
1
Figure 1. H NMR spectra (500 MHz, C6D6) of the crude product
mixtures obtained from the Ir-catalyzed polyborylation of corannulene.
Top: under standard conditions. Bottom: under new conditions. The
signals for hydrogens flanked by both an ortho- and a peri-Bpin
neighbor appear in the 9.65−9.75 ppm range. The signals for
hydrogens flanked by only one Bpin neighbor, either ortho- or peri-,
appear in the 8.75−9.05 ppm range.
rises at the expense of the two tetrasubstituted products (2 and
3). Thus, the success of these new polyborylation conditions
clearly is not a consequence of altered kinetics that favor
preferential formation of 1 but depends instead on the
operation of some slower substituent redistribution process.
This redistribution process does not go to completion if the
reaction is run for fewer than 4 days or at significantly lower
concentrations, lower temperatures, or lower catalyst loadings.
Catalytic amounts of base are not part of the standard
conditions for arene borylations but play a critical role in this
new procedure. Even Cs2CO3, K2CO3, and CsF can be used as
the base in this reaction. A screening of ligands revealed that
4,4′-dimethylbipyridyl is superior to the normal 4,4′-di-t-
butylbipyridyl, for reasons that are not immediately apparent
to us.8 Further optimization would likely uncover conditions
that allow lower catalyst loadings, but this is no longer our
highest priority.
The majority of the 1,3,5,7,9-pentakis(Bpin)corannulene (1)
can be isolated in analytically pure form simply by precipitating
it from the reaction mixture with methanol. The remaining
B2pin2, catalyst, ligand, base, and byproducts all remain in the
filtrate. Rather than trying to separate the remaining 1 from this
B
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Journal of the American Chemical Society
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Figure 3. The complicated mixture of di-, tri-, and tetraborylated
biphenyls formed under standard borylation conditions can be
efficiently converted to 3,5,3′,5′-tetrakis(Bpin)biphenyl (7) in high
yield.
(∼120°), and the cumulative effects of multiple steric
repulsions from peri-hydrogen atoms makes it more difficult
to accommodate Bpin groups adjacent to every ring junction.
The borylation of pyrene, for example, can be pushed to
2,4,7,9-tetrakis(Bpin)pyrene (8), which has Bpin groups
adjacent to two ring junctions, but we have been unable to
obtain 1,3,5,7,9-pentakis(Bpin)pyrene (9), which would put
Bpin groups adjacent to all four ring junctions.10,11 The
surprising absence of the 2,4,7,10-tetrakis(Bpin)pyrene (10), an
isomer of 8 that also has Bpin groups adjacent to only two ring
junctions, reflects the greater strain in the latter isomer.11 The
1,3,6,8-isomer of tetrakis(Bpin)pyrene (11) would have Bpin
groups adjacent to four of the ring junctions and is predicted to
be even more strained;11 that isomer is not seen, either. The
deborylation/reborylation process eventually puts four Bpin
groups on every molecule and ultimately funnels all the
tetrakis(Bpin)pyrenes to the most stable isomer, 8.
Coronene is another challenging polycyclic aromatic hydro-
carbon with 120° exocyclic CCC bond angles. Borylation of
coronene under standard conditions produces a complicated
mixture of Bpin-substituted coronenes with varying numbers of
Bpin groups attached, together with unsubstituted coronene.
Under our equilibrating conditions with excess B2pin2,
however, a significant fraction of the material gets converted
to the 1,4,7,10-isomer of tetrakis(Bpin)coronene (12), which
can be isolated pure by precipitation with methanol, albeit only
in 10−20% yield. Mass spectrometry confirms the formation
also of pentakis- and hexakis(Bpin)coronenes. Chromatography
yields a fraction enriched in the symmetrical 1,3,5,7,9,11-
hexakis(Bpin)coronene (13), which gives rise to a tall singlet at
1
10.26 ppm in the H NMR spectrum (see the Supporting
Information for details).
Catalysts facilitate reactions not only in the forward direction
(e.g., borylation) but, inescapably, also in the reverse direction.
In principle, therefore, all arene borylations should eventually
lead to exhaustive borylation, even under the normal borylation
conditions, without base, if they are run long enough with an
Figure 4. Conversion of 1 to 14, the precursor used for the first
chemical synthesis of a short, isomerically pure [5,5]nanotube (15).
Suzuki conditions: Pd(dppf)Cl2, Cs2CO3, THF, 95 °C, 50−70% yield
(87−93% for each C−C bond-forming step).
̂
excess of borylating agent (Le Chatlier’s principle). The more
exothermic the forward reaction, of course, the slower will be
the reverse reaction. What we have found is that catalytic
amounts of base accelerate the deborylation of arenes under the
borylation conditions, thus, making it feasible to achieve
maximum capacity in a finite time frame.
potassium t-butoxide. The iridium catalyst is required for the
deborylation.
It is tempting to speculate that the base adds to a Bpin
substituent, thereby activating it for transmetalation,12 but we
have no experimental evidence for this mechanistic hypothesis.
We do know that 1,4-bis(Bpin)benzene (5) does not suffer
deborylation in the absence of [Ir(OMe)COD]2, when heated
for 4 days at 85 °C in THF with 4,4′-dimethylbipyridyl and
We have begun using 1,3,5,7,9-pentakis(Bpin)corannulene
(1) for a variety of purposes. A 5-fold Suzuki coupling with 2-
bromo-1,3-dichlorobenzene, for example, provides an improved
route to 1,3,5,7,9-pentakis(2,6-dichlorophenyl)corannulene
(14), the precursor from which we have recently synthesized
a short, isomerically pure [5,5]nanotube (15) by a “bottom up”
C
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Journal of the American Chemical Society
Communication
approach (Figure 4).13 The isolated yield of 14 from 1 is 50−
70% (average from multiple experiments), which corresponds
to 87−93% for each Suzuki coupling reaction.14
J.; Steel, P. G.; Marder, T. B. Synlett 2009, 147. (o) Harrisson, P.;
Morris, J.; Marder, T. B.; Steel, P. G. Org. Lett. 2009, 11, 3586.
(p) Mkhalid, I. A. I.; Conventry, D. N.; Albesa-Jove, D.; Batsanov, A.
S.; Howard, J. A. K.; Perutz, R. N.; Marder, T. B. Angew. Chem., Int. Ed.
2006, 45, 489.
(3) The name 1,3,5,7,9-pentakis(Bpin)corannulene is a shorthand
name for 1,3,5,7,9-pentakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)corannulene.
We hope that others will find additional uses for this new
method to push the Ir-catalyzed C−H polyborylation of
aromatic compounds to maximum capacity.
ASSOCIATED CONTENT
* Supporting Information
(4) (a) Mattarella, M.; Siegel, J. S. Org. Biomol. Chem. 2012, 10, 5799.
(b) Butterfield, A. M.; Gilomen, B.; Siegel, J. S. Org. Process Res. Dev.
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(d) Eisenberg, D.; Quimby, J. M.; Jackson, E. A.; Scott, L. T.; Shenhar,
R. Chem. Commun. 2010, 46, 9010. (e) Steinberg, B. D.; Jackson, E. A.;
Filatov, A. S.; Wakamiya, A.; Petrukhina, M. A.; Scott, L. T. J. Am.
Chem. Soc. 2009, 131, 10537. (f) Jackson, E. A.; Steinberg, B. D.;
Bancu, M.; Wakamiya, A.; Scott, L. T. J. Am. Chem. Soc. 2007, 129,
484. (g) Mizyed, S.; Georghiou, P.; Bancu, M.; Cuadra, B.; Rai, A. K.;
Cheng, P.; Scott, L. T. J. Am. Chem. Soc. 2001, 123, 12770. (h) Scott,
L. T.; Jackson, E. A.; Zhang, Q.; Steinberg, B. D.; Bancu, M.; Li, B. J.
Am. Chem. Soc. 2012, 134, 107.
(5) See also: (a) Wu, Y.-T.; Bandera, D.; Maag, R.; Linden, A.;
Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 2008, 130, 10729.
(b) Hayama, T.; Baldridge, K. K.; Wu, Y.-T.; Linden, A.; Siegel, J. S. J.
Am. Chem. Soc. 2008, 130, 1583. (c) Grube, G. H.; Elliott, E. L.;
Steffens, R. J.; Jones, C. S.; Baldridge, K. K.; Siegel, J. S. Org. Lett.
2003, 5, 713. (d) Seiders, T. J.; Elliott, E. L.; Grube, G. H.; Siegel, J. S.
J. Am. Chem. Soc. 1999, 121, 7804. (e) Seiders, T. J.; Baldridge, K. K.;
Elliott, E. L.; Grube, G. H.; Siegel, J. S. J. Am. Chem. Soc. 1999, 121,
7439.
■
S
Spectra, combustion analysis, and experimental procedures for
the synthesis, isolation, and purification of 1; information about
the effects of varying the solvent, temperature, time, ligand,
base, borylating agent, concentration, and stoichiometry;
procedures for the recovery of corannulene from mixtures of
borylated corannulene (deborylation); details for the reaction
in Figure 2 and for the direct borylation of benzene, biphenyl,
pyrene, and coronene; spectra for new polyborylated hydro-
carbons 7, 8, 12, and 13; details for the Suzuki coupling
reaction in Figure 4; XYZ coordinates and energies from
calculations on the isomeric tetrakis(Bpin)pyrenes 8, 10, and
11. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
lawrence.scott@bc.edu
■
(6) We have previously prepared 1,3,5,7,9-pentakis(Bpin)corannu-
lene (1) in a less direct manner from 1,3,5,7,9-pentachloro-
corannulene: Steinberg, B. D. Ph.D. Dissertation, Boston College,
Chestnut Hill, MA, 2009.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(7) (a) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard, J. A.
K.; Marder, T. B.; Perutz, R. N. Chem. Commun. 2005, 2172.
(b) Crawford, A. G.; Liu, Z.; Mkhalid, I. A. I.; Thibault, M.-H.;
Schwarz, N.; Alcaraz, G.; Steffen, A.; Collings, J. C.; Batsanov, A. S.;
Howard, J. A. K.; Marder, T. B. Chem.–Eur. J. 2012, 18, 5022.
(c) Batsanov, A. S.; Howard, J. A. K.; Albesa-Jove, D.; Collings, J. C.;
Liu, Z.; Mkhalid, I. A. I.; Thibault, M.-H.; Marder, T. B. Cryst. Growth
Des. 2012, 12, 2794. (d) Crawford, A. G.; Dwyer, A. D.; Liu, Z.;
Steffen, A.; Beeby, A.; Palsson, L.-O.; Tozer, D. J.; Marder, T. B. J. Am.
Chem. Soc. 2011, 133, 13349.
■
The authors are extremely grateful to Prof. Dr. Jay S. Siegel and
Anna M. Butterfield (University of Zurich) for a generous gift
of corannulene and to Dr. Dustin Cefalo and Frontier
Scientific, Inc. (Logan, UT) for generous gifts of B2(pin)2.
This research was supported financially by the National Science
Foundation and the Department of Energy. We thank the
National Science Foundation also for funds to purchase an X-
ray diffractometer.
(8) This intriguing point is discussed further in the Supporting
Information.
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