Steric and chelate directing effects in aromatic borylation [3]

Full text of DOI:10.1021/ja0013069

12868
J. Am. Chem. Soc. 2000, 122, 12868-12869
Table 1. Isolated Yields (based on HBPin) and Isomer
Distributions for Catalytic Borylation of Aromatic Hydrocarbons
Catalyzed by Solutions of Compounds 1 and 3
Steric and Chelate Directing Effects in Aromatic
Borylation
Jian-Yang Cho, Carl N. Iverson, and Milton R. Smith, III*
Department of Chemistry, Michigan State UniVersity
East Lansing, Michigan 48824
ReceiVed April 14, 2000
ReVised Manuscript ReceiVed October 18, 2000
Hydrocarbon activation has attracted considerable attention
because hydrocarbon feedstocks are ubiquitous.1 Since metal-
catalyzed cross-couplings of aryl and alkyl boronic acids with
aryl halides represent one of the most general and widely applied
means for constructing C-C bonds, the generic conversion
depicted in eq 1 would have broad appeal.2 Indeed, stoichiometric,
photochemical catalytic, and thermal catalytic examples of this
type have been reported.3 We recently described the first thermal,
catalytic example shown in eq 1, where R-H is benzene and
R-H + H-BX2 f R-BX2 + H-H
(1)
HBX2 is pinacolborane (HBPin).4 Clearly, the synthetic utility
of catalytic borylation hinges on the demonstration of functional
group tolerance and regioselective activation for substituted
arenes. Herein, promising results in both respects are described.
Specifically, the compatibility of heteroatom substituents, as well
as amide and ester groups, is demonstrated. In addition, borylation
regioselectivity is sterically controlled for most substituted arenes.
Thus, catalytic borylations offer unique selectivities when com-
pared to traditional aromatic substitutions where electronic effects
determine the regioselectivity.5
In the initial borylations of substituted arenes, 20 mol %
solutions of Cp*Ir(PMe3)(H)(BPin) (1, Cp* ) η5-C5Me5) or
Cp*Ir(PMe3)(H)2 (2) were dissolved with HBPin in neat arene
solvents, and the reactions were run at 150 °C. Once borylation
had commenced, 31P NMR spectroscopy indicated that compound
1 was the predominant Ir species irrespective of the Ir starting
material. Analogous borylations were also performed using the
more active pre-catalyst Cp*Rh(η4-C6Me6) (3), which was recently
utilized by Hartwig and co-workers.3e After the borane was
consumed, product ratios were determined by GC analysis of
crude reaction mixtures. Isolated yields of isomer mixtures are
reported in Table 1, and product assignments were corroborated
by comparisons to authentic samples.6
a 20 mol % 1, generated in situ from compound 2 and HBPin at
150 °C. b 2 mol % 3 at 150 °C. c 20 mol % 1 at 150 °C. d GC yield
reported in ref 3e. e <1% of the isomer mixture is C6H5CH2BPin. f 3%
of the isomer mixture is C6H5CH2BPin. g 4% of the isolated product is
isomers of C6F4H(BPin). h 16% of the isolated product is isomers of
C6F4H(BPin). i Reaction was run in a 2:1 mixture of 1,3,5-C6H3F3:p-
xylene-d10. j C6HF3(BPin)2 (7%) and an isomer of C6H3F2(BPin) (6%).
l
k Products were not isolated. 3% of the isolated product is m-C6H4(Me)-
(CH2BPin). m 12% of the isolated product is m-C6H4(Me)(CH2BPin).
the catalytic borylation of C6D6 by HBPin in the presence of
m-C6H4Me(BPin) was examined. Under the reaction conditions
m-C6H4Me(BPin) did not isomerize and toluene was not gener-
ated. Thus, borylation products are kinetically determined. It is
noteworthy that arene C-H bonds are functionalized in the
presence of weaker benzylic C-H bonds.
A range of monosubstituted arenes was examined to determine
whether reaction conditions would tolerate heteroatom substituents
and to assess the generality for statistical meta/para substitution.
The results in Table 1 indicate that meta/para ratios are predomi-
nantly statistical with the largest deviations occurring for PhNMe2,
which favors para substitution, and anisole, which favors meta
substitution. For Rh-catalyzed reactions the deviations were
relatively small, but meta borylation of anisole is pronounced for
Ir. Since cumene gave a statistical distribution of meta and para
borylation products, electronic effects are responsible for enhanced
para selectivity for PhNMe2. Benzylic activation of toluene
increased for Rh (∼3% PhCH2BPin) versus Ir (∼1% PhCH2BPin).
Fluorinated arenes were also tested for compatibility. Ir- or
Rh-catalyzed borylation of C6HF5 gave C6F5BPin as the primary
product. Similarly, compound 3 catalyzed borylation in a 2:1
mixture of 1,3,5-C6H3F3 and p-xylene-d10 to yield C6H2F3BPin.
Attempts to prepare the di- and triborated compounds, C6HF3-
(BPin)2 and C6F3(BPin)3, from stoichiometric amounts of 1,3,5-
C6H3F3 in p-xylene-d10 yielded significant quantities of C6H3F2-
(BPin) (∼60% of the borylated products). The selectivity for C-H
activation is significant considering that Rh-catalyzed reactions
of silanes with C6F5H give C-F activation products exclusively.7
In a simple assay of regioselectivity toluene borylation primarily
gave a statistical distribution of m- and p-C6H4Me(BPin). To
ensure that the isomer distribution was kinetically determined,
* Author for correspondence. E-mail: smithmil@msu.edu.
(1) For accounts and reviews of hydrocarbon activation, please see: (a)
Jones, W. D.; Feher, F. J. Acc. Chem. Res. 1989, 22, 91-100. (b) Arndtsen,
B. A.; Bergman, R. G.; Mobley, T. A.; Peterson, T. H. Acc. Chem. Res. 1995,
28, 154-162. (c) Crabtree, R. H. Chem. ReV. 1995, 95, 987-1007. (d) Stahl,
S. S.; Labinger, J. A.; Bercaw, J. E. Angew. Chem., Int. Ed. 1998, 37, 2180-
2192.
(2) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483.
(3) (a) Waltz, K. M.; He, X.; Muhoro, C.; Hartwig, J. F. J. Am. Chem.
Soc. 1995, 117, 11357-11358. (b) Waltz, K. M.; Hartwig, J. F. Science 1997,
277, 211-213. (c) Waltz, K. M.; Muhoro, C. N.; Hartwig, J. F. Organome-
tallics 1999, 18, 3383-3393. (d) Chen, H. Y.; Hartwig, J. F. Angew. Chem.,
Int. Ed. 1999, 38, 3391-3393. (e) Chen, H. Y.; Schlecht, S.; Semple, T. C.;
Hartwig, J. F. Science 2000, 287, 1995-1997.
(4) Iverson, C. N.; Smith, M. R., III. J. Am. Chem. Soc. 1999, 121, 7696-
7697.
(5) (a) Some preliminary findings have been presented: Smith, M. R., III;
Cho, J.-Y.; Iverson, C. N.: 219th ACS National Meeting, San Francisco, CA,
March 26-30, 2000 (INOR 367). (b) Iverson, C. N., Ph.D. Dissertation,
Michigan State University, 1999.
(6) Experimental details and spectroscopic data are included in the
Supporting Information.
10.1021/ja0013069 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/06/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 51, 2000 12869
Table 2. Relative Ratios of Arylboronic Esters for Borylations of
Equimolar Mixtures of Substituted Arenes Catalyzed by Compounds
2 and 3
more, selective meta functionalization is difficult and generally
requires strong electron-withdrawing or -donating groups for
electrophilic or nucleophilic aromatic substitution, respectively.
Since most substituents in Table 1 block ortho activation, selective
borylation should be possible for 1,3-substituted arenes. Indeed,
this was observed for 1,3-C6H4(CF3)2, m-xylene, and 2,6-lutidine
where aromatic borylation is observed only at the common meta
position (Table 1). The difference in selectivity between the Ir
and Rh catalysts for benzylic versus aromatic activation of toluene
is amplified for m-xylene. For Rh, 12% of the borylation products
result from benzylic activation compared to 3% for Ir. Hence, Ir
catalysts may offer advantages over Rh systems if the turnover
numbers can be increased.
Two classes of arene functionalization that merit comparison
to catalytic borylation are ortho lithiations12,13 and metal-catalyzed
arene olefination and carbonylation reactions.14-16 Often, a
chelating group that directs functionalization at an ortho C-H
position is required. Ortho lithiation of arenes is achieved at low
temperature, and the aryllithium intermediates are reacted with
electrophiles, while olefination and carbonylation conditions are
more similar to those for aromatic borylation. In addition to
introducing a synthetically versatile B-C bond, catalytic bory-
lations do not require activating or directing groups. Also, the
chelate effects are weaker than in the aforementioned methods,
which may allow for differentiation between amides and weaker
chelating groups. The most unique feature of the borylation
reaction is the steric influence of aromatic substituents on the
regiochemistry of borylation. The extension of steric directing
effects to selective functionalization of 1,3-substituted aromatics
is nicely demonstrated in the case of m-xylene where aromatic
borylation occurs exclusively at the 5-position. The only other
examples where m-xylene is selectively functionalized at this site
are stoichiometric C-H activations by transition metal com-
plexes11,17 and alkylations with sterically hindered carbon elec-
trophiles.18
For arenes bearing ester or amide functionality reduction of
the carbonyl groups could potentially compete with aromatic
borylation. Rh-catalyzed borylations of ethyl benzoate and diethyl
benzamide gave primarily aromatic borylation. For ethyl benzoate,
the extent of meta/para borylation predominates with a modest
increase in ortho borylation, whereas diethyl benzamide gave
o-C6H4(C(O)NEt2)(BPin) as the major isomer. The shift in
substitution pattern is consistent with chelate-directed borylation
at the ortho position. Since resonance structure B has a larger
contribution for an amide relative to an ester, chelation of the
amide oxygen to Rh or B in the catalytically active species is
more favorable for the amide.8 The statistical meta:para ratio for
the minor isomers suggests that chelate and sterically directed
pathways compete.
To probe the role of electronic effects, relative product ratios
from catalytic borylations in equimolar mixtures of substituted
arenes were determined (Table 2). Electron-deficient arenes are
generally more reactive in both systems, and relative rate
differences for Ir are more pronounced than those for Rh. Ir-
catalyzed borylation in neat PhNMe2 was extremely slow. Factors
besides deactivation of the arene ring may be responsible because
cumene borylation in PhNMe2/cumene mixtures was suppressed
relative to borylation in neat cumene. The electronic effects on
relative reaction rates contrast those observed in arylboronate ester
formation from Fe boryl complexes3c and are similar to trends in
nucleophilic aromatic substitutions of arene metal complexes.9
However, the regioselectivity for nucleophilic substitutions is very
sensitive to electronic variations,10 in contrast to the statistical
product distributions in Table 1.
Statistical ratios for meta and para activation are typical for
C-H activations by Cp*Rh(PMe3). Although Jones and Perutz
have shown that activation of electron-deficient arenes by Cp*Rh-
(PMe3) is thermodynamically and perhaps kinetically preferred,11
the origins of the relative rate differences in Table 2 cannot be
interpreted until mechanisms for Ir- and Rh-catalyzed borylation
are firmly established. The potential mechanistic complexity is
exemplified by the observation of traces of Cp*BPin and Cp*H
in Ir-catalyzed reactions and Cp*H in Rh-catalyzed reactions at
20 mol % catalyst loading. Consequently, the generation of active
species via Cp* loss cannot be discounted.
In conclusion, this preliminary study demonstrates generality
and selectivities that bode favorably for synthetic applications of
aromatic borylations in arene functionalization.
Acknowledgment. We appreciate support from the National Science
Foundation (CHE-9817230). C.N.I. gratefully acknowledges support from
Carl H. Brubaker and Dow Fellowships. We thank Aaron Odom for
helpful discussions and the reviewers for their constructive comments.
Supporting Information Available: Synthetic and spectroscopic (1H,
19F, and 11B NMR data) details for all new compounds (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
JA0013069
(12) Snieckus, V. Chem. ReV. 1990, 90, 879-933.
(13) Buchwald has demonstrated that the benzyne complexes derived from
C-H activation of group 4 aryl complexes are versatile reagents for ortho
functionalization: Buchwald, S. L.; Nielsen, R. B. Chem. ReV. 1988, 88,
1047-1058.
(14) (a) Pd-catalyzed addition of CO2 to benzene proceeds under mild
conditions, and regioselectivities for substituted arenes follow electrophilic
substitution patterns. Please see: Lu, W. J.; Yamaoka, Y.; Taniguchi, Y.;
Kitamura, T.; Takaki, K.; Fujiwara, Y. J. Organomet. Chem. 1999, 580, 290-
294. (b) For Pd-catalyzed alkyne insertions into ortho aromatic C-H bonds
and references to related olefinations, see: Jia, C. G.; Piao, D. G.; Oyamada,
J. Z.; Lu, W. J.; Kitamara, T.; Fujiwara, Y. Science 2000, 287, 1992-1995.
(15) (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature 1993, 366, 529-531. (b) Murai, S.; Chatani,
N.; Kakiuchi, F. Pure Appl. Chem. 1997, 69, 589-594.
Steric effects in aromatic substitution are uncommon, and
electronic effects generally dictate substitution patterns. Further-
(7) Aizenberg, M.; Milstein, D. Science 1994, 265, 359-361.
(8) Related amide direction in regioselective olefin hydroboration has been
reported: Evans, D. A.; Fu, G. C. J. Am. Chem. Soc. 1991, 113, 4042-4043.
(9) Kane-Maguire, L. A. P.; Sweigart, D. A. Inorg. Chem. 1979, 18, 700-
706.
(10) Semmelhack, M. F.; Clark, G. J. Am. Chem. Soc. 1977, 99, 9, 1675-
1676.
(16) For related Rh-catalyzed ortho olefination of aromatic ketones, please
see: Lenges, C. P.; Brookhart, M. J. Am. Chem. Soc. 1999, 121, 6616-6623.
(17) Green, M. L. H.; Joyner, D. S.; Wallis, J. M. J. Chem. Soc., Dalton
Trans. 1987, 2823-2830.
(18) (a) Voronenkov, A. V.; Aliev, A. A.; Kutrakov, A. V.; Voronenkov,
V. V. Zh. Org. Khim. 1999, 35, 324-326. (b) For selective alkylation of
m-xylene at the 5-position, see: Fujita, K.; Oomori, H.; Yoshikazu, H.
(Mitsubishi Petrochemical Co. Ltd.). Jpn. Kokai Tokyo Koho 91 24,021, 1991.
(11) Selmeczy, A. D.; Jones, W. D.; Osman, R.; Perutz, R. N. Organo-
metallics 1995, 14, 5677-5685.