Rhodium(I)-catalyzed borylation of nitriles through the cleavage of carbon-cyano bonds

Article abstract of DOI:10.1021/ja2095975

The reaction of aryl cyanides with diboron in the presence of a rhodium/Xantphos catalyst and DABCO affords arylboronic esters via carbon-cyano bond cleavage. This unprecedented mode of reactivity for a borylrhodium species allows the regioselective intro

Full text of DOI:10.1021/ja2095975

Communication
pubs.acs.org/JACS
Rhodium(I)-Catalyzed Borylation of Nitriles through the Cleavage of
Carbon−Cyano Bonds
Mamoru Tobisu,*,†,‡ Hirotaka Kinuta,† Yusuke Kita,† Emmanuelle Remond,† and Naoto Chatani*,†
́
†Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
‡Center for Atomic and Molecular Technologies, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan
S
* Supporting Information
prompted us to investigate the potential of other main-group
reagents in regard to the cleavage of C−CN bonds.8 After some
ABSTRACT: The reaction of aryl cyanides with diboron
in the presence of a rhodium/Xantphos catalyst and
DABCO affords arylboronic esters via carbon−cyano bond
cleavage. This unprecedented mode of reactivity for a
borylrhodium species allows the regioselective introduc-
tion of a boryl group in a late stage of synthesis.
experimentation, we were intrigued to find that the rhodium-
catalyzed reaction of nitrile 1 in the presence of diboron 2
afforded trace levels of borylated product 3 (4% yield by GC;
Table 1, entry 1). Further investigation revealed that the
a
Table 1. Optimization Studies
rylboronic acids and their derivatives are versatile reagents
A
in modern organic synthesis.1 Traditional methods for
their preparation involve the reaction of either organolithium or
-magnesium reagents with boron-centered electrophiles. Recent
efforts have been focused on the development of more
functional-group-tolerant catalytic methods. In this context,
two types of catalytic borylation reactions have been
established. The catalytic borylation of aryl halides can be
achieved using diboron or hydroboron reagents (Scheme 1a).2
Scheme 1. Catalytic Borylation Reactions
a
Reaction conditions: 1 (0.50 mmol), 2 (1.0 mmol), [RhCl(cod)]2
(0.025 mmol), and ligand (0.050 mmol) in toluene (0.5 mL) at 100
b
°C for 3 h. Run for 15 h using 0.10 mol of the indicated ligand.
Aromatic C−H bonds can also be borylated directly in the
presence of a rhodium or iridium catalyst (Scheme 1b).3 Herein
we report a new class of catalytic borylation whereby aryl
cyanides can be borylated through cleavage of the carbon−
cyano (C−CN) bond (Scheme 1c).
We have recently developed a series of catalytic methods to
convert C−CN bonds into C−Si,4 C−H,5 and C−C4b,6 bonds
in the presence of a rhodium catalyst and organosilicon
reagents. In these reactions, a silylrhodium complex, which is
generated in situ through the reaction of a Rh(I) precatalyst
with an organosilicon reagent, is postulated to be the
catalytically active species. This active species mediates the
cleavage of the C−CN bond via silylrhodation of the cyano
group and the extrusion of silyl isocyanide.7 The unique
reactivity of this silylrhodium species toward C−CN bonds
addition of a base and phosphine ligands improved the yield of
3.9 The use of 1,4-diazabicyclo[2.2.2]octane (DABCO) as the
base and Xantphos as the ligand proved to be the optimal
combination for a successful rhodium-catalyzed nitrile
borylation (entry 10).10 To date, the activation of C−CN
bonds in catalytic reactions has required the use of either Ni(0)
or silylmetal complexes.11 The present reaction represents the
first example of C−CN bond cleavage in the presence of a
borylmetal species without the need for a silylmetal complex or
Ni(0).
Received: October 12, 2011
Published: December 13, 2011
© 2011 American Chemical Society
115
dx.doi.org/10.1021/ja2095975 | J. Am. Chem.Soc. 2012, 134, 115−118

Journal of the American Chemical Society
Communication
The optimized conditions for 1 proved to be general for the
rhodium-catalyzed borylation of a range of aryl cyanides (Table
demanding cyanides proceeded more efficiently using the less
bulky PPh3 ligand, to afford ortho-substituted arylboronic esters
in good yields (entries 11−13). A boryl group protected with
1,8-diaminonaphthalene was also tolerated, furnishing a
diborylated arene, which may be applied to sequential cross-
coupling cascades (entry 14).13 The methodology can also be
successfully applied to fused (entries 15 and 16) and ferrocene-
containing (entry 22) substrates. Moreover, a range of
heteroaromatic substrates, including pyrroles (entry 17),
thiophenes (entry 18), indoles (entries 19 and 20), and
quinolines (entry 21), underwent this decyanative borylation in
an efficient manner. Alkenyl cyanides were also examined as
potential substrates. Monosubstituted acrylonitrile derivatives
such as cinnnamonitrile did not deliver the desired products
under the optimized conditions.14 In contrast, α,β- and β,β-
disubstituted acrylonitriles proved to be suitable substrates,
producing their corresponding alkenylboronic esters (entries
23−25). Although alkyl cyanides were generally inapplicable,
benzylic substrates were exceptionally reactive, affording the
corresponding benzylboronic esters (entry 26). This protocol
can also be applied to nitriles in biorelated compounds such as
amino acid derivatives (entry 27) and pesticides (entry 28)15 to
afford the corresponding borylated products, which can act as
versatile platforms for further derivatization.
a
Table 2. Rh-Catalyzed Borylation of Nitriles with 2
A proposed mechanism for this rhodium-catalyzed nitrile
borylation is outlined in Scheme 2. The reaction of the
Scheme 2. A Possible Mechanistic Pathway
rhodium precatalyst A with diboron 2 initially generates
borylrhodium B. The formation of B(nep)−Cl (nep =
neopentylglycolate) was confirmed by 11B NMR analysis of
the stoichiometric reaction of [RhCl(cod)]2, Xantphos, and
2.16 The addition of B to the nitrile then forms the
iminylrhodium species C,17,18b which is followed by E/Z
isomerization. β-Aryl elimination18 generates arylrhodium E
and boryl cyanide F.19 Finally, the reaction of E with 2 affords
the borylated product and regenerates B.
a
Reaction conditions: nitrile (0.50 mmol), 2 (1.0 mmol), [RhCl-
(cod)]2 (0.025 mmol), Xantphos (0.10 mmol), and DABCO (0.5
b
mmol) in toluene (0.5 mL) at 100 °C for 15 h. Isolated yields based
c
d
on nitrile. Nep = neopentylglycolate. PPh3 (0.15 mmol) was used as
e
f
the ligand. Run for 48 h. Yield was determined by 1H NMR analysis
because of the instability of the boronic ester during purification.
The ortho-directing ability of the cyano group20 allows a
reactivity pattern that cannot be achieved using other
borylation methodologies (Scheme 3). The C−H bond at the
ortho position of benzonitrile (4) can be directly arylated using
palladium catalysis20g to form the 2-cyanobiphenyl derivative 6,
which can then be borylated using a rhodium catalyst and 2.
Thus, benzonitriles can serve as simple precursors for 2-
substituted phenylboronic acids. The inherent stability of the
cyano group under typical transition-metal-catalyzed conditions
allows the combined use of catalytic borylation methods. This
leads to the regioselective introduction of a boryl group at a
g
h
[Rh(cod)2]BF4 (0.10 mmol) was used as a catalyst at 80 °C. Rh
catalyst (0.050 mmol) and Xantphos (0.20 mmol) were used.
2). Common functional groups, including fluorides (entries 2,
4, and 28), esters (entry 3, 27, and 28), ethers (entries 6, 9, and
28), and amines (7 and 10), were all compatible with this
catalytic borylation reaction. Of particular note, aryl chlorides
survived under these conditions (entries 5 and 27),12 which
would allow orthogonal functionalization via conventional
cross-coupling technologies. The application of sterically
116
dx.doi.org/10.1021/ja2095975 | J. Am. Chem.Soc. 2012, 134, 115−118

Journal of the American Chemical Society
Communication
Instrumental Analysis Center, Faculty of Engineering, Osaka
University, for assistance with 11B and 31P NMR spectroscopy
and high-resolution mass spectrometry.
Scheme 3. Synthetic Applications
REFERENCES
■
(1) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Suzuki, A.; Brown, H. C. Organic Synthesis via Boranes; Aldrich:
Milwaukee, WI, 2003. (c) Hall, D. G. Boronic Acids; Wiley-VCH:
Weinheim, Germany, 2005. (d) Miyaura, N. Bull. Chem. Soc. Jpn. 2008,
81, 1535.
(2) Selected examples: (a) Ishiyama, T.; Miyaura, N. Chem. Rec.
2004, 3, 271. (b) Zhu, W.; Ma, D. Org. Lett. 2005, 8, 261. (c) Wilson,
D. A.; Wilson, C. J.; Moldoveanu, C.; Resmerita, A.-M.; Corcoran, P.;
Hoang, L. M.; Rosen, B. M.; Percec, V. J. Am. Chem. Soc. 2010, 132,
1800.
(3) Reviews: (a) Cho, J.-Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.;
Smith III, M. R.; Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.;
Anastasi, N. R.; Hartwig, J. F.; Kellogg, R. M. Chemtracts 2002, 15,
195. (b) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. Chem. Rev. 2010, 110, 890.
(4) (a) Tobisu, M.; Kita, Y.; Chatani, N. J. Am. Chem. Soc. 2006, 128,
8152. (b) Tobisu, M.; Kita, Y.; Ano, Y.; Chatani, N. J. Am. Chem. Soc.
2008, 130, 15982.
(5) (a) Tobisu, M.; Nakamura, R.; Kita, Y.; Chatani, N. J. Am. Chem.
Soc. 2009, 131, 3174. (b) Tobisu, M.; Nakamura, R.; Kita, Y.; Chatani,
N. Bull. Korean Chem. Soc. 2010, 31, 582.
(6) Kita, Y.; Tobisu, M.; Chatani, N. Org. Lett. 2010, 12, 1864.
(7) (a) Taw, F. L.; White, P. S.; Bergman, R. G.; Brookhart, M. J. Am.
Chem. Soc. 2002, 124, 4192. (b) Taw, F. L.; Mueller, A. H.; Bergman,
R. G.; Brookhart, M. J. Am. Chem. Soc. 2003, 125, 9808. (c) Nakazawa,
H.; Kawasaki, T.; Miyoshi, K.; Suresh, C. H.; Koga, N. Organometallics
2004, 23, 117. (d) Nakazawa, H.; Kamata, K.; Itazaki, M. Chem.
Commun. 2005, 4004. (e) Itazaki, M.; Nakazawa, H. Chem. Lett. 2005,
34, 1054. (f) Nakazawa, H.; Itazaki, M.; Kamata, K.; Ueda, K. Chem.
Asian J. 2007, 2, 882.
(8) It has been reported that Fe−CH3, Fe−GeMe3, and Fe−SnMe3
complexes failed to promote the cleavage of a CH3−CN bond (see ref
7c).
(9) (a) Bis(pinacolato)diboron, B2(pin)2, could also be used in place
of 2, although the yield was slightly decreased. For example, the
reaction of 1 with B2(pin)2 under conditions identical to those shown
in Table 2 except for a reaction time of 60 h afforded a borylated
product in 60% yield. (b) See the Supporting Information (SI) for a
complete table of results of the optimization studies.
(10) Although PPh3 and Xantphos afforded 3 in almost identical
yields after 3 h, 1 was completely consumed when PPh3 was used,
while ca. 30% of 1 was recovered when Xantphos was employed.
(11) Reviews of C−CN bond activation: (a) Tobisu, M.; Chatani, N.
Chem. Soc. Rev. 2008, 37, 300. (b) Nakao, Y.; Hiyama, T. Pure Appl.
Chem. 2008, 80, 1097. Recent reports on Ni(0)-catalyzed C−CN
bond cleavage reactions: (c) Nakao, Y.; Yada, A.; Hiyama, T. J. Am.
Chem. Soc. 2010, 132, 10024. (d) Sun, M.; Zhang, H.-Y.; Han, Q.;
Yang, K.; Yang, S.-D. Chem.Eur. J. 2011, 17, 9566. (e) Nakai, K.;
Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2011, 133, 11066.
(12) Aryl bromides were borylated under the presented conditions.
Competition studies revealed relative reactivities of ArBr and ArCN
towards Rh-catalyzed borylation to be ca. 1:2.4.
(13) (a) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc.
2007, 129, 758. (b) Noguchi, H.; Shioda, T.; Chou, C.-M.; Suginome,
M. Org. Lett. 2008, 10, 377.
(14) Unsuccessful applications to β-monosubstituted acrylonitriles
were due in part to the involvement of an undesired dehydrogenative
borylation pathway in which the borylrhodium species adds across the
alkene moiety rather than to a cyano group. See: Kondoh, A.;
Jamison, T. F. Chem. Commun. 2010, 46, 907.
later stage of a synthesis. For instance, the C−H bond
borylation of 821 followed by two sequential Suzuki−Miyaura
couplings at the iodide and bromide sites furnishes nitrile 11,
which can finally be converted into boronic ester 12 using our
rhodium methodology.
In summary, we have developed a rhodium-catalyzed nitrile
borylation using diboron 2. The reaction involves an
unprecedented C−CN bond activation that is promoted by a
borylrhodium complex. In addition, the reaction offers a new
strategy for the synthesis of complex boronic acid derivatives
wherein a cyano group can now be utilized as a boron
equivalent. Further mechanistic and synthetic studies are in
progress.
ASSOCIATED CONTENT
* Supporting Information
■
S
Detailed experimental procedures and characterization of
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
tobisu@chem.eng.osaka-u.ac.jp; chatani@chem.eng.osaka-u.ac.
jp
■
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas “Molecular Activation Directed
toward Straightforward Synthesis” from MEXT, Japan. M.T.
acknowledges the Ito Science Foundation. We also thank the
(15) Commercially available from Kanto Chemical Co., Inc. as
Cyhalohop butyl.
(16) See the SI for details.
117
dx.doi.org/10.1021/ja2095975 | J. Am. Chem.Soc. 2012, 134, 115−118

Journal of the American Chemical Society
Communication
(17) (a) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2005, 7, 2229.
(b) Miura, T.; Nakazawa, H.; Murakami, M. Chem. Commun. 2005,
2855. (c) Miura, T.; Murakami, M. Org. Lett. 2005, 7, 3339. (d) Ueura,
K.; Miyamura, S.; Satoh, T.; Miura, M. J. Organomet. Chem. 2006, 691,
2821. (e) Miura, T.; Harumashi, T.; Murakami, M. Org. Lett. 2007, 9,
741.
(18) (a) Zhao, P.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 11618.
(b) Zhao, P.; Hartwig, J. F. Organometallics 2008, 27, 4749.
(19) For a sole example of the synthesis of (RO)2B−CN-type
compounds, see: Jiang, B.; Kan, Y.; Zhang, A. Tetrahedron 2001, 57,
1581.
(20) (a) Krizan, T. D.; Martin, J. C. J. Am. Chem. Soc. 1983, 105,
6155. (b) Uchiyama, M.; Koike, M.; Kameda, M.; Kondo, Y.;
Sakamoto, T. J. Am. Chem. Soc. 1996, 118, 8733. (c) Naka, H.;
Uchiyama, M.; Matsumoto, Y.; Wheatley, A. E. H.; McPartlin, M.;
Morey, J. V.; Kondo, Y. J. Am. Chem. Soc. 2007, 129, 1921. (d) Usui,
S.; Hashimoto, Y.; Morey, J. V.; Wheatley, A. E. H.; Uchiyama, M. J.
Am. Chem. Soc. 2007, 129, 15102. (e) Kakiuchi, F.; Sonoda, M.;
Tsujimoto, T.; Chatani, N.; Murai, S. Chem. Lett. 1999, 28, 1083.
(f) Chotana, G. A.; Rak, M. A.; Smith, M. R. III. J. Am. Chem. Soc.
2005, 127, 10539. (g) Li, W.; Xu, Z.; Sun, P.; Jiang, X.; Fang, M. Org.
Lett. 2011, 13, 1286.
(21) Ishiyama, T.; Nobuta, Y.; Hartwig, J. F.; Miyaura, N. Chem.
Commun. 2003, 23, 2924.
118
dx.doi.org/10.1021/ja2095975 | J. Am. Chem.Soc. 2012, 134, 115−118