Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with Dimethylmalononitrile

Article abstract of DOI:10.1002/anie.201508122

An efficient transnitrilation of aryl boronic acids with dimethylmalononitrile (DMMN) is described. This rhodium-catalyzed electrophilic cyanation presents a novel approach to prepare aryl nitriles by using a carbon-bound cyanating reagent which undergoes cross-coupling with the aryl boronic acid. The reaction expands the degree of functional-group compatibility exhibited by the transnitrilation of aryl Grignard and aryllithium reagents. A variety of aryl boronic acid derivatives and dialkylmalononitriles were amenable to the transnitrilation.

Full text of DOI:10.1002/anie.201508122

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International Edition: DOI: 10.1002/anie.201508122
German Edition: DOI: 10.1002/ange.201508122
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Rhodium-Catalyzed Transnitrilation of Aryl Boronic Acids with
Dimethylmalononitrile
Christian A. Malapit, Jonathan T. Reeves,* Carl A. Busacca, Amy R. Howell, and
Chris H. Senanayake
Abstract: An efficient transnitrilation of aryl boronic acids
with dimethylmalononitrile (DMMN) is described. This rho-
We became interested in developing an electrophilic
cyanation of air-stable and readily available organometallic
reagents such as organoboron compounds. Organoboron
derivatives continue to emerge as essential coupling partners
in the construction of carbon–carbon and carbon–heteroatom
bonds.[16] The utility of aryl boronic acids in cyanation
chemistry has been reported. However, to our knowledge,
only one example utilizes an electrophilic cyanation
approach.[17,18] Beller and co-workers recently reported
a rhodium-catalyzed cyanation of aryl boronic acids using
NCTS as the electrophilic cyanating agent.[17] Transition metal
catalyzed additions of aryl boronic acids to nitriles have been
documented, but exclusively provide aryl ketone products
(Figure 1a).[19,20]
dium-catalyzed electrophilic cyanation presents
a novel
approach to prepare aryl nitriles by using a carbon-bound
cyanating reagent which undergoes cross-coupling with the
aryl boronic acid. The reaction expands the degree of func-
tional-group compatibility exhibited by the transnitrilation of
aryl Grignard and aryllithium reagents. A variety of aryl
boronic acid derivatives and dialkylmalononitriles were ame-
nable to the transnitrilation.
A
ryl nitriles are key structural motifs found in many
pharmaceuticals, natural products, and agrochemicals.[1] In
addition, the nitrile may serve as a versatile precursor to
diverse functional groups, including amines, carboxylic acids
and derivatives, aldehydes, and heterocycles.[2] A notable
development in the synthesis of aryl nitriles involves tran-
sition metal catalyzed cyanation of aryl halides with toxic
cyanide salts.[3] Subsequently less toxic cyanide sources have
been developed, such as K4[Fe(CN)6],[4] BnCN,[5] and NH3/
DMF.[6] Although promising, a major drawback of transition
metal catalyzed cyanation is the high affinity of the cyanide
anion for the catalyst, and this affinity can result in
deactivation of the catalytic system.[7]
A method which circumvents this problem is the electro-
philic cyanation of organomagnesium, organolithium, and
organozinc reagents.[8] Previously reported electrophilic cyan-
ating agents include cyanogen halides,[9] cyanates,[10] TsCN,[11]
and cyanamides.[12] These electrophilic cyanating agents are in
some cases either highly toxic or derived from highly toxic
cyanide sources, or are noncommercially available, or require
low-temperature storage. One remarkable exception is N-
cyano-N-phenyl-p-toluenesulfonamide (NCTS),[13] which can
be obtained from the reaction of phenylurea and p-toluene-
Figure 1. Reactions of organometallic reagents with nitriles.
We recently disclosed the first carbon-bound electrophilic
cyanating agent, dimethylmalononitrile (DMMN), for the
cyanation of aryl Grignard and lithium reagents via trans-
nitrilation (Figure 1b).[21] DMMN is a safe, bench-stable, and
commercially available reagent which has found use in the
synthesis of bis(oxazoline)s.[22] We envisioned that aryl
boronic acids, in the presence of a suitable metal catalyst,
could add to DMMN to give the metal/ketimine complex II.
Similar to the reaction with aryl Grignard and lithium
reagents, we thought that II would undergo a retro-Thorpe
fragmentation to release the desired aryl nitrile. Herein we
report the transnitrilation of aryl boronic acids utilizing the
carbon-bound cyanating agent DMMN.
At the outset of this work, we recognized two major
challenges. First, the general reactivity of DMMN with aryl
boronic acids for the initial 1,2-addition was unknown.
Second, was the challenge in product selectivity towards
transnitrilation over the formation of aryl ketones. The
investigation began by reacting phenyl boronic acid with
sulfonyl chloride.[14] Cyanation of aryl C H bonds has
À
recently emerged as an alternative approach.[15] However,
the need for directing groups or electron-rich arenes presents
a considerable challenge for substrate generality and product
regioselectivity.
[*] Dr. J. T. Reeves, Dr. C. A. Busacca, Dr. C. H. Senanayake
Chemical Development, Boehringer Ingelheim Pharmaceuticals, Inc.
900 Ridgebury Road, Ridgefield, CT 06877-0368 (USA)
E-mail: jonathan.reeves@boehringer-ingelheim.com
C. A. Malapit, Prof. Dr. A. R. Howell
Department of Chemistry, University of Connecticut
55 North Eagleville Road, Storrs, CT 06269-3060 (USA)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201508122.
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Table 1: Screening of transition-metal catalysts.
important for the selectivity. For example, when either K3PO4
or KOH was used instead of K2CO3, high conversion was
obtained, but with low selectivity (entries 1 and 2). Gratify-
ingly, the use of either Cs2CO3 or CsF provided significant
improvement in product selectivity (1/2 = 60: < 2–5) but with
moderate yields (entries 3 and 4). Additives such as ZnCl2 or
CuI resulted in low yields and selectivities. To our delight,
when the temperature was increased to 1008C using Cs2CO3,
1 was obtained in 94% yield after 4 hours with excellent
selectivity (entry 8). Under these reaction conditions, the
catalyst loading could be lowered to 1 mol% [{RhCl(cod)}2]
with similar yield and selectivity. When the reaction was
carried out with lower amounts of Cs2CO3, poor conversions
and selectivities were obtained (entries 9 and 10).
Entry
Catalyst
Yield [%][b]
1
2
1
2
3
4
5
6
7
8
9
none
0
35
52
3
0
51
43
17
45
70
<2
0
[{Rh(OH)(cod)}2]
[{RhCl(cod)}2]
[RhCl(PPh3)3]
[Rh(nor)2BF4]
[Rh(cod)2OTf]
[{IrCl(cod)}2]
[RuCl2(cod)]
5
12
<2
0
0
4
After identifying the optimized reaction conditions, we
explored the potential of several dialkylmalononitriles as
transnitrilation reagents with phenyl boronic acid
(Table 3).[24] Dialkylmalononitriles (entries 2–6) underwent
[PdCl2(cod)]
[Ni(cod)2]/5 mol% PCy3
0
<2
10
[a] Reaction conditions: 0.75 mmol PhB(OH)2, 0.50 mmol DMMN,
2 mol% catalyst, and 1 mmolK2CO3 in 1 mL 1,4-dioxane, 808C, 24 h; for
entries 4–6 and 8,9, 4 mol% catalyst was used. [b] HPLC assay yields.
cod=1,5-cyclooctadiene, nor=norbornene.
Table 3: Survey of several transnitrilation reagents.
DMMN using several transition metal catalysts in the
presence of potassium carbonate as an additive (Table 1).
Rhodium catalysts showed superior reactivity over other
transition metal catalysts screened. In particular, rhodium
dimers, [{RhCl(cod)}2] and [{Rh(OH)(cod)}2],[23] provided
high conversions with modest selectivities towards the desired
transnitrilation product benzonitrile (1) over the ketone 2
(entries 2 and 3). Throughout this work, it was found that
optimal yields of the 1 were obtained when DMMN was used
as the limiting reagent and the arylboronic acid was used in
1.5-fold excess, because of competitive proto-deborylation.
The use of 1:1 stoichiometry or of excess DMMN resulted in
reduced yields.
Entry Dinitrile Yield [%][b]
Entry
6
Dinitrile
Yield [%][b]
70[c]
1
<5
2
3
4
n=1
n=2 (3)
n=3
78
93
86
7
8
EWG=CO2Et
EWG=CONEt2
0[d]
0[d]
After identifying the effective catalyst, several parameters
were investigated to improve the selectivity towards trans-
nitrilation (Table 2). The choice of additive was found to be
5
88
[a] Reaction conditions: 0.75 mmol PhB(OH)2, 0.5 mmol nitrile, 1 mol%
[{Rh(cod)Cl}2] and 1 mmol Cs2CO3 in 1 mL 1,4-dioxane, 1008C, 4 h.
[b] HPLC assay yields. [c] Reaction was done in 24 h. [d] No reaction was
observed.
Table 2: Screening of additives and effect of temperature.
transnitrilation, thus providing 1 in good to excellent yields.
The dicyanocyclopropane (entry 1) gave complete conver-
sion, but very low product formation was detected. This low
yield could be due to the potential oxidative addition of
rhodium(I) to the strained and electron-deficient cyclopro-
pane moiety and subsequent side reactions.[25] Ester and
amide derivatives of DMMN (entries 7 and 8) did not show
any reactivity toward either 1,2-addition or nucleophilic acyl
substitution.
By using the optimized reaction conditions, we sought to
explore the scope of the transnitrilation of different arylbor-
onic acids with DMMN (Table 4). Several electron-rich and
electron-neutral arylboronic acids underwent transnitrilation
in good to excellent yields. Hindered ortho-substituted
arylboronic acids provided aryl nitriles in good yields
(entries 5–7). Aryl boronic acids having electron-deficient
Entry
Additive
Yield [%][b]
1
2
1
2
3
4
5
6
7
8
9
K3PO4
KOH
Cs2CO3
CsF
ZnCl2
CuI
Cs2CO3; THF, 608C
Cs2CO3; 1008C, 4 h
1 equiv Cs2CO3; 1008C
no additive, 1008C
20
55
61
62
6
61
35
<2
5
31
29
<2
6
59
94 (93)[c]
4 (5)[c]
56
12
0
10
6
[a] Reaction conditions: 0.75 mmol PhB(OH)2, 0.50 mmol DMMN,
2 mol% [{RhCl(cod)}2], and 1 mmol additive in 1 mL 1,4-dioxane at
808C, 24 h. [b] HPLC assay yields. [c] 1 mol% [{RhCl(cod)}2], 4 h.
THF=tetrahydrofuran.
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Table 4: Scope of the rhodium-catalyzed transnitrilation of arylboronic
Table 5: Scope of the rhodium-catalyzed transnitrilation of arylboronic
acids.
acid derivatives.
Entry
Aryl boronic acid
Product
Yield [%][b]
Aryl boronates
Nitrile product
Yield [%][b]
64
1
2
2
R = H: 89
4-Me: 94
4-OMe: 97
3-OMe: 80
2-OMe: 68
1[c]
2
Ph BF3K
1
1
À
72 (65)
4
5[c]
3
(45)
9
6
7
90
75
4[c]
Ph Bpin
1
À
1: 0
2: (40)
5[c]
8
9
X = Cl: 80
Br: 77
[a] Reaction conditions: 1.5 mmol arylboronate, 1.0 mmol DMMN,
2 mol% [{RhCl(cod)}2] and 2 mmol base in 2 mL 1,4-dioxane, 1008C,
24 h. [b] HPLC assay yield. Values within parentheses are yields of the
isolated products. [c] The use CsF or K2CO3 as additives provided similar
outcomes or slightly lower yields. pin=pinacol.
10
86
11
84
87
75
12[d]
13[e]
14[f]
71
isobutyronitrile anion during the transnitrilation of p-fluoro-
phenylmagnesium bromide with DMMN.[21]
15[f]
68
To further explore the potential of this novel rhodium-
catalyzed transnitrilation method, several aryl boronic acid
derivatives were examined (Table 5). Phenyl potassium
trifluoroborate underwent transnitrilation in moderate yield
(entry 1). Transnitrilation of neopentylglycol aryl boronic
acid esters with DMMN also provided aryl nitriles in accept-
able yields (entries 2 and 3). The sterically hindered phenyl
pinacolboronate ester gave very low conversion, while phenyl
boronic acid MIDA ester exclusively gave the adduct 2 in
40% yield. It is worth noting that the aryl boronates in
entries 1–4 did not give detectable amounts of ketone
adducts. The observed lower yields are mainly a result of
their lower reactivity under the reaction conditions used.
Based on mechanistic results we obtained for the trans-
nitrilation of aryl Grignard reagents[21] with DMMN and
previous reports on rhodium-catalyzed addition of arylbor-
onic acids to nitriles,[19] we propose the following mechanism
(Scheme 1). First, transmetallation of the RhI species A with
the arylboronic acid would generate the aryl rhodium B. Aryl
transfer to DMMN would result in formation of a rhodium
ketimine intermediate (C). This rhodium complex is analo-
gous to the magnesium ketimine intermediate observed in our
previous work.[21] Protonation of the ketimine with arylbor-
onic acid would give the rhodium borate D and ketimine E.
The rhodium borate D could directly form B, or alternatively,
it could undergo hydrolysis to A with regeneration of the
arylboronic acid. Hydrolysis of E would give the undesired b-
ketonitrile byproduct F.[26] Deprotonation of E with Cs2CO3
results in retro-Thorpe fragmentation to give the product aryl
nitrile and the isobutyronitrile anion G. The anion G may be
protonated by boric acid (or arylboronic acid) to give
isobutyronitrile. As with the transnitrilation of aryl Grignard
16[f]
65
17
78
52
18[c]
[a] Reaction conditions: 3.0 mmol arylboronic acid, 2.0 mmol DMMN,
1 mol% [{RhCl(cod)}2] and 4.0 mmol Cs2CO3 in 4 mL 1,4-dioxane,
1008C, 6 h. [b] Yields of isolated products. [c] 2.0 mol% [{RhCl(cod)}2].
[d] 2.0 mmol nitrile 3 was used. [e] 2.0 mmol nitrile 4 was used.
[f] 2 mol% [{RhCl(cod)}2] at 1108C, 20 h.
substituents were transformed into the corresponding nitriles
in good yields (entries 15 and 16). Likewise, heteroaryl
boronic acids underwent transnitrilation with DMMM in
moderate yields (entries 17 and 18). The use of the cyanating
agents 3 and 4 furnished 4-(dimethylamino)benzonitrile in
comparable yields to that obtained with DMMN (entries 11–
13).
The observed functional-group tolerance of this trans-
nitrilation method is remarkable. For example, benzonitriles
having vinyl, ketone, and ester substituents (Table 4,
entries 14–16) were obtained in good yields. Such functional
groups cannot be tolerated in the transnitrilation of aryl
Grignard or lithium reagents with DMMN.[21] Moreover, in
this rhodium-catalyzed transnitrilation method, p-fluoroben-
zonitrile was obtained in 77% yield (entry 9). This product
was found to undergo SNAr reaction with the byproduct
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extracted with MTBE (10 mL ” 3). The combined organic phases
and lithium reagents, we have confirmed that isobutyronitrile
is the byproduct of the reaction by GC-MS and 1H and
13C NMR analysis.
The significant effect of the base on the selectivity towards
transnitrilation versus b-ketonitrile formation deserves fur-
ther comment. We believe that a strong base is necessary to
efficiently promote the retro-Thorpe fragmentation of E by
were dried with anhydrous Na2SO4, filtered, and then concentrated in
vacuo. Purification of the crude residue by silica column chromatog-
raphy using MTBE/hexanes as the eluent afforded 4-methylbenzoni-
trile (220 mg, 94% yield) as a white solid.
Acknowledgements
À
deprotonation of the N H. In addition, we suspect that the
dessicant ability of the base could also affect the selectivity by
scrubbing any trace water from the reaction mixture, thus
minimizing hydrolysis of E to F. Finally, the solubility of the
base is likely important, as low solubility might reduce the
availability of the base to promote the retro-Thorpe reaction
and thus enable hydrolysis of the ketimine adduct to give b-
ketonitrile byproduct F.
We thank Prof. Dr. Scott E. Denmark for helpful discussions.
Keywords: boron · cross-coupling · nitriles · rhodium ·
synthetic methods
How to cite: Angew. Chem. Int. Ed. 2016, 55, 326–330
Angew. Chem. 2016, 128, 334–338
In summary, we have developed the first transnitrilation
of arylboronic acids with dimethylmalononitrile in an electro-
philic cyanation approach. Aryl boronic acid derivatives,
(potassium trifluoroborate and neopentylglycol ester) and
several dialkylmalononitriles could also undergo transnitrila-
tion. Complementary to the cyanation of aryl Grignard and
lithium reagents, this rhodium-catalyzed transnitrilation is
amenable to arylboronic acids having reactive functional
groups (such as ketone, ester, styryl, and fluoride), thus
providing aryl nitriles with valuable synthetic handles.
[1] a) A. Kleemann, J. Engel, B. Kutschner, D. Reichert, Pharma-
ceutical Substances: Syntheses, Patents, Applications, 4th ed.,
Georg Thieme, Stuttgart, 2001; b) J. S. Miller, J. L. Manson, Acc.
Chem. Res. 2001, 34, 563; c) F. F. Fleming, Q. Wang, Chem. Rev.
2003, 103, 2035.
[2] a) Z. Rappoport, Chemistry of the Cyano Group, Wiley, London,
1970; b) R. C. Larock, Comprehensive Organic Transformations:
A Guide to Functional Group Preparations, VCH, New York,
1989.
[3] For a recent review, see: a) P. Anbarasan, T. Schareina, M.
Beller, Chem. Soc. Rev. 2011, 40, 5049, and references therein;
For a recent report, see: b) Q. Wen, J. Jin, L. Zhang, Y. Luo, P.
Lu, Y. Wang, Tetrahedron Lett. 2014, 55, 1271.
[4] a) T. Schareina, A. Zapf, M. Beller, J. Organomet. Chem. 2004,
689, 4576; b) T. Schareina, A. Zapf, M. Beller, Chem. Commun.
2004, 1388; c) S. A. Weissman, D. Zewge, C. Chen, J. Org. Chem.
2005, 70, 1508; d) T. Schareina, A. Zapf, W. Magerlein, N.
Muller, M. Beller, Tetrahedron Lett. 2007, 48, 1087; e) O.
Grossmann, D. Gelman, Org. Lett. 2006, 8, 1189; f) N. E.
Leadbeater, S. Velmathi, Tetrahedron
Lett. 2008, 49, 4693.
Experimental Section
Typical procedure: Under a nitrogen atmosphere, a mixture of p-
tolylboronic acid (405 mg, 3.0 mmol), DMMN (188 mg, 2.0 mmol),
[{RhCl(cod)}2] (9.8 mg, 0.02 mmol), and Cs2CO3 (1.30 g, 4.0 mmol) in
1,4-dioxane (4 mL) was stirred at 1008C for 6 h. After cooling, the
reaction mixture was quenched with aqueous saturated NH4Cl and
[5] Q. Wen, J. Jin, B. Hu, P. Lu, Y. Wang, RSC
Adv. 2012, 2, 6167.
[6] J. Kim, S. Chang, J. Am. Chem. Soc. 2010,
132, 10272.
[7] a) A. Sekiya, N. Ishikawa, Chem. Lett.
1975, 277; K. Takagi, T. Okamoto, Y.
Sakakibara, A. Ohno, S. Oka, N. Hayama,
Bull. Chem. Soc. Jpn. 1976, 49, 3177; b) M.
Sundermeier, A. Zapf, S. Mutyala, W.
Baumann, J. Sans, S. Weiss, M. Beller,
Chem. Eur. J. 2003, 9, 1828.
[8] a) L. R. Subramanian, Sci. Synth. 2004, 19,
163; b) J. Kim, H. J. Kim, S. Chang, Angew.
Chem. Int. Ed. 2012, 51, 11948; Angew.
Chem. 2012, 124, 12114.
[9] V. Grignard, E. Bellet, C. R. Hebd. Seances
Acad. Sci. 1914, 158, 457.
[10] a) D. Martin, S. Rackow, Chem. Ber. 1965,
98, 3662; b) J. S. Koo, J. I. Lee, Synth.
Commun. 1996, 26, 3709.
[11] a) A. M. van Leusen, J. C. Jagt, Tetrahe-
dron Lett. 1970, 11, 967; b) I. Klement, K.
Lennick, C. E. Tucker, P. Knochel, Tetra-
hedron Lett. 1993, 34, 4623.
[12] a) T. V. Hughes, M. P. Cava, J. Org. Chem.
1999, 64, 313; b) P. Anbarasan, H. Neu-
Scheme 1. Proposed mechanism for the rhodium-catalyzed transnitrilation of arylboronic
mann, M. Beller, Chem. Eur. J. 2010, 16,
acids with DMMN. Ligands on rhodium omitted for simplicity.
4725.
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
329

Angewandte
Communications
Chemie
[13] P. Anbarasan, H. Neumann, M. Beller, Chem. Eur. J. 2011, 17,
Commun. 2005, 2855; c) K. Ueura, S. Miyamura, T. Satoh, M.
Miura, J. Organomet. Chem. 2006, 691, 2821; d) H. Shimizu, M.
Murakami, Chem. Commun. 2007, 2855.
4217.
[14] a) F. Kurzer, J. Chem. Soc. 1949, 1034; b) F. Kurzer, J. Chem. Soc.
1949, 3029.
[20] For related reactions using palladium, see a) L. Zhao, X. Lu,
Angew. Chem. Int. Ed. 2002, 41, 4343; Angew. Chem. 2002, 114,
4519; b) B. Zhao, X. Lu, Tetrahedron Lett. 2006, 47, 6765; c) B.
Zhao, X. Lu, Org. Lett. 2006, 8, 5987; d) C. Zhou, R. C. Larock, J.
Org. Chem. 2006, 71, 3551; using Ni, see: e) Y.-C. Wong, K.
Parthasarathy, C.-H. Cheng, Org. Lett. 2010, 12, 1736.
[21] J. T. Reeves, C. A. Malapit, F. G. Buono, K. P. Sidhu, M. A.
Marsini, C. A. Sader, K. R. Fandrick, C. A. Busacca, C. H.
Senanayake, J. Am. Chem. Soc. 2015, 137, 9481.
[22] a) V. K. Aggarwal, L. Bell, M. P. Coogan, P. J. Jubault, Chem.
Soc. Perkin Trans. 1 1998, 2037; b) J. A. Griffith, G. J. Rowlands,
Synthesis 2005, 3446.
[23] These rhodium dimers were also found by Beller and co-workers
to be effective catalysts in the electrophilic cyanation of aryl
boronic acids with NCTS (see Ref. [17]).
À
[15] For selected recent aryl C H cyanations, see: a) T.-J. Gong, B.
Xiao, W.-M. Cheng, W. Su, J. Xu, Z.-J. Liu, L. Liu, Y. Fu, J. Am.
Chem. Soc. 2013, 135, 10630; b) M. Chaitanya, D. Yadagiri, P.
Anbarasan, Org. Lett. 2013, 15, 4960; c) L.-J. Gu, C. Jin, R.
Wang, H.-Y. Ding, ChemCatChem 2014, 6, 1225; d) J. Han, C.
Pan, X. Jia, C. Zhu, Org. Biomol. Chem. 2014, 12, 8603; e) W.
Liu, L. Ackermann, Chem. Commun. 2014, 50, 1878; f) Y. Yang,
S. L. Buchwald, Angew. Chem. Int. Ed. 2014, 53, 8677; Angew.
Chem. 2014, 126, 8821; g) D.-G. Yu, T. Gensch, F. de Azambuja,
S. Vasquez-Cespedes, F. J. Glorius, J. Am. Chem. Soc. 2014, 136,
17722; h) J. Li, L. Ackermann, Angew. Chem. Int. Ed. 2015, 54,
3635; Angew. Chem. 2015, 127, 3706; i) A. B. Pawar, S. Chang,
Org. Lett. 2015, 17, 660.
[16] D. G. Hall, Boronic Acids: Preparation and Applications in
Organic Synthesis Medicine and Materials, 2nd ed., Wiley-VCH,
Weinheim, 2011.
[24] The use of malononitrile as the transnitrilation reagent resulted
in no product formation.
[17] P. Anbarasan, H. Neumann, M. Beller, Angew. Chem. Int. Ed.
2011, 50, 519; Angew. Chem. 2011, 123, 539.
[25] For a report on oxidative addition of rhodium(I), using a similar
precursor catalyst [{RhCl(cod)}2], onto cyclopropanes, see: T.
Matsuda, T. Tsuboi, M. Murakami, J. Am. Chem. Soc. 2007, 129,
12596.
[26] Although ketones are usually observed as byproducts under
these reaction conditions, when the reaction is carried out in the
presence of water (1 equiv), the amount of ketone byproduct is
significant.
[18] Other reports on the cyanation of aryl boronic acids occur in the
presence of stoichiometric amount of copper salts. The cyanide
source is either metal-bound or generated in situ: a) Z. Zhang,
L. S. Liebeskind, Org. Lett. 2006, 8, 4331; b) C. W. Liskey, X.
Liao, J. F. Hartwig, J. Am. Chem. Soc. 2010, 132, 11389; c) G.
Zhang, L. Zhang, M. Hu, J. Cheng, Adv. Synth. Catal. 2011, 353,
291; d) J. Kim, J. Choi, K. Shin, S. Chang, J. Am. Chem. Soc. 2012,
134, 2528; e) Y. Luo, Q. Wen, Z. Wu, J. Jin, P. Lu, Y. Wang,
Tetrahedron 2013, 69, 8400.
[19] For selected rhodium-catalyzed additions of boronic acids to
nitriles, see: a) K. Ueura, T. Satoh, M. Miura, Org. Lett. 2005, 7,
2229; b) T. Miura, H. Nakazawa, M. Murakami, Chem.
Received: August 30, 2015
Revised: October 4, 2015
Published online: October 20, 2015
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