Copper-mediated transformation of organosilanes to nitriles with DMF and ammonium iodide

Article abstract of DOI:10.1021/ol400659p

Cyanation of aryl-, diaryldimethyl-, and styrylsilanes was developed for the first time under copper-mediated oxidative conditions using ammonium iodide and DMF as the combined source of nitrogen and carbon atom of the introduced cyano unit, respectively. The reaction was observed to proceed in a two-step process: initial conversion of organosilanes to their iodo intermediates and then cyanation. This method has a broad substrate scope with high functional group tolerance.

Full text of DOI:10.1021/ol400659p

ORGANIC
LETTERS
2013
Vol. 15, No. 8
1990–1993
Copper-Mediated Transformation
of Organosilanes to Nitriles with DMF and
Ammonium Iodide
Zhen Wang and Sukbok Chang*
Center for Catalytic Hydrocarbon Functionalizations (IBS) and Department of
Chemistry, Korea Advanced Institute of Science and Technology (KAIST),
Daejeon 305-701, Republic of Korea
sbchang@kaist.ac.kr
Received March 12, 2013
ABSTRACT
Cyanation of aryl-, diaryldimethyl-, and styrylsilanes was developed for the first time under copper-mediated oxidative conditions using
ammonium iodide and DMF as the combined source of nitrogen and carbon atom of the introduced cyano unit, respectively. The reaction was
observed to proceed in a two-step process: initial conversion of organosilanes to their iodo intermediates and then cyanation. This method has a
broad substrate scope with high functional group tolerance.
Organo nitriles are a key building unit frequently found
in numerous natural and synthetic compounds such as
in dyes, herbicides, pharmaceuticals, agrochemicals, and
electronic materials.1 Moreover, the nitrile group is a
versatile precursor that can readily be converted to diverse
functional groups including tetrazoles, amines, amidines,
amides, aldehydes and other carboxy derivatives.2 For the
preparation of nitrile compounds, conventional methods
are most often used: Sandmeyer3 and RosenmundÀvon
Braun procedure4 employ stoichiometric amounts of CuCN
as the cyanating reagent. On the other hand, while recent
development of the transition-metal-catalyzed cyanation5
allows using certain metal- or metalloid-bound cyanide
sources such as KCN,6 NaCN,7 Zn(CN)2,8 or K4[Fe(CN)6,9
(6) For the transition metal-catalyzed cyanations using KCN, see: (a)
Sakakibara, Y.; Okuda, F.; Shimobayashi, A.; Kirino, K.; Sakai, M.;
Uchino, N.; Takagi, K. Bull. Chem. Soc. Jpn. 1988, 61, 1985. (b)
Anderson, B. A.; Bell, E. C.; Ginah, F. O.; Harn, N. K.; Pagh, L. M.;
Wepsiec, J. P. J. Org. Chem. 1998, 63, 8224. (c) Yang, C.; Williams, J. M.
Org. Lett. 2004, 17, 2837. (d) Cristau, H.-J.; Ouali, A.; Spindler, J.-F.;
Taillefer, M. Chem.ÀEur. J. 2005, 11, 2483.
(7) (a) Okano, T.; Iwahara, M.; Kiji, J. Y.; Sakakibara, F.; Okuda, A.
Synlett 1998, 243. (b) Zanon, J.; Klapars, A.; Buchwald, S. L. J. Am.
Chem. Soc. 2003, 125, 2890.
(1) (a) Kleemann, A.; Engel, J.; Kutscher, B.; Reichert, D. Pharma-
ceutical Substance: Synthesis, Patents, Applications, 4th ed.; Georg
Thieme: Stuttgart, 2001. (b) Miller, J. S.; Manson, J. L. Acc. Chem. Res.
2001, 34, 563. (c) Fleming, F. F.; Wang, Q. Chem. Rev. 2003, 103, 2035.
(2) (a) The Chemisty of the Cyano Group; Rappoport, Z., Ed.; Inter-
science: London, 1970. (b) Larock, R. C. Comprehensive Organic Trans-
formations: A Guide to Fucntional Group Preparations; VCH: New York,
1989.
(3) (a) Sandmeyer, T. Ber. Dtsch. Chem. Ges. 1884, 17, 1633. (b)
Hodgson, H. H. Chem. Rev. 1947, 40, 251. (c) Galli, C. Chem. Rev. 1988,
88, 765.
(4) (a) Rosenmund, K. W.; Struck, E. Ber. Dtsch. Chem. Ges. 1919,
2, 1749. (b) Lindley, J. Tetrahedron 1984, 40, 1433.
(8) (a) Tschaen, D. M.; Desmond, R.; King, A. O.; Fortin, M. C.;
Pipik, B.; King, S.; Verhoeven, T. R. Synth. Commun. 1994, 24, 887. (b)
Maligres, P. E.; Waters, M. S.; Fleitz, F.; Askin, D. Tetrahedron Lett.
1999, 40, 8193. (c) Alterman, M.; Hallberg, A. J. Org. Chem. 2000, 65,
7984. (d) Chidambaram, R. Tetrahedron Lett. 2004, 45, 1441. (e) Jensen,
R. S.; Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Tetrahedron
Lett. 2005, 46, 8645. (f) Buono, F. G.; Chidambaram, R.; Mueller, R. H.;
Waltermire, R. E. Org. Lett. 2008, 10, 5325. (g) Martin, M. T.; Liu, B.;
Cooley, B. E., Jr.; Eaddy, J. F. Tetrahedron Lett. 2007, 48, 2555.
(9) (a) Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004, 1388.
(b) Weissman, S. A.; Zewge, D.; Chen, C. J. Org. Chem. 2005, 70, 1508.
(c) Schareina, T.; Zapf, A.; Beller, M. Tetrahedron Lett. 2005, 46, 2585.
(d) Grossman, O.; Gelman, D. Org. Lett. 2006, 8, 1189. (e) Schareina, T.;
(5) (a) Ellis, G. P.; Romney-Alexander, T. M. Chem. Rev. 1987,
87, 779. (b) Anbarasan, P.; Schareina, T.; Beller, M. Chem. Soc. Rev.
2011, 40, 5049.
€
€
Zapf, A.; Magerlein, W.; Muller, N.; Beller, M. Tetrahedron Lett. 2007,
48, 1087.
r
10.1021/ol400659p
Published on Web 03/29/2013
2013 American Chemical Society

this approach also has some drawbacks. For example, the
cyanation sources are usually toxic and release hazardous
HCN gas, and stoichiometric amounts of metal wastes
accompany the reaction. Careful control of concentration
of reaction mixture is another issue to be addressed to
minimize catalyst poisoning due to the in situ formation of
inactive cyano transition metal complexes.10 Inresponse to
these issues, feasibility of using nonmetallic cyanation
species has been actively investigated in recent years.11 In
fact, a range of organic precursors bearing a “CN” moiety
was examined; acetone cyanohydrin and its analogues,12
alkyl nitriles,13 malononitrile,14 phenyl cyanates,15 benzyl
thiocyanates,16 N-cyanobenzimidazole,17 TMSCN,18 nitro-
methane,19 and N-cyano-N-phenyl-p-toluenesulfonamide
(NCTS).20 On the other hand, some research groups
recently reported cyanation reactions employing organic
precursors that do not contain the “CN” unit in their
molecular skeletons.21 Interestingly, there are two types of
precursors in this approach; either using single sources or
combining more than two compounds at the same time to
generate the cyano unit in situ.
Recently, we reported for the first time that the cyano
group could be generated in situ from the combined use of
aqueous ammonia and N,N-dimethylformamide (DMF)
under Cu-mediated oxidative conditions.21aÀc Isotopic
studies revealed that carbon and nitrogen atom consisting
“CN” were originated from the dimethylamino moiety of
DMF and ammonia, respectively. This protocol was then
utilized for the cyanation of 2-phenylpyridine in the presence
of a palladium cocatalyst. Subsequently, NH4I (instead of
aqueous ammonia) and DMF were combined for the
cyanation of aryl boronates and electron-rich arenes21b
and indoles21c under the similar conditions.
Interestingly, when ammonium iodide was used as the
nitrogen source, the reaction was found to proceed in a
sequential two-step process: initial iodination of substrates
and then cyanation of the aryliodo intermediates with in
situ generated “CN” moiety. During the course of the
transformation, ammonium iodide plays a dual role as a
supplier of both iodide and nitrogen atom. Jiao described
an efficient Pd-catalyzed cyanation of indoles with DMF
alone, but various reagents and additives were required.21d
Cheng and co-workers reported that Pd-catalyzed cyanation
of indoles21e and Cu-mediated cyanation of aryl halides using
combined cyano sources.21f Bhanage et al. also revealed
Pd-catalyzed cyanation of (hetero)aryl halides with for-
mamide.21g Herein, we present a new advance in the cyana-
tion of organosilanes under Cu-mediated oxidative conditions
using NH4I and DMF as the “CN” sources. Organosilicons
have gained increasing interests in organic synthesis and
materials science mainly due to their tamable reactivity,
nontoxicity, high stability, and ease of preparation and
handling.22 As a result, the present result will add a promis-
ing entry into a list of synthetic utilizations of organosilanes.
Table 1. Optimization of Reaction Conditionsa
(10) (a) Sekiya, A.; Ishikawa, N. Chem. Lett. 1975, 277. (b) Takagi,
K.; Okamoto, T.; Sakakibara, Y.; Ohno, A.; Oka, S.; Hayama, N.
Bull. Chem. Soc. Jpn. 1976, 49, 3177. (c) Sundermeier, M.; Zapf, A.;
Mutyala, S.; Baumann, W.; Sans, J.; Weiss, S.; Beller, M. Chem.ÀEur. J.
2003, 9, 1828.
(11) Kim, J.; Kim, H. J.; Chang, S. Angew. Chem., Int. Ed. 2012, 51,
11948.
(12) (a) Sundermeier, M.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed.
Cu species
(2.0 equiv)
additive
entry
NH4X
(2.0 equiv)
yieldb (%)
1
Cu(NO3)2 3H2O
aq NH3
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4OAc
NH4Cl
NH4I
NH4I
NH4I
NH4I
none
none
HOAc
HOAc
CsF
NaF
KF
0
24
40
48
60
78
81
67
74
58
<5
<5
<5
0
3
2
Cu(NO3)2 3H2O
3
3
Cu(NO3)2 3H2O
3
4c
5
Cu(NO3)2 3H2O
3
ꢀ
2003, 42, 1661. (b) Schareina, T.; Zapf, A.; Cotte, A.; Gotta, M.; Beller,
Cu(NO3)2 3H2O
3
M. Adv. Synth. Catal. 2011, 353, 777. (c) Ouchaou, K.; Georgi, D.;
Taran, F. Synlett 2010, 2083. (d) Park, E. J.; Lee, S.; Chang, S. J. Org.
Chem. 2010, 75, 2760.
(13) Luo, F.-H.; Chu, C.-I.; Cheng, C.-H. Organometallics 1998, 17,
1025.
(14) Jiang, Z.; Huang, Q.; Chen, S.; Long, L.; Zhou, X. Adv. Synth.
Catal. 2012, 354, 589.
(15) Sato, N.; Yue, Q. Tetrahedron 2003, 59, 5831.
(16) (a) Zhang, Z.; Liebeskind, L. S. Org. Lett. 2006, 8, 4331. (b)
Zhang, G.-Y.; Yu, J.-T.; Hu, M.-L.; Cheng, J. J. Org. Chem. 2013, 78,
2710.
(17) Kaupp, G.; Schmeyers, J.; Boy, J. Chem.ÀEur. J. 1998, 4, 2467.
(18) (a) Chatani, N.; Hanafusa, T. J. Org. Chem. 1986, 51, 4714. (b)
Sundermeier, M.; Mutyala, S.; Zapf, A.; Spannenberg, A.; Beller, M.
J. Organomet. Chem. 2003, 684, 50.
(19) Chen, X.; Hao, X.-S; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem.
Soc. 2006, 128, 6790.
(20) (a) Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int.
Ed. 2011, 50, 519. (b) Anbarasan, P.; Neumann, H.; Beller, M. Chem.À
Eur. J. 2011, 17, 4217. (c) Yang, Y.; Zhang, Y.; Wang, J. Org. Lett. 2011,
13, 5608.
(21) (a) Kim, J.; Chang, S. J. Am. Chem. Soc. 2010, 132, 10272. (b)
Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc. 2012, 134, 2528.
(c) Kim, J.; Kim, H.; Chang, S. Org. Lett. 2012, 14, 3924. (d) Ding, S.;
Jiao, N. J. Am. Chem. Soc. 2011, 133, 12374. (e) Ren, X.; Chen, J.; Chen,
F.; Cheng, J. Chem. Commun. 2011, 47, 6725. (f) Zhang, G.; Ren, X.;
Chen, J.; Hu, M.; Cheng, J. Org. Lett. 2011, 13, 5004. (g) Sawant, D. N.;
Wagh, Y. S.; Tambade, P. J.; Bhatte, K. D.; Bhanage, B. M. Adv. Synth.
Catal. 2011, 353, 781.
6
Cu(NO3)2 3H2O
3
7
Cu(NO3)2 3H2O
3
8
Cu(NO3)2 3H2O
NH4F
KF
3
9
Cu(CF3COO)2
CuI
10
11
12
13
14
15
16d
17e
18f
19g
KF
CuBr2
KF
CuSO4
KF
Cu(OAc)2
KF
Cu(NO3)2 3H2O
KF
3
Cu(NO3)2 3H2O
KF
0
3
Cu(NO3)2 3H2O
KF
52
73
66
71
3
Cu(NO3)2 3H2O
KF
3
Cu(NO3)2 3H2O
KF
3
Cu(NO3)2 3H2O
KF
3
a Conditions: 1a (0.3 mmol), NH4I (2.0 equiv), additive, and [Cu]
in DMF (2.0 mL). b 1H NMR yield (internal standard: 1,1,2,2-
tetrachloroethane). c AgBF4 (20 mol %) was added. d NH4I and copper
were used in 1.2 equiv each. e KF was used in 1.0 equiv. f Under air
balloon. g Run at 130 °C.
We initiated our study by examining a reaction of a readily
available compound (4-methoxyphenyl)triethoxysilane (1a)
Org. Lett., Vol. 15, No. 8, 2013
1991

under various conditions including our previous ones
(Table1). While low conversion wasobservedbythe action
of copper species alone (entries 1À2), certain additives were
found to affect the reactionefficiency. For example, the use
of AcOH (2 equiv) resulted in moderate product yields
(entries 3 and 4). Instead of acetic acid, which was an
additive of choice in our previous procedure of the cyana-
tion of arylboronic acids,21b fluoride additive turned out
to be more effective. Among those species screened, KF
afforded the highest product yield (entries 5À8). On the
other hand, while Cu(CF3COO)2 exhibited slightly lower
Scheme 1. Copper-Mediated Cyanatioin of Arylsilanesa
efficiency when compared to Cu(NO3)2 3H2O (entry 9),
3
reactivity of other copper salts was lower (entries 10À13).
The use of NH4I was essential for this cyanation as
demonstrated by entries 14 and 15. Upon decrease in the
amount of copper species, ammonium salt, or additive,
reaction efficiency was accordingly reduced (entries 16À19).
With the optimized conditions in hand, we next investi-
gated the substrate scopeofthis reaction (Scheme 1). Itwas
found that a range of functional groups (e.g., alkoxy,
phenyl, methylthio, benzyloxy, trifluoromethyl, or chloro)
was compatible with the employed conditions. Arylsilanes
bearing substituents at the para-, meta-, and ortho-position
were converted to the corresponding benzonitriles in good
yields (2b, 2h, and 2i, respectively). The cyanation was
more influenced by electronic property of substrates;
electron-donating substituents induced slightly higher prod-
uct yields than e-withdrawing groups. While cyanation of
disubstituted arylsilanes was smooth (2kÀm), fused aryl
substrates also underwent the desired reaction with high
efficiency (2nÀp). It was interesting to observe that while
trialkylarylsilanes were not reacted under the employed
conditions, the alkyl moiety of working trialkoxyarylsilane
substrates was more flexible leading to similar product yields
(e.g., 2a).
a Conditions: arylsilane (0.3 mmol), NH4I (2.0 equiv), Cu(NO3)2 3H2O
3
(2.0 equiv), KF (2.0 equiv) and DMF (2.0 mL) at 140 °C for 25 h under O2
balloon. b Isolated yield. c KF (1.0 equiv).
Table 2. Copper-Mediated Cyanation of Hiyama Silanesa
Nakao and Hiyama recently introduced a novel type of
silicon cross-coupling reagent; alkenyl- and aryl[2-(hydro-
xymethyl)phenyl]dimethylsilanes.23 One of the most at-
tractive aspects of these silanes is that a fluoride activator is
not required in the metal-mediated coupling reactions
(22) (a) Hiyama, T.; Shirakawa, E. Top. Curr. Chem. 2002, 219, 61.
(b) Denmark, S. E.; Sweis, R. F. In Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004; p 163. (c) Tsuji, J. In Palladium Reagents and Catalysts;
John Wiley & Sons: Chichester, 2004; p 338. (d) Miura, K.; Hosomi, A. In
Main Group Metals in Organic Synthesis; Yamamoto, H., Oshima, K., Eds.;
Wiley-VCH: Weinheim, 2004; Vol. 2, p 409.
(23) (a) Nakao, Y.; Imanaka, H.; Sahoo, A. K.; Yada, A.; Hiyama, T.
J. Am. Chem. Soc. 2005, 127, 6952. (b) Nakao, Y.; Takeda, M.;
Matsumoto, T.; Hiyama, T. Angew. Chem., Int. Ed. 2010, 49, 4447. (c)
Nakao, Y.; Chen, J.; Imanaka, H.; Hiyama, T.; Ichikawa, Y.; Duan,
W.-L.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2007, 129, 9137. (d)
Miki, Y.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2013, 15, 172. (e)
Nakao, Y.; Chen, J.; Tanaka, M.; Hiyama, T. J. Am. Chem. Soc. 2007,
129, 11694.
a Conditions: arylsilane (0.3 mmol), NH4I (2.0 equiv), Cu(NO3)2 3H2O
3
(2.0 equiv) and DMF (2.0 mL) at 140 °C for 35 h under O2 balloon. b Isolated
yield. c KF(2.0 equiv) was used.
(24) (a) Alvisi, D.; Blart, E.; Bonini, B. F.; Mazzanti, G.; Ricci, A.;
ꢀ
Zani, P. J. Org. Chem. 1996, 61, 7139. (b) Alacid, E.; Najera, C. Adv.
ꢀ
Synth. Catal. 2006, 348, 2085. (c) Alacid, E.; Najera, C. J. Org. Chem.
mainly due to an intramolecular interaction leading to a
pentacoordinated silicate intermediate. We were pleased
to find that conversion of aryl[2-(hydroxymethyl)phenyl]-
dimethylsilanes (3aÀc) was achieved indeed in the absence
of KF additive (Table 2). Interestingly, it was observed that
ꢀ
ꢀ
ꢀ
2008, 73, 2315. (d) Gordillo, A.; Jesus, E. D.; Lopez-Mardomingo, C.
J. Am. Chem. Soc. 2009, 131, 4584.
(25) Smith, A. B., III; Tong, R. Org. Lett. 2010, 12, 1260.
(26) Iida, S.; Togo, H. Tetrahedron 2007, 63, 8274.
(27) When benzylamine was subjected to the current reaction condi-
tions, benzonitrile was observed to form in high yield.
1992
Org. Lett., Vol. 15, No. 8, 2013

a fluoride additive slightly lowered the reaction efficiency
of a phenanthrenyl derivative (3c). Due to the fact that
vinylsilanes are readily prepared for the use of various
reactions including cross-couplings,24 we were interested in
investigating their feasibility for the cyanation under our
present conditions.
It was found that the cyanation took place smoothly
giving rise to the corresponding alkenyl nitrile products
(Scheme 2). Interestingly, substrates bearing electron-
donating substituents at the aryl moiety underwent the
cyanaton with a slight loss of stereochemistry leading to a
mixture of stereoisomeric products (5a,b). In contrast,
(E)-styrylsilanes containing e-withdrawing groups were
cyanated with a complete retention of stereochemistry
(5cÀe). Cyanation of (E)-naphthalenylvinylsilane was also
facile with retention (5f).
Figure 1. Reaction profile in the Cu-mediated cyanation of 1a.
Scheme 2. Copper-Mediated Cyanation of Vinylsilanesa
In order to gain mechanistic insight of the cyanation of
arylsilanes, a reaction profile was obtained using 1a under
the standard conditions (Figure 1). Within 30 min, 1a was
converted almost quantitatively to 4-iodoanisole (7a), and
then 4-methoxybenzonitrile (2b) was started to form over
time with the disappearance of 7a. In fact, when iodoarene
7a was subject to the reaction conditions, the correspond-
ing benzonitrile 2b was obtained in 74% yield even in the
absence of KF (eq 2), suggesting that iodoarenes are a key
intermediate in the present cyanation process.
a Conditions: styrylsilane (0.3 mmol), Cu(NO3)2 3H2O (2.0 equiv),
3
NH4I (2.0 equiv), KF (2.0 equiv) and DMF (2.0 mL) at 140 °C for 25 h
under O2 balloon.
In conclusion, we have developed for the first time a
copper-mediated oxidative cyanation of organosilanes
using ammonium iodide and DMF asthe combined source
of “CN” unit. A range of substrates including aryl-, di-
aryldimethyl-, styryl-, and benzylsilanes were efficiently
cyanated with high functional group tolerance. The reac-
tion was proposed to proceed in two sequential steps:
initial iodination and subsequent cyanation.
We next briefly examined cyanation of benzylsilane
derivatives.25 To our surprise, instead of obtaining pheny-
lacetonitriles, benzonitriles were observed to form albeit in
moderate yields (eq 1). All reagents were required for this
conversion: NH4I, copper species, KF, and O2 in DMF.
Considering a previous report by Togo and Iida that alkyl
halides are oxidatively converted to nitriles with molecular
iodine in aqueous ammonia,26 this cyanation of benzylsilanes
is proposed to proceed in a sequential process; initial iodina-
tion of benzylsilanes to benzyl iodides followed by formation
of benzylamines which are finally oxidized to benzonitriles
under the employed copper-mediated oxidative conditions.27
Acknowledgment. This research was supported by the
Institute for Basic Science (IBS). We thank Mr. Jinwoo
Kim (KAIST) and Mr. Sangjoon Shin (KAIST) for their
experimental helps.
Supporting Information Available. Experimental de-
1
tails and H and 13C NMR spectra of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 8, 2013
1993