Tris(trimethylsilyl)silane-mediated reductive decyanation and cyano transfer reactions of malononitriles

Article abstract of DOI:10.1246/cl.171231

Reductive decyanation reactions of malononitriles were achieved with tris(trimethylsilyl)silane as a radical mediator. The reaction proceeds via a radical chain mechanism involving a silyl radical addition to the malononitrile to form an imidoyl radical followed by α-cleavage to give a silyl isocyanide and an α-cyano radical. The reaction of a 3-butenyl-substituted malononitrile afforded a decyano/cyanosilylation product in good yield through 1,4-cyano transfer.

Full text of DOI:10.1246/cl.171231

Received: December 30, 2017 | Accepted: January 22, 2018 | Web Released: February 2, 2018
CL-171231
Tris(trimethylsilyl)silane-mediated Reductive Decyanation
and Cyano Transfer Reactions of Malononitriles
Takuji Kawamoto,*1 Yudai Shimaya,1 Dennis P. Curran,2 and Akio Kamimura1
1Department of Applied Chemistry, Yamaguchi University, Ube, Yamaguchi 755-8611, Japan
2Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA
E-mail: tak102@yamaguchi-u.ac.jp
Reductive decyanation reactions of malononitriles were
achieved with tris(trimethylsilyl)silane as a radical mediator.
The reaction proceeds via a radical chain mechanism involving
a silyl radical addition to the malononitrile to form an imidoyl
radical followed by α-cleavage to give a silyl isocyanide and
an α-cyano radical. The reaction of a 3-butenyl-substituted
malononitrile afforded a decyano/cyanosilylation product in
good yield through 1,4-cyano transfer.
20 mol%) as initiator (Table 1, Entry 1). The reaction was
conducted in benzene with heating at 80 °C. After purification
by flash chromatography, the target decyanation product 2a was
obtained in 88% yield.11
Table 1 shows the results of other malononitriles that
were reductively decyanated by the same procedure. Substrates
Table 1. TTMSS-mediated reductive decyanation reactions
AIBN (20 mol %)
R1 R2
R1 R2
+
(Me3Si)3SiH
2 equiv
Keywords: Radical
| Malononitriles | Decyanation
PhH (1 mL)
80 °C, 2 h
NC CN
NC
H
1
2
0.5 mmol
Nitriles can be found in a wide variety of pharmaceuticals,
agrochemicals, and optoelectronic materials.1 They also serve
as versatile synthetic intermediates for carboxylic acids, esters,
amides, and amines.2 Accordingly, the development of novel
and efficient synthetic methods for nitriles has been a major
topic in synthetic organic chemistry.
yielda
88%
entry
1
2
CN
CN
CN
1
H
H
MeO
MeO
Cl
1a
1b
2a
2b
CN
CN
CN
Malononitrile is the simplest geminal dinitrile. It has a
highly acidic proton, thus it is easy to functionalize.3 Once the
dinitrile has served its purpose in the course of a synthesis,
it often becomes necessary to replace one of the cyano groups
with a hydrogen atom.4 However, thus far, decyanation reactions
of malononitriles are rarely reported.5-7 Tributyltin hydride-
mediated reductive decyanation of malononitriles were reported
in 1991 (Scheme 1, eq 1),8 but the use of tin hydride is declining
due to tin toxicity. Recently, we reported reductive decyanation
of malononitriles with N-heterocyclic carbene boranes (e.g. 1,3-
dimethylimidazol-2-ylidene borane (diMe-Imd-BH3)) (eq 2).9
Other groups reported reductive decyanation of malononitriles
via one electron reduction.5c-5e Here we report radical decyana-
tions of malononitriles with tris(trimethylsilyl)silane (TTMSS).10
Related decyano/cyanosilylation and decyano/allylation reac-
tions are also presented.
2
3
69%
72%
Cl
Cl
Cl
CN
CN
CN
CN
H
H
Cl
1c
Cl
2c
CN
CN
4
5
90%
90%
NC
NC
1d
2d
2e
CN
CN
CN
CN
Ph
Ph
Ph
1e
Ph
Ph
Ph
6b
67%
79%
NC CN
NC
H
1f
2e
Initially, the reductive decyanation reaction was examined
with 2-(4-methoxybenzyl)malononitrile (1a) as a model sub-
strate in the presence of tris(trimethylsilyl)silane (TTMSS,
2 equiv) as reductant and azobisisobutyronitrile (AIBN,
7b
NC CN
NC H
1g
2g
8c
70%
74%
65%
NC CN
NC H
CO2Me
CN
CO2Me
CN
Previous Work
MeO
MeO
MeO
MeO
MeO
MeO
R1 R2
NC CN
R1 R2
NC
AIBN
1h
2h
+
+
HSnBu3
N
(1)
(2)
H
9c
NC CN
NC
H
H
R1 R2
NC CN
t-BuOOt-Bu
R1 R2
NC
1i
2i
H3B
H
N
10c
NC CN
NC
COMe
COMe
diMe-Imd-BH3
This Work
1j
2j
R1 R2
NC CN
R1 R2
NC
AIBN
+
HSi(SiMe3)3
(3)
aIsolated yield after silica gel column chromatography. bt-
BuOOt-Bu (1 equiv) was used instead of AIBN and the reaction
performed at 120 °C for 4 h. AIBN (40 mol%) was used.
H
c
Scheme 1. Radical reductive decyanation of malononitriles.
Chem. Lett. 2018, 47, 573–575 | doi:10.1246/cl.171231
© 2018 The Chemical Society of Japan | 573

(a) radical probe experiments
AIBN (20 mol %)
+
Y
H
NC CN
PhH (1 mL)
80 °C, 16 h
MeO
AIBN (20 mol %)
H
CN
CN
+
Y
H
H
1l
PhH or PhCF3 (1 mL)
80 °C, 16 h
Ph
CN
Y
1k
CN
CN
H
CN
CN
Ph
Ph
CN
Ph
H
MeO
2k
1e
2e
Y = Si(SiMe3)3
Y = SnBu3
3l (70%)
3l' (66%)
Y = Si(SiMe3)3
Y = SnBu3
0%
0%
48% (51%)
42%
4%
39%
0%
Y = diMe-Imd-BH2 (4 h) 27% (14%)
0%
Scheme 3. Reaction of 3-butenyl substituted malononitrile 1l.
The yields were determined by 1H NMR using internal standard.
Isolated yields are shown in parentheses.
a) formation of iminyl radical F
(b) mechanistic pathways
Y
CN
H
CN
N
R
N
Y
H
–
5-exo
Y
1e and 2e
Ph
Ph
C
CN
Y• adds
to N
N
Y
Y
E
Y
Y
R
A
B
R
N
1k
N
imidoyl radical
CN
CN
1l
F
Y
SHi
R
R
H
H
Y• adds
to C
CN
CN
Y
H
5-exo
Y
2k
N Y
N
Y
CN
CN
Ph
Ph
–
–
Y
YCN
N
G
H
C
D
iminyl radical
b) fragmentation and hydrogen transfer
CN
H
Scheme 2. Reactions of 2-phenylcyclopropane-1,1-dicarbonitrile.
β-cleavage
R
Y
Y
H
Y
Y
R
R
– Y
CN
N
N
CN
CN
having chlorine (1b and 1c) or cyanide (1d) substituents on the
benzene ring afforded the corresponding decyanation products
2b-2d in 69-90% yields (Entries 2-4). The reaction of 2-
phenethylmalononitrile (1e) also worked well (Entry 5). The
reaction of bis-substituted malononitrile 1f and 1g gave
decyanation product 2f and 2g in 67% and 79% yield with
slightly harsh conditions, respectively (Entries 6 and 7).
Substrates 1h-1j, which are easily prepared by Michael
reactions of 1a,12 gave the corresponding decyanation products
2h-2j in 65-74% yields (Entries 8-10).
F
I
3l or 3l'
Scheme 4. Plausible mechanisms for formation of 3l:
R = CH2C6H4-4-OMe, Y = Si(SiMe3)3 or SnBu3.
contrast, the NHC-borane radical-mediated decyanation reaction
proceeds via an iminyl radical intermediate C (Y = diMe-Imd-
BH2). This undergoes a β-fragmentation to form NHC-BH2CN
and D, which in turn abstracts a hydrogen atom from the borane
to give 2k.
Radical probe experiments were then carried out to offer
insights into the reaction mechanism. In the prior tin hydride
decyanations, we speculated that the tin radical probably adds
to the nitrile nitrogen to give an imidoyl radical, followed by
α-fragmentation.8 To support this speculation, we conducted
reactions of 2-phenylcyclopropane-1,1-dicarbonitrile (1k) with
TTMSS or Bu3SnH, respectively. The reaction with TTMSS
under those standard conditions for 16 h afforded the ring-
opening product 1e in 51% yield (Scheme 2). In the absence of
AIBN, starting material 1k was recovered. The corresponding
reaction with Bu3SnH also gave dinitrile 1e in 42% yield along
with mononitrile 2e in 39% yield. Mononitrile 2e is a secondary
product that forms by reductive decyanation of 1e.
Having learned that imidoyl radicals are intermediates in
both silyl- and tin-mediated transformations, we wondered
whether such intermediates could be trapped by other radical
reactions besides cyclopropane cleavage. To address this
question, we examined the behavior of 3-butenyl substituted
malononitrile 1l, which has an alkene poised to undergo 5-exo
cyclization with an imidoyl radical (Scheme 3). However,
the reaction of 1l with (Me3Si)3SiH did not give a cyclized
product but instead gave decyano/cyanosilylation product 3l
in 70% yield. A reaction with Bu3SnH gave the corresponding
stannylated product 3l¤ in 66% yield.13
Scheme 4 shows possible mechanisms for the cyanosilyla-
tion or cyanostannylation reactions of 1l. A key intermediate is
iminyl radical F, which can form by two routes (Scheme 4a). In
the first route, a silyl (Y = Si(SiMe3)3) or stannyl (Y = SnBu3)
radical adds to the terminal alkene of 1l to give E, followed by
5-exo cyclization to give iminyl radical F.14 β-Cleavage of F to
give α-cyano radical I is followed by hydrogen atom transfer to
afford 3l (Scheme 4b). In a second route to F (Scheme 4a), the
silyl or stannyl radical adds to a nitrile to give an imidoyl radical
G, which undergoes 5-exo cyclization to afford H. Then H
undergoes intramolecular homolytic substitution (SHi)15 to give
the iminyl radical F.
Next we conducted the reaction of 1k with diMe-Imd-BH3
and this gave decyanation product 2k.
These results show that silyl- and tin-mediated decyanation
reactions proceed via an imidoyl radical intermediate such as
A (Y = Si(SiMe3)3 or SnBu3), which usually undergoes an
α-fragmentation to give an α-cyano radical and isocyanide
(:CNSi(SiMe3)3 or :CNSnBu3). However, with the radical probe
1k, scission of the cyclopropane ring to give B is more rapid.
This leads to product 1e (and eventually 2e) by H-transfer
reaction and protodesilylation or protodestannylation of the
resulting ketene imine. The generating Y• (Y = Si(SiMe3)3 or
SnBu3) adds to nitrile, thus maintaining the radical chain. In
Differentiating the two possible paths to F is difficult
because additions to both the alkene9 and the nitrile may be
574 | Chem. Lett. 2018, 47, 573–575 | doi:10.1246/cl.171231
© 2018 The Chemical Society of Japan

t-BuOOt-Bu
Bu
Bu
NC CN
3
4
F. Freeman, Malononitrile. e-EROS Encyclopedia of Reagents
for Organic Synthesis, 2001. doi:10.1002/047084289X.rm015.
Chiba et al. reported a synthesis of bicyclic lactones through
Bu3SnH-mediated decyanation reaction, see Scheme 3 in:
B. M. K. Tong, H. Chen, S. Y. Chong, Y. L. Heng, S. Chiba,
Org. Lett. 2012, 14, 2826.
(1 equiv)
Y
+
NC
R
MeO
MeO
1m
4m (R = allyl) 2m (R = H)
Y = Si(SiMe3)3
Y = SnBu3
21%
51%
34%
21%
140 °C, 2 h
120 °C, 16 h, MS 4Å (10 wt%)
5
a) H.-Y. Kang, W. S. Hong, Y. S. Cho, H. Y. Koh, Tetrahedron
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Scheme 5. Decyano/allylation reaction.
reversible and because the rates of addition (and fragmentation)
may be different for tris(trimethylsilyl) and tributylstannyl
radicals. However, while intramolecular SHi reactions are well
known for both silicon and tin,15 most migration examples
involve 1,5- or 1,6-group transfer. The conversion of H to F is
a 1,4-migration, and SHi reactions in such settings usually occur
not by migration but by displacement of one of the other groups
on silicon or tin (SiMe3 or Bu) to give a silacycle or a
stannacycle. Such products are not observed, so the alkene
addition pathway probably predominates.
To close the study, we examined a decyano/allylation
reaction leading to an α-allylated quaternary nitrile (Scheme 5).
When a mixture of disubstituted malononitrile 1m and di-
tert-butyl peroxide (t-BuOOt-Bu) was heated at 140 °C in the
presence of allyl tris(trimethylsilyl)silane,16 the allylated product
4m was obtained in 21% yield, along with decyanation product
2m in 34% yield. When allylstannane was used, the yield of 4m
improved to 51%.
6
7
For a review of decyanation reactions, see: a) J.-M. Mattalia,
C. Marchi-Delapierre, H. Hazimeh, M. Chanon, ARKIVOC
2006, Part iv, 90. b) J.-M. R. Mattalia, Beilstein J. Org. Chem.
2017, 13, 267.
For a recent example of decyanation, see: P. C. Too, G. H.
Chan, Y. L. Tnay, H. Hirao, S. Chiba, Angew. Chem., Int. Ed.
2016, 55, 3719.
8
9
D. P. Curran, C. M. Seong, Synlett 1991, 107.
a) T. Kawamoto, S. J. Geib, D. P. Curran, J. Am. Chem. Soc.
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2017, 82, 13746.
10 For a review of TTMSS mediated radical reaction, see: C.
Chatgilialoglu, Chem.®Eur. J. 2008, 14, 2310.
11 The reaction of 1a with 1.5 equiv of TTMSS gave 2a in 90%
yield. When the TTMSS loading was decreased to 1.2 equiv,
1a remained.
In conclusion, we have developed reductive decyanation
reactions of malononitriles with tris(trimethylsilyl)silane. A 3-
butenyl substituted malononitrile gave silylcyano/decyanation
product and a reaction with allyl tris(trimethylsilyl)silane gave
an allylated product. Mechanistic experiments revealed that both
the new silane reaction and the known tin reaction proceed via
imidoyl radical intermediates.
12 A. G. Campaña, N. Fuentes, E. Gómez-Bengoa, C. Mateo,
J. E. Oltra, A. M. Echavarren, J. M. Cuerva, J. Org. Chem.
2007, 72, 8127.
13 Bu3SnH-mediated cyano transfer reaction have been reported,
see: a) D. P. Curran, C. M. Seong, Tetrahedron 1992, 48, 2175.
b) W. R. Bowman, C. F. Bridge, P. Brookes, Tetrahedron Lett.
2000, 41, 8989. c) K. Vervisch, M. D’hooghe, K. W. Törnroos,
N. De Kimpe, Org. Biomol. Chem. 2012, 10, 3308. d) X. Feng,
Z. Zhou, X. Yin, R. Li, Y.-C. Chen, Eur. J. Org. Chem. 2014,
5906.
14 For recent examples on C-CN bond cleavage reactions via
iminyl radical intermediates, see: a) S. Kamijo, S. Yokosaka,
M. Inoue, Tetrahedron Lett. 2012, 53, 4324. b) Z. Wu, R. Ren,
C. Zhu, Angew. Chem., Int. Ed. 2016, 55, 10821. c) N. Wang,
L. Li, Z.-L. Li, N.-Y. Yang, Z. Guo, H.-X. Zhang, X.-Y. Liu,
Org. Lett. 2016, 18, 6026. d) M. Ji, Z. Wu, J. Yu, X. Wan, C.
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Huan, C. Zhu, Adv. Synth. Catal. 2017, 359, 3052.
15 For a review of SHi reactions, see: S. H. Kyne, C. H. Schiesser,
in Encyclopedia of Radicals in Chemsitry, Biology and
Materials, ed. by C. Chatgilialoglu, A. Studer, John Wiley &
Sons, Chichester, 2012, Vol. 2, p. 629.
This work was partially supported by a JSPS Grant-in-Aid
for Young Scientists (B) (16K17869), Tokuyama Science
Foundation, The Naito Foundation, Yamaguchi University, and
Yamaguchi University Foundation. US support came from the
National Science Foundation.
Supporting Information is available on http://dx.doi.org/
10.1246/cl.171231.
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Chem. Lett. 2018, 47, 573–575 | doi:10.1246/cl.171231
© 2018 The Chemical Society of Japan | 575