Cleavage of carbon-carbon triple bond: Direct transformation of alkynes to nitriles

Article abstract of DOI:10.1021/ol401311h

A new cleavage reaction of carbon-carbon triple bonds proceeds efficiently with NIS and TMSN₃, giving the corresponding nitriles in moderate to good yields.

Full text of DOI:10.1021/ol401311h

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Cleavage of CarbonÀCarbon Triple Bond:
Direct Transformation of Alkynes to Nitriles
Noriko Okamoto,† Minoru Ishikura,‡ and Reiko Yanada*,†
Faculty of Pharmaceutical Sciences, Hiroshima International University,
5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan, and Faculty of Pharmaceutical
Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu,
Hokkaido 061-0293, Japan
ryanada@ps.hirokoku-u.ac.jp
Received April 9, 2013
ABSTRACT
A new cleavage reaction of carbonÀcarbon triple bonds proceeds efficiently with NIS and TMSN3, giving the corresponding nitriles in moderate
to good yields.
Cleavage of carbonÀcarbon bonds is a useful transfor-
mation in organic chemistry.1 Although many studies on
CÀC single- and double-bond cleavage reactions have
been reported,2,3 only a few examples on CÀC triple bond
cleavage reactions have been reported. Recently, Jun et al.
reported CÀC triple bond cleavages through hydroimi-
noacylation by Rh(I) catalyst and hydroacylation-
triggered cleavages by the same catalyst.4 Yamamoto et al.
reported the CÀC triple bond cleavage of diynes by
transition-metal catalysts.5 Ru-catalyzed CÀC triple bond
cleavages and Au(I)-catalyzed CÀC triple bond cleavages
via cascade cyclization/oxidative cleavage were also
reported.6 Recently, Jiang et al. reported Pd(II)-catalyzed
reactions.7 Cleavage of the CÀC triple bonds without
a metal catalyst is rare.8 Described herein is a novel
reaction for the cleavage of CÀC triple bonds by NIS
(N-iodosuccinimide) and TMSN3 (trimethylsilylazide)
without metal catalyst through iodoazidation, followed by
2-iodo-2H-azirine formation, and then 2-azide-2H-azirine
formation. As in the schematic representation (Scheme 1),
the CÀC triple bond of alkyne 1 is divided into an aromatic
nitrile 2 and a second nitrile 3.
† Hiroshima International University.
‡ Health Sciences University of Hokkaido.
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Scheme 1. Cleavage of CÀC Triple Bond
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Chem. 2001, 66, 4814. (b) Takemori, T.; Inagaki, A.; Suzuki, H. J. Am.
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r
10.1021/ol401311h
XXXX American Chemical Society

Initially, we applied the CÀC triple bond cleavage
reaction to 1,2-bis(4-methoxyphenyl)ethyne (1a) in order
to discover the optimized reaction conditions. As summar-
ized in Table 1, the best result was obtained when the
amounts of both NIS and TMSN39 were 2.4 equiv (entries
1À3). The triple bond cleavage reaction proceeded effi-
ciently in DCE:MeCN (1:1), starting at room temperature
and rising to 70 °C (entries 3À8). Interestingly, an unstable
intermediate was observed on TLC when the cleavage
reaction proceeded at room temperature for 2 h in DCE:
MeCN (1:1). We assumed the intermediate might be iodo
vinyl azide A (Scheme 2). Intermediate A disappeared
when the reaction temperature was elevated to 70 °C and
was converted to nitrile 2a. Under the same reaction
conditions, the use of NBS or NCS instead of NIS failed
Table 2. Triple Bond Cleavage Reaction via Iodoazidationa
Table 1. Optimization of Reaction Conditions
NIS
TMSN3
temp and
time
yield
(%)a
entry (equiv) (equiv)
solvent
1
2
3
1.3
1.3
2.4
1.3
2.4
2.4
DCE/MeCN (1:1) rt (2 h) then
70 °C (1 h)
55b
65c
84
DCE/MeCN (1:1) rt (2 h) then
70 °C (1 h)
DCE/MeCN (1:1) rt (2 h) then
70 °C (1 h)
4
5
2.4
2.4
2.4
2.4
DCE/MeCN (1:1)
DCE
70 °C (4 h)
rt (2 h) then
70 °C (1 h)
rt (2 h) then
70 °C (1 h)
rt (2 h) then
70 °C (1 h)
rt (2 h) then
70 °C (1 h)
75
76
6
2.4
2.4
2.4
2.4
2.4
2.4
2.4
2.4
MeCN
DMF
THF
75
55
20d
19
23
70
7
8
9
(NBS)
2.4
(NCS)
2.4
DCE/MeCN (1:1) rt (2 h) then
70 °C (2 h)
10
11
DCE/MeCN (1:1) rt (2 h) then
70 °C (2 h)
2.4
(NaN3) DCE/AcOH (5:1)
rt (2 h)
2.4
a Isolated yield. b Recovery of starting material (18%). c Recovery of
starting material (17%). d Recovery of starting material (80%).
to give a significant amount of 2a (entries 9 and 10).
Although the yield of 2a was lower, the use of sodium
azide instead of TMSN3 was also found effective for the
triple bond cleavage reaction (entry 11).
Having in hand the optimized reaction conditions, we
next examined the scope and limitation of this CÀC triple
bond cleavage reaction. The results are shown in Table 2.
Symmetrical internal alkynes 1bÀf provided the desired
nitriles 2bÀf in good to moderate yields (entries 1À5). We
a Reaction conditions: alkyne (0.4 mmol), NIS (0.96 mmol), TMSN3
(0.96 mmol), DCE (1 mL), MeCN (1 mL). b Isolated yields. c Longer
reaction time was needed (room temperature (2 h) then 70 °C (5 h)). d The
yields were determined by 1H NMR. e 3-Iodo-2-phenylbenzofuran was
also obtained in 29% yield.
€
(9) (a) Brase, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew.
Chem., Int. Ed. 2005, 44, 5188. (b) Hajra, S.; Bhowmick, M.; Sinha, D.
J. Org. Chem. 2006, 71, 9237.
B
Org. Lett., Vol. XX, No. XX, XXXX

Scheme 2. Plausible Reaction Mechanism
Scheme 3. Isolation of A1 and Transformation to Nitrile
iodo azides like A led to the loss of nitrogen to give like
2-iodo-2H-azirines B as highly strained compounds.11 In
our experiment, the EDG on the aromatic ring of com-
pound A possibly accelerated the formation of 2-iodo-2H-
azirine intermediate B,12 which was accompanied by
release of nitrogen gas under the thermal condition (at
70 °C). Then the iodo azirine B underwent halide displace-
ment with the azide anion to generate 2-azide-2H-azirine
C13 accompanied by molecular iodine. The color of the
reaction mixture gradually changed to purplish red iodine
color asthe reactionprogressed. Thering-opening reaction
of azide azirine C using the strain release produced sub-
stituted benzonitrile 2 and the other nitrile 3.
To support this proposed mechanism, we performed the
following experiment (Scheme 3). After the reaction of
diphenylacetylene 1d, NIS, and TMSN3 was carried out at
room temperature for 3 h, unstable intermediate A114 was
isolated in 39% yield (mixture of E- and Z-stereoisomers).10,15
Further continuous treatment of A1 by additional NIS and
TMSN3 at 70 °C for 5 h also gave benzonitrile 2d in 41% yield.
In summary, we have demonstrated that the new CÀC
triple bond cleavage reaction without metal catalyst proceeds
efficiently with NIS and TMSN3, affording nitriles in mod-
erate to good yields. Clarification of the reaction mechanism
and further application of this chemistry are in progress.
applied this method to unsymmetrical internal alkynes. By
analogy with the symmetrical internal alkynes, the unsym-
metrical internal alkynes were cleaved into two different
nitriles (entries 6À27). Alkynes with an electron-donating
group (EDG) on the aromatic rings tend to give nitriles
easily. Terminal alkyne gave the corresponding nitrile in
moderate yield (entry 18). It is worth noting that internal
alkynes, bearing two aromatic substituents or bearing
aromaticÀaliphatic substituents, are both cleaved to fur-
nish the desired nitriles. However, the latter alkynes gave
nitriles in lower yields (entries 16, 17, and 24). Some kinds
of functionalities such as ether, carbamate, ester, and
amide are tolerated in this cleavage reaction.
On the basis of the results obtained above, we propose a
plausible reaction mechanism (Scheme 2). We envisaged
iodo vinyl azide A as the key intermediate, derived from
new regioselective iodoazidation10 of alkynes 1 with
ꢀ
NIS and TMSN3. Suarez reported that irradiation with a
medium-pressure mercury lamp of trisubstituted alkenyl
Acknowledgment. We gratefully acknowledge a Grant-
in-Aid for Scientific Research (C) from JSPS KAKENHI
(23590032). N.O. is grateful for the Sasakawa Scientific
Research Grant from The Japan Science Society.
Supporting Information Available. Experimental de-
tails and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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N.; Miwa, Y.; Minami, H.; Takeda, K.; Yanada, R. J. Org. Chem. 2011, 76,
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´
guez, M. S.;
ꢀ
Suarez, E. Tetrahedron Lett. 2007, 48, 7207. (b) Alonso-Cruz, C. R.;
ꢀ
Kennedy, A. R.; Rodrıguez, M. S.; Suarez, E. J. Org. Chem. 2008, 73,
´
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€
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(12) Storr reported that the reaction with R-chloroenamine and azide
ion gave azide aminoazirine via perhaps the chloroaminoazirine inter-
mediate. (a) Gallagher, T. C.; Storr, R. C. Tetrahedron Lett. 1981, 22,
(15) The structure of iodo vinyl azide A1 was supported by 1H and
13C NMR, IR, and MS spectra. Details are provided in the Supporting
Information.
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´
E.; Manuel de los Santos, J. E. J. Org. Chem. 2001, 2401. (c) Pinho e
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~
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The authors declare no competing financial interest.
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