Copper-catalyzed oxidative transformation of aryl propargylic azides to aryl propiolonitriles

Article abstract of DOI:10.1002/adsc.201201056

A concise copper(I)-catalyzed oxidative transformation of aryl propargyl azides to aryl propiolonitriles has been developed. Aryl propiolonitrile derivatives can be obtained in moderate to good yields by this strategy. An oxidative Schmidt rearrangement is involved in this transformation. Copyright

Full text of DOI:10.1002/adsc.201201056

UPDATES
DOI: 10.1002/adsc.201201056
Copper-Catalyzed Oxidative Transformation of Aryl Propargylic
Azides to Aryl Propiolonitriles
Teng Wang,a,b Hang Yin,a and Ning Jiaoa,c,*
a
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, School of Pharmaceutical Sciences, Peking
University, Xue Yuan Rd. 38, Beijing 100191, Peopleꢀs Republic of China
Fax : (+86)-010-8280-5297; e-mail: jiaoning@bjmu.edu.cn
Department of Chemistry, Tianjin University, Tianjin 300072, Peopleꢀs Republic of China
State Key Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, Peopleꢀs Republic
b
c
of China
Received: November 29, 2012; Revised: February 21, 2013; Published online: April 8, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201056.
Abstract: A concise copper(I)-catalyzed oxidative
transformation of aryl propargyl azides to aryl pro-
piolonitriles has been developed. Aryl propioloni-
trile derivatives can be obtained in moderate to
good yields by this strategy. An oxidative Schmidt
rearrangement is involved in this transformation.
compounds as nitrogen resources via a benzyl or allyl
azide intermediate has been achieved.[8] However, to
the best of our knowledge, the direct approach to aryl
propiolonitriles has not been realized yet. According
to these reported processes, primary azides as the key
intermediates underwent an analogous oxidative rear-
rangement to produce nitriles. Thus, the central issue
is the selection of the proper oxidative system with
azide precursors. Herein we demonstrate a novel ap-
proach to aryl propiolonitriles from aryl propargyl
azides [Eq. (1)].
Keywords: azides; copper; dehydrogenation; ni-
triles; oxidation; Schmidt rearrangement
Aryl propiolonitriles have been identified in many
cases as versatile building blocks (Scheme 1).[1] Many
functionalized derivatives based on them have intrigu-
ing chemical and biological activities. Their impor-
tance in synthesis has encouraged organic chemists to
Our research was commenced with the oxidative
develop new synthetic methods to prepare these com- rearrangement of the easily prepared 1-(3-azidoprop-
pounds.[2] In general, many elegant protocols for pro- 1-ynyl)-4-methylbenzene 1a (Table 1). When the reac-
ducing nitriles have been established to date,[3] in tion was carried out with 2,3-dichloro-5,6-dicyanoben-
which toxic cyanide salts or harsh conditions are often zoquinone (DDQ) in the presence of FeCl2, the de-
required. Although much progess has been made in sired 3-p-tolylpropiolonitrile 2a was obtained in 22%
the exploration of nitrogen resources,[4–7] it is still yield (entry 1).[9] Subsequently, a variety of oxidants
highly desirable to develop new approaches to aryl such as ceric ammonium nitrate (CAN), phenyliodo-
propiolonitriles from simple starting materials.
nium diacetate (PIDA), potassium peroxomonosulfate
Recently, a series of concise and economical trans- (Oxone) and molecular oxygen, were investigated
formations for the synthesis of nitriles utilizing azide (entries 2 to 5). However, no product was detected.
To our delight, 2a was obtained in 71% yield in the
presence of 5 mol% (CuOTf)2·PhMe using tert-butyl
hydroperoxide (TBHP) as an oxidant (entry 6). Other
copper and iron salts exhibited lower efficiency than
(CuOTf)2·PhMe as the catalyst (entries 8 to 13).[10]
Only a trace amount of 2a was detected by GC in the
absence of catalyst (entry 14), illustrating that the
copper salt plays an important role in the catalytic ox-
idative rearrangement.
Scheme 1. Applications of aryl propiolonitriles.
Adv. Synth. Catal. 2013, 355, 1207 – 1210
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Table 1. Optimation of the transformation of aryl propargyl-
ic azides 1a to aryl propiolonitriles 2a.[a]
Table 2. The conversion from aryl propargylic azides 1 to
aryl propiolonitriles 2.[a]
[a]
Reaction conditions: 1a (0.2 mmol), catalyst and oxidant
in dry solvent (2 mL), stirred under Ar for 10 h.
Isolated yield.
(CuOTf)2 stands for (CuOTf)2·PhMe.
[b]
[c]
[a]
Reaction conditions:
1
(0.2 mmol), (CuOTf)2·PhMe
(0.01 mmol) and TBHP (0.24 mmol) in DCE (2 mL) at
808C under argon, 10 h. Yields are of the isolated prod-
ucts.
With the optimized conditions in hand, the scope of
substrates was investigated (Table 2). Aryl propargyl
azides containing electron-donating groups at the aryl
ring worked well under these conditions, producing
the corresponding propiolonitriles 2 in moderate to
good yields (2a to 2h, Scheme 2). Aryl propiolonitriles
bearing electron-withdrawing groups could also be
obtained (2l and 2m). The position of the substituents
(para-, meta-, and ortho-positions) did not affect the
efficiencies (2a to 2c). Substrates containing halogen-
ated arenes also are tolerated in this transformation
under the standard conditions (2i to 2l), which provid-
ed the possibility to carry out subsequent transforma-
tions. Notably, 1-(3-azidoprop-1-ynyl)-naphthalene 1n
gave 2n in 64% yield. Heterocyclic substrates like 1o
exhibited reactivity in this transformation (49%, 2o).
A scale up run at 1 mmol was carried out to produce
2p in 76% yield. Unfortunately, alkyl propiolonitriles
could not be obtained under these conditions (2q).
To probe the mechanism of this oxidative rear-
rangement, several control reactions were investigat-
[b]
The reaction was carried out on a 1 mmol scale.
Scheme 2. Proposed mechanism for the transformation.
ed. The reaction in the presence of 2.0 equivalents of sible radical intermediates with 2,2,6,6-tetramethylpi-
2,6-di-tert-butyl-4-methylphenol (BHT) as the radical peridine 1-oxyl (TEMPO) failed [Eq. (3)]. Neither
scavenger, did not afford the desired product 2a, al- the desired product 2p nor the TEMPO adduct was
though the starting material was consumed complete- observed as expected. These results demonstrate that
ly [Eq. (2)].[11] Moreover, the attempt to trap the pos-
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Adv. Synth. Catal. 2013, 355, 1207 – 1210

Copper-Catalyzed Oxidative Transformation of Aryl Propargylic Azides to Aryl Propiolonitriles
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salts has been developed. A series of substrates was
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Experimental Section
Typical Procedure: 3-(p-Tolyl) Propiolonitrile (2a)
The solution of 1-(3-azidoprop-1-yn-1-yl)-4-methylbenzene
1a (34.3 mg, 0.2 mmol) in DCE (2.0 mL) was added to a 25-
mL Schlenk tube containing (CuOTf)2·PhMe (5.2 mg,
0.01 mmol) under argon. Then TBHP in decane (5.5M,
43.6 mL, 0.24 mmol) was added to the stirred mixture. The
reaction was conducted at 808C for 10 h. The crude product
was purified by flash column chromatography on silica gel
(eluent: petroleum ether/dichloromethane=10:1) to afford
2a as a solid; yield: 20.1 mg (71%). 1H NMR: (CDCl3,
400 MHz): d=7.50 (d, J=8.1 Hz, 2H), 7.21 (d, J=8.1 Hz,
2H), 2.40 (s, 3H); 13C NMR: (100 MHz, CDCl3) d=142.8,
133.4, 129.6, 114.4, 105.6, 83.5, 62.7, 21.8; IR (KBr): nmax
=
2926, 2266, 786, 686 cmÀ1; MS (70 eV): m/z=141.1 [M]+.
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Financial support from National Basic Research Program of
China (973 Program) (Grant No. 2009CB825300), National
Science Foundation of China (No. 21172006), and Peking
University is greatly appreciated. We thank Guolin Wu in this
group for reproducing the results of 2a and 2f.
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