Gold-catalyzed 1,2-iminonitronation of electron-deficient alkynes with nitrosoarenes to afford α-imidoyl nitrones

Article abstract of DOI:10.1039/c4cc06962e

Gold-catalyzed 1,2-iminonitronation of propiolate derivatives with nitrosoarenes to give α-imidoyl nitrones is described; this new reaction is applicable to diverse propiolate derivatives and nitrosoarenes.

Full text of DOI:10.1039/c4cc06962e

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Gold-catalyzed 1,2-iminonitronation of
electron-deficient alkynes with nitrosoarenes
to afford a-imidoyl nitrones†
Cite this: Chem. Commun., 2014,
50, 15864
Received 3rd September 2014,
Accepted 21st October 2014
RahulKumar Rajmani Singh and Rai-Shung Liu*
DOI: 10.1039/c4cc06962e
www.rsc.org/chemcomm
Table 1 Reactions over various catalysts
Gold-catalyzed 1,2-iminonitronation of propiolate derivatives
with nitrosoarenes to give a-imidoyl nitrones is described;
this new reaction is applicable to diverse propiolate derivatives
and nitrosoarenes.
Although alkenes and alkynes are two important unsaturated
hydrocarbon motifs in organic synthesis, catalytic oxidation
of alkynes1 is much less explored than for alkenes.2,3 One
important advent in Au- and Pt-catalyzed reactions is the
functionalization of electrophilically activated alkynes with
diverse nucleophiles.4 Pyridine N-oxides or sulfoxides allow
gold-catalyzed 1,2-double oxidation of alkynes to afford
1,2-dicarbonyl products (I) efficiently5 (eqn (1)). Metal-catalyzed
reactions of terminal alkynes with nitrosoarenes were reported
to produce indole derivatives.6 To implement 1,2-oxidative
difunctionalization of alkynes, we reported 1,2-oxoimination
of ynamides using nitrosoarenes to enable a reaction of meta-
thesis type (eqn (2)).7 We are aware of no precedent for catalytic
1,2-dual imination reactions of alkynes using suitable nitrogen
sources. Here we report gold-catalyzed 1,2-iminonitronation
reactions using electron-deficient alkynes, nitrosoarenes
and a suitable gold catalyst, which represent a special case of
Yieldb (%)
Entry
Catalyst
Solventa
Time (h)
1a
3a
4
1
2
3
4
5
6
7
8
9
10
LAuCI/AgNTf2
LAuCI/AgSbF6
AuCIPPh3/AgNTf2
IPrAuCI/AgNTf2
AuCI3
AgNTf2
PtCI2/CO
LAuCI/AgNTf2
LAuCI/AgNTf2
LAuCI/AgNTf2
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCM
CH3NO2
Toluene
6
6
6
10
7
12
12
24
12
18
—
—
—
—
—
65
71
—
12
45
77
67
64
71
63
—
—
75
63
27
13c
21
19
9
22
—
—
14
13
28
L
= P(t-Bu)2(o-biphenyl), IPr = 3-bis(diisopropylphenyl)imidazol-2-
a b
ylidene. [1a] = 0.20 M. Product yields are reported after purifica-
c
tion from a silica column. Diazene oxide 40 was isolated in 0.14 equiv.
in entry 1 whereas this species was undetermined in other entries.
1,2-dual imination reactions. The contrasting outcome in eqn (2) (entry 1). A switch of its silver source to LAuCl/AgSbF6 (entry 2)
and (3) is due to their distinct mechanisms involving non- gave compound 3a in a slightly decreased yield, ca. 64%
carbene7 versus carbene routes.
whereas dicarbonyl product 4 was obtained in 19% yield.
Table 1 presents conditions to achieve a 1,2-iminonitronation Other gold catalysts including PPh3AuCl/AgNTf2, IPrAuCl/
using various metal catalysts (5 mol%) and solvents. We tested AgNTf2 (IPr 3-bis(diiso-propylphenyl)imidazol-2-ylidene)
=
this reaction first involving ethyl propiolate 1a and PhNO and AuCl3 were also active, affording desired 3a in 63–71%
(2a, 2.3 equiv.) in dichloroethane (25 1C, 6 h) with LAuCl/AgNTf2 yields with side product 4 in 9–22% yields (entries 3–5).
(L = P(t-Bu)2(o-biphenyl)), leading to a complete conversion to afford AgNTf2 and PtCl2/CO were catalytically inactive to give initial
an a-imidoyl nitrone 3a in 77% yield together with a,b-dioxo ester 4 1a with 65–71% recovery (entries 6 and 7). For LAuCl/AgNTf2,
(13%) and diazene oxide 40 (0.14 equiv.) in minor proportions other solvents including dichloromethane (DCM), nitro-
methane and toluene yielded compound 3a in 75%, 63%
and 27% yields respectively; its byproduct 4 was obtained in
13–28% yields (entries 8–10). Structural characterization of
National Tsing Hua university, Chemistry, 101, Section 2, Kuang Fu Road, Hsinchu,
Taiwan. E-mail: rsliu@mx.nthu.edu.tw
compound 3a relies on the X-ray diffraction study of its indole
† Electronic supplementary information (ESI) available. CCDC 1020243 and
derivative 3j (Table 2, entry 9).8 Our control experiment
1022207. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c4cc06962e
indicates that a,b-dioxo ester 4 arises from the alkyne
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Table 2 Catalytic reactions with various alkynesa
N-tosyl indolyl, yielding desired products (3f–3j) in 64–74% yields
(entries 5–9). This reaction was extendible to an alkenyl-substituted
propiolate 1k, providing desired 3k in 79% yield (entry 10). To our
delight, the reactions were also compatible with alkyl-substituted
propiolates 1l and 1m (R = cyclohexyl and cyclopropyl), affording
a-imidoyl nitrones 3l and 3m in satisfactory yield 63%–71% (entries 11
and 12). Although the reaction was extendible to n-butyl-substituted
propiolate, we were unable to obtain its product in pure form. For
terminal alkyne propiolate, a complicated mixture of products was
obtained. Among these products, the molecular structure of species 3j
is elucidated by X-ray diffraction to characterize its structure.8
We also studied the scope of the substrates of various nitro-
soarenes 2b–2f (2.3 equiv.); their reactions with ethyl propiolate 1a
were examined with P(t-Bu)2(o-biphenyl) AuCl/AgNTf2 (5 mol%) in
DCE (25 1C, 7–9 h, Table 3). The catalytic reactions worked efficiently
for electron-rich nitrosoarenes 2b–d including 3,5-dimethylphenyl,
t-butylphenyl and 4-methoxyphenyl analogues (entries 1–3); resulting
products 5b–5d were produced in 67–73% yields. For their electron-
deficient phenyl analogues 2e and 2f (XC6H4, X = Br and Cl, entries 4
and 5), the same reactions afforded a-imidoyl nitrones 5e–5f in 73%
and 69% yields, respectively.
We tested the reaction of highly electron-deficient diethyl
but-2-ynedioate (1n) to examine the reaction chemoselectivity
(eqn (4)). The HRMS, 1H and 13C-NMR data support the structure of
a bis-nitrone species 6a with a plane of symmetry; this proposed
structure was confirmed by the X-ray diffraction study.8
a
[1] = 0.20 M. Product yields are reported after purification from a silica
column. L = P(t-Bu)2(o-biphenyl).
We postulate that the two ester groups stabilize their own
conjugated nitrones, thus forming bis-nitrone groups safely.
Formation of compound 6a confirms the intermediacy of
species A, in which gold carbene is replaced with nitrosobenzene
to form a second nitrone functionality. Such a carbene reaction
has analogous precedents in literature,9 further manifesting the
diversity of the carbene/nitrosoarene reactions.10–12
oxidation of initial 1a rather than from the hydration of
product 3a (see eqn (5)).
(1)
(2)
(4)
(3)
Table 3 Catalytic reactions with various nitrosoarenesa
We prepared additional propiolate derivatives (1b–1m) to assess
the scope of the reaction. The 1,2-iminonitronation of nitroso-
benzene (2.3 equiv.) with various ethyl propiolate derivatives (1b–1m)
is shown in Table 2. In most cases, a,b-dioxo esters were also produced
in minor proportions, but we did not isolate them. The reactions were
run with P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 (5 mol%) in DCE (25 1C,
0.2 M). Entries 1–4 show the applicability of this catalytic reaction
to several propiolate substrates 1b–1d bearing various p-phenyl sub-
stituents (4-XC6H4,
X
=
methyl, methoxy and 4-chloro);
their corresponding a-imidoyl nitrones 3b–3d were obtained in
satisfactory yields (61–76%). For ortho-methyl substituted derivative
1e, its corresponding product was obtained in 61% yield (entry 4).
The scope of this catalysis is further extended to heteroaryl substrates
a
b
[1a] = 0.20 M. Product yields are reported after purification from a
including 2-thienyl, 3-furanyl, 3-benzothienyl 2-benzofuranyl, and silica column. L = P(t-Bu)2(o-biphenyl).
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propiolate derivatives and nitrosoarenes. This outcome is
distinct from the gold 1,2-oxoimination reactions of ynamides
(eqn (2)) using the same oxidant, further reflecting the diversity
of gold catalysis. Further development of this new catalytic
reaction to access 1,2-difunctionalized compounds is under
current investigation.
Scheme 1 Formation of diazene oxide.
Notes and references
1 Reviews for gold-catalyzed oxidations of alkynes, see: (a) L. Zhang,
Acc. Chem. Res., 2014, 47, 877; (b) J. Xiao and X. Li, Angew. Chem., Int.
Ed., 2011, 50, 7226.
Diazene oxide 40 represents the reducing form of nitrosobenzene
2a and its detection in the system (Table 1, entry 1) urges us to
perform additional experiments as depicted in Scheme 1. Treatment
of nitrosobenzene 2a with a gold catalyst (5 mol%) in DCE delivered
diazene oxide 40 in 3% yield, but additional water (2 equiv.)
increased the yield of species 40 to 5.5%. We believe that water
can facilitate the formation of diazene oxide 40, presumably via
N-hydroxyaniline, which is unstable in solution to form diazene
oxide 40.13 Literature has documented a fast equilibrium between
nitrosobenzene and N-hydroxyaniline in HCl/water/acetone.14
a-Imidoyl nitrone 3a is robust toward the hydration with P(t-Bu)2
(o-biphenyl)AuCl/AgNTf2 in wet DCE. Hence, formation of ester 4
from propiolate 1a in Table 1 (entry 1) is unlikely caused by the
hydration of a-imidoyl nitrone 3a. Shown in eqn (5) is the successful
hydration of species 3a with HCl (1 equiv.) in THF/water (2 : 1)
to yield a,b-dioxo ester 4 in 45% yield.
2 For wacker oxidations, epoxidations and aziridination of alkenes,
see selected reviews: (a) R. I. McDonald, G. Liu and S. S. Stahl,
Chem. Rev., 2011, 111, 2981; (b) Y. Zhu, Q. Wang, R. G. Cornwall and
Y. Shi, Chem. Rev., 2014, 114, 8199; (c) L. Degennaro, P. Trinchera
and R. Luisi, Chem. Rev., 2014, 114, 7881; (d) J. B. Sweeney,
Chem. Soc. Rev., 2002, 31, 247; (e) T. Ibuka, Chem. Soc. Rev., 1998,
27, 145.
3 For catalytic dihydroxylation and diamination reactions, see
selected reviews: (a) H. C. Kolb, M. S. VanNieuwenhze and
K. B. Sharpless, Chem. Rev., 1994, 94, 2483; (b) D. Lucet, T. L. Gall
and C. Mioskowski, Angew. Chem., Int. Ed., 1998, 37, 2580;
(c) P. N. Becker and R. G. Bergman, Organometallics, 1983, 7, 789.
4 Reviews for gold catalysis: (a) A. Fu¨rstner, Chem. Soc. Rev., 2009,
38, 3208; (b) N. T. Patil and Y. Yamamoto, Chem. Rev., 2008, 108, 3395;
(c) A. Das, S. M. A. Abu and R.-S. Liu, Org. Biomol. Chem., 2010, 8, 960;
(d) A. Arcadi, Chem. Rev., 2008, 108, 3266; (e) E. Jimenez-Nunez and
A. M. Echavarren, Chem. Rev., 2008, 108, 3326; ( f ) D. J. Gorin,
B. D. Sherry and F. D. Toste, Chem. Rev., 2008, 108, 3351;
(g) A. S. K. Hashmi, Chem. Rev., 2007, 107, 3180.
5 (a) S. Shi, T. Wang, V. Weingand, M. Rudolph and A. S. K. Hashmi,
Angew. Chem., Int. Ed., 2014, 53, 1148; (b) S. Shi, T. Wang, W. Yang,
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(c) C.-F. Xu, M. Xu, Y.-X. Jia and C.-Y. Li, Org. Lett., 2011, 13, 1556.
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K. M. Nicholas, J. Am. Chem. Soc., 2009, 131, 653; (b) S. Murru,
A. A. Gallo and R. S. Srivastava, ACS Catal., 2011, 1, 29; (c) A. Penoni
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7 A. Mukherjee, R. B. Dateer, R. Chaudhuri, S. Bhunia, S. N. Karad and
R.-S. Liu, J. Am. Chem. Soc., 2011, 133, 15372.
8 Crystallographic data of compounds 3j and 6a were deposited at
Cambridge Crystallographic Data Center with CCDC 1020243 (3j)
and CCDC 1022207 (6a).
9 For the reaction of gold-carbene with nitrosoarenes to form nitrone
species, see selected examples: (a) Z.-J. Xu, D. Zhu, X. Zeng, F. Wang,
B. Tan, Y. Hou, Y. Ly and G. Zhong, Chem. Commun., 2010, 46, 2504;
(b) N. Asao, K. Sato and Y. Yamamoto, Tetrahedron Lett., 2003,
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A. Degterev, Eur. J. Org. Chem., 2010, 5955.
10 Nitrosoarenes can react with gold carbene to form reactive dipole
species to undergo [3+2]-cycloaddition with alkenes. See A. M.
Jadhav, S. Bhunia, H.-Y. Liao and R.-S. Liu, J. Am. Chem. Soc., 2011,
133, 1769.
(5)
Scheme 2 presents a plausible mechanism for 1,2-iminonitronation
reactions. A coordination of LAu+ with ethyl propiolate 1a induces an
attack of nitrosobenzene to give intermediate C that also possesses gold
carbene resonance C0. We postulate an initial formation of bis-nitrone
species D in accord with the result in eqn (4). The ester group
of bis-nitrone D will decrease the oxygen negative charge of the
conjugated nitrone, and the other nitrone group becomes an
active oxygen donor. We speculate that N-hydroxyaniline might
serve as a reducing species to react with bis-nitrone D to give
a-imidoyl nitrone 3a. Alternatively, bis-nitrone species D might
serve as an oxidant to oxidize propiolate 3 to give a-imidoyl
nitrone 3a, but this route is less important because the resulting
a,b-dioxo ester 4 was obtained in low yield.
In summary, we report gold-catalyzed 1,2-iminonitronation
of propiolate derivatives with nitrosoarenes, giving a-imidoyl
nitrones efficiently. This new reaction is applicable to diverse
11 Nitrosobenzene can serve as an oxygen donor to oxidize
a
gold carbene to give a carbonyl product in a catalytic process, see:
C.-H. Chen, Y.-C. Tsai and R.-S. Liu, Angew. Chem., Int. Ed., 2013,
52, 4599.
12 For a deoxygenation process in the reaction of gold carbene with
nitrones, see V. V. Pagar, A. M. Jadhav and R.-S. Liu, J. Am. Chem.
Soc., 2011, 133, 20728.
13 In our previous work,13a we reported that N-hydroxyaniline alone in
D2Cl2 under N2 will generate diazene oxide 4 in 7.5% yield whereas
unreacted N-hydroxyaniline was present as the only remaining
species. See related work (a) J.-M. Chen, C.-J. Chang, Y.-J. Ke and
R.-S. Liu, J. Org. Chem., 2014, 79, 4306; (b) Y. Wang, L. Ye and
L. Zhang, Chem. Commun., 2011, 47, 7815.
14 A small redox potential 0.5–0.6 V rationalizes an facile interconver-
sion between N-nitrosobenzene and N-hydroxyaniline. See R. E. Lutz
and M. R. Lytton, J. Org. Chem., 1937, 2, 68.
Scheme 2 A plausible reaction mechanism.
15866 | Chem. Commun., 2014, 50, 15864--15866
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