Gold-catalyzed 1,2-oxoarylations of nitriles with pyridine-derived oxides

Article abstract of DOI:10.1002/anie.201403015

We report the first success in the gold-catalyzed oxoarylations of nitriles with pyridine-derived N-oxides using gold carbenes as initiators. These oxoarylations were also achieved satisfactorily in intermolecular three-component oxidations, including diverse alkenyldiazo esters, nitriles, and pyridine-based oxides. Spill the (car)benes: Reported herein is the first successful gold-catalyzed oxoarylation of nitriles with pyridine-derived N-oxides using gold carbenes as initiators (see scheme; DCE=1,2-dichloroethane, IPr=1,3-bis(diisopropylphenyl)imidazol-2-ylidene). These oxoarylations were also achieved satisfactorily in intermolecular three-component oxidations using a variety of alkenyldiazo esters, nitriles, and pyridine-based N-oxides.

Full text of DOI:10.1002/anie.201403015

Angewandte
Chemie
DOI: 10.1002/anie.201403015
Homogeneous Catalysis
Gold-Catalyzed 1,2-Oxoarylations of Nitriles with Pyridine-Derived
Oxides**
Somnath Narayan Karad and Rai-Shung Liu*
Abstract: We report the first success in the gold-catalyzed
oxoarylations of nitriles with pyridine-derived N-oxides using
gold carbenes as initiators. These oxoarylations were also
achieved satisfactorily in intermolecular three-component
oxidations, including diverse alkenyldiazo esters, nitriles, and
pyridine-based oxides.
C
atalytic oxidations of alkynes with organic oxides emerge
as thriving topics in current gold and platinum catalysis.[1–5]
These oxidations lead to 1,2-oxofunctionalization products by
two paths. With pyridine-derived N-oxides, the oxidations
typically generate a-oxo carbenes which can be functional-
ized with a tethered or external nucleophile.[2,3] For sulfoxides
and some nitrones, the initial intermediates (I and II,
respectively) undergo 3,3-sigmatropic shifts to afford the
1,2-oxoarylation products 2 and 3, respectively (Scheme
1a).[4,5] Although nitriles and alkynes are two common
triple-bond motifs, catalytic oxidations of nitriles with organic
or inorganic oxides still remain a formidable task.[6,7] Com-
monly used nitrile oxides are not prepared from direct
oxidations of nitriles.[8] In the presence of an oxidant, nitriles
Scheme 1. 1,2-Oxyarylation reactions.
typically undergo either a hydration reaction[6] or a C H
ꢀ
oxidation with an elimination of the nitrile.[7] The develop-
ment of a new strategy to achieve a nitrile oxidation is
significant and highly desired in catalysis. Herein, we report
the catalytic 1,2-oxoarylations[9] of nitriles through a three-
component coupling reaction (Scheme 1b). Our approach
involves the initial generation of gold carbenes to trap the
nitrile and generate a gold-containing nitrilium species, which
is subsequently oxidized by pyridine-based N-oxides to afford
N-(pyridin-2-yl)amide derivatives in an atom-economic fash-
ion. Related to this work are the stoichiometric reactions
between stable nitrilium salts and quinoline N-oxides, which
produced distinctly different products resulting from a 1,5-
shift.[10] Although similar N-(pyridin-2-yl)amides were
yielded from the reactions between imidoyl chlorides and
pyridine N-oxides, these noncatalytic reactions also produced
the undesired 3-chloropyridine in an appreciable amount.[11]
The utility of this synthesis allows a rapid entry to the N-
(pyridin-2-yl)amide framework, which is found as the core
structure in several bioactive molecules, including piroxio-
Figure 1. Representative bioactive molecules.
cam,[12] variolin B,[13] pirenzepin,[14] and piketoprofen
(Figure 1).[15]
Table 1 shows the realization of an unprecedented 1,2-
oxoarylation of 2-cyanomethyl-1-ethynylbenzene (4a) with 8-
methyl quinioline N-oxide (3 equiv) using various gold
catalysts. Our initial trial with AuCl3 (5 mol%) in hot 1,2-
dichloroethane (808C, 12 h) resulted in an incomplete
conversion, from which the double oxidation product 5a
was isolated in 22% yield, together with unreacted 4a (55%;
entry 1). We switched to cationic gold catalysts such as
PPh3AuCl/AgSbF6, P(tBu)2(o-biphenyl)AuCl/AgSbF6, and
IPrAuCl/AgSbF6 (IPr= 1,3-bis(diisopropylphenyl)imidazol-
2-ylidene), which provided 5a in 48, 75, and 82% yield,
respectively (entries 2–4). Different counter anions to
IPrAuCl/AgX (X = OTf and NTf2) maintained satisfactory
product yields (entries 5 and 6). AgSbF6 and HNTf2 were
catalytically inactive (entries 7 and 8). We tested the reactions
[*] S. N. Karad, Prof. Dr. R.-S. Liu
Department of Chemistry, National Tsing-Hua University
Hsinchu (30013) (Taiwan)
E-mail: rsliu@mx.nthu.edu.tw
[**] We thank the National Science Council, Taiwan, for financial support
of this work.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201403015.
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Table 1: Catalyst screening for 1,2-oxoarylations of nitriles.
Table 2: Gold-catalyzed oxoarylations of 5-cyano-3-en-1-ynes.
Entry
Catalyst
Solvent[b]
t [h]
Yield [%][c]
4a 5a
1
2
3
4
5
6
7
8
9
AuCl3
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
12
12
10
7.5
9
9.5
9.5
24
10.5
12.5
55
15
–
–
–
22
48
75
82
80
79
–
–
72
54
PPh3AuCl/AgSbF6
LAuCl/AgSbF6[a]
IPrAuCl/AgSbF6
IPrAuCl/AgOTf
IPrAuCl/AgNTf2
AgSbF6
HNTf2
IPrAuCl/AgSbF6
IPrAuCl/AgSbF6
–
85
80
–
C6H5Cl
1,4-dioxane
10
–
[a] L=P(tBu)2(o-biphenyl). [b] [4a]=0.20m. [c] Product yields are
reported for product isolated after purification using a silica gel column.
DCE=1,2-dichloroehtane, IPr=1,3-bis(diisopropyl phenyl)imidazol-2-
ylidene), Tf=trifluoromethanesulfonyl.
in other solvents, such as chlorobenzene and 1,4-dioxane, thus
affording 5a in 72 and 54% yields, respectively (entries 9 and
10). The molecular structure of 5a was verified by an X-ray
diffraction study,[16] thus confirming the working mechanism
(Scheme 1b), which involves the initial formation of the a-
oxo gold carbene A.
[a] N-Oxide (3.0 equiv). [4]=0.20m. [b] Product yields are reported for
product isolated after purification using a silica gel column.
Table 2 shows the substrate scope of such 1,2-oxoaryla-
tions using various 5-cyano-3-en-1-ynes and pyridine-derived
N-oxides. The results show the reactions for the benzenoid
substrates 4b–d bearing various 4-phenyl substituents (R1 = F,
Cl and OMe), thus yielding the desired oxoarylation products
5b–d in 75–81% with 8-methylquinoline N-oxide as an
oxidant. The same reactions were extended to the analogous
benzenoid substrates 4e–g, and yielded the desired 5e–g in
72–85% yields. For the nonbenzenoid substrates 4h and 4i,
the corresponding products 5h and 5i were obtained in 84 and
62% yield, respectively. Such oxoarylations were compatible
with 2-substituted pyridine N-oxides (R’ = phenyl, 2-naph-
thyl, isobutyl; R’’ = H), thus affording the oxoarylation
products 5j–l in 31–53% yields. The presence of the 2-
pyridinyl substituents impede its coordination with gold(I) to
maintain the acidity of the gold species. Gold-catalyzed
reactions between 4h and 2-substitued pyridine N-oxides
(R’ = phenyl and 2-naphthyl) proceeded smoothly to afford
the desired products 5m and 5n in 56 and 65% yield,
respectively. We also prepared 2-cyano-1-ethynylbenzene
(4o) which was recovered in 58% yield after a longer reaction
time (18 h). For the internal alkyne substrates 4p (R = cyclo-
propyl) and 4q (R = phenyl) we obtained the 1,2-diketone
species 4p’ (75%) and 4q’ (77%), respectively. The reactions
were inapplicable to 2-chloro- or bromo-substituted pyridine
N-oxides, which worked well in the intermolecular three-
component system (see Table 3) and they failed to oxidize 5-
cyano-3-en-1-yne (4a).
Although a catalytic 1,2-oxoarylation of nitriles was
proven to be feasible, it is imperative to achieve an
intermolecular reaction among gold carbenes, nitriles, and
organic oxides to access acyclic molecules. The a-oxo metal
carbenes III were reported to undergo facile [3+2] cyclo-
additions to form the oxazole products 6 [Eq. (1)].[17] We thus
sought to use the alkenyldiazo ester 7a to form a gold alkenyl
carbene species to induce a nucleophilic attack of the nitrile at
the alkenyl C3. Such regioselectivity avoids the formation of
undesired oxazole products.[18b,19] The reaction between 7a,
IPrAuSbF6 (8 mol%), 8-methylquinoline N-oxide (1.1 equiv),
and CH3CN (8 equiv) in DCE (288C, 6 h, 0.2m) gave the
oxoarylation product 8a in 80% yield [Eq. (2)]. Notably, we
found no pyrrole derivatives resulting from a [3+2] cyclo-
addition of the alkenylgold carbene with nitriles.[18b] The yield
was slightly decreased to 74% when using a smaller amount
of acetonitrile (4 equiv).
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oxoarylation products 8j and 8k, respectively, in 58–71%
yield. The reactions were also suitable for the 3-substituted
alkenyldiazo ester 7d (R1 = H, R2 = Et), which reacted with 8-
methylquinoline N-oxide and 2-naphthylpyridine N-oxide to
afford desired compounds 8l (68%) and 8m (65%), respec-
tively .
We postulate a mechanism to rationalize the 1,2-oxoar-
ylations of 2-cyanomethyl-1-ethynylbenzene (4a) with pyri-
dine-based N-oxides, as depicted in Scheme 2. In the presence
The scope of this intermolecular process was assessed with
various diazo species (7), IPrAuSbF6 (8 mol%), nitriles
(4 equiv), and N-oxides (1.1 equiv), as shown in Table 3.
Notably, the resulting 1,2-oxoarylation products 8c and 8d
resulted from the addition of benzonitrile and styrylnitrile,
respectively, which reacted with the vinyldiazo ester 7a (R1 =
R2 = H) at C3 of the alkenylgold carbene intermediates, and is
consistent with the reported regiochemistry in the litera-
ture.[18b,19,20] The results also show the applicability of this
oxoarylation to n-butynitrile to afford the desired product 8b
in satisfactory yield. These gold-catalyzed reactions were
amenable to halo-containing pyridine N-oxides, including 2-
bromo, 2-chloro, and 2,4-dichloro substrates, thus yielding
desired products 8e–g in 42–71% yields. The less basic
pyridines tended to bind to gold(I) weakly to maintain the
acidity of the gold complex. For 2-phenyl- and 2-(2-naph-
thyl)pyridine N-oxides, the corresponding products 8h,i were
obtained in reasonable yields (62–68%). We prepared the 2-
substituted alkenyldiazo esters 7b (R1 = Me, R2 = H) and 7c
(R1 = Ph, R2 = H), both of which provided desired the 1,2-
Scheme 2. Proposed mechanism for 1,2-oxoarylations of nitriles.
of IPrAuSbF6, this mixture is expected to generate the a-oxo
gold carbene A which is attacked by a tethered nitrile to form
the seven-membered nitrilium species B. The species B might
possess a vinyl cation resonance form (B’) to reduce the ring
strain. A subsequent attack of the pyridine-based oxide on B’
(or B) is expected to form the adduct C, and the pyridinium
ring then usndergoes attack by the iminyl nitrogen atom to
produce the azacyclic species D. A ring cleavage of this
azacyclic species forms the gold-containing N-(pyridin-2-
yl)amide E, together with a loss of proton. Notably, a 2,3-
sigmatropic shift in the transformation C!E is distinct from
the reported 1,5-shift for the reactions of quinoline N-oxide
with imidoyl chlorides or nitrilium species, and thus yields
a pyridine derivative.[10,21–22] The proton ultimately imple-
ments the protodeauration of E to afford the observed N-
(pyridin-2-yl)amides 5a and 5j–l. This nitrile oxoarylation
failed to work with 4o (Table 2) because the corresponding
six-membered nitrilium intermediate is too strained. This
proposed mechanism also rationalizes the 1,2-oxoarylation
products 8 resulting from the three-component couplings
involving nitriles, alkenyldiazo esters, and pyridine-based
oxides as depicted in Table 3 (see details in the Supporting
Information).
Table 3: Gold-catalyzed intermolecular 1,2-oxoarylations of nitriles.
Although alkynes and nitriles are two common triple-
bond species, catalytic oxidations of nitriles with oxidants
have no precedent. We report herein the first successful gold-
catalyzed oxoarylation of nitriles with pyridine-derived N-
oxides using gold carbenes as initiators. Initial investigations
indicate that a variety of oxoarylation products can be
accessed from a number of 5-cyano-3-en-1-ynes and pyri-
dine-based N-oxides.[23] Seven-membered cyclic nitriliums
were involved as key intermediates. These gold-catalyzed
nitrile oxoarylations were also achieved satisfactorily for
[a] [7]=0.20m, nitrile (4 equiv), N-oxide (1.1 equiv). [b] Product yields
are reported for product isolated after purification using a neutral
alumina column.
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Watt, J. Org. Chem. 1974, 39, 2799 – 2800; e) S. J. Selikson, D. S.
Watt, J. Org. Chem. 1975, 40, 267 – 268.
intermolecular three-component oxidations, including vari-
ous alkenyldiazo esters, nitriles, and pyridine-based N-oxides.
This work reports the first examples of the oxidations of
nitriles with organic N-oxides. Expansion of this nitrile
oxoarylation, which involves distinct nitrilium species,[21,22]
to generate organic and inorganic oxides is under current
investigation.
[8] See selected examples: a) K.-C. Liu, B. R. Shelton, R. K. Howe,
J. Org. Chem. 1980, 45, 3916 – 3918; b) H. Gnichtel, L. Auten-
rieth, P. Luger, K. Vangehr, Liebigs Ann. Chem. 1982, 1091 –
1095; c) J. H. Boyer, T. Manimaran, V. T. Ramakrishanan, J.
Chem. Soc. Perkin Trans. 1 1987, 2163 – 2169; d) T. V. Hansen, P.
Wu, V. V. Fokin, J. Org. Chem. 2005, 70, 7761 – 7764; e) S.
Kanemasa, M. Nishiuchi, Tetrahedron Lett. 1993, 34, 4011 – 4014.
[9] Although some 1,2-oxoarylations of nitriles were named in the
literature, such reactions actually proceeded by initial hydration
of the nitrile. See: S.-K. Xiang, D.-X. Zhang, H. Hu, J.-L. Shi, L.-
G. Liao, C. Feng, B.-Q. Wang, K.-Q. Zhao, P. Hu, H. Yang, W.-H.
Yu, Adv. Synth. Catal. 2013, 355, 1495 – 1499.
[10] For a 1,5-shift occurring with quinoline N-oxide and imidoyl
chlorides or nitriliums, see: R. A. Abramovitch, R. B. Rogers,
G. M. Singer, J. Org. Chem. 1975, 40, 41 – 42.
[11] a) R. A. Abramovitch, G. M. Singer, J. Am. Chem. Soc. 1969, 91,
5672 – 5673; b) R. A. Abramovitch, G. M. Singer, J. Org. Chem.
1974, 39, 1795 – 1802; c) R. A. Abramovitch, P. Tomasik, J.
Heterocycl. Chem. 1975, 12, 501 – 503.
[12] a) J. G. Lombardino, J. Med. Chem. 1981, 24, 39 – 42; b) J. G.
Lombardino, E. H. Wiseman, J. Chiani, J. Med. Chem. 1973, 16,
493 – 496; c) G. Caron, G. Ermondi, J. Med. Chem. 2005, 48,
3269 – 3279.
[13] a) S. R. Walker, E. J. Carter, B. C. Huff, J. C. Morris, Chem. Rev.
2009, 109, 3080 – 3098, and references therein; b) T. C. Leboho,
S. F. Van Vuuren, J. P. Michael, C. B. de Koning, Org. Biomol.
Chem. 2014, 12, 307 – 315.
[14] a) W. D. Bechtel, J. Mierau, H. Palzer, Arzneim.-Forsch. 1986,
36, 793 – 796; b) W. G. Eberlein, W. W. Engel, G. Trummlitz, G.
Schmidt, R. Hammer, J. Med. Chem. 1988, 31, 1169 – 1174; c) R.
Hammer, A. Giachetti, Trends Pharmacol. Sci. 1984, 5, 18 – 20;
d) B. H. Jaub, Scand. J. Gastroenterol. Suppl. 1981, 6, 68.
[15] a) J. C. Miralles, J. M. Negro, F. Sꢂnchez-Gascꢁn, M. G. Garcꢃa,
Alergol Inmunol. Clin. 2001, 16, 105 – 108; b) J. Rodrꢃguez-
Lozano, J. J. Goday Bujꢂn, J. Del Pozo, E. Fonseca, Contact
Dermatitis 2005, 52, 110 – 111.
[16] CCDC 983208 (14) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.
ccdc.cam.ac.uk/data_request/cif.
[17] For catalytic [3+2]-cycloadditions between nitriles and a-oxo or
a-imino carbene species, see Ref. [3b] and selected examples:
a) Y. Xiao, L. Zhang, Org. Lett. 2012, 14, 4662 – 4665; b) K. J.
Doyle, C. J. Moody, Tetrahedron 1994, 50, 3761 – 3772; c) T.
Ibata, K. Fukushima, Chem. Lett. 1992, 2197 – 2200.
[18] For synthesis of pyrrole compounds from the [3+2] cycloaddi-
tions of nitriles and alkenylmetal carbenes, see: a) R. J. Bill-
edeau, K. R. Klein, D. Kaplan, Y. Lou, Org. Lett. 2013, 15, 1421 –
1423; b) G. Lonzi, L. A. Lꢁpez, Adv. Synth. Catal. 2013, 355,
1948 – 1954.
[19] For a nucleophilic addition at C3 of alkenylgold carbenes, see:
Ref. [16b] and a) V. V. Pagar, A. M. Jadhav, R.-S. Liu, J. Am.
Chem. Soc. 2011, 133, 20728 – 20731; b) J. Barluenga, G. Lonzi,
M. Tomꢂs, L. A. Lꢁpez, Chem. Eur. J. 2013, 19, 1573 – 1576.
[20] For the same regioselectivity of alkenylrhodium carbenes, see
selected examples: a) X. Xu, P. Y. Zavalij, M. P. Doyle, Angew.
Chem. 2013, 125, 12896 – 12900; Angew. Chem. Int. Ed. 2013, 52,
12664 – 12668; b) X. Wang, X. Xu, P. Y. Zavalij, M. P. Doyle, J.
Am. Chem. Soc. 2011, 133, 16402 – 16405; c) X. Xu, P. Y. Zavalij,
M. P. Doyle, Angew. Chem. 2012, 124, 9967 – 9971; Angew.
Chem. Int. Ed. 2012, 51, 9829 – 9833; d) D. Valette, Y. Lian, J. P.
Haydek, K. I. Hardcastle, H. M. L. Davies, Angew. Chem. 2012,
124, 8764 – 8767; Angew. Chem. Int. Ed. 2012, 51, 8636 – 8639;
e) Y. Lian, H. M. L. Davies, Org. Lett. 2012, 14, 1934 – 1937.
Received: March 5, 2014
Published online: && &&, &&&&
Keywords: carbenes · gold · heterocycles · nitrogen oxides ·
.
synthetic methods
[1] Review: a) J. Xiao, X. Li, Angew. Chem. 2011, 123, 7364 – 7375;
Angew. Chem. Int. Ed. 2011, 50, 7226 – 7236; b) L. Zhang, Acc.
Chem. Res. 2014, 47, 877 – 888.
[2] a) L. Ye, L. Cui, G. Zhang, L. Zhang, J. Am. Chem. Soc. 2010,
132, 3258 – 3259; b) L. Ye, W. He, L. Zhang, J. Am. Chem. Soc.
2010, 132, 8550 – 8551; c) L. Ye, W. He, L. Zhang, Angew. Chem.
2011, 123, 3294 – 3297; Angew. Chem. Int. Ed. 2011, 50, 3236 –
3239; d) S. Shi, T. Wang, W. Yang, M. Rudolph, A. S. K. Hashmi,
Chem. Eur. J. 2013, 19, 6576 – 6580; e) A. S. K. Hashmi, T. Wang,
S. Shi, M. Rudolph, J. Org. Chem. 2012, 77, 7761 – 7767.
[3] a) B. Lu, C. Li, L. Zhang, J. Am. Chem. Soc. 2010, 132, 14070 –
14072; b) W. He, C. Li, L. Zhang, J. Am. Chem. Soc. 2011, 133,
8482 – 8485; c) Y. Luo, K. Ji, Y. Li, L. Zhang, J. Am. Chem. Soc.
2012, 134, 17412 – 17415; d) S. Ghorpade, M.-D. Su, R.-S. Liu,
Angew. Chem. 2013, 125, 4323 – 4328; Angew. Chem. Int. Ed.
2013, 52, 4229 – 4234; e) S. Bhunia, S. Ghorpade, D. B. Huple, R.-
S. Liu, Angew. Chem. 2012, 124, 2993 – 2996; Angew. Chem. Int.
Ed. 2012, 51, 2939 – 2942; f) D. Vasu, H.-H. Hung, S. Bhunia,
S. A. Gawade, A. Das, R.-S. Liu, Angew. Chem. 2011, 123, 7043 –
7046; Angew. Chem. Int. Ed. 2011, 50, 6911 – 6914; g) L. Wang,
X. Xie, Y. Liu, Angew. Chem. 2013, 125, 13544 – 13548; Angew.
Chem. Int. Ed. 2013, 52, 13302 – 13306; h) J. Fu, H. Shang, Z.
Wang, L. Chang, W. Shao, Z. Yang, Y. Tang, Angew. Chem. 2013,
125, 4292 – 4296; Angew. Chem. Int. Ed. 2013, 52, 4198 – 4202;
i) G. Henrion, T. E. J. Chavas, X. L. Goff, F. Gagosz, Angew.
Chem. 2013, 125, 6397 – 6402; Angew. Chem. Int. Ed. 2013, 52,
6277 – 6282; j) S. K. Pawar, C.-D. Wang, S. Bhunia, A. M. Jadhav,
R.-S. Liu, Angew. Chem. 2013, 125, 7707 – 7711; Angew. Chem.
Int. Ed. 2013, 52, 7559 – 7563; k) K. Graf, C. L. Rꢀhl, M.
Rudolph, F. Rominger, A. S. K. Hashmi, Angew. Chem. 2013,
125, 12960 – 12964; Angew. Chem. Int. Ed. 2013, 52, 12727 –
12731; l) P. Nçsel, L. N. dos Santos Comprido, T. Lauterbach,
M. Rudolph, F. Rominger, A. S. K. Hashmi, J. Am. Chem. Soc.
2013, 135, 15662 – 15666.
[4] a) N. D. Shapiro, F. D. Toste, J. Am. Chem. Soc. 2007, 129, 4160 –
4161; b) A. B. Cuenca, S. Montserrat, K. M. Hossain, G. Mancha,
A. Lledꢁs, M. Medio-Simꢁn, G. Ujaque, G. Asensio, Org. Lett.
2009, 11, 4906 – 4909; c) C.-W. Li, K. Pati, G.-Y. Lin, S. M.
Abu Sohel, H.-H. Hung, R.-S. Liu, Angew. Chem. 2010, 122,
10087 – 10090; Angew. Chem. Int. Ed. 2010, 49, 9891 – 9894; d) B.
Lu, Y. Li, Y. Wang, D. H. Aue, Y. Luo, L. M. Zhang, J. Am.
Chem. Soc. 2013, 135, 8512 – 8524.
[5] a) A. Mukherjee, R. B. Dateer, R. Chaudhuri, S. Bhunia, S. N.
Karad, R.-S. Liu, J. Am. Chem. Soc. 2011, 133, 15372 – 15375;
b) S. Bhunia, C.-J. Chang, R.-S. Liu, Org. Lett. 2012, 14, 5522 –
5525.
[6] a) R. S. Varma, K. P. Naicker, Org. Lett. 1999, 1, 189 – 191; b) L.
McMaster, F. B. Langreck, J. Am. Chem. Soc. 1917, 39, 103 – 109.
[7] a) H. G. Aurich, Tetrahedron Lett. 1964, 5, 657 – 658; b) M. S.
Kharasch, G. Sosnovsky, Tetrahedron 1958, 3, 97 – 104; c) S. S.
Kulp, M. J. McGee, J. Org. Chem. 1983, 48, 4097 – 4098; d) D. S.
4
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[21] We attempted to realize an oxoarylation reaction with the
nitrilium intermediates F generated from diphenylmethanol and
acetonitrile (10 equiv) according to Hashmiꢄs report[22] [Eq. (3)].
We obtained the amide 10 and ether 11 in 53 and 36% yield,
respectively, without any oxidant. In the presence of 8-methyl-
quinoline N-oxide (1.2 equiv), we obtained no oxoarylation
product in tractable amount [Eq. (4)] whereas species 10 and 11
were still formed. Accordingly, not every nitrilium species can be
used in the oxoarylation reaction.
[22] N. Ibrahim, A. S. K. Hashmi, F. Rominger, Adv. Synth. Catal.
2011, 353, 461 – 468.
[23] Unsubstituted pyridine and quinoline N-oxides were inapplica-
ble substrates for the reaction is Tables 2–3 because the released
pyridine and quinoline were expected to poison gold catalyst.
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
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Angewandte
Communications
Communications
Homogeneous Catalysis
S. N. Karad, R.-S. Liu*
&&&& — &&&&
Gold-Catalyzed 1,2-Oxoarylations of
Nitriles with Pyridine-Derived Oxides
Spill the (car)benes: Reported herein is
the first successful gold-catalyzed oxoar-
ylation of nitriles with pyridine-derived N-
oxides using gold carbenes as initiators
(see scheme; DCE=1,2-dichloroethane,
IPr=1,3-bis(diisopropylphenyl)imidazol-
2-ylidene). These oxoarylations were also
achieved satisfactorily in intermolecular
three-component oxidations using a vari-
ety of alkenyldiazo esters, nitriles, and
pyridine-based N-oxides.
6
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
These are not the final page numbers!