Oxidant-dependent chemoselectivity in the gold-catalyzed oxidative cyclizations of 3,4,6,6-tetrasubstituted 3,5-dien-1-ynes

Article abstract of DOI:10.1021/jo401161h

A distinct chemoselectivity in the gold-catalyzed oxidative cyclization of 3,5-dien-1-ynes was observed when 3,5-dichloropyridine N-oxide replaced 8-methylquinoline N-oxide as the oxidant; the resulting cyclopentadienyl aldehydes were obtained in good yields. The altered chemoselectivity is attributed to a prior enyne cyclization in the presence of 3,5-dichloropyridine N-oxides. The use of N-iminopyridium ylide enables a similar iminocyclization reaction to give cyclopentadienyl imines efficiently. Our experimental data support a prior gold-catalyzed cyclization of 3,5-dien-1-ynes to form gold carbene, followed by the oxidation with N-oxide.

Full text of DOI:10.1021/jo401161h

Article
pubs.acs.org/joc
Oxidant-Dependent Chemoselectivity in the Gold-Catalyzed
Oxidative Cyclizations of 3,4,6,6-Tetrasubstituted 3,5-Dien-1-ynes
Hsiao-Hua Hung, Yi-Ching Liao, and Rai-Shung Liu*
Department of Chemistry, National Tsing-Hua University, Hsinchu, Taiwan, ROC
S
* Supporting Information
ABSTRACT: A distinct chemoselectivity in the gold-catalyzed
oxidative cyclization of 3,5-dien-1-ynes was observed when 3,5-
dichloropyridine N-oxide replaced 8-methylquinoline N-oxide as
the oxidant; the resulting cyclopentadienyl aldehydes were
obtained in good yields. The altered chemoselectivity is
attributed to a prior enyne cyclization in the presence of 3,5-
dichloropyridine N-oxides. The use of N-iminopyridium ylide
enables a similar iminocyclization reaction to give cyclopentadienyl imines efficiently. Our experimental data support a prior gold-
catalyzed cyclization of 3,5-dien-1-ynes to form gold carbene, followed by the oxidation with N-oxide.
3,5-dien-1-ynes and 8-methylquinoline N-oxide (8-MQO)
resulted in an oxidative cyclopropanation with high stereo-
specificity;2b this process involves α-oxo gold carbenes as
intermediates.1,2 Herein, we report the use of 3,5-dichloropyr-
idine N-oxide in the reactions to give cyclopentadienyl
aldehydes 3 instead and present experimental results to clarify
the reaction mechanisms.
INTRODUCTION
■
Gold-catalyzed intermolecular oxidation of terminal alkynes
with pyridine-based oxides is a powerful tool to access α-
functionalized carbonyl compounds (eq 1).1−3 This oxidation
RESULTS AND DISCUSSION
■
Table 1 (entry 1) shows our previously reported reaction
between dienyne 1a, IPrAuCl/AgNTf2 (5 mol %, IPr = 1,3-
bis(diisopropylphenyl)imidazol-2-ylidene), and 8-methylquino-
line N-oxide (8-MQO, 1.2 equiv) in hot DCE (80 °C, 0.33 h),
resulting in an oxidative cyclopropanation product 2a in 60%
yield.2b The yield was increased to 78% using the same N-
oxidant in a large proportion (3 equiv). We tested the reactions
with alterable pyridine-based N-oxides; Brønsted acids were
excluded here to avoid the polymerization of starting 1a. With
pyridine N-oxide and its 2-ethyl derivative (1.2 equiv) in hot
DCE (80 °C, 24−48 h), we obtained a new compound,
cyclopentadienyl aldehyde 3a, in low yield (<35%) together
with indanone 2a and unreacted 1a in a substantial proportions
(>18%, entries 2 and 3). The yields of aldehyde 3a were
enhanced to 56−60% yields with electron-deficient pyridine N-
oxides bearing a chloro or bromo substituent at the C(2)- or
C(3)-carbons (entries 4−6). To our pleasure, the use of 3,5-
dichloropyridine N-oxide in hot DCE (80 °C, 0.33 h) effected a
complete suppression of cyclopropyl indanone 2a to deliver
compound 3a with 83% yield (entry 7). IPrAuCl/AgSbF6 also
maintained a high efficiency to give aldehyde 3a in 76% yield
(entry 9). P(t-Bu)2(o-biphenyl)AuCl/AgNTf2 and PPh3AuCl/
AgNTf2 were less chemoselective in giving compound 3a in less
yield together with undesired 2a in 16−22% yields (entries 10
involves an initial attack of N-oxides at the alkynyl C(2)-carbon
to generate α-oxo gold carbenes I that are trapped in situ with a
suitable substrate (S).1,2 The chemoselectivity in this alkyne
oxidation is generally invariant with diverse derivatives of
pyridine-based oxides. We are aware of no report in which the
reaction chemoselectivity varied with a change of N-oxide. In
this work, we report a distinct chemoselectivity in the oxidative
cyclization of 3,5-dien-1-ynes with alterable pyridine-based N-
oxides.
Shown in Scheme 1 is the oxidant-dependent chemo-
selectivity. We reported that gold-catalyzed reactions between
Scheme 1. Two Distinct Oxidative Cyclizations
Received: May 28, 2013
© XXXX American Chemical Society
A
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Table 1. Reactions with Various N-Oxides and Gold Catalysts
c
compounds (yields)
a
b
entry
catalyst (mol %)
N-oxide
°C/h
la
2a
3a
d
1
IPrAuCl/AgNTf2
IPrAuCl/AgNTf2
IPrAuC1/AgNTf2
IPrAuCl/AgNTf2
IPrAuCVAgNTf2
IPrAuCyAgNTf2
IPrAuCl/AgNTf2
IPrAuCVAgNTf2
IPrAuCl/AgSbF6
LAuCl/AgNTf2
PPh3AuCl/AgNTf2
Ph2SO
8-MQO
R = H
80/0.3
80/48
80/24
80/0.7
80/0.2
80/0.3
80/0.3
25/0.6
25/0.8
25/1.0
25/1.2
25/0.5
60 (78)
2
59
25
24
35
24
26
30
6
3
R = 2-Et
R = 2-Br
R = 3-Br
18
60
57
56
83
81
76
57
56
e
4
5
6
R = 2-C1
R = 3,5-Cl2
R = 3,5-Cl2
R = 3,5-Cl2
R = 3,5-Cl2
R = 3,5-Cl2
Ph2SO
7
8
9
10
11
12
22
16
a
b
8-MQO = 8-methylquinoline N-oxide, IPr = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, L = P(t-Bu)2(o-biphenyl), [la] = 0.05 M. N-Oxide
c
d
e
(1.2 equiv). Product yields are reported after separation on a silica column. This value corresponds to 8-MQO with 3.0 equiv. Polymerization of
starting la was observed.
and 11). We tested the reaction with Ph2SO (1.2 equiv),4 which
led to a polymerization of starting 1a (entry 12); the same
polymerization was observed in the absence of oxides, reflecting
the sensitivity of starting 1a toward an acidic gold catalyst. Only
basic N-oxides can reduce the acidity of IPrAuNTf2 to secure
the stability of starting 1a.
Table 2 shows the gold-catalyzed reactions between various
3,5-dien-ynes 1b−1j with 3,5-dichloropyridine N-oxide, giving
only cyclopentadienyl aldehydes 3b−3j, whereas competitive
cyclopropyl indanones 2 were completely suppressed. In entries
1 and 4, starting 1b was prepared as a mixture of E/Z isomers
(E/Z = 1.4), whereas species 1e was prepared as the E-isomer.
Entries 1−4 show the applicability of this new oxidative
cyclization to 3,5-dien-1-ynes 1b−1e bearing various sub-
stituted alkenes; the resulting aldehydes 3b−3d were obtained
in satisfactory yields (60−75%) with the exception of
compound 3e that was obtained in a low yield (39%). We
tested the reactions on 3,5-dien-1-ynes 1f−1h bearing a
substituted cyclohexenyl bridge; the corresponding products
3f−3h were produced with 54−69% yields. This reaction was
applicable also to substrate 1i bearing a cycloheptenyl bridge,
giving desired product 3i in 80% yield. For an acyclic 3,5-dien-
1-yne 1j, its gold-catalyzed reaction delivered cyclopentadienyl
aldehyde 3j in 68% yield. Our attempted reaction on 3,5-dien-
1-yne bearing a single phenyl substituent in the 6-position,
unlike compound 1e, gave a complicated mixture of products.5
We examined the reaction of a benzenoid substrate 4 with
3,5-dichloropyridine N-oxide, which delivered cyclopropyl
indanone 5 instead (eq 1). The same reaction pattern was
observed using N-iminopyridium ylide6,7 to afford cyclopropyl
indanimine 6 in 80% yield (eq 2), whereas for non-benzenoid
Table 2. Oxidative Cyclization with Various 3,5-Dien-1-
a
ynes
3,5-dien-1-yne 1a, a different chemoselectivity occurred to give
cyclopentadienyl imine 7a in 84% yield (eq 3). NaBH3CN-
reduction of imine species 7a provided primary imine 8a in
67% yield, which was characterized by X-ray diffraction (eq 3).8
Table 3 shows the gold-catalyzed synthesis of cyclo-
pentadienyl imines from the same 3,5-dien-1-ynes 1b−1j as
in Table 2. The reaction proceeded with high chemoselectivity
to afford cyclopentadienyl imines 7b−7j exclusively. For 3,5-
dien-1-ynes 1b−1e bearing various trisubstituted alkenes, their
resulting cyclopentadienyl imines 7b−7e were produced in 57−
76% yields (entries 1−4). This iminocyclization was operable
with additional 3,5-dien-1-ynes 1f−1h bearing a varied
cyclohexenyl bridge, giving desired imines 7f−7h with 66−
a
IPr = l,3-bis(2,6-dii8opropylphenyl)imidazol-2-ylidene, L = P(t-
Bu)2(o-biphenyl), [la] = 0.05 M, N-oxide (1.2 equiv). Product yields
are reported after separation on a silica column. 1b, E/Z = 1.4. 1e is E-
isomer.
B
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idine N-oxide for the alkyne oxidation and is inactive toward
the carbene oxidation.
Scheme 3 shows the deuterium labeling experiments. The
treatment of deuterated d1-1a with 3-bromopyridine N-oxide
Scheme 3. Deuterium Labeling Experiments
a
Table 3. Scope for Gold-Catalyzed Iminocyclizations
(1.1 equiv) in DCE at 28 °C (0.5 h) led to a 80% conversion,
giving unreacted d1-1a and cyclopropyl indanone d1-2a and
cyclopentadienyl aldehyde d1-3a in 16%, 24%, and 54%
recovery or yields, respectively. Notably, the deuterium
contents X, Y, and Z are nearly the same (40−42%).
Alternatively, the use of undeuterated 1a and D2O (1.0
equiv) in this reaction also provided deuterated d1-2a and d1-3a
with the same level of deuterium contents (58−60%). These
results indicates that the loss of deuterium content of d1-2a and
d1-3a is attributed to a quick equilibrium between π-alkyne A
and alkynyl gold B (Scheme 4). This A/B equilibrium allows a
quick change between d1-1a and water before the production of
d1-2a and d1-3a.
a
IPr = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylideiie, L = P(t-
Bu)2(o-biphenyl), [la] = 0.05 M. N-oxide (1.2 equiv). Product yields
are reported after separation on a silica column. 1b, E/Z = 1.4. 1e, E/Z
= 1.0.
Scheme 4 depicts possible mechanisms to rationalize the
formation of cyclopropyl indanone 2a and cyclopentadienyl
Scheme 4. Possible Reaction Mechanisms
72% yields (entries 5−7). The reaction worked also with
substrate 1i bearing a cycloheptenyl bridge, giving the
corresponding product 7i in 75% yield (entry 8). Acyclic 3,5-
dien-1-yne 1j was also suitable for this iminocyclization, giving
desired 7j in 72% yield (entry 9).
As shown in Scheme 2, we performed a reaction with 8-
methylquinoline N-oxide and 3,5-dichloropyridine N-oxide in
Scheme 2. Oxidation Properties of N-Oxides
aldehyde 3a; the latter was produced with less nucleophlic N-
oxides that attack π-alkyne A inefficiently. The deuterium
labeling experiments in Scheme 3 indicate that an equili-
brium10,11 between π-alkyne A and alkynylgold species B is
rapidly attained before products 2a and 3a are formed. N-
Oxides are reported to catalyze this A/B equibrium.10
Besides a prior cyclization route (path a) involving the
transformation π-alkyne A → gold carbene C, a small portion of
species B might undergo protonation at the dienyl C(3)-carbon
to give an allylic cation D (path b), which induces a cyclization
to generate gold allenylidene E, ultimately giving gold carbene
C. We sought suitable experiments to probe the feasibility of
the two paths (a and b).
equal proportions ((3,5-DCPO, 1.5 equiv, Scheme 2) and
obtained desired cyclopropyl indanone 2a together with a new
product 9 in 33% and 39% yields respectively; cyclopentadienyl
aldehyde 3a was obtained in a negligible proportion. Pyranyl
aldehyde 9 was generated with 6-π electrocyclization of α-
carbonyl aldehyde 9′ that resulted from a second oxidation of
gold carbenes C (vide ante, Scheme 4).9 Compound 3a were
generated in 15% yield with a decreasing loading of 8-
methylquinoline N-oxide (1.1 equiv, entry 2). These data
provide insight into the effects of two N-oxides, namely, that 8-
methylquinoline N-oxide is more active than 3,5-dichloropyr-
We assessed the role of alkynylgold intermediate B to
participate the alkyne oxidation, as depicted in path b. As
depicted in Table 4, we prepared alkynylgold species 1012 and
C
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a
satisfactory yields. The change of chemoselectivity is attributed
to the weak nucleophilicity of 3,5-dichloropyridine N-oxide
such that a prior cyclization of 3,5-dien-1-ynes occurs
preferably. The reactions were extensible to their iminocycliza-
tions when the same 3,5-dien-1-ynes were treated with N-
iminopyridium ylide. Our experimental results support a prior
gold-catalyzed cyclization of 3,5-dien-1-ynes to form gold
carbene C, followed by the oxidation with N-oxide.14 In a case
involving alkynylgold as the catalyst, a prior protonation of
alkynylgold to give π-alkyne occurred preferably.
Table 4. Alkynylgold Species as the Catalysts
b
entry
oxidant
mol % HNTf2
min
yield
1
2
3
4
Z = NTs
Z = NTs
Z = O
1.0
0
20
600
120
600
7a (86%)
7a (56%)
3a (75%)
1a (55%)
1.0
0
Z = O
EXPERIMENTAL SECTION
a
b
■
[1a] = 0.05 M. N-oxide (1.2 equiv). Product yields are reported
after separation on a silica column.
General Comments. Unless otherwise noted, all reactions to
prepare the substrates were performed in oven-dried glassware under a
nitrogen atmosphere with freshly distilled solvents. The catalytic
reactions were performed under a nitrogen atmosphere. Toluene,
DCE, and methanol were distilled from CaH2 under nitrogen.
Methanol and triethylamine (Et3N) were stored over molecular sieves
(4 Å) before use. All other commercial reagents were used without
further purification, unless otherwise indicated. 1H NMR and 13C
NMR spectra were recorded on 400 and 600 MHz spectrometers
using chloroform-d1 (CDCl3), CD2Cl2, or DMSO-d6 as the internal
standard. EI/MS-MS, ESI/FTMS, and ESI/orbitrap mass spectrom-
etry were used for the HRMS measurements. All 1,5-enynes (1a−1i)
were prepared from the reported procedure in the literature.15
General Procedure for Gold-Catalyzed Oxidative Cyclization
between 1,5-Enyne (1a) and 3,5-Dichloropyridine N-Oxide. A
1,2-dichloroethane solution (4.2 mL) of compound 1a (50 mg, 0.31
mmol) and 3,5-dichloropyridine N-oxide (60.7 mg, 0.37 mmol) was
added to a 1,2-dichloroethane solution (2.0 mL) of IPrAuNTf2 (13.9
mg, 0.016 mmol). The mixture was heated to 80 °C for 0.5 h before it
was filtered over a short silica bed. The solvent was evaporated under
reduced pressure; the crude product was eluted through a silica gel
column to afford 3a as a yellow oil (45.4 mg, 0.26 mmol, 83%).
General Procedure for Gold-Catalyzed Oxidative Cyclization
between 1,5-Enyne (1a) and (3,5-Dichloro-pyridinium-1-yl)-
tosylamide. To a 1,2-dichloroethane solution (4.2 mL) of compound
1a (50 mg, 0.31 mmol) and (3,5-dichloro-pyridinium-1-yl)tosylamide
(117.4 mg, 0.37 mmol) was added a 1,2- dichloroethane solution (2.0
mL) of IPrAuNTf2 (13.9 mg, 0.016 mmol); the mixture was heated to
80 °C for 0.5 h before it was filtered over a short silica bed. The
solvent was evaporated under reduced pressure; the crude product was
eluted through a silica column to afford 7a as an orange red oil (85.8
mg, 0.26 mmol, 84%).
Procedure for Gold-Catalyzed Oxidative Cyclization be-
tween Deuterated 1-Ethynyl-2-(2-methylprop-1-en-1-yl)-
cyclohex-1-ene (d1-1a) and 3-Bromo Pyridine N-Oxide. A 1,2-
dichloroethane solution (3.7 mL) of compound d1-1a (50 mg, 0.31
mmol) and 3-bromopyridine N-oxide (64.4 mg, 0.37 mmol) was
added to a 1,2-dichloroethane solution (2.5 mL) of IPrAuNTf2 (13.8
mg, 0.016 mmol). The mixture was heated to 80 °C for 0.5 h before it
was filtered over a short silica bed. The solvent was evaporated under
reduced pressure; the crude product was eluted through a silica gel
column to afford compound d1-1a as a pale yellow oil (8.0 mg, 0.05
mol, 16%), compound d1-2a as a colorless oil (13.2 mg, 0.07 mmol,
24%), and compound d1-3a as a yellow oil (29.7 mg, 0.17 mmol, 54%).
Synthesis of N-((2,2-Dimethyl-4,5,6,7-tetrahydro-2H-inden-
1-yl)methyl)-4-methylbenzenesulfonamide (8a). To a THF
solution (5.2 mL) of compound 7a (86 mg, 0.26 mmol) was added
NaBH3CN (18 mg, 0.26 mmol), and the mixture was stirrred for 4 h at
room temperature, quenched with water, and extracted with ethyl
acetate (20 mL × 3). The combined organic layer was dried over
anhydrous MgSO4 and concentrated on an evaporator. The residue
was eluted through a short pad of silica column to afford compound 8a
as pale yellow solid (58 mg, 0.17 mmol, 67%).
used it as a catalyst (5 mol %) in both oxidation and nitrene
reactions. In the nitrene reaction, we obtained excellent yields
(86%) for desired product 7a with HNTf2 (1 mol %). To our
surprise, the catalytic reaction still proceeded in the absence of
HNTf2 to give compound 7a in 56% yield over a protracted
period (10 h, entry 2). In contrast, HNTf2 was required for the
oxidation reactions using alkynylgold 10 catalyst (entries 3 and
4).
To understand the role of alkynylgold species B in path b, we
performed a control experiment in eq 4, involving 1a (1 equiv),
N-iminopyridium ylide (1 equiv) and alkynylgold species 11
(0.15 equiv). Heating this mixture in hot DCE for a brief period
(1 h) gave no desired iminocyclization products 7a and 7f, but
we obtained a mixture of 3,5-dien-1-ynes 1a and 1f with a 1a/1f
ratio of 7.7/1. Accordingly, alkynylgold species B preferably
underwent protonation to produce gold-π-alkyne species A,
rather than giving gold-vinylidene E, thus excluding the route b
in Scheme 4. Herein, N-iminopyridium ylide serves as a proton
shuttle with dien-1-yne 1a as the proton source. At a protracted
period (16 h), the same reaction gave desired iminocylization
products 7a and 7f, albeit in low yields (30−35%); in this case,
alkynylamide 12 was obtained in minor proportion (eq 5). This
result reveals that alkynylgold species 11 was a poor catalyst for
this iminocyclization; the corresponding mechanism might be
different. The isolation of alkynylamide 12 allows us to
understand the reaction mechanism in eq 4.13
CONCLUSIONS
■
A distinct chemoselectivity in the gold-catalyzed oxidative
cyclization of 3,5-dien-1-ynes occurred when 8-methylquinoline
N-oxide was replaced with 3,5-dichloropyridine N-oxide; the
resulting cyclopentadienyl aldehydes were obtained in
Synthesis of 3,3-Dimethyl-5,6,7,8-tetrahydro-3H-isochro-
mene-1-carbaldehyde (9). A 1,2-dichloroethane solution (3.7
mL) of compound 1a (50 mg, 0.31 mmol), 8-methylquinoline N-
oxide (74.8 mg, 0.47 mmol), and 3,5-dichloropyridine N-oxide (152.5
D
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mg, 0.93 mmol) was added to a 1,2-dichloroethane solution (2.5 mL)
of IPrAuNTf2 (13.8 mg, 0.016 mmol). The mixture was heated to 80
°C for 0.5 h before it was filtered over a short silica bed. The solvent
was evaporated under reduced pressure; the crude product was eluted
through a silica gel column to afford compound 2a as a pale yellow oil
(18 mg, 0.10 mol, 33%), compound 9 as a yellow oil (23.0 mg, 0.12
mmol, 39%), and a trace amount of compound 3a with yellow oil.
Synthesis of 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-
ylidene((2-(2-methylprop-1-en-1-yl)cyclohex-1-en-1-yl)-
ethynyl)gold (10). A round-bottom flask (10 mL) was charged with
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold chloride (76.7
mg, 0.12 mmol) and NaOH (9.6 mg, 0.24 mmol). After the flask was
evacuated and refilled with nitrogen, methanol (3.0 mL) was added by
syringe, and the reaction mixture was stirred for 20 min. Dichloro-
methane (1.5 mL) was added until a homogeneous solution was
obtained. Compound 1a (20.0 mg, 0.12 mmol) was added directly to
this solution. The reaction was covered in foil and stirred for 36 h
followed by removal of the volatiles under vacuum and extraction of
the residue with benzene (10 mL × 3). After filtration to remove
insoluble salts and purification by recrystallization (benzene and
pentane), the desired compound 10 was obtained as white solid (61.0
mg, 0.082 mmol, 68%).
Synthesis of 1,3-Bis(2,6-diisopropylphenyl)imidazol-2-
ylidene((5,5-dimethyl-2-(2-methylprop-en-1-yl)cyclohex-1-en-
1-yl)ethynyl)gold (11). A MeOH solution (4.2 mL) of NaOtBu
(15.4 mg, 0.16 mmol) and compound 1f (30.0 mg, 0.16 mmol) was
stirred for 10 min before addition of a MeOH solution (2.0 mL) of
1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene gold chloride (49.7
mg, 0.08 mmol). The reaction was covered in foil and stirred for 48 h
followed by removal of the volatiles under vacuum and extraction of
the residue with dichloromethane (10 mL × 3). After filtration to
remove insoluble salts and purification by recrystallization (benzene
and pentane), the desired compound 11 was obtained as a pale yellow
solid (84.0 mg, 0.11 mmol, 68%).
0.57 (td, J = 7.2 Hz, 0.8 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
183.7, 161.8, 149.2, 144.4, 140.6, 55.5, 28.8, 24.7, 24.0, 22.9, 22.5, 20.6,
9.4; HRMS calcd for C13H18O 190.1358, found 190.1364.
4′,5′,6′,7′-Tetrahydrospiro[cyclopentane-1,2′-indene]-1′-
1
carbaldehyde (3c). Yellow oil; (36 mg, 67%); H NMR (400 MHz,
CDCl3) δ 9.85 (s, 1 H), 6.50 (s, 1 H), 2.87 (t, J = 6.0 Hz, 2 H), 2.46 (t,
J = 6.0 Hz, 2 H), 2.20−2.13 (m, 2 H), 1.98−1.93 (m, 2 H), 1.80−1.62
(m, 6 H), 1.45−1.41 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 183.7,
161.6, 148.4, 142.7, 139.0, 61.7, 32.4, 26.2, 24.8, 24.1, 22.9, 22.4;
HRMS calcd for C14H18O 202.1358, found 202.1350.
4′,5′,6′,7′-Tetrahydrospiro[cyclohexane-1,2′-indene]-1′-car-
1
baldehyde (3d). Pale yellow solid; (40 mg, 75%); H NMR (400
MHz, CDCl3) δ 9.84 (s, 1 H), 6.92 (s, 1 H), 2.84 (t, J = 6.0 Hz, 2 H),
2.47 (t, J = 5.6 Hz, 2 H), 2.15 (td, J = 12.8, 3.2 Hz, 2 H), 1.76−1.61
(m, 6 H), 1.48−1.33 (m, 4 H), 1.05−1.02 (m, 2 H); 13C NMR (100
MHz, CDCl3) δ 184.0, 160.7, 146.8, 145.6, 140.8, 56.1, 31.4, 25.6,
25.0, 24.9, 24.1, 22.8, 22.4; HRMS calcd for C15H20O 216.1514, found
216.1512.
2-Methyl-2-phenyl-4,5,6,7-tetrahydro-2H-indene-1-carbal-
dehyde (3e). Yellow oil; (29 mg, 39%); 1H NMR (400 MHz, CDCl3)
δ 9.85 (s, 1 H), 7.23−7.12 (m, 5 H), 6.44 (s, 1 H), 3.03−2.88 (m, 2
H), 2.54−2.52 (m, 2 H), 1.78−1.68 (m, 4 H), 1.65 (s, 3 H); 13C NMR
(100 MHz, CDCl3) δ 183.6, 161.6, 150.2, 146.0, 140.2, 139.9, 128.2,
126.3, 125.9, 57.6, 24.7, 24.3, 22.8, 22.4, 20.1; HRMS calcd for
C17H18O 238.1358, found 238.1355.
2,2,6,6-Tetramethyl-4,5,6,7-tetrahydro-2H-indene-1-carbal-
dehyde (3f). Yellow oil; (29 mg, 54%); 1H NMR (400 MHz, CDCl3)
δ 9.83 (s, 1 H), 6.31 (s, 1 H), 2.60 (s, 2 H), 2.50 (td, J = 6.8, 1.2 Hz, 2
H), 1.49 (t, J = 6.8 Hz, 2 H), 1.21 (s, 6 H), 0.96 (s, 6 H); 13C NMR
(100 MHz, CDCl3) δ 183.8, 160.9, 151.3, 146.1, 138.0, 51.7, 37.7,
35.4, 29.8, 28.0, 21.9, 20.8; HRMS calcd for C14H20O 204.1514, found
204.1507.
5-(tert-Butyl)-2,2-dimethyl-4,5,6,7-tetrahydro-2H-indene-1-
carbaldehyde (3g). Yellow oil; (37 mg, 69%); 1H NMR (400 MHz,
CDCl3) δ 9.84 (s, 1 H), 6.28 (s, 1 H), 3.21 (ddd, J = 18.4, 4.4, 2.4 Hz,
1 H), 2.68−2.62 (m, 1 H), 2.53 (ddd, J = 18.4, 12.4, 5.2 Hz, 1 H), 2.07
(ddd, J = 16.4, 12.4, 2.4 Hz, 1 H), 1.98−1.92 (m, 1 H), 1.28 (ddd, J =
12.4, 4.4, 1.6 Hz, 1 H), 1.31 (s, 3 H), 1.20−1.16 (m, 4 H), 0.89 (s, 9
H); 13C NMR (100 MHz, CDCl3) δ 183.8, 160.7, 151.3, 145.0, 140.5,
51.5, 45.1, 32.4, 27.2, 26.2, 24.5, 24.1, 21.8 (2 × CH3); HRMS calcd
for C16H24O 232.1827, found 232.1815.
2,2-Dimethyl-4,5-dihydro-2H-cyclopenta[a]naphthalene-1-
carbaldehyde (3h). Yellow oil; (35 mg, 64%); 1H NMR (400 MHz,
CDCl3) δ 10.20 (s,1 H), 7.69 (dd, J = 6.0, 2.0 Hz, 1 H), 7.37−7.33 (m,
1 H), 7.31−7.28 (m, 2 H), 6.38 (s, 1 H), 2.84 (t, J = 6.0 Hz, 2 H),
2.59−2.55 (m, 2 H), 1.35 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ
185.9, 153.0, 148.2, 144.9, 140.8, 140.2, 130.2, 130.0 (2 × CH), 128.9,
126.9, 52.8, 30.6, 23.8, 22.4; HRMS calcd for C16H16O 224.1201,
found 224.1198.
2,2-Dimethyl-2,4,5,6,7,8-hexahydroazulene-1-carbaldehyde
(3i). Yellow oil; (44 mg, 80%); 1H NMR (400 MHz, CDCl3) δ 9.86 (s,
1 H), 6.24 (s, 1 H), 2.77 (br, 2 H), 2.41−2.39 (m, 2 H), 1.72−1.70
(m, 2 H), 1.65−1.62 (m, 2 H), 1.57−1.54 (m, 2 H), 1.20 (s 6 H); 13C
NMR (100 MHz, CDCl3) δ 184.0, 165.5, 151.2, 146.0, 145.4, 50.8,
32.2, 30.1, 29.4, 28.7, 27.0, 21.8; HRMS calcd for C13H18O 190.1358,
found 190.1361.
3,5,5-Trimethyl-2-phenylcyclopenta-1,3-dienecarbaldehyde
(3j). Yellow oil; (37 mg, 68%); 1H NMR (400 MHz, CDCl3) δ9.49 (s,
1 H), 7.42−7.39 (m, 3 H), 7.30−7.28 (m, 2 H), 6.43 (s, 1 H), 1.85 (s,
3 H), 1.32 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ187.0, 162.4,
152.6, 148.6, 138.0, 133.0, 129.3, 128.6, 128.2, 51.0, 21.7, 13.8; HRMS
calcd for C15H16O 212.1201, found 212.1205.
N-((2,2-Dimethyl-4,5,6,7-tetrahydro-2H-inden-1-yl)-
methylene)-4-methylbenzenesulfonamide (7a). Orange red oil;
(86 mg, 84%); 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 1 H), 7.81 (d, J
= 8.4 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.45 (s, 1 H), 2.79 (t, J = 6.0
Hz, 2 H), 2.46 (t, J = 5.6 Hz, 2 H), 2.39 (s, 3 H), 1.73−1.63 (m, 4 H),
1.19 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 165.4, 158.8, 154.4,
143.3, 142.1, 140.2, 137.2, 129.4, 127.2, 51.6, 24.8, 24.5, 22.7, 22.2,
21.9, 21.5; HRMS calcd for C19H23NO2S 329.1449, found 329.1447.
Synthesis of (3,5-Dichloropyridin-1-ium-1-yl)((2-(2-methyl-
prop-1-en-1-yl)cyclohex-1-en-1-yl)ethynyl)amide (12). To a 1,2-
dichloroethane solution (4.2 mL) of compound 1a (50 mg, 0.31
mmol) and (3,5-dichloro-pyridinium-1-yl)tosylamide (104.7 mg, 0.33
mmol) was added a 1,2-dichloroethane solution (2.0 mL) of
compound 11 (36.0 mg, 0.047 mmol); the mixture was heated to
80 °C for 1 h before it was filtered over a short silica bed. The solvent
was evaporated under reduced pressure; the crude product was eluted
through a silica column to afford compound 1a as a yellow oil (42 mg,
0.26 mmol, 85%), compound 1f as a yellow oil (6.5 mg, 0.034 mmol,
0.11 equiv), and compound 12 as a yellow oil (7.0 mg, 0.022 mmol,
0.07 equiv).
Deuterated 1,1-Dimethyl-1,2,3,4,5,6a-hexahydrocyclo-
propa[a]inden-6(1aH)-one (d1-2a). Pale yellow oil; (13 mg,
1
24%); H NMR (400 MHz, CDCl3) δ 2.40−2.34 (m, 1 H), 2.17−
2.11 (m, 2 H), 2.10−2.03 (m, 2 H), 1.92 (d, J = 4.4 Hz, 0.6 H), 1.70−
1.61 (m, 3 H), 1.52−1.48 (m, 1 H), 1.17 (s, 3 H), 1.04 (s, 3 H); 13C
NMR (150 MHz, CDCl3) δ 204.3, 168.8, 137.3, 48.3, 48.2, 38.1, 37.9
(t, J = 26 Hz), 37.3, 37.2, 28.7, 27.2, 27.1, 22.2, 21.7, 19.5, 14.3; HRMS
calcd for C12H16O 176.1201, found 176.1197, 177.1262.
2,2-Dimethyl-4,5,6,7-tetrahydro-2H-indene-1-carbaldehyde
1
(3a). Yellow oil; (45 mg, 83%); H NMR (400 MHz, CDCl3) δ 9.86
(s, 1 H), 6.28 (s, 1 H), 2.86 (t, J = 6.4 Hz, 2 H), 2.47 (td, J = 6.4, 2.0
Hz, 2 H), 1.72−1.59 (m, 4 H), 1.21 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 183.8, 160.6, 151.1, 145.5, 139.3, 51.1, 24.8, 24.0, 22.8, 22.4,
21.8; HRMS calcd for C12H16O 176.1201, found 176.1195.
Deuterated 2,2-Dimethyl-4,5,6,7-tetrahydro-2H-indene-1-
carbaldehyde (d1-3a). Pale yellow oil; (30 mg, 54%); 1H NMR
(400 MHz, CDCl3) δ 9.87 (s, 0.58 H), 6.29 (s, 1 H), 2.87 (t, J = 6.0
Hz, 2 H), 2.47 (t, J = 5.6 Hz, 2 H), 1.72−1.63 (m, 4 H), 1.22 (s, 6 H);
13C NMR (150 MHz, CDCl3) δ 183.8, 183.5 (t, J = 102 Hz), 160.6,
151.1, 145.4, 139.3, 51.1, 24.7, 24.0, 22.8, 22.4, 21.8; HRMS calcd for
C12H16O 176.1201, found 176.1206, 177.1268.
2-Ethyl-2-methyl-4,5,6,7-tetrahydro-2H-indene-1-carbalde-
hyde (3b). Yellow oil; (36 mg, 60%); 1H NMR (400 MHz, CDCl3) δ
9.85 (s, 1 H), 6.27 (s, 1 H), 2.88 (t, J = 5.6 Hz, 2 H), 2.48 (t, J = 5.2
Hz, 2 H), 1.78 (q, J = 7.2 Hz, 2 H), 1.71−1.64 (m, 4 H), 1.21 (s, 3 H),
E
dx.doi.org/10.1021/jo401161h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
N-((2-Ethyl-2-methyl-4,5,6,7-tetrahydro-2H-inden-1-yl)-
methylene)-4-methylbenzenesulfonamide (7b). Orange red oil;
(61 mg, 57%); 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1H), 7.80 (d, J
= 8.4 Hz, 2 H), 7.26 (d, J = 8.4 Hz, 2 H), 6.43 (s, 1 H), 2.80 (t, J = 6.4
Hz, 2 H), 2.47 (t, J = 6.4 Hz, 2 H), 2.39 (s, 3 H), 1.78 (q, J = 7.2 Hz, 2
H), 1.71−1.65 (m, 4 H), 1.17 (s, 3 H), 0.46 (t, J = 7.2 Hz, 3 H); 13C
NMR (100 MHz, CDCl3) δ 166.6, 158.9, 152.7, 143.3, 141.6, 140.9,
137.2, 129.4, 127.1, 56.1, 28.9, 24.8, 24.5, 22.7, 22.2, 21.5, 20.8, 9.2;
HRMS calcd for C20H25NO2S 343.1606, found 343.1608.
4-Methyl-N-((4′,5′,6′,7′-tetrahydrospiro[cyclopentane-1,2′-
inden]-1′-yl)methylene)benzenesulfonamide (7c). Orange red
oil; (72 mg, 65%); 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1 H), 7.80
(d, J = 8.4 Hz, 2 H), 7.26 (d, J = 8.4 Hz, 2 H), 6.67 (s, 1 H), 2.81 (t, J
= 6.0 Hz, 2 H), 2.46 (t, J = 5.6 Hz, 2 H), 2.39 (s, 3 H), 2.19−2.12 (m,
2 H), 1.98−1.90 (m, 2 H), 1.75−1.65 (m, 6 H), 1.42−1.37 (m, 2 H);
13C NMR (100 MHz, CDCl3) δ 166.4, 158.7, 152.1, 143.3, 140.0,
(m,2 H), 1.57−1.55 (m,2 H), 1.19 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 170.3, 159.3, 154.3, 146.0, 143.3, 142.3, 137.2, 129.4, 127.2,
51.2, 32.1, 30.0, 29.2, 28.5, 28.1, 21.9, 21.5; HRMS calcd for
C20H25NO2S 343.1606, found 343.1609.
4-Methyl-N-((3,5,5-trimethyl-2-phenylcyclopenta-1,3-dien-
1-yl)methylene)benzenesulfonamide (7j). Orange red solid; (82
1
mg, 72%); H NMR (400 MHz, CDCl3) δ 8.47 (s, 1 H), 7.77 (d, J =
8.4 Hz, 2 H), 7.43−7.42 (m, 3 H), 7.26 (d, J = 8.4 Hz, 2 H), 7.20−
7.18 (m, 2 H), 6.56 (s, 1 H), 2.39 (s, 3 H), 1.87 (s, 3 H), 1.29 (s, 6 H);
13C NMR (100 MHz, CDCl3) δ 166.1, 162.0, 155.6, 145.0, 143.5,
138.7, 136.6, 132.7, 129.4, 129.0 (2 × CH), 128.5, 127.4, 51.5, 21.9,
21.5, 13.9; HRMS calcd for C22H23NO2S 365.1449, found 365.1444.
N-((2,2-Dimethyl-4,5,6,7-tetrahydro-2H-inden-1-yl)methyl)-
4-methylbenzenesulfonamide (8a). Pale yellow solid; (58 mg,
67%); 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.4 Hz, 2 H), 7.31
(d, J = 8.4 Hz, 2 H), 5.73 (s, 1 H), 3.97 (br, 1 H), 3.65 (d, J = 5.2 Hz,
2 H), 2.43 (s, 3 H), 2.35−2.34 (m, 2 H), 2.18 (br, 2 H), 1.53−1.51
(m, 4 H), 0.98 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 143.3, 140.2,
139.5, 138.4, 136.5, 129.6 (2 × CH), 127.2, 51.5, 37.8, 25.3, 23.5, 23.4,
23.2, 22.2, 21.5; HRMS calcd for C19H25NO2S 331.1606, found
331.1602.
139.5, 137.3, 129.4, 127.2, 62.1, 32.8, 26.2, 24.9, 24.6, 22.8, 22.2, 21.5;
HRMS calcd for C21H25NO2S 355.1606, found 355.1607.
4-Methyl-N-((4′,5′,6′,7′-tetrahydrospiro[cyclohexane-1,2′-
inden]-1′-yl)methylene)benzenesulfonamide (7d). Orange red
oil; (88 mg, 76%); 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1 H), 7.81
(d, J = 7.6 Hz, 2 H), 7.28 (d, J = 7.6 Hz, 2 H), 7.09 (s, 1 H), 2.78 (t, J
= 6.0 Hz, 2 H), 2.48 (t, J = 6.0 Hz, 2 H), 2.40 (s, 3 H), 2.20 (td, J =
13.2 Hz, 3.2 Hz, 2 H), 1.76−1.65 (m, 6 H), 1.48−1.30 (m, 4 H), 0.98
(d, J = 13.2 Hz, 2 H); 13C NMR (100 MHz, CDCl3) δ165.1, 159.1,
150.6, 143.3, 142.3, 141.7, 137.1, 129.4, 127.2, 56.7, 31.5, 25.5, 24.9,
24.8, 24.7, 22.7, 22.2, 21.5; HRMS calcd for C22H27NO2S 369.1762,
found 369.1770.
4-Methyl-N-((2-methyl-2-phenyl-4,5,6,7-tetrahydro-2H-
inden-1-yl)methylene)benzenesulfonamide (7e). Orange red oil;
(78 mg, 64%); 1H NMR (400 MHz, CDCl3) δ 8.75 (s, 1 H), 7.43 (d, J
= 8.4 Hz, 2 H), 7.11 (d, J = 8.4 Hz, 2 H), 7.08−7.07 (m, 3 H), 7.03−
7.01 (m, 2 H), 6.58 (s, 1 H), 2.95−2.80 (m, 2 H), 2.54−2.52 (m, 2 H),
2.35 (s, 3 H), 1.75−1.69 (m, 4 H), 1.67 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 166.2, 159.0, 153.2, 143.2, 142.9, 141.1, 139.3, 137.2,
129.1, 128.0, 126.7, 126.2, 126.1, 58.1, 25.1, 24.6, 22.7, 22.2, 21.4, 20.0;
HRMS (ESI (+)) C24H25NO2S, calcd 391.1606 [M], found 391.1606.
4-Methyl-N-((2,2,6,6-tetramethyl-4,5,6,7-tetrahydro-2H-
inden-1-yl)methylene)benzenesulfonamide (7f). Orange red oil;
(78 mg, 70%); 1H NMR (400 MHz, CDCl3) δ 8.79 (s, 1 H), 7.83 (d, J
= 8.0 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 6.48 (s, 1 H), 2.54 (s, 2 H),
2.51 (t, J = 6.8 Hz, 2 H), 2.40 (s, 3 H), 1.50 (t, J = 6.8 Hz, 2 H), 1.19
(s, 6 H), 0.96 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 165.9, 158.8,
154.7, 143.3, 142.7, 138.9, 137.4, 129.4, 127.2, 52.2, 38.4, 35.3, 29.9,
27.9, 22.0, 21.5, 20.7; HRMS calcd for C21H27NO2S 357.1762, found
357.1761.
3,3-Dimethyl-5,6,7,8-tetrahydro-3H-isochromene-1-carbal-
dehyde (9). Yellow oil; (23 mg, 39%); 1H NMR (400 MHz, CDCl3)
δ 9.78 (s, 1 H), 5.35 (s, 1 H), 2.74 (t, J = 6.0 Hz, 2 H), 2.28 (t, J = 6.0
Hz, 2 H), 1.67−1.56 (m, 4 H), 1.31 (s, 6 H); 13C NMR (100 MHz,
CDCl3) δ 184.4, 149.2, 142.9, 131.1, 129.4, 75.2, 29.1, 26.7, 23.3, 23.0,
22.8; HRMS calcd for C12H16O2: 192.1150, found 192.1147.
1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene((2-(2-
methylprop-1-en-1-yl) cyclohex-1-en-1-yl)ethynyl)gold (10).
1
White solid; (61 mg, 68%); H NMR (600 MHz, CDCl3) δ 7.44 (t,
J = 7.8 Hz, 2 H), 7.24 (d, J = 7.8 Hz, 4 H), 7.08 (s, 2 H), 5.96 (s, 1 H),
2.59−2.55 (m, 4 H), 2.10−2.08 (m, 4 H), 1.62 (s, 3 H), 1.58 (s, 3 H),
1.45−1.44 (m, 4 H), 1.33 (d, J = 7.2 Hz, 12 H), 1.18 (d, J = 7.2 Hz, 12
H); 13C NMR (150 MHz, CDCl3) δ 191.7, 145.7, 138.9, 134.4, 132.7,
131.6, 130.4, 127.1, 124.1, 123.0, 118.8, 105.6, 31.5, 30.0, 28.8, 27.0,
24.5, 24.0, 22.9, 22.7, 20.7; HRMS calcd for C39H51AuN2: 744.3718,
found 744.3712.
1,3-Bis(2,6-diisopropylphenyl)imidazol-2-ylidene((5,5-di-
methyl-2-(2-methylprop-1-en-1-yl)cyclohex-1-en-1-yl)-
1
ethynyl)gold (11). Pale yellow solid; (84 mg, 68%); H NMR (600
MHz, CDCl3) δ 7.44 (t, J = 7.8 Hz, 2 H), 7.24 (d, J = 7.8 Hz, 4 H),
7.08 (s, 2 H), 5.95 (s, 1 H), 2.59−2.55 (m, 4 H), 2.10 (t, J = 6.6 Hz, 2
H), 1.90 (s, 2 H), 1.63 (s, 3 H), 1.59 (s, 3 H), 1.33 (d, J = 7.2 Hz, 12
H), 1.21 (t, J = 6.6 Hz, 2 H), 1.18 (d, J = 7.2 Hz, 12 H), 0.78 (s, 6 H);
13C NMR (150 MHz, CDCl3) δ 191.7, 145.6, 137.2, 134.4, 132.9,
131.1, 130.3, 126.6, 124.1, 123.0, 118.0, 105.8, 45.1, 35.6, 28.8, 28.7,
N-((5-(tert-Butyl)-2,2-dimethyl-4,5,6,7-tetrahydro-2H-inden-
1-yl)methylene)-4-methylbenzenesulfonamide (7g). Orange red
oil; (87 mg, 72%); 1H NMR (400 MHz, CDCl3) δ 8.78 (s, 1 H), 7.82
(d, J = 8.0 Hz, 2 H), 7.27 (d, J = 8.0 Hz, 2 H), 6.46 (s, 1 H), 3.14−3.09
(m, 1 H), 2.67−2.63 (m, 1 H), 2.54−2.45 (m, 1 H), 2.40 (s, 3 H),
2.12−2.05 (m, 1 H), 2.01−1.97 (m, 1 H), 1.36−1.27 (m, 2 H), 1.20
(s, 3 H), 1.18 (s, 3 H), 0.90 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ
165.5, 158.8, 154.6, 143.3, 141.7, 141.4, 137.2, 129.4, 127.2, 52.0, 45.0,
32.4, 27.2, 26.0, 25.3, 23.8, 22.0, 21.9, 21.5; HRMS calcd for
C23H31NO2S 385.2075, found 385.2070.
+
28.0, 27.5, 27.0, 24.5, 24.0, 20.7; HRMS (ESI (+)) C41H56AuN2 , calcd
773.4104 [M + H]+, found 773.4128.
(3,5-Dichloropyridin-1-ium-1-yl)((2-(2-methylprop-1-en-1-
yl)cyclohex-1-en-1-yl)ethynyl)amide (12). Yellow oil; (7 mg, 7%);
1H NMR (600 MHz, CDCl3) δ 8.32 (s, 1 H), 7.05 (d, J = 1.2 Hz, 1
H), 6.64 (d, J = 0.6 Hz, 1 H), 5.80 (s, 1 H), 2.59−2.56 (m, 2 H),
2.19−2.18 (m, 2 H), 1.77−1.67 (m, 7 H), 1.43 (s, 3 H); 13C NMR
(150 MHz, CDCl3) δ 156.5, 137.9, 137.3, 133.6, 126.7, 125.6, 125.1,
123.5, 123.2, 117.6, 97.7, 31.5, 28.7, 25.6, 22.9, 22.7, 19.3; HRMS calcd
for C17H18Cl2N2 320.0847, found 320.0854.
N-((2,2-Dimethyl-4,5-dihydro-2H-cyclopenta[a]naphthal-
ene-1-yl)methylene)-4-methylbenzenesulfonamide (7h). Or-
1
ange red oil; (78 mg, 66%); H NMR (400 MHz, CDCl3) δ 9.16
ASSOCIATED CONTENT
■
(s, 1 H), 7.84 (d, J = 8.4 Hz, 2 H), 7.56 (d, J = 7.2 Hz, 1 H), 7.38−7.33
(m, 2 H), 7.31−7.28 (m,3 H), 6.50 (s, 1 H), 2.82 (t, J = 6.0 Hz, 2 H),
2.59−2.55 (m, 2 H), 2.41 (s, 3 H), 1.31 (s, 6 H); 13C NMR (100
MHz, CDCl3) δ 161.4, 157.0, 151.0, 143.5, 141.0, 140.8 (2 × C),
136.8, 130.5, 130.1, 129.5, 129.4, 129.0, 127.4 (2 × CH), 53.2, 30.4,
23.7, 22.5, 21.5; HRMS calcd for C23H23NO2S 377.1449, found
377.1447.
S
* Supporting Information
1
HRMS H and 13C NMR spectra of compounds d1-2a, 3a−3j,
d1-3a, 7a−7j, 8a, 9, 10, 11, and 12, and crystallographic data for
compound 8a. This material is available free of charge via the
Internet at http://pubs.acs.org.
N-((2,2-Dimethyl-2,4,5,6,7,8-hexahydroazulen-1-yl)methyl-
ene)-4-methylbenzenesulfonamide (7i). Orange red oil; (80 mg,
AUTHOR INFORMATION
■
1
75%); H NMR (400 MHz, CDCl3) δ 8.86 (s, 1 H), 7.82 (d, J = 8.4
Corresponding Author
*E-mail: rsliu@mx.nthu.edu.tw.
Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.41 (s, 1 H), 2.73−2.71 (m, 2 H),
2.44−2.41 (m, 2 H), 2.40 (s, 3 H), 1.75−1.72 (m, 2 H), 1.64−1.63
F
dx.doi.org/10.1021/jo401161h | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank National Science Council, Taiwan, for financial
support of this work.
■
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■
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(3) For other pyridine N-oxides, see selected examples: (a) Ye, L.;
Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 3258.
(b) Ye, L.; He, W.; Zhang, L. J. Am. Chem. Soc. 2010, 132, 8550.
(c) Ye, L.; He, W.; Zhang, L. Angew. Chem., Int. Ed. 2011, 50, 3236.
(14) For gold-catalyzed oxidations of 1,n-enynes following path a, see
ref 4a and Taduri, B. P.; Abu Sohel, S. Md.; Cheng, H.-M.; Liu, R.-S.
Chem. Commun. 2007, 2530.
(15) (a) Lian, J.-J.; Odedra, A.; Wu, C.-J.; Liu, R.-S. J. Am. Chem. Soc.
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(4) (a) Witham, C. A.; Mauleon, P.; Shapiro, N. D.; Sherry, B. D.;
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(5) For 6-phenyl-substituted substrates, we envisage that their
resulting carbene intermediates are prone to a loss of proton, giving
chemically reactive fulvene products:
(6) Li, C.; Zhang, L. Org. Lett. 2011, 13, 1738.
(7) Hung, H.-H.; Liao, Y.-C.; Liu, R.-S. Adv. Synth. Catal. 2013, 355,
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(8) X-ray crystallographic data were deposited at Cambridged
Crystallographic Data Center (CCDC 939601).
(9) A double oxidation of terminal alkynes was reported by Hashmi
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(11) (a) Hashmi, A. S. K.; Braun, I.; Nosel, P.; Schadlich, J.; Wieteck,
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(13) We postulated a mechanism to rationalize the formation of
alkynylamide species 12, which involves a proton transfer from 3,5-
dien-1-yne 1a to N-iminopyridium ylide to give G. In this ion pair,
acetylide anion is stabilized with an electron-deficient pyridine core.
An attack of the acetylide of species G at the electrophilic NHTs
terminus gives intermediate H that provides a proton for the
demetalation of species 11; this process is expected to give 3,5-dien-
1-yne 1f and compound 11. We speculate that the poor activity of this
reaction is caused by the presence of NTf- as a counteranion or
alkynylamide 12 to inhibit the reaction.
G
dx.doi.org/10.1021/jo401161h | J. Org. Chem. XXXX, XXX, XXX−XXX