Gold(I)-catalyzed ring-expanding spiroannulation of cyclopropenones with enynes

Article abstract of DOI:10.1021/jo500045n

The gold(I)-catalyzed ring-expanding spiroannulation of cyclopropenones with enynes is reported here. A molecule of water is incorporated into the products during the spiroannulation to afford spirocyclic cyclopentenones containing an alcohol functionality.

Full text of DOI:10.1021/jo500045n

Note
pubs.acs.org/joc
Gold(I)-Catalyzed Ring-Expanding Spiroannulation of
Cyclopropenones with Enynes
Takanori Matsuda* and Yusuke Sakurai
Department of Applied Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
S
* Supporting Information
ABSTRACT: The gold(I)-catalyzed ring-expanding spiroannulation of
cyclopropenones with enynes is reported here. A molecule of water is
incorporated into the products during the spiroannulation to afford
spirocyclic cyclopentenones containing an alcohol functionality.
he transition-metal-catalyzed cyclization of enynes
cyclopentenone ring of the spirocyclic skeleton. A hydroxy
Trepresents fertile ground for the discovery of new group was introduced to 3a by the incorporation of a water
reactions and the preparation of diverse cyclic molecules.1 In
molecule to the product. The traces of water present in the
solvent used were probably responsible for this incorporation of
water. 1H NMR spectral analysis showed the formation of only
one diastereomer of the product in this reaction.
particular, the gold- and platinum-catalyzed cyclizations of
enynes have been extensively studied in the past decade to
expand the synthetic repertoire.
Next, the reaction conditions were optimized for the gold(I)-
catalyzed ring-expanding spiroannulation using 1a and 2a
(Table 1). The use of (IPr)AuNTf25 as the catalyst significantly
The transition-metal-catalyzed reactions of small-ring com-
pounds involving the cleavage of a strained C−C bond have
also been an active research area,2 and diverse ring-opening/
expanding reactions have been developed. However, the
transition-metal-catalyzed reactions of cyclopropenones remain
relatively unexplored.3 Recently, we reported the palladium-
catalyzed ring-opening alkynylation of cyclopropenones with
terminal alkynes and the application of this reaction to the [3 +
2] annulation giving cyclopentenones.4 Herein, we report the
successful utilization of cyclopropenones in the gold(I)-
catalyzed ring expansion, which is accompanied by the
spiroannulation with enynes affording spiro[4.4]octane skel-
etons.
Table 1. Optimization of Reaction Conditions for Gold(I)-
Catalyzed Ring-Expanding Spiroannulation
a
entry
1a:2a
solvent
time
yield of 3a
N-Prenyl-N-propargyltosylamide (1a) and diphenylcyclo-
propenone (2a) were selected as the substrates for our studies.
The reaction of 1a with 2a (1a:2a = 1:1) in DCE (1,2-
dichloroethane) in the presence of 2 mol % (SPhos)AuNTf25 at
room temperature for 12 h afforded 3a (Scheme 1). However,
the structure of 3a could not be determined from its NMR
spectrum. The crystals suitable for the X-ray diffraction analysis
were obtained by the crystallization of mesylamide counterpart
3b (vide infra). The product was identified as a spirocyclic
ketone containing an alcohol functionality; the yield of 3a was
53%. The three-membered ring of 2a expanded to form the
1
2
3
4
5
6
1:1
DCE
12
12
24
24
12
12
12
12
77%
85%
1:1
DCM
b
1:1
toluene
MeNO2
DCM
64%
c
1:1
40%
1.2:1
1.2:1
1.2:1
92%
d
MeOH
DCM
−
e
f
7
48%
g
h
8
1.2:1
b
DCM
−
a
c
d
Isolated yield. 3a:4a = 69:31. 3a:4a = 48:52. 4b was isolated in
65% yield. The reaction was performed in the presence of 5 equiv of
H2O. 3a:4a = 56:44. The reaction was performed in the presence of
5 equiv of MeOH. 4b was isolated in 64% yield.
e
f
g
h
Scheme 1. Gold(I)-Catalyzed Reaction of 1,6-Enyne 1a and
Cyclopropenone 2a
Received: January 9, 2014
Published: February 26, 2014
© 2014 American Chemical Society
2739
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
improved the yield of 3a to 77% yield (entry 1).6 When the
solvent was replaced with DCM (dichloromethane), the yield
of 3a further increased to 85% (entry 2).7 The reactions
performed in other solvents such as toluene and nitromethane
formed byproduct 4a, resulting from the hydroxycyclization of
enyne 1a in the presence of the gold(I) catalyst (entries 3 and
4).8 Finally, a slight excess (1.2 equiv) of 1a was found to be
the optimal quantity, resulting in a 92% yield of 3a (entry 5).
When the reaction was examined in MeOH as the solvent, in an
attempt to incorporate MeOH instead of water to the product,
enyne 1a afforded alkoxycyclization product 4b (65% yield)
without any detectable amount of the expected corresponding
spiro compound (entry 6). The reaction of 1a with 2a was also
conducted in the presence of added water or MeOH. The
addition of 5 equiv of water reduced the yield of spiro product
3a (48%) due to the competing hydroxycyclization of 1a
affording 4a (37%) (entry 7). On the other hand, exclusive
alkoxycyclization occurred when 5 equiv of MeOH were added
to the reaction mixture (entry 8).
a
Table 2. Substrate Scope of Enynes 1
The optimized reaction conditions were used to investigate
the substrate scope of the gold(I)-catalyzed spiroannulation of
diverse enynes 1 with 2a. The reaction of enyne 1a-d with a
deuterium atom at the alkyne terminus provided single
diastereomer 3a-d in 87% yield (Table 2, entry 1).9 Similar
to N-tosyl enyne 1a, nitrogen-tethered 1,6-enynes 1b−d with
different N-sulfonyl protecting groups smoothly afforded the
corresponding spiro products 3b−d in excellent yields (entries
2−4), whereas the reaction of N-phenyl derivative 1e resulted
in a low yield (entry 5). Oxygen- and carbon-tethered enynes 1f
and 1g also reacted with 2a to give 3f and 3g in 68% and 41%
yields, respectively (entries 6 and 7). The reaction of enyne 1h
bearing a cyclohexylidene moiety with 2a gave 3h in 77% yield
(entry 8), and 3,3-diphenylallyl derivative 1i also participated in
the reaction (entry 9). The reaction was only found to be
applicable to the enynes bearing a prenyl-type group; the
attempted reactions of the N-allyl, N-cyclohex-2-en-1-yl, N-
cinnamyl, and N-methallyl derivatives with 2a failed under the
reaction conditions.10 In addition, no reaction was observed for
the enynes with an internal alkyne moiety.
The reaction of other cyclopropenones 2b−e was also
examined using 1a as the coupling partner (Table 3). The ring-
expanding spiroannulation of enyne 1a with diarylcyclopro-
penones 2b and 2c afforded the corresponding spirocyclic
ketones 3j and 3k, respectively, in high yields (entries 1 and 2).
Dipropylcyclopropenone 2d also underwent the spiroannula-
tion with 1a to afford 3l in 85% yield (entry 3). Single
regioisomer 3m was obtained in an excellent yield by the
reaction of unsymmetrically substituted cyclopropenone 2e
with 1a (entry 4).11 In this case, clean conversion was achieved
by performing the reaction at 0 °C. However, an attempted
reaction using monosubstituted phenylcyclopropenone gave
only a complex mixture of products.
The gold(I)-catalyzed reactions of enynes with carbonyl
compounds have been reported.12 Echavarren et al. reported
the gold(I)-catalyzed reaction of 1,6-enynes with aldehydes12f
and found that the reaction proceeded via the formation of
(cyclopropylcarbene)gold(I) species, affording an oxocarbe-
nium ion by the ring opening of the cyclopropane ring with an
aldehyde. Based on their proposed mechanism, the following
catalytic cycle may have operated in our spiroannulation
reaction (Scheme 2).13 Similar to the case for the reaction with
aldehydes, (cyclopropylcarbene)gold(I) species A is produced
by the reaction of enyne 1 with the Au(I) catalyst; then the
a
Enyne 1 and cyclopropenone 2a (1:2a = 1.2:1) were reacted in DCM
at room temperature in the presence of (IPr)AuNTf2 (2 mol %).
b
c
d
Isolated yield. Obtained as a single diastereomer. Ns = (2-
e
nitrophenyl)sulfonyl. The reaction was performed at 0 °C.
carbonyl group of cyclopropenone 2 opens the cyclopropane
ring of A to generate oxocarbenium ion intermediate B. The
resulting alkenylgold(I) moiety of B attacks the carbonyl sp2
carbon with the β-carbon to form carbenegold(I) C with a 3-
oxabicyclo[3.3.0]octane system with a spirocyclic cyclopropene
moiety.14 Then, the cyclopropene sp2 carbon migrates onto the
carbon α to the Au(I), resulting in the ring expansion to
generate tricyclic oxocarbenium ion D. The cyclopentene
2740
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
a
The spirocyclic products were derivatized (Scheme 3). The
2-hydroxypropan-2-yl groups of 3a and 3c were dehydrated
Table 3. Substrate Scope of Cyclopropenones 2
Scheme 3. Derivatization of Spiroannulation Products 3
with 9 mol % p-toluenesulfonic acid in toluene at 80 °C to
produce the corresponding alkenes 5a and 5b, respectively, in
good yields. The (2-nitrophenyl)sulfonyl group of 5b was
removed by reacting with 1-dodecanethiol and Cs2CO3 in
DMF to furnish 6 in 88% yield.16
In summary, we have developed a gold(I)-catalyzed
spiroannulation reaction of enynes with cyclopropenones
involving ring expansion of the cyclopropenone ring. The
reaction proceeds with the incorporation of a water molecule to
afford [4.4]-spirocyclic cyclopentenones containing an alcohol
functionality, in excellent yields and with high diastereoselec-
tivity.
a
EXPERIMENTAL SECTION
Enyne 1 and cyclopropenone 2a (1:2a = 1.2:1) were reacted in DCM
■
at room temperature in the presence of (IPr)AuNTf2 (2 mol %).
General Methods. All reactions were carried out with standard
Schlenk techniques under an argon atmosphere. Proton chemical shifts
were referenced to a residual CHCl3 signal at 7.26 ppm. Carbon
chemical shifts were referenced to CDCl3 at 77.0 ppm. Gold
complexes,17 enynes (1a,18 1e,19 1f,20 and 1g21), and cyclopropenones
(2b,22 2c,23 2d,24 and 2e3c) were prepared according to the literature
methods.
b
c
Isolated yield. The reaction was performed at 0 °C.
Scheme 2. Proposed Mechanism for the Gold(I)-Catalyzed
Spiroannulation
4-Methyl-N-(3-methylbut-2-en-1-yl)-N-[(3-2H)prop-2-yn-1-
yl]benzenesulfonamide (1a-d). The deuteration of 1a was
performed according to the reported procedure.25 White solid, mp
60−61 °C. 1H NMR (300 MHz, CDCl3) δ 1.67 (s, 3H), 1.72 (s, 3H),
1.98 (t, J = 2.6 Hz, 90% D), 2.42 (s, 3H), 3.81 (d, J = 12.5 Hz, 2H),
4.06 (s, 2H), 5.06−5.14 (m, 1H), 7.29 (d, J = 7.8 Hz, 2H), 7.70−7.76
(m, 2H); 13C NMR (126 MHz, CDCl3) δ 17.8, 21.5, 25.8, 35.3, 43.8,
73.1 (t, J = 38.4 Hz), 76.5 (t, J = 7.2 Hz), 117.8, 127.7, 129.3, 136.0,
139.0, 143.3; HRMS (ESI) calcd for C15H18DNNaO2S [M + Na]+
301.1091, found 301.1087.
N-(3-Methylbut-2-en-1-yl)-N-(prop-2-yn-1-yl)methane-
sulfonamide (1b). Step 1: Prenyl chloride (523 mg, 5.00 mmol) was
added to a suspension of methanesulfonamide (713 mg, 7.50 mmol)
and K2CO3 (691 mg, 5.00 mmol) in acetone (10 mL), and the
resulting mixture was heated at 60 °C for 12 h. The reaction mixture
was filtered, and the filtrate was concentrated. The residue was purified
by column chromatography on silica gel (hexane/AcOEt = 5:1) to
afford N-prenylmethanesulfonamide (498 mg, 3.05 mmol, 61%).
Step 2: Propargyl bromide (535 mg, 4.50 mmol) was added to a
mixture of N-prenylmethanesulfonamide (489 mg, 3.00 mmol) and
K2CO3 (622 mg, 4.50 mmol) in acetonitrile (10 mL), and the resulting
mixture was heated at 80 °C for 12 h. The reaction mixture was
filtered, and the filtrate was concentrated. The residue was purified by
column chromatography on silica gel (hexane/AcOEt = 10:1) to afford
1b (531 mg, 2.64 mmol, 88%) as a colorless oil. 1H NMR (500 MHz,
CDCl3) δ 1.75 (s, 3H), 1.77 (s, 3H), 2.35 (t, J = 2.5 Hz, 1H), 2.95 (s,
3H), 3.88 (d, J = 7.5 Hz, 2H), 4.04 (d, J = 2.0 Hz, 2H), 5.19 (t, J = 7.2
Hz, 1H); 13C NMR (75.6 MHz, CDCl3) δ 17.8, 25.9, 35.3, 38.0, 43.9,
structure of D is formed by the stepwise intramolecular [3 + 2]
annulation of the vinylgold with the cyclopropene moieties of B
via C. Finally, D is hydrolyzed with water present in the solvent
to furnish product 3,15 and the Au(I) catalyst is regenerated.
The results of the deuterium-labeling experiment indicate that
both the ring expansion and protodeauration steps proceeded
in diastereoselective manners.
2741
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
74.0, 77.6, 117.7, 139.5; HRMS (ESI) calcd for C9H15NNaO2S [M +
Na]+ 224.0716, found 224.0718.
concentrated under reduced pressure, and the residue was purified by
preparative TLC on silica gel to afford spirocyclic cyclopentenones 3.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-7,8-diphenyl-2-tosyl-2-
azaspiro[4.4]non-7-en-6-one (3a). The general procedure was
followed using 1a (33.2 mg, 0.120 mmol) and 2a (20.6 mg, 0.100
mmol). The purification by preparative TLC on silica gel (hexane/
AcOEt = 2:1) afforded 3a (46.0 mg, 0.092 mmol, 92%) as a white
N-(3-Methylbut-2-en-1-yl)-2-nitro-N-(prop-2-yn-1-yl)ben-
zenesulfonamide (1c). The title compound was prepared according
to the procedure described for 1b, starting with 2-nitrobenzene-
sulfonamide (Step 1: 432 mg, 32%; Step 2: 308 mg, 62%). White solid,
1
mp 49−51 °C. H NMR (300 MHz, CDCl3) δ 1.69 (s, 3H), 1.72 (s,
1
solid. Mp 122−124 °C; H NMR (500 MHz, CDCl3) δ 1.13 (s, 3H),
3H), 2.14 (t, J = 2.4 Hz, 1H), 4.00 (d, J = 7.5 Hz, 2H), 4.12 (d, J = 2.4
Hz, 2H), 5.03−5.11 (m, 1H), 7.60−7.74 (m, 3H), 8.02−8.08 (m, 1H);
13C NMR (75.6 MHz, CDCl3) δ 17.8, 25.8, 35.6, 44.4, 73.3, 77.3,
1.17 (s, 3H), 2.44 (s, 3H), 2.61 (dd, J = 9.0, 8.0 Hz, 1H), 3.11 (d, J =
10.0 Hz, 1H), 3.18 (d, J = 18.0 Hz, 1H), 3.27 (t, J = 9.5 Hz, 1H), 3.38
(d, J = 18.5 Hz, 1H), 3.51 (d, J = 9.0 Hz, 1H), 3.77−3.84 (m, 2H),
7.14−7.19 (m, 2H), 7.26−7.40 (m, 10H), 7.72 (d, J = 8.0 Hz, 2H);
13C NMR (126 MHz, CDCl3) δ 21.6, 29.3, 29.4, 48.7, 50.2, 56.1, 59.6,
61.2, 70.6, 128.0, 128.4, 128.6, 128.7, 129.3, 129.9, 130.9, 131.5, 131.8,
134.1, 139.0, 144.0, 166.6, 210.2; HRMS (ESI) calcd for
C30H31NNaO4S [M + Na]+ 524.1866, found 524.1868; IR (ν/
cm−1): 3448, 1689, 1350, 1157.
117.5, 124.1, 130.9, 131.6, 133.0, 133.6, 139.7, 148.2; HRMS (ESI)
calcd for C14H16N2NaO4S [M + Na]+ 331.0723, found 331.0722.
N-(3-Methylbut-2-en-1-yl)-1-phenyl-N-(prop-2-yn-1-yl)-
methanesulfonamide (1d). The title compound was prepared
according to the procedure described for 1b, starting with phenyl-
methanesulfonamide (Step 1: 526 mg, 44%; Step 2: 494 mg, 89%).
1
White solid, mp 49−50 °C. H NMR (500 MHz, CDCl3) δ 1.68 (s,
3a-d. The general procedure was followed using 1a-d (32.8 mg,
0.118 mmol) and 2a (20.6 mg, 0.100 mmol). The purification by
preparative TLC on silica gel (hexane/AcOEt = 2:1) afforded 3a-d
3H), 1.73 (s, 3H), 2.38 (t, J = 2.5 Hz, 1H), 3.72 (d, J = 7.0 Hz, 2H),
3.98 (d, J = 2.5 Hz, 2H), 4.30 (s, 2H), 5.08 (t, J = 7.7 Hz, 1H), 7.35−
7.40 (m, 3H), 7.44−7.49 (m, 2H); 13C NMR (75.6 MHz, CDCl3) δ
17.7, 25.8, 35.4, 44.6, 58.4, 73.5, 78.5, 118.4, 128.57, 128.59, 128.7,
130.9, 138.8; HRMS (ESI) calcd for C15H19N2NaO2S [M + Na]+
300.1029, found 300.1032.
1
(43.9 mg, 0.087 mmol, 87%) as a white solid. Mp 117−119 °C; H
NMR (500 MHz, CDCl3) δ 1.13 (s, 3H), 1.17 (s, 3H), 2.44 (s, 3H),
2.61 (dd, J = 9.8, 7.8 Hz, 1H), 3.11 (d, J = 9.5 Hz, 1H), 3.16 (s, 1H),
3.27 (t, J = 9.5 Hz, 1H), 3.51 (d, J = 9.5 Hz, 1H), 3.78−3.83 (m, 2H),
7.14−7.18 (m, 2H), 7.24−7.40 (m, 10H), 7.70−7.73 (m, 2H); 13C
NMR (75.6 MHz, CDCl3) δ 21.6, 29.3, 29.4, 48.2 (t), 50.2, 56.0, 59.5,
61.1, 70.5, 127.9, 128.0, 128.4, 128.59, 128.65, 129.3, 129.9, 130.9,
131.5, 131.8, 134.1, 139.0, 144.0, 166.5, 210.2; HRMS (ESI) calcd for
C30H30DNNaO4S [M + Na]+ 525.1929, found 525.1928; IR (ν/
cm−1): 3502, 3433, 1689, 1342, 1157.
N-(3-Methylbut-2-en-1-yl)-N-(prop-2-yn-1-yl)aniline (1e).
1
Pale yellow oil. H NMR (500 MHz, CDCl3) δ 1.76 (s, 6H), 2.17
(t, J = 2.2 Hz, 1H), 3.93 (d, J = 6.5 Hz, 2H), 4.01 (d, J = 2.5 Hz, 2H),
5.24−5.30 (m, 1H), 6.80 (t, J = 7.2 Hz, 1H), 6.89 (d, J = 8.0 Hz, 2H),
7.27 (t, J = 7.2 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 18.0, 25.8,
39.4, 48.7, 71.6, 80.1, 114.6, 118.2, 120.8, 129.1, 135.7, 148.6; HRMS
(ESI) calcd for C14H18N [M + H]+ 200.1434, found 200.1434.
3-Methyl-1-(prop-2-yn-1-yloxy)but-2-ene (1f). Colorless oil.
1H NMR (300 MHz, CDCl3) δ 1.70 (s, 3H), 1.75 (s, 3H), 2.41 (t, J =
2.2 Hz, 1H), 4.05 (d, J = 7.2 Hz, 2H), 4.12 (d, J = 2.4 Hz, 2H), 5.28−
5.37 (m, 1H); 13C NMR (75.6 MHz, CDCl3) δ 18.0, 25.8, 56.7, 65.9,
74.1, 80.0, 120.1, 138.4; HRMS (ESI) calcd for C8H12NaO [M + Na]+
147.0780, found 147.0782.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-2-(methylsulfonyl)-7,8-
diphenyl-2-azaspiro[4.4]non-7-en-6-one (3b). The general pro-
cedure was followed using 1b (23.9 mg, 0.119 mmol) and 2a (20.6
mg, 0.100 mmol). The purification by preparative TLC on silica gel
(hexane/AcOEt = 2:1) afforded 3b (38.8 mg, 0.091 mmol, 91%) as
pale yellow crystals. Mp 176−178 °C; 1H NMR (500 MHz, CDCl3) δ
1.18 (s, 3H), 1.22 (s, 3H), 2.46 (br s, 1H), 2.67 (dd, J = 10.3, 7.8 Hz,
1H), 2.94 (s, 3H), 3.17 (d, J = 18.0 Hz, 1H), 3.30 (d, J = 18.5 Hz, 1H),
3.54 (d, J = 9.5 Hz, 1H), 3.58 (d, J = 11.0 Hz, 1H), 3.64−3.69 (m,
1H), 3.72−3.76 (m, 1H), 7.15−7.34 (m, 10H); 13C NMR (126 MHz,
CDCl3) δ 29.7, 30.0, 35.0, 43.7, 49.1, 54.5, 58.3, 58.4, 71.1, 128.2,
128.3, 128.6, 128.7, 129.3, 130.5, 131.8, 134.5, 139.0, 165.3, 209.8;
HRMS (ESI) calcd for C24H27NNaO4S [M + Na]+ 448.1553, found
448.1554; IR (ν/cm−1): 3487, 1689, 1327, 1149.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-2-[(2-nitrophenyl)-
sulfonyl]-7,8-diphenyl-2-azaspiro[4.4]non-7-en-6-one (3c). The
general procedure was followed using 1c (36.7 mg, 0.119 mmol) and
2a (20.6 mg, 0.100 mmol). The purification by preparative TLC on
silica gel (hexane/AcOEt = 1:1) afforded 3c (42.0 mg, 0.079 mmol,
79%) as a white solid. Mp 155−156 °C; 1H NMR (500 MHz, CDCl3)
δ 1.20 (s, 3H), 1.24 (s, 3H), 2.68 (dd, J = 10.5, 8.0 Hz, 1H), 3.22 (br s,
1H), 3.30 (s, 2H), 3.71 (s, 2H), 3.78 (t, J = 10.0 Hz, 1H), 3.94 (dd, J =
9.5, 8.0 Hz, 1H), 7.16−7.20 (m, 2H), 7.27−7.40 (m, 8H), 7.63−7.67
(m, 1H), 7.69−7.74 (m, 2H), 8.10−8.13 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 29.56, 29.63, 46.1, 49.8, 55.6, 59.0, 59.7, 70.9, 124.2,
128.3, 128.6, 128.7, 129.3, 130.68, 130.74, 131.4, 131.6, 131.9, 133.7,
134.3, 139.0, 148.5, 165.9, 209.5; HRMS (ESI) calcd for
C29H28N2NaO6S [M + Na]+ 555.1560, found 555.1558; IR (ν/
cm−1): 3548, 3525, 1689, 1543, 1365, 1165.
N-(2-Cyclohexylideneethyl)-4-methyl-N-(prop-2-yn-1-yl)-
benzenesulfonamide (1h). A solution of diisopropyl azodicarbox-
ylate (1.0 M toluene solution, 1.1 mL, 1.1 mmol) was added dropwise
to a mixture of 2-cyclohexylideneethan-1-ol26 (139 mg, 1.10 mmol), 4-
methyl-N-propargylbenzenesulfonamide (209 mg, 1.00 mmol), and
PPh3 (288 mg, 1.10 mmol) in THF (11 mL) at 0 °C, and then the
resulting mixture was warmed to room temperature and further stirred
for 12 h. The reaction mixture was concentrated in vacuo, and the
residue was purified by column chromatography on silica gel (hexane/
AcOEt = 15:1) to afford 1h (222 mg, 0.699 mmol, 70%) as a white
1
solid. Mp 71−72 °C. H NMR (300 MHz, CDCl3) δ 1.41−1.59 (m,
6H), 1.96 (t, J = 2.4 Hz, 1H), 2.01−2.20 (m, 4H), 2.42 (s, 3H), 3.81
(d, J = 7.5 Hz, 2H), 4.07 (d, J = 2.1 Hz, 2H), 5.04 (t, J = 7.4 Hz, 1H),
7.28 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H); 13C NMR (75.6
MHz, CDCl3) δ 21.5, 26.6, 27.9, 28.5, 28.7, 35.2, 37.2, 43.0, 73.3, 76.9,
114.4, 127.8, 129.4, 136.1, 143.3, 147.2; HRMS (ESI) calcd for
C18H23NNaO2S [M + Na]+ 340.1342, found 340.1346.
N-(3,3-Diphenylallyl)-4-methyl-N-(prop-2-yn-1-yl)benzene-
sulfonamide (1i). The title compound was prepared according to the
procedure described for 1h, starting with 3,3-diphenylprop-2-en-1-ol27
(313 mg, 78%). Pale yellow solid, mp 88−90 °C. 1H NMR (500 MHz,
CDCl3) δ 1.89 (t, J = 2.5 Hz, 1H), 2.40 (s, 3H), 3.95 (d, J = 7.0 Hz,
2H), 4.11 (d, J = 7.2 Hz, 2H), 6.02 (t, J = 7.0 Hz, 1H), 7.12−7.38 (m,
12H), 7.69 (d, J = 8.5 Hz, 2H); 13C NMR (126 MHz, CDCl3) δ 21.4,
36.4, 45.7, 73.5, 76.7, 122.7, 127.3, 127.5, 127.7, 128.1, 128.17, 128.20,
128.9, 129.4, 129.7, 136.1, 138.3, 143.4, 146.0; HRMS (ESI) calcd for
C25H23NNaO2S [M + Na]+ 424.1342, found 424.1342.
General Procedure for Gold-Catalyzed Reaction of Enynes 1
and Cyclopropenones 2. A Schlenk tube was charged with
(IPr)AuNTf2 (2.0 μmol), enyne 1 (0.12 mmol), and cyclopropenone
2 (0.10 mmol), and the tube was evacuated and backfilled with argon.
DCM (1.0 mL) was added via a syringe through the septum, and the
mixture was stirred at 25 °C for 12 h. Then, the reaction mixture was
(4R*,5S*)-2-(Benzylsulfonyl)-4-(2-hydroxypropan-2-yl)-7,8-
diphenyl-2-azaspiro[4.4]non-7-en-6-one (3d). The general pro-
cedure was followed using 1d (33.4 mg, 0.120 mmol) and 2a (20.6
mg, 0.100 mmol). The purification by preparative TLC on silica gel
(hexane/AcOEt = 2:1) afforded 3d (43.1 mg, 0.086 mmol, 86%) as a
white solid. Mp 148−150 °C; 1H NMR (500 MHz, CDCl3) δ 1.16 (s,
3H), 1.20 (s, 3H), 2.59 (dd, J = 10.3, 7.8 Hz, 1H), 3.17 (d, J = 18.0 Hz,
1H), 3.23 (d, J = 18.5 Hz, 1H), 3.47 (d, J = 11.0 Hz, 1H), 3.52 (d, J =
10.0 Hz, 1H), 3.67−3.72 (m, 1H), 3.73−3.78 (m, 1H), 4.29 (d, J =
15.0 Hz, 1H), 4.36 (d, J = 13.5 Hz, 1H), 7.14−7.19 (m, 2H), 7.21−
7.36 (m, 11H), 7.39−7.43 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ
2742
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
29.7, 29.8, 45.0, 49.5, 55.4, 56.3, 58.9, 59.2, 71.0, 128.28, 128.31, 128.5,
128.6, 128.68, 128.72, 128.8, 129.3, 130.6, 130.9, 131.7, 134.4, 139.0,
165.7, 209.9; HRMS (ESI) calcd for C30H31NNaO4S [M + Na]+
524.1866, found 524.1863; IR (ν/cm−1): 3502, 1682, 1342, 1149, 694.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-2,7,8-triphenyl-2-aza-
spiro[4.4]non-7-en-6-one (3e). The general procedure was
followed using 1e (24.1 mg, 0.121 mmol) and 2a (20.6 mg, 0.100
mmol). The purification by preparative TLC on silica gel (hexane/
AcOEt = 5:1) afforded 3e (4.6 mg, 0.011 mmol, 11%) as a yellow
solid. Mp 138−139 °C; 1H NMR (500 MHz, CDCl3) δ 1.31 (s, 3H),
1.32 (s, 3H), 2.69 (t, J = 8.0 Hz, 1H), 3.22 (br s, 1H), 3.24 (d, J = 18.0
Hz, 1H), 3.36 (d, J = 7.2 Hz, 1H), 3.51 (d, J = 9.0 Hz, 1H), 3.70−3.74
(m, 3H), 6.64 (dd, J = 8.5, 1.0 Hz, 2H), 6.73 (t, J = 7.5 Hz, 1H), 7.22−
7.38 (m, 12H); 13C NMR (126 MHz, CDCl3) δ 28.9, 29.9, 47.0, 50.3,
55.9, 58.6, 60.1, 71.7, 112.4, 116.7, 128.2, 128.3, 128.5, 128.6, 129.1,
129.4, 130.4, 131.9, 134.8, 139.1, 147.6, 165.0, 210.5; HRMS (ESI)
calcd for C29H30NO2 [M + H]+ 424.2271, found 424.2272; IR (ν/
cm−1): 3502, 1689, 1597, 1504, 1365, 748, 694.
7.12−7.42 (m, 20H), 7.65 (d, J = 8.0 Hz, 2H); 13C NMR (126 MHz,
CDCl3) δ 21.7, 49.9, 51.4, 56.4, 58.0, 61.8, 78.2, 124.9, 125.3, 126.5,
127.0, 128.0, 128.06, 128.14, 128.2, 128.3, 128.6, 128.7, 129.2, 129.8,
130.8, 130.9, 131.3, 134.3, 139.6, 144.1, 145.3, 147.0, 166.9, 209.1;
HRMS (ESI) calcd for C40H35NNaO4S [M + Na]+ 648.2179, found
648.2179; IR (ν/cm−1): 3363, 1674, 1350, 1165, 748, 702, 663.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-7,8-bis(4-methyl-
phenyl)-2-tosyl-2-azaspiro[4.4]non-7-en-6-one (3j). The general
procedure was followed using 1a (33.2 mg, 0.120 mmol) and 2b (22.4
mg, 0.096 mmol). The purification by preparative TLC on silica gel
(hexane/AcOEt = 2:1) afforded 3j (48.0 mg, 0.091 mmol, 95%) as a
1
pale yellow solid. Mp 141−143 °C; H NMR (500 MHz, CDCl3) δ
1.12 (s, 3H), 1.15 (s, 3H), 2.35 (s, 3H), 2.36 (s, 3H), 2.44 (s, 3H),
2.60 (dd, J = 9.5, 8.0 Hz, 1H), 3.06 (d, J = 9.5 Hz, 1H), 3.14 (d, J =
18.5 Hz, 1H), 3.24 (t, J = 9.7 Hz, 1H), 3.36 (d, J = 18.0 Hz, 1H), 3.48
(d, J = 10.0 Hz, 1H), 3.80 (t, J = 8.5 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H),
7.10 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 9.0 Hz,
2H), 7.35 (d, J = 8.0 Hz, 2H), 7.70 (d, J = 8.0 Hz, 2H); 13C NMR
(126 MHz, CDCl3) δ 21.4, 21.5, 21.6, 29.2, 29.5, 48.8, 50.3, 56.1, 59.6,
61.5, 70.4, 128.0, 128.4, 128.7, 129.1, 129.3, 129.4, 129.9, 131.3, 131.6,
138.2, 138.3, 141.6, 144.0, 166.3, 210.5; HRMS (ESI) calcd for
C32H35NNaO4S [M + Na]+ 552.2179, found 552.2182; IR (ν/cm−1):
3471, 1689, 1350, 1165, 818, 663.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-7,8-diphenyl-2-oxa-
spiro[4.4]non-7-en-6-one (3f). The general procedure was followed
using 1f (15.2 mg, 0.122 mmol) and 2a (20.6 mg, 0.100 mmol). The
purification by preparative TLC on silica gel (hexane/AcOEt = 10:1)
afforded 3f (23.8 mg, 0.068 mmol, 68%) as a yellow solid. Mp 111−
1
112 °C; H NMR (500 MHz, CDCl3) δ 1.14 (s, 3H), 1.22 (s, 3H),
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-7,8-bis(4-methoxy-
phenyl)-2-tosyl-2-azaspiro[4.4]non-7-en-6-one (3k). The general
procedure was followed using 1a (33.2 mg, 0.120 mmol) and 2c (25.5
mg, 0.096 mmol). The purification by preparative TLC on silica gel
(hexane/AcOEt = 2:1) afforded 3k (52.2 mg, 0.093 mmol, 97%) as a
2.55 (t, J = 8.5 Hz, 1H), 3.16 (d, J = 18.0 Hz, 1H), 3.30 (d, J = 18.5
Hz, 1H), 3.85 (d, J = 8.5 Hz, 1H), 3.94 (d, J = 8.5 Hz, 1H), 4.19−4.27
(m, 2H), 4.48 (br s, 1H), 7.13−7.36 (m, 10H); 13C NMR (126 MHz,
CDCl3) δ 29.9, 48.9, 58.5, 61.7, 70.3, 71.1, 81.7, 128.3, 128.6, 128.7,
129.4, 130.6, 131.8, 134.5, 139.6, 166.6, 211.1; HRMS (ESI) calcd for
C23H24NaO3 [M + Na]+ 371.1618, found 371.1619; IR (ν/cm−1):
3433, 1674, 1350, 694.
1
pale yellow solid. Mp 149−152 °C; H NMR (500 MHz, CDCl3) δ
1.11 (s, 3H), 1.15 (s, 3H), 2.44 (s, 3H), 2.59 (dd, J = 9.5, 8.0 Hz, 1H),
3.03 (d, J = 10.0 Hz, 1H), 3.12 (d, J = 18.5 Hz, 1H), 3.22 (t, J = 9.8
Hz, 1H), 3.37 (d, J = 18.5 Hz, 1H), 3.46 (d, J = 10.0 Hz, 1H), 3.77−
3.82 (m, 1H), 3.82 (s, 3H + 3H), 4.11 (br s, 1H), 6.78−6.82 (m, 2H),
6.88−6.91 (m, 2H), 7.10−7.13 (m, 2H), 7.33−7.36 (m, 4H), 7.69−
7.71 (m, 2H); 13C NMR (75.6 MHz, CDCl3) δ 21.6, 29.2, 29.5, 48.8,
50.3, 55.2, 55.4, 56.0, 59.7, 61.6, 70.4, 114.0, 114.3, 124.2, 126.6, 128.0,
129.9, 130.3, 130.6, 131.5, 136.9, 144.0, 159.5, 161.7, 165.5, 210.4;
HRMS (ESI) calcd for C32H35NNaO6S [M + Na]+ 584.2077, found
584.2079; IR (ν/cm−1): 3448, 1597, 1512, 1350, 1257, 1165.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-7,8-dipropyl-2-tosyl-2-
azaspiro[4.4]non-7-en-6-one (3l). The general procedure was
followed using 1a (33.2 mg, 0.120 mmol) and 2d (13.8 mg, 0.100
mmol). The purification by preparative TLC on silica gel (hexane/
AcOEt = 2:1) afforded 3l (36.8 mg, 0.085 mmol, 85%) as a colorless
oil. 1H NMR (300 MHz, CDCl3) δ 0.85 (t, J = 7.3 Hz, 3H), 0.95 (t, J
= 7.3 Hz, 3H), 1.01 (s, 3H), 1.05 (s, 3H), 1.20−1.61 (m, 4H), 2.12 (t,
J = 7.6 Hz, 2H), 2.32−2.50 (m, 6H), 2.60 (d, J = 18.9 Hz, 1H), 2.79−
2.87 (m, 2H), 3.11−3.22 (m, 2H), 3.71 (t, J = 8.5 Hz, 1H), 4.17 (s,
1H), 7.32 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 8.1 Hz, 2H); 13C NMR
(126 MHz, CDCl3) δ 13.97, 14.03, 20.6, 21.49, 21.51, 25.11, 28.8,
29.4, 32.8, 49.3, 50.3, 55.7, 59.0, 61.6, 70.3, 127.9, 129.8, 131.7, 140.3,
143.9, 174.2, 212.4; HRMS (ESI) calcd for C24H35NNaO4S [M +
Na]+ 456.2179, found 456.2179; IR (ν/cm−1): 3410, 2962, 1682,
1628, 1342, 1165, 756, 663.
Dimethyl (4R*,5S*)-4-(2-hydroxypropan-2-yl)-6-oxo-7,8-di-
phenylspiro[4.4]non-7-ene-2,2-dicarboxylate (3g). The general
procedure was followed using 1g (28.3 mg, 0.119 mmol) and 2a (20.6
mg, 0.100 mmol). The purification by preparative TLC on silica gel
(hexane/AcOEt = 3:1) afforded 3g (18.9 mg, 0.041 mmol, 41%) as a
1
pale yellow oil. H NMR (500 MHz, CDCl3) δ 1.19 (s, 3H), 1.21 (s,
3H), 2.44−2.51 (m, 2H), 2.60 (ddd, J = 13.1, 6.6, 1.4 Hz, 1H), 2.76
(d, J = 14.0 Hz, 1H), 2.81 (t, J = 12.8 Hz, 1H), 3.18 (d, J = 18.5 Hz,
1H), 3.25 (d, J = 18.0 Hz, 1H), 3.75 (s, 3H), 3.80 (s, 3H + 1H), 7.20
(dd, J = 7.5, 1.5 Hz, 2H), 7.26−7.38 (m, 8H); 13C NMR (126 MHz,
CDCl3) δ 29.0, 30.5, 36.4, 48.5, 48.8, 52.9, 53.0, 55.8, 58.8, 58.9, 71.0,
128.2, 128.2, 128.5, 128.6, 129.3, 130.4, 131.9, 134.7, 138.8, 166.1,
171.2, 172.8, 213.5; HRMS (ESI) calcd for C28H30NaO6 [M + Na]+
485.1935, found 485.1935; IR (ν/cm−1): 3448, 2962, 1736, 1682,
1442, 1265, 756, 694.
(4R*,5S*)-4-(1-Hydroxycyclohexyl)-7,8-diphenyl-2-tosyl-2-
azaspiro[4.4]non-7-en-6-one (3h). The general procedure was
followed using 1h (38.2 mg, 0.120 mmol) and 2a (20.6 mg, 0.100
mmol). The purification by preparative TLC on silica gel (hexane/
AcOEt = 2:1) afforded 3h (41.8 mg, 0.077 mmol, 77%) as a colorless
oil. 1H NMR (500 MHz, CDCl3) δ 1.08−1.65 (m, 10H), 2.44 (s, 3H),
2.63 (dd, J = 10.3, 7.8 Hz, 1H), 3.03 (d, J = 9.5 Hz, 1H), 3.19 (d, J =
18.5 Hz, 1H), 3.22 (t, J = 9.8 Hz, 1H), 3.39 (d, J = 18.5 Hz, 1H), 3.50
(d, J = 10.0 Hz, 1H), 3.72−3.82 (m, 2H), 7.14−7.19 (m, 2H), 7.27−
7.40 (m, 10H), 7.70 (d, J = 8.0 Hz, 2H); 13C NMR (126 MHz,
CDCl3) δ 21.51, 21.54, 21.6, 25.5, 36.7, 37.0, 48.9, 49.7, 56.0, 59.2,
61.6, 71.4, 128.0, 128.3, 128.56, 128.63, 129.3, 129.9, 130.8, 131.5,
134.1, 138.9, 144.0, 166.4, 210.5; HRMS (ESI) calcd for
C33H35NNaO4S [M + Na]+ 564.2179, found 564.2182; IR (ν/
cm−1): 3425, 2931, 1689, 1350, 1165, 756.
(4R*,5S*)-4-(2-Hydroxypropan-2-yl)-8-methyl-7-phenyl-2-
tosyl-2-azaspiro[4.4]non-7-en-6-one (3m). The general procedure
was followed using 1a (33.2 mg, 0.120 mmol) and 2e (14.6 mg, 0.101
mmol) at 0 °C. The purification by preparative TLC on silica gel
(hexane/AcOEt = 2:1) afforded 3m (38.0 mg, 0.086 mmol, 85%) as a
pale yellow solid. Mp 89−91 °C. 1H NMR (500 MHz, CDCl3) δ 1.09
(s, 3H), 1.12 (s, 3H), 2.19 (s, 3H), 2.43 (s, 3H), 2.52 (dd, J = 10.5, 8.0
Hz, 1H), 2.81 (d, J = 19.0 Hz, 1H), 2.98 (d, J = 10.0 Hz, 1H), 3.01 (d,
J = 20.5 Hz, 1H), 3.20 (t, J = 9.8 Hz, 1H), 3.39 (d, J = 10.0 Hz, 1H),
3.74−3.78 (m, 1H), 3.92 (br s, 1H), 7.20−7.24 (m, 2H), 7.31−7.36
(m, 3H), 7.37−7.42 (m, 2H), 7.68 (d, J = 8.5 Hz, 2H); 13C NMR
(75.6 MHz, CDCl3) δ 18.2, 21.5, 29.1, 29.4, 50.2, 51.4, 56.1, 59.2, 61.3,
70.4, 127.9, 128.1, 128.4, 128.9, 129.8, 130.6, 131.6, 139.9, 144.0,
171.6, 210.2; HRMS (ESI) calcd for C25H29NNaO4S [M + Na]+
462.1710, found 462.1709; IR (ν/cm−1): 3896, 3417, 2978, 1689,
1342, 1157, 756, 663.
(4R*,5S*)-4-(Hydroxydiphenylmethyl)-7,8-diphenyl-2-tosyl-
2-azaspiro[4.4]non-7-en-6-one (3i). The general procedure was
followed using 1i (47.3 mg, 0.118 mmol) and 2a (20.6 mg, 0.100
mmol). The purification by preparative TLC on silica gel (hexane/
AcOEt = 2:1) afforded 3i (33.2 mg, 0.053 mmol, 53%) as a white
solid. Mp 126−127 °C; 1H NMR (500 MHz, CDCl3) δ 2.50 (s, 3H),
3.11 (d, J = 9.5 Hz, 1H), 3.17 (dd, J = 9.8, 8.2 Hz, 1H), 3.34 (d, J =
19.5 Hz, 1H), 3.42 (t, J = 9.3 Hz, 1H), 3.53 (d, J = 9.0 Hz, 1H), 3.71
(d, J = 19.5 Hz, 1H), 3.93 (t, J = 8.5 Hz, 1H), 6.41−6.44 (m, 2H),
2743
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
(4R*,5S*)-7,8-Diphenyl-4-(prop-1-en-2-yl)-2-tosyl-2-aza-
spiro[4.4]non-7-en-6-one (5a). Toluene (0.6 mL) was added to a
Schlenk tube containing p-toluenesulfonic acid monohydrate (p-
TsOH·H2O, 1.0 mg, 5.3 μmol) and 3a (30.1 mg, 0.060 mmol) via a
syringe through the septum, and the mixture was heated at 80 °C for 4
h. The reaction mixture was passed through a plug of Florisil and
eluted with hexane−AcOEt (1:1). The eluate was concentrated under
reduced pressure, and the residue was purified by preparative TLC on
silica gel (hexane/AcOEt = 3:1) to afford 5a (23.2 mg, 0.048 mmol,
80%) as a white solid. Mp 156−158 °C. 1H NMR (500 MHz, CDCl3)
δ 1.61 (s, 3H), 2.44 (s, 3H), 2.93 (dd, J = 9.5, 7.0 Hz, 1H), 3.01−3.11
(m, 2H), 3.58−3.73 (m, 4H), 4.72 (s, 1H), 4.85 (t, J = 1.5 Hz, 1H),
7.04−7.09 (m, 2H), 7.22−7.37 (m, 10H), 7.78−7.82 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 21.6, 22.3, 43.0, 50.6, 55.1, 55.5, 114.7,
127.6, 128.0, 128.45, 128.51, 129.3, 129.7, 130.2, 131.7, 134.2, 134.7,
138.4, 140.0, 143.5, 164.1, 206.1; HRMS (ESI) calcd for
C30H29NNaO3S [M + Na]+ 506.1760, found 506.1762; IR (ν/
cm−1): 1697, 1342, 1157.
(4R*,5S*)-2-[(2-Nitrophenyl)sulfonyl]-7,8-diphenyl-4-(prop-
1-en-2-yl)-2-azaspiro[4.4]non-7-en-6-one (5b). The title com-
pound was prepared in a similar manner as described for 5a, using 3c
(31.9 mg, 0.060 mmol) to afford 5b (25.3 mg, 0.049 mmol, 82%) as a
white solid. Mp 172−175 °C. 1H NMR (500 MHz, CDCl3) δ 1.67 (s,
3H), 3.09 (dd, J = 10.7, 6.7 Hz, 1H), 3.13−3.22 (m, 2H), 3.74 (d, J =
10.0 Hz, 1H), 3.83 (dd, J = 9.0, 7.0 Hz, 1H), 3.95 (d, J = 10.0 Hz, 1H),
3.95 (dd, J = 10.8, 9.2 Hz, 1H), 4.85 (s, 1H), 4.91 (t, J = 1.5 Hz, 1H),
7.09−7.13 (m, 2H), 7.27−7.37 (m, 8H), 7.64−7.75 (m, 3H), 8.20 (dd,
J = 7.7, 1.7 Hz, 1H); 13C NMR (126 MHz, CDCl3) δ 22.2, 41.2, 50.3,
54.6, 54.9, 55.3, 115.3, 124.2, 128.1, 128.50, 128.55, 129.3, 130.31,
130.35, 131.7, 131.9, 132.3, 133.3, 134.6, 138.4, 139.1, 148.3, 164.7,
206.8; HRMS (ESI) calcd for C29H26N2NaO5S [M + Na]+ 537.1455,
found 537.1456; IR (ν/cm−1): 1704, 1350, 1165.
(4R*,5S*)-7,8-Diphenyl-4-(prop-1-en-2-yl)-2-azaspiro[4.4]-
non-7-en-6-one (6). A solution of 1-dodecanethiol (19.4 mg, 0.096
mmol) and 5b (20.6 mg, 0.040 mmol) in DMF (0.40 mL) was added
to a Schlenk tube containing Cs2CO3 (65.2 mg, 0.200 mmol) via a
syringe through the septum, and the mixture was stirred at 0 °C for 3
h. Then, the reaction mixture was concentrated under reduced
pressure, and the residue was purified by preparative TLC on silica gel
(CHCl3/MeOH/28% NH3 solution = 45:3:1) to afford 6 (11.6 mg,
0.035 mmol, 88%) as a pale yellow solid. 1H NMR (500 MHz, CDCl3)
δ 1.70 (s, 3H), 2.62 (br s, 1H), 3.02−3.08 (m, 1H), 3.11 (d, J = 18.5
Hz, 1H), 3.16 (d, J = 11.0 Hz, 1H), 3.18 (d, J = 17.5 Hz, 1H), 3.25−
3.31 (m, 1H), 3.43 (d, J = 11.5 Hz, 1H), 3.51 (t, J = 10.5 Hz, 1H), 4.82
(s, 1H), 4.86 (s, 1H), 7.14−7.19 (m, 2H), 7.26−7.36 (m, 8H); 13C
NMR (126 MHz, CDCl3) δ 22.2, 41.2, 49.8, 56.9, 57.0, 57.1, 113.9,
127.9, 128.1, 128.5, 129.3, 130.0, 132.1, 135.1, 138.6, 141.2, 165.2,
209.0; HRMS (ESI) calcd for C23H24NO [M + H]+ 330.1852, found
330.1853; IR (ν/cm−1): 2924, 1689, 1350, 694.
REFERENCES
■
(1) For reviews, see: (a) Obradors, C.; Echavarren, A. M. Acc. Chem.
Res., Article ASAP, DOI: 10.1021/ar400174p. (b) Zhang, D.-H.;
Zhang, Z.; Shi, M. Chem. Commun. 2012, 48, 10271−10279.
(c) Watson, I. D. G.; Toste, F. D. Chem. Sci 2012, 3, 2899−2919.
(d) Furstner, A. Chem. Soc. Rev. 2009, 38, 3208−3221. (e) Lee, S. I.;
̈
Chatani, N. Chem. Commun. 2009, 371−384. (f) Jimen
Echavarren, A. M. Chem. Rev. 2008, 108, 3326−3350. (g) Michelet, V.;
Toullec, P. Y.; Genet, J.-P. Angew. Chem., Int. Ed. 2008, 47, 4268−
4315. (h) Villar, H.; Frings, M.; Bolm, C. Chem. Soc. Rev. 2007, 36,
55−66. (i) Nieto-Oberhuber, C.; Lopez, S.; Jimenez-Nunez, E.;
́
ez-Nunez, E.;
́
̃
̂
́
́
́
̃
Echavarren, A. M. Chem.Eur. J. 2006, 12, 5916−5923. (j) Zhang, L.;
Sun, J.; Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271−2296.
(k) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200−203.
(l) Bruneau, C. Angew. Chem., Int. Ed. 2005, 44, 2328−2334.
(m) Diver, S. T.; Giessert, A. J. Chem. Rev. 2004, 104, 1317−1382.
(n) Echavarren, A. M.; Nevado, C. Chem. Soc. Rev. 2004, 33, 431−436.
(o) Lloyd-Jones, G. C. Org. Biomol. Chem. 2003, 1, 215−236.
(p) Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813−
834.
(2) For reviews, see: (a) Perthuisot, C.; Edelbach, B. L.; Zubris, D. L.;
Simhai, N.; Iverson, C. N.; Muller, C.; Satoh, T.; Jones, W. D. J. Mol.
̈
Catal. A: Chem. 2002, 189, 157−168. (b) Nishimura, T.; Uemura, S.
Synlett 2004, 201−216. (c) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610−
618. (d) Kondo, T.; Mitsudo, T. Chem. Lett. 2005, 34, 1462−1467.
(e) Tobisu, M.; Chatani, N. Chem. Soc. Rev. 2008, 37, 300−307.
(f) Nakao, Y.; Hiyama, T. Pure Appl. Chem. 2008, 80, 1097−1107.
(g) Seiser, T.; Cramer, N. Org. Biomol. Chem. 2009, 7, 2835−2840.
(h) Satoh, T.; Miura, M. Synthesis 2010, 3395−3409. (i) Bonesi, S. M.;
Fagnoni, M. Chem.Eur. J. 2010, 16, 13572−13589. (j) Murakami,
M.; Matsuda, T. Chem. Commun. 2011, 47, 1100−1105. (k) Aïssa, C.
Synthesis 2011, 3389−3407. (l) Ruhland, K. Eur. J. Org. Chem. 2012,
2683−2706. (m) Dong, G. Synlett 2013, 24, 1−5.
(3) (a) Noyori, R.; Umeda, I.; Takaya, H. Chem. Lett. 1972, 1189−
1190. (b) Kondo, T.; Kaneko, Y.; Taguchi, Y.; Nakamura, A.; Okada,
T.; Shiotsuki, M.; Ura, Y.; Wada, K.; Mitsudo, T. J. Am. Chem. Soc.
2002, 124, 6824−6825. (c) Wender, P. A.; Paxton, T. J.; Williams, T. J.
J. Am. Chem. Soc. 2006, 128, 14814−14815. (d) Schuster-Haberhauer,
A.; Gleiter, R.; Korner, O.; Leskovar, A.; Werz, D. B.; Fischer, F. R.;
̈
Rominger, F. Organometallics 2008, 27, 1361−1366. (e) Korner, O.;
̈
Gleiter, R.; Rominger, F. Synthesis 2009, 3259−3262. (f) Yu, S.; Li, X.
Org. Lett., Article ASAP, DOI: 10.1021/ol500140e.
(4) Matsuda, T.; Sakurai, Y. Eur. J. Org. Chem. 2013, 4219.
(5) Abbreviations: SPhos = 2-dicyclohexylphosphino-2′,6′-dimethox-
ybiphenyl; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene
(6) Product 3a was obtained in 29% yield using PtCl2 (10 mol%),
and 1,2,6,7-tetraphenyl-4-oxaspiro[2.4]hepta-1,6-dien-5-one was ob-
tained in 66% yield by the dimerization of 2a (ref 3e) when a mixture
of 1a and 2a was treated with AgNTf2 (10 mol%).
(7) The use of reagent grade DCM afforded reliable and satisfactory
results.
(8) For gold- and platinum-catalyzed hydroxy- and alkoxycyclization
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H and 13C NMR spectra of new compounds and X-
ray crystallographic data for 3b (ORTEP drawing and CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
of enynes, see: (a) Men
Am. Chem. Soc. 2000, 122, 11549−11550. (b) Nieto-Oberhuber, C.;
Munoz, M. P.; Bunuel, E.; Nevado, C.; Cardenas, D. J.; Echavarren, A.
́
dez, M.; Munoz, M. P.; Echavarren, A. M. J.
̃
́
̃
̃
M. Angew. Chem., Int. Ed. 2004, 43, 2402−2406. (c) Munoz, M. P.;
̃
Adrio, J.; Carretero, J. C.; Echavarren, A. M. Organometallics 2005, 24,
1293−1300. (d) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127,
AUTHOR INFORMATION
■
6962−6963. (e) Nieto-Oberhuber, C.; Munoz, M. P.; Lop
́
ez, S.;
ez, E.; Raducan, M.;
̃
Corresponding Author
Jimen
́
ez-Nunez, E.; Nevado, C.; Herrero-Gom
́
́
̃
*E-mail: mtd@rs.tus.ac.jp.
Echavarren, A. M. Chem.Eur. J. 2006, 12, 1677−1693. (f) Buzas, A.
Notes
K.; Istrate, F. M.; Gagosz, F. Angew. Chem., Int. Ed. 2007, 46, 1141−
̂
1144. (g) Genin, E.; Leseurre, L.; Toullec, P. Y.; Genet, J.-P.; Michelet,
The authors declare no competing financial interest.
V. Synlett 2007, 1780−1784. (h) Chao, C.-M.; Genin, E.; Toullec, P.
Y.; Genet, J.-P.; Michelet, V. J. Organomet. Chem. 2009, 694, 538−545.
(i) Sanjuan, A. M.; Martínez, A.; García-García, P.; Fernandez-
̂
ACKNOWLEDGMENTS
■
́
́
This work was supported in part by a Grant-in-Aid for Scientific
Research (C) (25410054) from MEXT, Japan.
Rodríguez, M. A.; Sanz, R. Beilstein J. Org. Chem. 2013, 9, 2242−2249.
(9) The stereochemical configuration has not been assigned.
2744
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745

The Journal of Organic Chemistry
Note
(10) When N-allyl-N-propargyltosylamine and 2a were reacted, both
the substrates were largely recovered unchanged.
(11) The regiochemistry of 3m was tentatively assigned based on
NOESY experiments.
(12) For intramolecular reactions, see: (a) Jimen
Claverie, C. K.; Nieto-Oberhuber, C.; Echavarren, A. M. Angew. Chem.,
Int. Ed. 2006, 45, 5452−5455. (b) Jimenez-Nunez, E.; Molawi, K.;
́
ez-Nunez, E.;
́
̃
́
́
̃
Echavarren, A. M. Chem. Commun. 2009, 7327−7329. (c) Huguet, N.;
Echavarren, A. M. Synlett 2012, 49−53. (d) Jin, T.; Yamamoto, Y. Org.
Lett. 2008, 10, 3137−3139. For intermolecular reactions, see:
(e) Schelwies, M.; Dempwolff, A. L.; Rominger, F.; Helmchen, G.
Angew. Chem., Int. Ed. 2007, 46, 5598−5601. (f) Escribano-Cuesta, A.;
Lop
́
ez-Carrillo, V.; Janssen, D.; Echavarren, A. M. Chem.Eur. J.
2009, 15, 5646−5650. (g) Schelwies, M.; Moser, R.; Dempwolff, A. L.;
Rominger, F.; Helmchen, G. Chem.Eur. J. 2009, 15, 10888−10900.
(h) Huple, D. B.; Liu, R.-S. Chem. Commun. 2012, 48, 10975−10977.
(i) Obradors, C.; Echavarren, A. M. Chem.Eur. J. 2013, 19, 3547−
3551.
(13) An attempted reaction of 4a with 2a under the reaction
conditions failed.
(14) Alkenylgold(I) species tend to react with an electrophile at the
α-position rather than at the β-position. See: Zhang, G.; Catalano, V.
J.; Zhang, L. J. Am. Chem. Soc. 2007, 129, 11358−11359. For example,
alkenylgold(I) species underwent nucleophilic attack at the β-carbon;
see: ref 12c, f.
(15) For examples of protodeauration of alkylgold species, see:
(a) Yang, C.-G.; He, C. J. Am. Chem. Soc. 2005, 127, 6966−6967.
(b) Han, X.; A. Widenhoefer, R. Angew. Chem., Int. Ed. 2006, 45,
1747−1749. (c) Tian, G.-Q.; Shi, M. Org. Lett. 2007, 9, 4917−4920.
(d) McGonigal, P. R.; de Leon, C.; Wang, Y.; Homs, A.; Solorio-
́
Alvarado, C. R.; Echavarren, A. M. Angew. Chem., Int. Ed. 2012, 51,
13093−13096.
(16) (a) Kan, T.; Fukuyama, T. Chem. Commun. 2004, 353−359.
(b) Kurosawa, W.; Kan, T.; Fukuyama, T. Org. Synth. 2002, 79, 186.
(17) Ricard, L.; F. Gagosz, F. Organometallics 2007, 26, 4704−4707.
(18) Wang, W.; Yang, J.; Wang, F.; Shi, M. Organometallics 2011, 30,
3859−3869.
(19) Tayama, E.; Sugai, S. Tetrahedron Lett. 2007, 48, 6163−6166.
(20) Hart-Cooper, W. M.; Clary, K. N.; Toste, F. D.; Bergamn, R. G.;
Raymond, K. N. J. Am. Chem. Soc. 2012, 134, 17873−17876.
(21) Faller, J. W.; Fontaine, P. P. J. Organomet. Chem. 2006, 691,
1912−1918.
(22) Vanos, C. M.; Lambert, T. H. Angew. Chem., Int. Ed. 2011, 50,
12222−12226.
(23) Nacsa, E. D.; Lambert, T. H. Org. Lett. 2013, 15, 38−41.
(24) Netland, K. A.; Gundersen, L.-L.; Rise, F. Synth. Commun. 2000,
30, 1767−1777.
(25) Hashmi, A. S. K.; Rudolph, M.; Siehl, H.-U.; Tanaka, M.; Bats, J.
W.; Frey, W. Chem.Eur. J. 2008, 14, 3703−3708.
(26) Comito, R. J.; Finelli, F. G.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2013, 135, 9358−9361.
(27) Rueping, M.; Leiendecker, M.; Das, A.; Poisson, T.; Bui, L.
Chem. Commun. 2011, 47, 10629−10631.
2745
dx.doi.org/10.1021/jo500045n | J. Org. Chem. 2014, 79, 2739−2745