NIS-mediated electrophilic cyclization of 3-silyloxy-1, n-enynes

Article abstract of DOI:10.1021/jo302751p

The electrophilic cyclization of 3-silyloxy-1,5-enynes and 3-silyloxy-1,6-enynes was investigated. In the presence of N-iodosuccinimide (NIS), the title compounds are transformed under metal-free conditions into five-membered carbocycles with all-carbon s

Full text of DOI:10.1021/jo302751p

Note
pubs.acs.org/joc
NIS-Mediated Electrophilic Cyclization of 3‑Silyloxy-1,n‑enynes
Florian Huber and Stefan F. Kirsch*
Organic Chemistry, Bergische Universitat Wuppertal, Gaußstr. 20, 42119 Wuppertal, Germany
̈
S
* Supporting Information
ABSTRACT: The electrophilic cyclization of 3-silyloxy-1,5-enynes and 3-
silyloxy-1,6-enynes was investigated. In the presence of N-iodosuccinimide
(NIS), the title compounds are transformed under metal-free conditions into
five-membered carbocycles with all-carbon stereogenic centers following a
sequence of iodonium activation of the triple bond, carbocyclization, and
pinacol-type 1,2-shift.
he creation of all-carbon quaternary stereogenic centers is
though both processes catalyzed by gold give rise to the same
Ta major challenge in contemporary synthetic chemis- scaffolds, iodine incorporation allows for further functionaliza-
try.1−3 In particular when these structural elements shall be
embedded in cyclic frameworks, domino reactions4−6 consist-
ing of carbocyclization and subsequent 1,2-shift have emerged
as a powerful strategy to form the desired quaternary
centers.7−13 In most cases, the 1,2-shift is designed as an
integral part of a cationic reaction cascade; the key question
then is how to initiate the cationic cyclization step. To this end,
we and others14−18 focused on the activation of alkynes to
initiate a carbocyclization/1,2-migration sequence. For exam-
ples, we showed in 2007 that, under gold catalysis,19−21 3-
silyloxy-1,5-enynes (e.g., 1a) smoothly convert into cyclo-
pentenyls via an initial 6-endo cyclization pathway (Scheme
1).22−24 The corresponding 3-silyloxy-1,6-enynes (e.g., 3a) give
the related products of an initial 6-exo cyclization having an
exocyclic double bond.25,26
tions of the scaffold by use of, for example, traditional cross-
coupling reactions; therefore, tetrasubstituted olefinic moieties
are accessible instead of only trisubstituted ones. Over the past
years it also became evident that, if classical cationic
intermediates are assumed, quite a number of processes that
were previously shown to be possible with gold catalysis can be
triggered by direct iodonium activation in the absence of gold
catalysts.32−45 As a logical extension, we speculated about the
realization of the carbocyclization/1,2-migration cascades
shown in Scheme 1 by using simple iodine electrophiles
under metal-free conditions. To investigate the iodonium-
triggered cyclization of 3-silyloxy-1,5-enynes and 3-silyloxy-1,6-
enynes,46,47 we started a research program, the results of which
are presented herein.
Our studies began with the reaction of silyl ether 1a with
several electrophilic iodine sources in the absence of transition-
metal additives. To our pleasure, we found that aldehyde 5a
containing the desired vinyl iodide moiety could be formed in
dichloromethane at room temperature in low yields (I2/
NaHCO3, 21%; ICl, 33%); in all cases, quite long reaction
times around 24 h were required to obtain full conversion of
the starting material (Scheme 2).48 After careful optimization,
best yields (i.e., 49%) for iodide 5a were obtained when using
N-iodosuccinimide (NIS) at 30 °C in dichloromethane. As also
shown in Scheme 2, the yield was further increased up to 58%
by switching the silyl group from triethylsilyl to the more labile
trimethylsilyl. We note that this observation is not analogous to
the gold-catalyzed transformations where trimethylsilyl ether
1a′ resulted in significantly lower yields than triethylsilyl ether
1a. As shown by the transformation of silyl ether 1b derived
from a tertiary alcohol, ketones (as 5b) are also produced in
moderate yield. However, it can be concluded that 3-silyloxy-
1,5-enynes can indeed undergo iodonium-triggered carbocyc-
lization/1,2-migration cascades under metal-free conditions,
albeit not as rapid and high-yielding as under the gold-catalyzed
conditions.
Scheme 1. Gold-Catalyzed Reactivities of 3-Silyloxy-1,n-
enynes
In the majority of the processes that are initiated by a
nucleophilic attack onto a gold-activated alkyne, the final step
to regenerate the catalytic species is a protodeauration of a
vinylgold intermediate.27,28 In an analogous way, several
reactions were described where vinylgold intermediates were
successfully trapped by iodine electrophiles to incorporate
iodine rather than hydrogen at the final product.29−31 Even
Received: December 20, 2012
© XXXX American Chemical Society
A
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To our surprise, cyclopentanol derived silyl ether 3j fully
decomposed under the conditions at 30 °C (Scheme 4). The
Scheme 2. Transformation of 3-Silyloxy-1,5-enynes 1a, 1a′,
and 1b
Scheme 4. Transformation of 3-Silyloxy-1,6-enynes (2)
After this proof of concept regarding 3-silyloxy-1,5-enynes,
we focused on the electrophilic conversion of 3-silyloxy-1,6-
enynes into five-membered carbocycles with an exocyclic
double bond; due to the two possible double bond isomers
that can be formed in the course of the reaction, this
transformation was believed to be more challenging. As
summarized in Scheme 3, it was found that 3-silyloxy-1,6-
expected product could be obtained only when the reaction
temperature was decreased to −6 °C, albeit in low yield. The
phenyl-substituted product 6k was obtained in 60% yield upon
reaction with NIS at 30 °C. Acyclic substrates as 3l and 3m also
gave the products where the initial 6-exo cyclization is followed
by a 1,2-alkyl migration that proceeds with ring contraction.
Notably, in the case of 3m the alternative migration of the
phenyl group was not observed.
Scheme 3. Transformation of 3-Silyloxy-1,6-enynes (1)
Scheme 5 summarizes a plausible mechanism. Coordination
of the iodine electrophile to the triple bond produces iodonium
Scheme 5. Plausible Mechanism
intermediate A, which after nucleophilic attack of the olefinic
carbon produces cyclic carbenium ion B. The anti-mode of the
initial 6-exo cyclization explains well why the exocyclic double
bond is exclusively formed with E-configuration.49 Subsequent
1,2-shift then creates the quaternary stereogenic center under
ring contraction.
In conclusion, 3-silyloxy-1,5-enynes and 3-silyloxy-1,6-enynes
with an alkyl substituent at the olefinic C2-position were
transformed into polyfunctional five-membered carbocycles by
use of NIS as a simple iodine electrophile under metal-free
conditions. The reaction likely proceeds by a mechanism
involving cyclization and subsequent 1,2-shift of the cationic
intermediate. This protocol represents a synthetically valuable
alternative to the previously reported ones on gold catalysis
enynes are smoothly converted into the iodine-containing
carbocycles under the reaction conditions (3 equiv of NIS, 30
°C, CH2Cl2). Reactions of enynes having aryl substituents at
the alkyne terminus were high-yielding with both electron-rich
and electron-poor aryls reacting equally well. Alkyl-substituted
alkynes and terminal alkynes are also converted into the bicyclic
products, although yields are slightly lower in these cases. As
exemplified by the failed attempt to convert enyne 3i, the
starting 1,6-enynes require a substituent at the olefinic C2-
position. This observation might point to a classical cationic
mechanism where the stabilization of cationic intermediates is
crucial (vide infra).
B
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Note
(73), 235 (13), 211 (65), 195 (15), 167 (23), 153 (17), 128 (17), 115
(27). HRMS m/z: 380.0628 [380.0632 calculated for C18H21OI
(M+)].
since it, for the first time, provides a general access to iodinated
carbocyclic products containing tri- and tetrasubstituted olefins.
rel-(3aR,8aS,E)-2-(Iodo(naphthalen-1-yl)methylene)-3a-
methyloctahydroazulen-4(2H)-one (6b). Compound 3b (30.2 mg,
80.2 μmol) was converted following the general procedure A (30 °C,
24 h). After flash chromatography on silica (pentanes/Et2O 9:1), 6b
(30.1 mg, 69.9 μmol, 87%) was obtained as a colorless oil: Rf = 0.2
(pentanes/Et2O 95:5), [CAM/UV]. 1H NMR (500 MHz, CDCl3,
ppm) δ = 1.13−1.19 (m, 3 H), 1.30−1.41 (m, 2 H), 1.47−1.55 (m, 1
H), 1.71−1.77 (m, 1 H), 1.83−2.05 (m, 3 H), 2.09−2.13 (m, 1 H),
2.26−2.29 (m, 1 H), 2.36−2.59 (m, 2 H), 2.67−2.71 (m, 1 H), 3.12−
3.17 (m, 1 H), 7.37−7.54 (m, 4 H), 7.77−7.96 (m, 3 H). 13C NMR
(63 MHz, CDCl3, ppm) δ = 24.7/25.0, 27.8/27.9, 30.3/30.4, 35.7/
35.8, 38.7/39.1, 40.7, 46.3, 47.8/48.1, 60.4/60.6, 88.1/88.1, 125.2/
125.2, 125.7/125.8, 126.0/126.1, 126.2/126.3, 126.3/126.5, 128.4/
128.5, 128.6, 129.9/130.1, 134.1/134.2, 140.9/141.27, 150.2/150.3,
216.5/216.6. LRMS (GC−MS) m/z [%]: 430 (4) [M+], 304 (13), 303
(56), 220 (14), 205 (71), 179 (22), 164 (20), 125 (27), 86 (86), 84
(100), 57 (28). HRMS m/z: 430.0785 [430.0788 calculated for
C22H23OI (M+)].
rel-(3aR,8aS,E)-2-(Iodo(3-methoxyphenyl)methylene)-3a-
methyloctahydroazulen-4(2H)-one (6c). Compound 3c (31.0 mg,
86.9 μmol) was converted following the general procedure A (30 °C,
24 h). After flash chromatography on silica (pentanes/Et2O 9:1), 6c
(35.1 mg, 85.5 μmol, 98%) was obtained as a colorless oil: Rf = 0.12
(pentanes/Et2O 9:1), [CAM/UV]. 1H NMR (250 MHz, CDCl3,
ppm) δ = 1.14 (s, 3 H), 1.36−1.72 (m, 4 H), 1.90−2.08 (m, 3 H),
2.23−2.35 (m, 3 H), 2.67−2.76 (m, 2 H), 2.95−3.07 (m, 1 H), 3.80
(s, 3 H), 6.75−6.89 (m, 3 H), 7.17−7.26 (m, 1 H). 13C NMR (91
MHz, CDCl3, ppm) δ = 24.8, 27.9, 30.4, 35.7, 39.4, 40.7, 46.0, 49.1,
55.4, 60.6, 91.4, 113.4, 114.7, 121.3, 129.3, 144.9, 148.4, 159.3, 216.6.
LRMS (GC−MS) m/z [%]: 410 (21) [M+], 304 (26), 303 (100), 283
(32), 179 (39), 165 (36), 125 (40). HRMS m/z: 410.0731 [410.0737
calculated for C19H23O2I (M+)].
EXPERIMENTAL SECTION
■
General. All reactions were carried out in sealed reaction vials. All
commercial reagents were used as received. Thin-layer chromatog-
raphy (TLC) was conducted with precoated glass-backed plates and
visualized by exposure to UV light (254 nm) or stained with ceric
ammonium molybdate (CAM). Flash chromatography was performed
with silica gel (43−60 μm); the eluent used is reported in parentheses.
1H NMR spectra were recorded on 600 MHz FT-NMR, 500 MHz FT-
NMR, 400 MHz FT-NMR, 360 MHz FT-NMR, and 250 MHz FT-
NMR spectrometers. 13C NMR spectra were recorded at 151, 126,
101, 91, or 63 MHz. Chemical shifts are reported in ppm relative to
solvent signal. Multiplicity is indicated as follows: s (singlet); d
(doublet); t (triplet); q (quartet); m (multiplet); dd (doublet of
doublets). Low resolution mass spectra were recorded applying GC−
MS, EI or ESI techniques. High resolution mass spectra were obtained
using ESI or APCI ionization methods on a MicroTOF. The
compounds 1a, 1a′, 3a, 3b, 3f, and 3g were reported earlier.23,25
The remaining substrates 1 and 3 were synthesized in a fully analogous
way.
General Procedure A for the Electrophilic Cyclization. rel-
(3aR,7aS)-2-Iodo-3-phenyl-3a,4,5,6,7,7a-hexahydro-1H-in-
dene-7a-carbaldehyde (5a). Compound 1a′ (32.8 mg, 0.11 mmol)
was dissolved in 1.1 mL of dichloromethane, and N-iodosuccinimide
(NIS; 74.2 mg, 0.33 mmol) was added at once. The mixture was
stirred at the given temperature (30 °C, 24 h) until TLC indicated full
conversion. The reaction was quenched by addition of 20 mL of a
saturated aqueous Na2S2O3 solution. The reaction mixture was
extracted with Et2O (3 × 20 mL). The combined organic phases
were washed with brine and dried over MgSO4. The solvent was
evaporated, and the residue was purified by flash chromatography on
silica (pentanes/Et2O 98:2) to give compound 5a (22.6 mg, 64.2
μmol, 58%) as a colorless oil; Rf = 0.32 (pentanes/Et2O 95:5), [UV].
1H NMR (400 MHz, CDCl3, ppm) δ = 1.23−1.36 (m, 2 H), 1.44−
1.53 (m, 3 H), 1.64−1.71 (m, 2 H), 1.82−1.88 (m, 1 H), 2.73 (dd, J =
16.0, 1.7 Hz, 1 H), 3.04 (dd, J = 16.0, 1.9 Hz, 1 H), 3.27 (t, J = 6.2 Hz,
1 H), 7.34−7.42 (m, 5 H), 9.66 (s, 1 H). 13C NMR (101 MHz,
CDCl3, ppm) δ = 21.6, 21.7, 26.4, 27.6, 47.1, 50.1, 57.0, 89.0, 127.9,
128.0, 128.2, 136.5, 151.3, 203.5. The analytical data are in accordance
with those previously reported.23
rel-1-(3aR,7aS)-(2-Iodo-3-phenyl-3a,4,5,6,7,7a-hexahydro-
1H-inden-7a-yl)ethanone (5b). Compound 1b (31.4 mg, 100
μmol) was converted following the general procedure A (30 °C, 24 h).
After flash chromatography on silica (pentanes/Et2O 95:5), 5b (18.0
mg, 49.1 μmol, 49%) was obtained as a colorless oil: Rf = 0.21
(pentanes/Et2O 95:5), [CAM/UV]. 1H NMR (400 MHz, CDCl3,
ppm) δ = 1.13−1.17 (m, 3 H), 1.48−1.56 (m, 2 H), 1.63−1.71 (m, 1
H), 1.80 (ddd, J = 14.2, 10.5, 3.8 Hz, 1 H), 1.94−1.99 (m, 1 H), 2.24
(s, 3 H), 2.73 (dd, J = 15.7, 1.8 Hz, 1 H), 3.01 (dd, J = 15.7, 2.8 Hz, 1
H) 3.53−3.55 (m, 1 H), 7.31−7.35 (m, 3 H), 7.38−7.42 (m, 2 H). 13C
NMR (101 MHz, CDCl3, ppm) δ = 21.8, 21.9, 25.2, 25.8, 31.0, 47.3,
53.4, 58.9, 88.2, 127.7, 128.0, 128.2, 136.9, 151.8, 210.6. LRMS (GC−
MS) m/z [%]: 254 (7), 239 (14) [M+ − I], 197 (8), 165 (11), 127
(100), 115 (16), 77 (10). HRMS m/z: 389.0358 [389.0373 calculated
for C17H19OINa (M + Na+)].
rel-(3aR,8aS,E)-2-(Iodo(phenyl)methylene)-3a-methyl-
octahydroazulen-4(2H)-one (6a). Compound 3a (30.0 mg, 91.9
μmol) was converted following the general procedure A (30 °C, 24 h).
After flash chromatography on silica (pentanes/Et2O 95:5), 6a (28.2
mg, 74.2 μmol, 80%) was obtained as a colorless oil: Rf = 0.35
(pentanes/Et2O 9:1), [CAM/UV]. 1H NMR (500 MHz, CDCl3,
ppm) δ = 1.13 (s, 3 H), 1.31−1.53 (m, 3 H), 1.66−1.70 (m, 1 H),
1.90−1.93 (m, 2 H), 2.02−2.06 (m, 1 H), 2.23−2.33 (m, 3 H), 2.68−
2.76 (m, 2 H), 2.99−3.05 (m, 1 H), 7.19−7.22 (m, 1 H), 7.26−7.29
(m, 4 H). 13C NMR (63 MHz, CDCl3, ppm) δ = 24.8, 27.9, 30.4, 35.8,
39.3, 40.7, 46.0, 49.2, 60.7, 91.8, 127.7, 128.3, 129.0, 143.6, 148.3,
216.6. LRMS (GC−MS) m/z [%]: 380 (100) [M+], 323 (10), 253
rel-(3aR,8aS,E)-2-(Iodo(4-nitrophenyl)methylene)-3a-
methyloctahydroazulen-4(2H)-one (6d). Compound 3d (27.3 mg,
73.5 μmol) was converted following the general procedure A (30 °C,
24 h). After flash chromatography on silica (pentanes/Et2O 9:1), 6d
(30.6 mg, 72.0 μmol, 98%) was obtained as a colorless oil: Rf = 0.28
(pentanes/Et2O 8:2), [CAM/UV]. 1H NMR (250 MHz, CDCl3,
ppm) δ = 1.14 (s, 3 H), 1.35−1.48 (m, 2 H), 1.54−1.73 (m, 2 H),
1.89−1.98 (m, 2 H), 2.07 (t, J = 9.6 Hz, 1 H), 2.19 (d, J = 17.3 Hz, 1
H), 2.27−2.34 (m, 2 H), 2.66−2.82 (m, 2 H), 3.05 (ddd, J = 18.6, 8.5,
2.7 Hz, 1 H), 7.46 (d, J = 8.9 Hz, 2 H), 8.16 (d, J = 8.9 Hz, 2 H). 13C
NMR (63 MHz, CDCl3, ppm) δ = 24.8, 27.9, 30.3, 35.7, 39.7, 40.6,
45.9, 49.4, 60.8, 87.9, 123.7, 130.0, 146.9, 149.8, 151.5, 216.1. LRMS
(GC−MS) m/z [%]: 425 (100) [M+], 410 (15), 368 (38), 298 (27),
280 (13), 256 (94), 239 (17), 209 (15), 165 (29), 152 (23), 115 (13).
HRMS m/z: 425.0475 [425.0482 calculated for C18H20O3NI (M+)].
rel-(3aR,8aS,E)-2-(1-Iodo-2-((triethylsilyl)oxy)ethylidene)-3a-
methyloctahydroazulen-4(2H)-one (6e). Compound 3e (30.1 mg,
76.3 μmol) was converted following the general procedure A (30 °C,
24 h). After flash chromatography on silica (pentanes/Et2O 98:2), 6e
(29.0 mg, 64.7 μmol, 86%) was obtained as a colorless oil: Rf = 0.14
1
(pentanes/Et2O 95:5), [CAM]. H NMR (250 MHz, CDCl3, ppm) δ
= 0.64 (q, J = 7.4 Hz, 6 H), 0.98 (t, J = 7.9 Hz, 9 H), 1.17 (s, 3 H),
1.37−1.62 (m, 4 H), 1.85−2.00 (m, 3 H), 2.16−2.47 (m, 3 H), 2.68−
2.90 (m, 3 H), 4.31 (d, J = 12.2 Hz, 1 H), 4.22 (d, J = 12.6 Hz, 1 H).
13C NMR (63 MHz, CDCl3, ppm) δ = 4.7, 7.0, 25.2, 27.9, 30.4, 35.5,
38.2, 40.8, 45.5, 48.5, 60.6, 67.5, 99.3, 146.9, 216.8. LRMS (GC−MS)
m/z [%]: 419 (12) [M+ − C2H5], 321 (7), 316 (22), 299 (8), 190
(15), 189 (100), 161 (22), 91 (18), 75 (19). HRMS m/z: 419.0895
[419.0898 calculated for C17H28O2ISi (M+ − C2H5)].
rel-(3aR,8aS,E)-2-(1-Iodoethylidene)-3a-methyloctahydro-
azulen-4(2H)-one (6f). Compound 3f (30.7 mg, 116 μmol) was
converted following the general procedure A (30 °C, 24 h). After flash
chromatography on silica (pentanes/Et2O 98:2), 6f (30.6 mg, 96.2
μmol, 83%) was obtained as a colorless oil: Rf = 0.45 (pentanes/Et2O
8:2), [CAM]. 1H NMR (250 MHz, CDCl3, ppm) δ = 1.17−1.31 (m, 4
C
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Note
H), 1.37−1.62 (m, 3 H), 1.84−1−99 (m, 3 H), 2.10−2.17 (m, 1 H),
2.30−2.43 (m, 5 H), 2.65−2.88 (m, 3 H). 13C NMR (63 MHz, CDCl3,
ppm) δ = 25.3, 27.9, 30.3, 30.4, 35.5, 37.7, 40.8, 46.1, 48.3, 60.7, 89.6,
144.7, 217.1. LRMS (GC−MS) m/z [%]:318 (100) [M+], 303 (25),
261 (30), 191 (36), 148 (36), 147 (25), 105 (27), 91 (35), 44 (42).
HRMS m/z: 318.0474 [318.0481 calculated for C13H19OI (M+)].
rel-(3aR,8aS,E)-2-(Iodomethylene)-3a-methyloctahydro-
azulen-4(2H)-one (6g). Compound 3g (35.7 mg, 122 μmol) was
converted following the general procedure A (30 °C, 24 h). After flash
chromatography on silica (pentanes/Et2O 95:5), 6g (28.3 mg, 93.0
μmol, 76%) was obtained as a colorless oil: Rf = 0.1 (pentanes/Et2O
71.0, 155.2, 204.6. LRMS (GC−MS) m/z [%]:290 (79) [M+], 272
(4), 261 (6), 248 (4), 233 (4), 219 (4), 163 (100), 145 (23), 135 (15),
91 (50). HRMS m/z: 290.0157 [290.0162 calculated for C11H15OI
(M+)].
(E)-(3-(Iodo(3-methoxyphenyl)methylene)-1-methylcyclo-
pentyl)(phenyl)methanone (6m). Compound 3m (30.6 mg, 80.8
μmol) was converted following the general procedure A (30 °C, 24 h).
After flash chromatography on silica (pentanes/Et2O 95:5), 6m (20.0
mg, 46.3 μmol, 57%) was obtained as a colorless oil: Rf = 0.21
(pentanes/Et2O 95:5), [CAM/UV]. 1H NMR (500 MHz, CDCl3,
ppm) δ = 1.39 (s, 3 H), 1.98−2.04 (m, 1 H), 2.35−2.39 (m, 1 H),
2.41−2.45 (m, 1 H), 2.54−2.66 (m, 2 H), 3.01 (d, J = 16.6 Hz, 1 H),
3.80 (s, 3 H), 6.76−6.78 (m, 1 H), 6.83−6.84 (m, 1 H), 6.85−6.87
(m, 1 H), 7.20 (t, J = 7.9 Hz, 1 H), 7.39−7.42 (m, 2 H), 7.47−7.50
(m, 1 H), 7.76−7.78 (m, 2 H). 13C NMR (63 MHz, CDCl3, ppm) δ =
24.6, 36.1, 39.6, 44.2, 55.4, 56.6, 91.2, 113.5, 114.5, 121.2, 128.4, 128.7,
129.3, 132.0, 136.9, 145.1, 149.4, 159.4, 205.7. LRMS (GC−MS) m/z
[%]: 432 (34) [M+], 327 (4), 305 (88), 287 (8), 263 (20), 200 (8),
185 (12), 145 (16), 105 (100), 77 (21). HRMS m/z: 432.0574
[432.0581 calculated for C21H21O2I (M+)].
1
98:2), [CAM]. H NMR (500 MHz, CDCl3, ppm) δ = 1.16 (s, 3 H),
1.21−1.30 (m, 1 H), 1.37−1.51 (m, 2 H), 1.58−1.62 (m, 1 H), 1.86−
1.94 (m, 2 H), 2.01−2.05 (m, 1 H), 2.07−2.11 (m, 1 H), 2.26−2.29
(m, 1 H), 2.32−2.35 (m, 1 H), 2.70−2.78 (m, 3 H), 5.93 (m, 1 H).
13C NMR (63 MHz, CDCl3, ppm) δ = 24.9, 27.9, 30.4, 35.7, 40.7,
41.2, 44.7, 46.2, 60.3, 70.4, 152.6, 216.4. LRMS (GC−MS) m/z [%]:
304 (33) [M+], 247 (28), 177 (31), 159 (20), 105 (25), 91 (100), 77
(48). HRMS m/z: 305.0396 [305.0397 calculated for C12H18OI (M +
H+)]
rel-(6aS,11aS,E)-5-(Iodomethylene)decahydro-1H-benzo[c]-
azulen-11(2H)-one (6h). Compound 3h (29.8 mg, 103 μmol) was
converted following the general procedure A (30 °C, 24 h). After flash
chromatography on silica (pentanes/Et2O 95:5), 6h (28.2 mg, 81.9
μmol, 80%) was obtained as a colorless oil: Rf = 0.27 (petrolether/
((2-(Cyclohex-1-en-1-yl)-5-phenylpent-4-yn-2-yl)oxy)tri-
methylsilane (1b). Rf = 0.83 (pentanes/ethylacetate 8:2), [CAM/
UV]. 1H NMR (400 MHz, CDCl3, ppm) δ = 0.16 (s, 9 H), 1.54 (s, 3
H), 1.58−1.69 (m, 4 H), 2.09−2.11 (m, 4 H), 2.61−2.72 (m, 2 H),
5.76−5.78 (m, 1 H), 7.28−7.31 (m, 3 H), 7.38−7.41 (m, 2 H). 13C
NMR (100 MHz, CDCl3, ppm) δ = 2.3, 22.4, 23.1, 24.3, 25.3, 26.3,
33.9, 77.5, 82.4, 87.9, 121.3, 124.2, 127.4, 128.2, 131.5, 141.4. LRMS
(GC−MS) m/z [%]: 312 (2) [M+], 198 (17), 197 (100), 115 (8), 73
(57). HRMS m/z: 335.1799 [335.1802 calculated for C20H28OSiNa
(M + Na+)].
1
Et2O 95:5), [CAM]. H NMR (400 MHz, CDCl3, ppm) δ = 0.96−
1.08 (m, 1 H), 1.15−1.49 (m, 8 H), 1.84−1.94 (m, 5 H), 2.00−2.06
(m, 2 H), 2.21−2.25 (m, 1 H), 2.75−2.87 (m, 3 H), 5.86−5.88 (m, 1
H). 13C NMR (101 MHz, CDCl3, ppm) δ = 20.9, 22.7, 23.6, 28.3,
30.5, 31.7, 34.9, 39.7, 43.8, 44.4, 44.6, 62.4, 70.2, 154.9, 215.9. LRMS
(GC−MS) m/z [%]: 344 (41) [M+], 326 (16), 287 (47), 217 (100),
199 (21), 91 (20). HRMS m/z: 367.0527 [367.0529 calculated for
C15H21OINa (M + Na+)].
rel-(1R,2R)-2-(3-(3-Methoxyphenyl)prop-2-yn-1-yl)-1-(prop-
1-en-2-yl)cyclohexyl)oxy)trimethylsilane (3c). Rf = 0.35 (pen-
1
tanes/Et2O 99:1), [CAM]. H NMR (250 MHz, CDCl3, ppm) δ =
0.10 (s, 9 H), 1.48 (s, 3 H), 2.04−2.23 (m, 1 H), 2.32−2.52 (m, 3 H),
3.82 (s, 3 H), 5.03−5.04 (m, 1 H), 5.39 (m, 1 H), 6.83−6.88 (m, 1 H),
6.94−7.02 (m, 2 H), 7.18−7.43 (m, 6 H). 13C NMR (63 MHz, CDCl3,
ppm) δ = 1.9, 12.4, 19.5, 38.0, 55.4, 80.4, 81.0, 90.6, 111.6, 114.3,
116.6, 124.3, 125.2, 126.3, 127.0, 128.1, 129.3, 144.6, 148.8, 159.4.
LRMS (GC−MS) m/z [%]: 378 (48) [M+], 363 (81), 350 (15), 337
(56), 323 (40), 301 (29), 288 (19), 273 (29), 260 (21), 219 (92), 186
(23), 145 (56), 115 (25), 73 (100). HRMS (APCI) m/z: 357.2223
[357.2244 calculated for C22H33O2Si (M + H+)].
rel-Trimethyl(((1R,2R)-2-(3-(4-nitrophenyl)prop-2-yn-1-yl)-1-
(isopropenyl)-cyclohexyl)oxy)silane (3d). Rf = 0.68 (pentanes/
Et2O 95:5), [CAM/UV]. 1H NMR (250 MHz, CDCl3, ppm) δ = 0.17
(m, 9 H), 1.27−1.51 (m, 2 H), 1.55−1.78 (m, 9 H), 1.88−1.94 (m, 1
H), 2.20 (dd, J = 17.4, 10.3 Hz, 1 H), 2.53 (dd, J = 17.4, 3.6 Hz, 1 H),
4.93−4.94 (m, 1 H), 5.03−5.04 (m, 1 H), 7.49 (d, J = 8.9 Hz, 2 H),
8.14 (d, J = 8.9 Hz, 2 H). 13C NMR (63 MHz, CDCl3, ppm) δ = 3.0,
20.6, 20.7, 21.9, 25.5, 27.0, 35.5, 42.7, 79.9, 81.3, 97.8, 112.2, 123.6,
131.7, 132.3, 146.6, 149.0. LRMS (GC−MS) m/z [%]: 371 (48) [M+],
356 (54), 328 (75), 314 (29), 300 (17), 266 (17), 169 (23), 73 (100).
HRMS m/z: 372.1995 [372.1990 calculated for C21H30O3NSi (M +
H+)].
rel-(3aS,7aR,E)-2-(Iodomethylene)-3a-methylhexahydro-1H-
inden-4(2H)-one (6j). Compound 3j (23.1 mg, 97.7 μmol) was
converted following the general procedure A (−6 °C, 24 h). After flash
chromatography on silica (pentanes/Et2O 98:2), 6j (6.8 mg, 23.4
μmol, 24%) was obtained as a colorless oil: Rf = 0.28 (pentanes/Et2O
1
9:1), [CAM]. H NMR (500 MHz, CDCl3, ppm) δ = 1.20 (s, 3 H),
1.60−1.67 (m, 1 H), 1.80−1.87 (m, 1 H), 1.91−1.97 (m, 2 H), 2.00−
2.03 (m, 1 H), 2.08−2.14 (m, 1 H), 2.26−2.31 (m, 1 H), 2.32−2.36
(m, 1 H), 2.42−2.50 (m, 2 H), 3.09 (d, J = 16.2 Hz, 1 H), 5.96−5.97
(m, 1 H). 13C NMR (126 MHz, CDCl3, ppm) δ = 22.9, 23.6, 25.9,
38.1, 41.4, 43.6, 48.0, 56.5, 71.0, 152.0, 214.2. LRMS (GC−MS) m/z
[%]: 290 (100) [M+], 275 (42), 247 (15), 232 (27), 219 (4), 205 (6),
163 (19), 145 (8), 105 (19), 91 (21). HRMS m/z: 290.0161
[290.0162 calculated for C11H15OI (M+)].
rel-(3aS,7aR,E)-2-(Iodo(phenyl)methylene)-3a-methyl-
hexahydro-1H-inden-4(2H)-one (6k). Compound 3k (32.5 mg,
104 μmol) was converted following the general procedure A (30 °C,
24 h). After flash chromatography on silica (pentanes/Et2O 9:1), 6k
(22.8 mg, 62.3 μmol, 60%) was obtained as a colorless oil: Rf = 0.32
1
(petrolether/Et2O 8:2), [CAM/UV]. H NMR (600 MHz, CDCl3,
ppm) δ = 1.19 (s, 3 H), 1.71−1.74 (m, 1 H), 1.88−1.92 (m, 1 H),
1.96−2.04 (m, 3 H), 2.33−2.39 (m, 2 H), 2.47−2.51 (m, 1 H), 2.64−
2.73 (m, 1 H), 3.11 (dd, J = 16.6, 1.7 Hz, 1 H), 7.23−7.36 (m, 5 H).
13C NMR (151 MHz, CDCl3, ppm) δ = 22.9, 23.4, 25.6, 38.0, 41.8,
rel-Triethyl((4-((1R,2R)-2-(isopropenyl)-2-((trimethylsilyl)-
oxy)cyclohexyl)but-2-yn-1-yl)oxy)silane (3e). Rf = 0.72 (pen-
1
tanes/Et2O 98:2), [CAM]. H NMR (250 MHz, CDCl3, ppm) δ =
0.13−0.16 (m, 9 H), 0.64 (q, J = 7.8 Hz, 6 H), 0.97 (t, J = 7.9 Hz, 9
H), 1.22−1.40 (m, 2 H), 1.50−1.72 (m, 9 H), 1.87−1.99 (m, 2 H),
2.28 (ddd, J = 17.0, 5.3, 2.3 Hz, 1 H), 4.28 (t, J = 2.2 Hz, 2 H), 4.88−
4.89 (m, 1 H), 4.97 (m, 1 H). 13C NMR (63 MHz, CDCl3, ppm) δ =
2.9, 4.7, 6.9, 19.7, 20.5, 22.1, 25.5, 26.8, 35.6, 42.7, 51.8, 79.0, 81.4,
85.9, 111.9, 149.2. LRMS (GC−MS) m/z [%]: 394 (6) [M+], 379
(13), 351 (13), 337 (13), 262 (23), 247 (27), 233 (13), 219 (25), 197
(100), 169 (17), 147 (17), 73 (52). HRMS m/z: 417.2616 [417.2616
calculated for C22H42O2NaSi2 (M + Na+)].
rel-Trimethyl(((1R,2R)2-(prop-2-yn-1-yl)-[1,1′-bi(cyclo-
hexan)]-1′-en-1-yl)oxy)silane (3h). Rf = 0.35 (petrolether),
[CAM]. 1H NMR (400 MHz, CDCl3, ppm) δ = 0.15 (s, 9 H),
1.34−1.72 (m, 12 H), 1.85−1.97 (m, 5 H), 2.06−2.11 (m, 2 H), 2.31
45.4, 47.7, 56.7, 91.5, 127.6, 128.2, 128.7, 143.7, 147.8, 213.8. LRMS
(GC−MS) m/z [%]: 366 (25) [M+], 240 (62), 239 (100), 197 (34),
181 (47), 155 (30), 115 (49), 91 (42). HRMS m/z: 389.0372
[389.0373 calculated for C17H19OINa (M + Na+)].
rel-(3aS,7aR,E)-1-(Iodomethylene)octahydro-1H-indene-3a-
carbaldehyde (6l). 3l (31.5 mg, 133 μmol) was converted following
the general procedure A (30 °C, 4 h). After flash chromatography on
silica (pentanes/Et2O 95:5), 6l (7.9 mg, 27.2 μmol, 20%) was obtained
1
as a colorless oil: Rf = 0.33 (pentanes/Et2O 95:5), [CAM]. H NMR
(500 MHz, CDCl3, ppm) δ = 1.28−1.38 (m, 4 H), 1.49−1.55 (m, 2
H), 1.59−1.64 (m, 1 H), 1.76−1.85 (m, 3 H), 2.39−2.43 (m, 2 H),
2.81 (s, 1 H), 5.95 (q, J = 2.5 Hz, 1 H), 9.49 (s, 1 H). 13C NMR (63
MHz, CDCl3, ppm) δ = 21.0, 22.4, 25.1, 26.5, 29.8, 34.9, 46.6, 57.9,
D
dx.doi.org/10.1021/jo302751p | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(dt, J = 6.3 Hz, 3.4 Hz, 1 H), 5.69−5.70 (m, 1 H). 13C NMR (101
MHz, CDCl3, ppm) δ = 2.8, 19.2, 22.0, 22.4, 23.3, 25.1, 25.2, 25.7,
26.6, 35.1, 42.5, 68.2, 80.8, 85.5, 122.04, 140.4. LRMS (GC−MS) m/z
[%]: 290 (18) [M+], 247 (100), 233 (35), 209 (89), 181 (18), 91
(23), 73 (84). HRMS (APCI) m/z: 291.2111 [291.2139 calculated for
C18H31OSi (M + H+)].
rel-Trimethyl(((1R,2R)-1-(isopropenyl)-2-(prop-2-yn-1-yl)-
cyclopentyl)oxy)silane (3j). Rf = 0.37 (pentanes), [CAM]. 1H NMR
(360 MHz, CDCl3, ppm) δ = 0.09−0.11 (m, 9 H), 1.50−1.69 (m, 2
H), 1.73−1.82 (m, 5 H), 1.86−2.09 (m, 5 H), 2.21−2.28 (m, 1 H),
4.87−4.97 (m, 2 H). 13C NMR (63 MHz, CDCl3, ppm) δ = 2.1, 17.8,
19.9, 21.7, 29.5, 36.8, 47.7, 67.8, 85.4, 86.0, 111.8, 147.7. LRMS (GC−
MS) m/z [%]: 235 (4) [M+ - H], 221 (46), 207 (25), 193 (63), 181
(25), 169 (25), 155 (15), 131 (19), 73 (100). HRMS (APCI) m/z:
237.1652 [237.1669 calculated for C14H25OSi (M + H+)].
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((1-(Cyclohex-1-en-1-yl)pent-4-yn-1-yl)oxy)trimethylsilane
(3l). Rf = 0.15 (pentanes), [CAM]. 1H NMR (250 MHz, CDCl3, ppm)
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1.92 (t, J = 2.7 Hz, 1 H), 2.00−2.08 (m, 3 H), 2.15−2.22 (m, 2 H),
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((7-(3-Methoxyphenyl)-2-methyl-3-phenylhept-1-en-6-yn-3-
yl)oxy)trimethylsilane (3m). Rf = 0.35 (pentanes/Et2O 99:1),
[CAM]. 1H NMR (250 MHz, CDCl3, ppm) δ = 0.10 (s, 9 H), 1.48 (s,
3 H), 2.04−2.23 (m, 1 H), 2.32−2.52 (m, 3 H), 3.82 (s, 3 H), 5.03−
5.04 (m, 1 H), 5.39 (m, 1 H), 6.83−6.88 (m, 1 H), 6.94−7.02 (m, 2
H), 7.18−7.43 (m, 6 H). 13C NMR (63 MHz, CDCl3, ppm) δ = 1.9,
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126.3, 127.0, 128.1, 129.3, 144.6, 148.8, 159.4. LRMS (GC−MS) m/z
[%]: 378 (48) [M+], 363 (81), 350 (15), 337 (56), 323 (40), 301
(29), 288 (19), 273 (29), 260 (21), 219 (92), 186 (23), 145 (56), 115
(25), 73 (100). HRMS m/z: 378.2003 [378.2010 calculated for
C24H30O2Si (M+)].
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of all and 2D-NMR data of selected
examples. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: sfkirsch@uni-wuppertal.de.
Notes
The authors declare no competing financial interest.
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̈
ACKNOWLEDGMENTS
■
We gratefully acknowledge the opening works of Dr. Benedikt
Crone. The research was supported by Deutsche Forschungs-
gemeinschaft (DFG) and Fonds der Chemischen Industrie
(FCI).
Gonzal
Int. Ed. 1998, 37, 3136.
́
ez, J. M.; García-Rodríguez, E.; García-Granda, S. Angew. Chem.,
E
dx.doi.org/10.1021/jo302751p | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
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(48) Other products were not identified from the reaction mixture.
(49) The structures of the products were established by analysis of
1H−1H COSY, HMBC, and NOESY data.
F
dx.doi.org/10.1021/jo302751p | J. Org. Chem. XXXX, XXX, XXX−XXX