Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl Enol Ethers

Article abstract of DOI:10.1021/acs.joc.6b01016

Visible-light-promoted oxidative [4 + 2] cycloadditions of μ,3-unsaturated silyl enol ethers have been developed to efficiently and diastereoselectively construct polycyclic skeletons under mild conditions. The diastereoselectivities were dependent on the stereoconfiguration of silyl enol ether, substitutions on the link, as well as electric properties of substitutions on aryl rings. The intermediates could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron oxidation of the silyl enol ether.

Full text of DOI:10.1021/acs.joc.6b01016

Note
pubs.acs.org/joc
Visible-Light-Promoted Oxidative [4 + 2] Cycloadditions of Aryl Silyl
Enol Ethers
Bo Yang and Zhan Lu*
Department of Chemistry, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, China
S
* Supporting Information
ABSTRACT: Visible-light-promoted oxidative [4 + 2] cyclo-
additions of ε,3-unsaturated silyl enol ethers have been
developed to efficiently and diastereoselectively construct
polycyclic skeletons under mild conditions. The diastereose-
lectivities were dependent on the stereoconfiguration of silyl
enol ether, substitutions on the link, as well as electric
properties of substitutions on aryl rings. The intermediates
could be trapped by TEMPO, oxygen or methanol. Mechanistic studies indicated the reaction was initiated by one-electron
oxidation of the silyl enol ether.
olycyclic cyclohexanone is a core skeleton in natural
products (Scheme 1).1 Biogenetically, it can be hypothe-
strategy is the reactions of the corresponding Grignard reagent
with arylaldehydes following oxidation by PCC to give 1a.
The reaction of ε,3-unsaturated enol silyl ether 2a in the
presence of Ru(bpy)3(PF6)2 as photosentisizer and dioxygen as
a terminal oxidant using 4 Å MS as a desiccant under the
irradiation of 18W CFL in a solution of methanol afforded the
desired cycloaddition product 3a but only in 8% yield (entry 1,
Table 1). Various oxidants such as TBHP, m-CPBA, Na2S2O8,
(NH4)2S2O8 were used instead of dioxygen, (NH4)2S2O8 is
particularly suitable to afford 3a in 91% yield with 5:1 dr (entry
5).9 Using iridium-photosentisizers or organic dyes instead of
Ru(bpy)3(PF6)2, rare products were observed (entries 6−9).
Interestingly, the Fe(phen)3(PF6)2 as a visible light photo-
sentisizer10 could promote the cycloaddition to give 3a in 23%
yield (entry 10). Additionally, acetone, acetonitrile, dichloro-
methane, dimethylformamide, and dimethyl sulfoxide were
used as solvents to dramatically inhibit reactions. The control
experiments indicated that all essentials such as photosentisier,
(NH4)2S2O8, or visible light were necessary.
With optimal conditions in hands, the scope of the substrates
was shown in Table 2. The reaction of para-mehoxy substrate
2b afforded 3b in 75% yield with 7:1 dr. Due to difficult
separation of two diastereoisomers, the condensation reaction
of the crude mixture with 2,4-dinitrophenylhydrazine followed
by filtrated and washed by methanol gave the pure major
condensation product 4b in 61% isolated yield. When meta-
methoxyphenyl silyl enol ether 2c was subjected to this process,
two regioisomers were isolated in 66% and 23% yields,
respectively, with excellent diastereoselectivities. Steric hin-
dered othro-methoxy substitution 2d was also tolerated to
generate 3d in 55% yield with 20:1 dr. Various silyl protecting
groups were investigated that the larger silyl groups were used,
P
sized that the phenyl substituted enols formed by enolization of
ε,3-unsaturated 1,3-dicarbonyl compounds undergo an intra-
molecular cyclization followed by oxidation of intermediates.1g
Oxidative [4 + 2] cycloaddition is one of the useful methods
to construct this structure (Scheme 2). The Diels−Alder
reactions of both electron-rich dienes and alkenes are
forbidden. When the electron-rich diene was oxidized to be
radical cation whose HOMO did match with the LUMO of
electron-rich alkenes, the formal [4 + 2] reaction could undergo
smoothly following by one-electron oxidation of the
intermediate to give the cyclization product. Snider reported
an elegant oxidative cyclization of ε,3-unsaturated silyl enol
ethers using the stoichiometric amount of copper(II) or
cerium(IV).2 Visible light as a clean reagent has been shown
wide utility in organic synthesis.3 [4 + 2] Cycloaddition
reactions could be also promoted by visible light through a
redox-neutral pathway.4 However, to the best of our knowl-
edge, visible light promoted oxidative [4 + 2] cycloaddition
reactions are still limited. Our group has previously reported a
visible light-promoted nitro-initiated [3 + 2] cycloaddition via
one-electron reduction process.5 Inspired by the biogenetic
process and oxidative cycloadditions, here, we reported a
visible-light-promoted oxidative [4 + 2] cycloaddition of ε,3-
unsaturated silyl enol ethers initiated by one-electron oxidation
process.
We chose silyl enol 2a as a model substrate6 which could be
easily obtained from the corresponding phenyl ketone 1a
through deprotonation by LDA and then trapped by
trifluoromethanesulfonic acid tert-butyldimethylsilyl ester
(TBDMSOTf) (Scheme 3). The synthesis using known
procedures was starting from commercially available tetrahy-
dro-2-pyran through bromination, oxidation7 and wittig
reaction8 to afford S2. The corresponding Grignard reagent
prepared by S2 and meganisum turnings in Et2O reacted with
acyl chloride in the prescence of CuI to give 1a. Another
Special Issue: Photocatalysis
Received: May 2, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
Scheme 1. Selected Natural Products Containing Polycyclic Cyclohexanone
Scheme 2. Oxidative [4 + 2] Cycloadditions
Table 1. Optimizations
a
entry
photocatalyst
oxidant
O2
solvent
yield (%)
1
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ir(ppy)3
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
DCM
8
2
TBHP
0
3
m-CPBA
7
4
Na2S2O8
21
b
5
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
(NH4)2S2O8
−
91
6
0
7
Ir(ppy)2(dtbbpy)PF6
Rosebengal
6
8
0
9
EosinY
<5
23
<5
9
Scheme 3. Synthesis of Silyl Enol Ether 2
10
11
12
13
14
15
Fe(phen)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
Ru(bpy)3(PF6)2
−
MeCN
acetone
DMF
0
0
DMSO
MeOH
MeOH
MeOH
<5
0
c
16
17
18
0
Ru(bpy)3(PF6)2
0
a
1
Yields were determined by H NMR using mesitylene as an internal
b
c
standard. Isolated yield with 5:1 dr. Without light.
enol ether 2o did be converted to α-mehoxylation product 5o
in 33% yield without any cyclic product. These results
suggested that a five-membered ring was easily formed, and
the newly formed radical could be oxidized to cation if
cyclization reaction did not efficiently occur. The reaction of 2p
containing 1,2-disubstituted alkene afforded 3p in 39% yield
with 12:1 dr.2
Various polycycles 6−8 could be easily obtained from the
product 3j by vinylation or removal of the carbonyl group
(Scheme 4).
To gain further understanding of the mechanism, some
experiments conducted were showed in Scheme 5. The radical
intermediate was captured by addition of TEMPO to afford 9
in 21% yield which elucidated that one-electron oxidation of
silyl enol to radical cation was the initiated step. The reaction of
silyl enol ether 10 with oxygen in the presence of
Ru(bpy)3(PF6)2 in a solution of acetonitrile under the
irradiation of 18 W CFL afforded the silyl peroxide 11 in
82% yield.11 It was possible that the excited state of
Ru(bpy)3(PF6)2 might oxidize the silyl enol; however, direct
oxygen-participated oxidation of silyl enol could not be ruled
out. Interestingly, the reaction of a Z/E mixture of 2j was
carried out to afford the cycloaddition products 3j and 3j′ in
99% combined yield with 4:1 diastereoselectivity which
the higher yields and diastereoselectivities were observed.
Morever, halides were also tolerated to give the corresponding
cyclization products 3f−g in 58−64% yield with moderate
diastereoselectivities. The pure major diastereoisomers could be
obtained after condensation with 2,4-dinitrophenylhydrazine in
40−49% yields. An excellent diastereoselectivity can be
achieved in the formation of 2,5-dimethoxy product 2h in
93% yield. The reaction of 2-naphthyl silyl enol ether gave 3i in
32% yield. Notably, 2-indyl silyl enol ethers were applicable to
deliver 3j−k in high yields with one single diastereoisomer.
Using stoichiometric CAN or visible light iron-photocatalyst,
reactions of 2j underwent smoothly, however, were not
efficient. The diester (3l) or a methyl substitution (3m) on
the link dramatically diminished the diastereselectivity. The
substitutions on the link might decelerate the ring-closing step
which delivered divergent diastereoselectivities. The stereo-
chemistry was determined by compared the data of known
compounds 3m and 3m′ to those reported in the literature.2
Due to a similar reason, the reaction of 2n was too messy to
identify the diastereoselectivity, and only the bicyclohexane
product 3n was isolated in 13% yield. The δ,ε-unsaturated silyl
B
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
a
Table 2. Substrate Scope
a
Standard conditions: 0.3 mmol of 2, 1.5 mol % of Ru(bpy)3(PF6)2, 3 equiv of (NH4)2S2O8, 100 wt % of 4 Å MS in a solution of MeOH (0.05 M)
under the irradiation of 18 W CFL for 17 h. Isolated yield of products 3 or 5o. The data in the parentheses is the isolated yield of the corresponding
compound 4.
indicated that the new formed radical cation was not exclusively
distonic and did not easily undergo the configuration-reversible
reaction. The reaction of 2a was performed for 40 min to afford
3a in 3% yield. Additionally, the same reaction was conducted
for 40 min then stirred without light for 16 h to give 3a in 5%
yield. These fluorescence quenching experiments indicated that
reaction is visible light photocatalysis, however, the radical
chain reaction cannot exclusively be ruled out.
susceptible to be oxidized by sulfate radical anion 12 to give the
methoxylation product followed by nucleophilic trapping by
methanol. Further radical cyclization following oxidation of 17
gave 3a followed by elimination of proton. Another pathway
involving oxidation of 17 to the corresponding cation followed
by cyclization could not be ruled out conclusively; however,
nucleophilic trapping of 17 with methanol was not observed.
The stereochemical information in the reactants was mainly
retained in the products. This phenomenon could be explained
by the model proposed by Snider.2 In the three possible
Newman configurations (Scheme 7), configuration a is more
favorable for 13 because the number of gauche interactions are
minimized.
In summary, visible-light-promoted oxidative [4 + 2]
cycloadditions of ε,3-unsaturated silyl enol ethers to access
various polycyclic rings have been reported. This protocol
features mild conditions and a broad scope without
stoichiometric transition-metal oxidants. Additionally, some
intermediates could be trapped by TEMPO, oxygen or
On the basis of above results and others previously reported
in literatures, plausible mechanisms for the oxidative [4 + 2]
reactions are proposed in Scheme 6. The [Ru]II obsorbs the
visible light to produce excited state *[Ru]II which could be
oxidized by persulfate to generate sulfate radical anion 12 and
[Ru]III. The oxidation potential of 2 measured is +1.424 V
(SCE) which is higher than the oxidation potential of RuIII/
/
RuII (1.29 V, SCE). This means that 2 could not be oxidized by
RuIII directly. Oxidation of silyl enol by 12 can lead to radical
cation 13 which can undergo intramolecular radical cyclization
to give 17. Either way, the newly formed radical species 13 is
C
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
(77.00 ppm, CDCl3). The following abbreviations (or combinations
thereof) were used to explain multiplicities: s = singlet, d = doublet, t =
triplet, m = multiplet, br = broad, q = quadruplet. IR spectra were
recorded on a FTIR spectrometer with diamond ATR accessory. High-
resolution mass spectra (HRMS) were recorded on EI-TOF
(electrospray ionization-time-of-flight). Element analyses were per-
formed on Vario Micro elemental analyzer.
Scheme 4. Further Derivatizations
5-Bromopentanal. Prepared according to literature methods.12
To a solution of BBr3 (7.1 mL, 74 mmol) in dichloromethane (70 mL)
was added dropwise tetrahydropyran (17.2260 g, 200 mmol) at 0 °C.
The mixture was then heated to reflux for 1 h. After allowing this
mixture to cool, it was transferred via syringe to a flask containing PCC
(47.4232 g, 220 mmol) and dichloromethane (200 mL). The resulting
dark solution was then heated to reflux for 1 h and allowed to cool.
Et2O was added and the mixture was filtered through a pad of silica
gel. The filtrate was evaporated in vacuo to give a crude brown liquid
which was then distilled in vacuo to give 17.4690 g (53% yield) of the
title compound as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 9.79
(t, J = 1.5 Hz, 1H), 3.43 (t, J = 6.4 Hz, 2H), 2.50 (td, J = 7.0, 1.5 Hz,
2H), 1.97−1.73 (m, 4H).
1-Bromo-6-methyl-hept-5-ene. Prepared according to the
modified literature methods.13 Isopropyl triphenyl phosphonium
bromide12 (52.3981 g, 136 mmol) was suspended in 200 mL THF.
After cooling to 0 °C, the mixture was added with n-BuLi (50.0 mL,
2.4 M in hexane, 118.0 mmol). The simulation was stirred for 30 min
at 0 °C and for another 30 min at room temperature. The mixture was
cooled to −78 °C and slowly injected the aldehyde (15.12 g, 90.9
mmol)). After completion of the addition, the mixture was stirred for
10 min at −78 °C, warmed to room temperature and then stirred at 30
°C overnight. Then petroleum ether was added and filtered through a
pad of Celite, the residue was concentrated and distilled in vacuo to
methanol to elucidate the mechanism. The diastereoselectivities
were dependent on stereoconfiguration of silyl enol ether,
substitutions on the link, as well as electric properties of
substitutions on aryl rings.
EXPERIMENTAL SECTION
■
Ether, THF and toluene were distilled from sodium benzophenone
ketyl prior to use. DCM and NEt3 were distilled from calcium hydride.
Methanol was distilled from sodium. Lithium diisopropylamide (LDA)
(1.0 mol/L in THF) and TBDMSOTf (Trifluoromethanesulfonic acid
tert-butyldimethylsilyl ester) were purchased from Energy Chemical.
The other commercial available chemicals were used as received. NMR
1
give the title compound (13.4309 g, 77% yield) as a colorless oil. H
NMR (400 MHz, CDCl3) 5.13−5.07 (m, 1H), 3.41 (t, J = 6.9 Hz,
2H), 2.01 (q, J = 7.3 Hz, 2H), 1.91−1.81 (m, 2H), 1.69 (s, 3H), 1.60
(s, 3H), 1.51−1.42 (m, 2H).
1
spectra were recorded on a 400 or 300 MHz instrument. H NMR
General Procedure A for Synthesis of Aryl Ketones.13 1-
Bromo-6-methyl-hept-5-ene (10 mmol, 1.0 equiv) was added to a
suspension of Mg turnings (360 mg, 15 mmol, 1.5 equiv) in THF (12
chemical shifts were referenced to the solvent resonance (7.26 ppm),
13C NMR chemical shifts were referenced to the solvent resonance
Scheme 5. Mechanistic Studies
D
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
Scheme 6. Plausible Mechanism
and purified by column chromatography (SiO2, PE/EtOAc) to afford
the corresponding aryl ketones.
Scheme 7. Primary Newman Models to Predict the
Stereochemistry of Products
7-Methyl-1-phenyloct-6-en-1-one (1a). Prepared according to the
general procedure A using benzoyl chloride (1.5500 g, 11.0 mmol), 1-
bromo-6-methyl-hept-5-ene (1.9996 g, 10.4 mmol), Mg turnings
(0.3850 g, 16.0 mmol), CuI (0.1052 g, 0.5 mmol) and THF (22 mL)
as starting materials to afford 1a (1.2686 g, 5.9 mmol, 56% yield). IR ν
3061, 2928, 2857, 1687, 1598, 1450 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.99−7.93 (m, 2H), 7.57−7.52 (m, 1H), 7.45 (t, J = 8.0 Hz,
2H), 5.15−5.09 (m, 1H), 2.96 (t, J = 7.6 Hz, 2H), 2.03 (q, J = 7.2 Hz,
2H), 1.80−1.70 (m, 2H), 1.69 (s, 3H), 1.61 (s, 3H), 1.47−38 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 200.5, 137.1, 132.8, 131.6,
128.5, 128.0, 124.3, 38.5, 29.5, 27.8, 25.7, 24.0, 17.7; HRMS (EI-TOF)
Calcd for C15H20O [M]+: 216.1514, found 216.1514.
mL) at room temperature. The resulting mixture was then refluxed for
40 min. In another flask, CuI (0.05 equiv) was added to a solution of
benzoyl chloride (1.0 equiv) in THF (10 mL) at −15 °C. The
Grignard reagent previously prepared was then added dropwise over
30 min at −15 °C. The mixture was stirred at −10 °C for additionally
1 h and then allowed to warm to room temperature and stirred
overnight. THF was removed under reduced pressure and the residue
was treated with CH2Cl2 (20 mL) and aqueous HCl (1.0 M, 10 mL).
The two layers were separated and the aqueous one was extracted with
CH2Cl2 (3 × 20 mL). The combined organic layers were washed with
aqueous NaHCO3 (saturated), dried over MgSO4, filtered, concen-
trated and purified by column chromatography (SiO2, PE/EtOAc) to
afford the corresponding ketones.
General Procedure B for Synthesis of Aryl Ketones. Prepared
according to a previously reported literature method.13 1-bromo-6-
methyl-hept-5-ene (10 mmol, 1.0 equiv) was added to a suspension of
Mg turnings (1.5 equiv) in Et2O (12 mL) at room temperature. The
resulting mixture was then refluxed for 40 min. The mixture was
cooled to room temperature and added dropwise to a solution of aryl
aldehyde in Et2O (20 mL) at 0 °C. The mixture was treated with
saturated NH4Cl, The two layers were separated and the aqueous one
was extracted with Et2O (3 × 20 mL). The combined organic layers
were dried over MgSO4, filtered, concentrated and used directly
without further purification. The residue was dissolved in DCM
followed by adding PCC (1.5 equiv). The mixture was stirred at room
temperature and monitored by TLC. Et2O was added and the mixture
was filtered through a pad of silica gel. The residue was concentrated
1-(4-Methoxyphenyl)-7-methyloct-6-en-1-one (1b). Prepared ac-
cording to the general procedure A using 4-methoxybenzoyl chloride
(1.7055 g, 10.0 mmol), 1-bromo-6-methyl-hept-5-ene (1.9061 g, 10.0
mmol), Mg turnings (0.3587 g, 15.0 mmol), CuI (0.1066 g, 0.5 mmol)
and THF (22 mL) as starting materials to afford 1b (1.3062 g, 5.3
mmol, 53% yield) as a colorless oil. IR ν 2931, 2856, 1677, 1601, 1511,
1
1258 cm−1; H NMR (300 MHz, CDCl3) δ 7.80 (d, J = 9.3 Hz, 2H),
6.78 (d, J = 9.0 Hz, 2H), 5.03−4.98 (m, 1H), 3.70 (s, 3H), 2.76 (t, J =
7.2 Hz, 2H), 1.91 (q, J = 7.2 Hz, 2H), 1.68−1.52 (m, 2H), 1.57 (s,
3H), 1.49 (s, 3H), 1.36−1.24 (m, 2H); 13C NMR (101 MHz, CDCl3)
δ 198.2, 162.9, 130.9, 129.8, 129.7, 124.0, 113.2, 54.8, 37.7, 29.2, 27.5,
25.3, 23.8, 17.2; HRMS (EI-TOF) Calcd for C16H22O2 [M]+:
246.1620, found 246.1618.
1-(3-Methoxyphenyl)-7-methyloct-6-en-1-one (1c). Prepared ac-
cording to the general procedure A using 3-methoxybenzoyl chloride
(1.3695 g, 8.0 mmol), CuI (0.0706 g, 0.37 mmol), Mg turnings
(0.2661 g, 11.1 mmol), 1-bromo-6-methyl-hept-5-ene (1.2995 g, 6.8
mmol) and THF (18 mL) as starting materials to afford 1c (0.9570 g,
3.9 mmol, 57% yield) as a colorless oil. IR ν 2928, 2857, 1686, 1594,
1
1258 cm−1; H NMR (300 MHz, CDCl3) δ 7.53 (d, J = 5.7 Hz, 1H),
7.49 (dd, J = 2.1, 1.2 Hz, 1H), 7.36 (t, J = 6.0 Hz, 1H), 7.10 (ddd, J =
6.3, 2.1, 0.6 Hz, 1H), 5.15−5.09 (m, 1H), 3.86 (s, 3H), 2.94 (t, J = 5.7
Hz, 2H), 2.03 (q, J = 5.4 Hz, 2H), 1.79−1.70 (m, 2H), 1.68 (s, 3H),
E
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Note
1.61 (s, 3H), 1.47−1.37 (m, 2H); 13C NMR (101 MHz, CDCl3) δ
200.3, 159.8, 138.5, 131.6, 129.5, 124.3, 120.7, 119.3, 112.3, 55.4, 38.6,
29.5, 27.8, 25.7, 24.1, 17.7; HRMS (EI-TOF) Calcd for C16H22O2
[M]+: 246.1620, found 246.1618.
25.7, 24.1, 17.6; HRMS (EI-TOF) Calcd for C17H24O3 [M]+:
276.1725, found 276.1726.
7-Methyl-1-(naphthalen-2-yl)oct-6-en-1-one (1i). Prepared ac-
cording to the general procedure A using 2-naphthoyl chloride
(1.9197 g, 10.1 mmol), 1-bromo-6-methyl-hept-5-ene (1.9197 g, 10.0
mmol), Mg turnings (0.3841 g, 16.0 mmol), CuI (0.0963 g, 0.5 mmol)
and THF (22 mL) as starting materials to afford 1i (1.8444 g, 6.9
mmol, 69% yield) as a colorless oil. IR ν 2925, 2856, 1682, 1461 cm−1;
1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.04 (dd, J = 8.4, 1.6 Hz,
1H), 7.97 (d, J = 7.6 Hz, 1H), 7.91−7.85 (m, 2H), 7.62−7.51 (m,
2H), 5.18−5.12 (m, 1H), 3.13−3.06 (t, J = 7.6 Hz, 2H), 2.06 (q, J =
7.2 Hz, 2H), 1.87−1.76 (m, 2H), 1.70 (s, 3H), 1.62 (s, 3H), 1.53−1.42
(m, 2H); 13C NMR (101 MHz, CDCl3) δ 200.4, 135.5, 134.4, 132.5,
131.6, 129.6, 129.5, 128.34, 128.27, 127.7, 126.7, 124.3, 123.9, 38.6,
29.6, 27.8, 25.7, 24.2, 17.7; HRMS (EI-TOF) Calcd for C19H22O
[M]+: 266.1671, found 266.1674.
Methyl 1H-indole-2-carboxylate. Prepared according to a
previously reported literature method14 using 1H-indole-2-carboxylic
acid (8.06 g, 50.0 mmol) and MeOH (20 mL) as starting materials to
afford methyl 1H-indole-2-carboxylate (8.4800 g, 48.4 mmol, 97%
yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 9.07 (br, 1H),
7.70 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz, 1H), 7.34 (dd, J = 8.0, 7.2
Hz, 1H), 7.25−7.23 (m, 1H), 7.17 (t, J = 7.2 Hz, 1H), 3.96 (s, 3H).
Methyl 1-methyl-1H-indole-2-carboxylate. Prepared according
to a previously reported literature method1 using methyl 1H-indole-2-
carboxylate (5.2658 g, 30 mmol), CH3I (2.2 mL, 36 mmol), NaH
(60%, 0.8651 g, 36 mmol) and THF (60 mL) as starting materials to
afford the title compound (3.7198 g, 19.7 mmol, 65% yield) as a white
solid. 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.0 Hz, 1H), 7.41−
7.32 (m, 2H), 7.29 (s, 1H), 7.18−7.11 (m, 1H), 4.09 (s, 3H), 3.92 (s,
3H).
1-(2-Methoxyphenyl)-7-methyloct-6-en-1-one (1d). Prepared ac-
cording to the general procedure A using 2-methoxybenzoyl chloride
(1.2208 g, 7.1 mmol), 1-bromo-6-methyl-hept-5-ene (1.3457 g, 7.0
mmol), Mg turnings (0.2644 g, 11.0 mmol), CuI (0.0670 g, 0.35
mmol) and THF (18 mL) as starting materials to afford 1d (0.5288 g,
2.1 mmol, 30% yield) as a colorless oil. IR ν 2930, 2856, 1675, 1598,
1485, 1288, 1245 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J =
7.6, 2.0 Hz, 1H), 7.46−7.39 (m, 1H), 7.02−6.91 (m, 2H), 5.15−5.07
(m, 1H), 3.88 (s, 3H), 2.95 (t, J = 7.2 Hz, 2H), 2.00 (q, J = 7.2 Hz,
2H), 1.73−1.64 (m, 5H), 1.59 (s, 3H), 1.43−1.33 (m, 2H); 13C NMR
(101 MHz, CDCl3) δ 203.1, 158.2, 133.0, 131.3, 130.0, 128.8, 124.4,
120.5, 111.4, 55.4, 43.6, 29.6, 27.8, 25.6, 24.0, 17.6; HRMS (EI-TOF)
Calcd for C16H22O2 [M]+: 246.1620, found 246.1618.
1-(4-Ethylphenyl)-7-methyloct-6-en-1-one (1e). Prepared accord-
ing to the general procedure B using 1-bromo-6-methyl-hept-5-ene
(2.1410 g, 11.2 mmol), Mg turnings (0.5403 g, 22.5 mmol) 4-
ethylbenzaldehyde (1.3446 g, 10.0 mmol), Et2O (40 mL), PCC
(3.2691 g, 15.2 mmol) and DCM (60 mL) as starting materials to
afford 1e (2.0576 g, 8.4 mmol, 84% yield) as a colorless oil. IR ν 3349,
2966, 2931, 2860, 1683, 1608, 1454 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.88 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 5.15−5.08
(m, 1H), 2.97−2.90 (t, J = 7.2 Hz, 2H), 2.70 (q, J = 7.6 Hz, 2H), 2.03
(q, J = 7.2 Hz, 2H), 1.78−1.69 (m, 2H), 1.68 (s, 3H), 1.60 (s, 3H),
1.46−1.37 (m, 2H), 1.25 (t, J = 7.6 Hz, 3H); 13C NMR (101 MHz,
CDCl3) δ 200.1, 149.7, 134.8, 131.5, 128.2, 128.0, 124.3, 38.4, 29.5,
28.9, 27.8, 25.7, 24.1, 17.6, 15.2; HRMS (EI-TOF) Calcd for C17H24O
[M]+: 244.1827, found 244.1824.
1-(4-Fluorophenyl)-7-methyloct-6-en-1-one (1f). Prepared accord-
ing to the general procedure B using 4-fluorobenzaldehyde (1.2469 g,
10.0 mmol), 1-bromo-6-methyl-hept-5-ene (2.1410 g, 11.2 mmol), Mg
turnings (0.5403 g, 22.5 mmol), Et2O (40 mL), PCC (3.2951 g, 15.3
mmol) and DCM (60 mL) as starting materials to afford 1f (1.5017 g,
6.4 mmol, 64% yield) as a colorless oil. IR ν 2929, 2858, 1686, 1598,
1506, 1410, 1231 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.00−7.90 (m,
2H), 7.11 (t, J = 8.8 Hz, 2H), 5.11 (t, J = 7.2 Hz, 1H), 2.92 (t, J = 7.2
Hz, 2H), 2.02 (q, J = 7.2 Hz, 2H), 1.78−1.69 (m, 2H), 1.68 (s, 3H),
1.60 (s, 3H), 1.47−1.36 (m, 2H); 13C NMR (101 MHz, CDCl3) δ
198.8, 165.6 (d, J = 241.4 Hz), 133.5 (d, J = 2.9 Hz), 131.7, 130.6 (d, J
= 36.0 Hz), 124.2, 115.6 (d, J = 22.2 Hz), 38.4, 29.5, 27.8, 25.7, 24.0,
17.7; 19F NMR (376 MHz, CDCl3) δ −105.76; HRMS (EI-TOF)
Calcd for C15H19OF [M]+: 234.1420, found 234.1422.
1-Methyl-1H-indole-2-carboxylic acid. Prepared according to a
previously reported literature method15 using methyl 1-methyl-1H-
indole-2-carboxylate (3.1408 g, 16.6 mmol) and KOH (12%, 150 mL)
as starting materials to afford the title compound (2.8708 g, 16.4
mmol, 99% yield) as a white solid. H NMR (400 MHz, CDCl3) δ
7.74−7.69 (m, 1H), 7.48 (s, 1H), 7.43−7.36 (m, 2H), 7.17 (ddd, J =
8.0, 6.0, 2.4 Hz, 1H), 4.11 (s, 3H).
1-Methyl-1H-indole-2-carbonyl chloride. Prepared according
to a general procedure using 1-methyl-1H-indole-2-carboxylic acid
(2.6312 g, 15.0 mmol) and thionyl chloride (2.9 mL) as starting
materials refluxing in dichloromethane for 2 h. The solvent was
removed under reduced pressure and dried in vacuo to afford the
desired product. The crude product was used directly without further
purification.
1
1-(4-Bromophenyl)-7-methyloct-6-en-1-one (1g). Prepared ac-
cording to the general procedure B using 4-bromobenzaldehyde
(1.8527 g, 10.0 mmol), 1-bromo-6-methyl-hept-5-ene (2.1410 g, 11.2
mmol), Mg turnings (0.5403 g, 22.5 mmol), Et2O (40 mL), PCC
(3.2579 g, 15.1 mmol) and DCM (60 mL) as starting materials to
afford 1g (2.3506 g, 8.0 mmol, 80% yield) as a white solid. mp = 46−
48 °C. IR ν 3028, 2961, 2929, 1649, 1463, 1255 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.4 Hz, 2H),
5.09 (t, J = 6.8 Hz, 1H), 2.89 (t, J = 7.2 Hz, 2H), 2.00 (q, J = 6.4 Hz,
2H), 1.76−1.67 (m, 2H), 1.66 (s, 3H), 1.58 (s, 3H), 1.45−1.34 (m,
2H); 13C NMR (101 MHz, CDCl3) δ 199.3, 135.7, 131.8, 131.7,
129.5, 127.9, 124.2, 38.4, 29.4, 27.7, 25.7, 23.9, 17.6; HRMS (EI-TOF)
Calcd for C15H19OBr [M]+: 294.0619, found 294.0611.
Methyl 5-methyl-1H-indole-2-carboxylate. Prepared according
to a similar procedure for synthesis of methyl 1-methyl-1H-indole-2-
carboxylate using 5-methyl-1H-indole-2-carboxylic acid (1.9211 g, 11.0
mmol) and MeOH (18 mL) as starting materials to afford the title
compound (1.6240 g, 8.6 mmol, 78% yield) as a white solid. 1H NMR
(400 MHz, CDCl3) δ 8.83 (s, 1H), 7.47 (s, 1H), 7.31 (d, J = 8.4 Hz,
1H), 7.15 (dd, J = 10.0, 1.2 Hz, 1H), 3.94 (s, 3H), 2.44 (s, 3H).
Methyl-1,5-dimethyl-1H-indole-2-carboxylate. Prepared ac-
cording to a similar procedure for synthesis of methyl 1-methyl-1H-
indole-2-carboxylate using methyl 5-methyl-1H-indole-2-carboxylate
(1.5087 g, 8.0 mmol), NaH (0.2155 g, 10.5 mmol), MeI (0.74 mL, 9.6
mmol) and THF (20 mL) as starting materials to afford the title
compound (1.0187 g, 5.0 mmol, 63% yield) as a yellow solid. 1H NMR
(400 MHz, CDCl3) δ 7.43 (s, 1H), 7.26 (d, J = 8.6 Hz, 1H), 7.21−
7.15 (m, 2H), 4.04 (s, 3H), 3.89 (s, 3H), 2.44 (s, 3H).
1-(2,5-Dimethoxyphenyl)-7-methyloct-6-en-1-one (1h). Prepared
according to the general procedure B using 2,5-dimethoxybenzalde-
hyde (1.6689 g, 10.0 mmol), 1-bromo-6-methyl-hept-5-ene (2.1410 g,
11.2 mmol), Mg turnings (0.5403 g, 22.5 mmol), PCC (2.6770 g, 15.0
mmol), Et2O (40 mL) and DCM (60 mL) as starting materials to
afford 1h (2.0023 g, 7.2 mmol, 72% yield) as a colorless oil. IR ν 2931,
1,5-Dimethyl-1H-indole-2-carboxylic acid. Prepared according
to a similar procedure for synthesis of 1-methyl-1H-indole-2-carboxylic
acid using methyl-1,5-dimethyl-1H-indole-2-carboxylate (1.0176 g, 5.0
mmol) and KOH (12% in water) as starting materials to afford the
1
1
2856, 1675, 1495, 1278, 1222 cm−1; H NMR (400 MHz, CDCl3) δ
title compound (0.8731 g, 4.6 mmol, 92% yield) as a white solid. H
7.21 (d, J = 3.2 Hz, 1H), 7.01−6.97 (m, 1H), 6.88 (d, J = 8.8 Hz, 1H)
5.14−5.08 (m, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 2.96 (t, J = 7.2 Hz,
2H), 2.00 (q, J = 7.2 Hz, 2H), 1.73−1.62 (m, 5H), 1.59 (s, 3H), 1.42−
1.33 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 202.7, 153.4, 152.8,
131.4, 128.9, 124.5, 119.4, 113.9, 113.1, 56.0, 55.8, 43.6, 29.6, 27.9,
NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.37 (s, 1H), 7.30 (d, J = 8.6
Hz, 1H), 7.22 (d, J = 8.5 Hz, 1H), 4.07 (s, 3H), 2.45 (s, 3H).
1,5-Dimethyl-1H-indole-2-carbonyl chloride. Prepared accord-
ing to the same procedure for synthesis of methyl-1H-indole-2-
carbonyl chloride.
F
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
7-Methyl-1-(1-methyl-1H-indol-2-yl)oct-6-en-1-one (1j). Prepared
according to the general procedure A using 1-methyl-1H-indole-2-
carbonyl chloride16 (1.9482 g, 10.0 mmol), 1-bromo-6-methyl-hept-5-
ene (2.0797 g, 109 mmol), Mg turnings (0.3613 g, 15.0 mmol), CuI
(0.1043 g, 0.55 mmol) and THF (22 mL) as starting materials to
afford 1j (1.7365 g, 6.4 mmol, 64% yield) as a colorless oil. IR ν 2928,
2857, 1663, 1614, 1514, 1464, 1392 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.71 (d, J = 8.0 Hz, 1H), 7.38 (d, J = 3.6 Hz, 2H), 7.29 (s,
1H), 7.20−7.14 (m, 1H), 5.16 (t, J = 6.6 Hz, 1H), 4.08 (s, 3H), 3.01−
2.93 (t, J = 7.6 Hz, 2H), 2.07 (q, J = 7.2 Hz, 2H), 1.84−1.75 (m, 2H),
1.72 (s, 3H), 1.64 (s, 3H), 1.51−1.42 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 194.5, 139.9, 134.8, 131.5, 125.71, 125.65, 124.3, 122.7,
120.6, 111.0, 110.2, 39.8, 32.1, 29.5, 27.8, 25.7, 24.8, 17.6; HRMS (EI-
TOF) Calcd for C18H23NO [M]+: 269.1780, found 269.1775.
(t, J = 8.0 Hz, 2H), 5.14−5.06 (m, 1H), 2.96 (dd, J = 15.6, 5.2 Hz,
1H), 2.74 (dd, J = 15.6, 8.0 Hz, 1H), 2.25−2.14 (m, 1H), 2.11−1.91
(m, 2H), 1.68 (s, 3H), 1.61 (s, 3H), 1.45−1.40 (m, 1H), 1.35−1.23
(m, 1H), 0.97 (d, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
200.4, 137.4, 132.8, 131.5, 128.5, 128.1, 124.4, 45.9, 37.2, 29.5, 25.7,
25.5, 19.9, 17.6; HRMS (EI-TOF) Calcd for C16H22O [M]+: 230.1671,
found 230.1675.
6-Bromohexanal.19 Prepared according to a general procedure
using 6-bromohexan-1-ol (4.8732 g, 26.9 mmol), PCC (12.5900 g,
58.4 mmol) and DCM (160 mL) as starting materials. The mixture
was stirred for 24 h at room temperature. Et2O was added and the
mixture was filtered through a pad of silica gel. The residue was
concentrated and distilled in vacuo (with oil pump) to afford the title
1
compound (2.7416 g, 15.3 mmol, 57% yield) as a colorless oil. H
NMR (400 MHz, CDCl3) δ 9.80−9.74 (m, 1H), 3.42 (t, J = 6.8 Hz,
2H), 2.47 (td, J = 7.2, 1.6 Hz, 2H), 1.95−1.83 (m, 2H), 1.73−1.60 (m,
2H), 1.54−1.43 (m, 2H).
1-(1,5-Dimethyl-1H-indol-2-yl)-7-dimethyloct-6-en-1-one (1k).
Prepared according to the general procedure A using 1,5-dimethyl-
1H-indole-2-carbonyl chloride (0.9800 g, 4.7 mmol), 1-bromo-6-
methyl-hept-5-ene (0.6734 g, 3.5 mmol), CuI (0.0362 g, 0.19 mmol),
Mg turnings (0.1434 g, 6.0 mmol) and THF (20 mL) as starting
materials to afford 1k (0.4753 g, 1.2 mmol, 35% yield) as a colorless
1-Bromo-7-methyloct-6-ene.20 Prepared by a procedure smiliar
to 1-bromo-6-methyl-hept-5-ene using 6-bromohexanal (2.7400 g,
15.3 mmol), isopropyl triphenyl phosphonium bromide (9.1200 g,
23.7 mmol) and THF (100 mL) as atarting materials to afford the title
1
oil. H NMR (400 MHz, CDCl3) δ 7.43 (s, 1H), 7.24 (d, J = 1.6 Hz,
1
compound (2.0646 g, 10.1 mmol, 66% yield) as a colorless oil. H
1H), 7.19 (d, J = 1.2 Hz, 1H), 7.17 (s, 1H), 5.11 (t, J = 7.2 Hz, 1H),
4.03 (s, 3H), 2.95−2.89 (t, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.02 (q, J =
7.2 Hz, 2H), 1.79−1.69 (m, 2H), 1.67 (s, 3H), 1.59 (s, 3H), 1.47−1.35
(m, 2 H); 13C NMR (101 MHz, CDCl3) δ 194.7, 138.6, 134.9, 131.6,
129.9, 127.8, 126.0, 124.3, 122.0, 110.6, 110.0, 39.9, 32.2, 29.6, 27.8,
25.7, 25.0, 21.3, 17.7; IR ν 2923, 2856, 1660, 1523, 1459, 1177, 732
cm−1; HRMS (EI-TOF) Calcd for C19H25NO [M]+: 283.1936, found
283.1935.
NMR (400 MHz, CDCl3) δ 5.14−5.06 (m, 1H), 3.40 (t, J = 7.2 Hz,
2H), 1.98 (q, J = 7.2 Hz, 2H), 1.91−1.82 (m, 2H), 1.69 (s, 3H), 1.60
(s, 3H), 1.49−1.30 (m, 4H).
8-Methyl-1-phenylnon-7-en-1-one (1n). Prepared according to the
general procedure A using benzoyl chloride (1.3970 g, 10.0 mmol), 1-
bromo-7-methyl-hept-5-ene (2.0640 g, 10.0 mmol), Mg turnings
(0.3710 g, 15.5 mmol), CuI (0.0957 g, 0.5 mmol) and THF (40 mL)
as starting materials to afford 1n (1.7469 g, 7.6 mmol, 76% yield) as a
colorless oil. IR ν 2926, 2855, 1686, 1449, 1222 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.96 (d, J = 7.2 Hz, 2H), 7.55 (dd, J = 7.6, 7.2 Hz,
1H), 7.45 (t, J = 8.0 Hz, 2H), 5.17−5.07 (m, 1H), 2.96 (t, J = 7.6 Hz,
2H), 2.05−1.91 (m, 2H), 1.79−1.70 (m, 2H), 1.68 (s, 3H), 1.59 (s,
3H), 1.42−1.34 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 200.4,
137.0, 132.8, 131.3, 128.5, 128.0, 124.6, 38.5, 29.7, 29.0, 27.8, 25.7,
24.3, 17.6; HRMS (EI-TOF) Calcd for C16H22O [M]+: 230.1671,
found 230.1671.
Diethyl 2-(3-methylbut-2-en-1-yl)malonate. Prepared accord-
ing to a previously reported procedure17 using 1-bromo-3-methylbut-
2-ene (3.6339 g, 22 mmol), diethyl malonate (5.5368 g, 20 mmol),
K2CO3 (5.5368 g, 40 mmol) and acetons (50 mL) as atarting
materials. The mixture was refluxed overnight. Then K2CO3 was
filtered and the solvent was removed. The residue was purified by flash
column chromatography (PE/EtOAc, 30:1) to give the title
1
compound as a colorless oil (3.9206 g, 17.2 mmol, 86% yield). H
NMR (400 MHz, CDCl3) δ 5.11−5.02 (m, 1H), 4.18 (q, J = 7.2 Hz,
4H), 3.32 (t, J = 7.6 Hz, 1H), 2.58 (t, J = 7.6 Hz, 2H), 1.68 (s, 3H),
1.63 (s, 3H), 1.25 (t, J = 7.1 Hz, 6H).
4-Bromobutanal.21 Prepared by a procedure smiliar to synthesis
of 5-bromopentanal using tetrahydrofuran (8.1 mL, 100 mmol), BBr3
(3.6 mL, 37.0 mmol), PCC (23.7400 g, 110.1 mmol) and DCM (135
mL) as starting materials to afford the title compound (7.6563 g, 51%
yield, purity 68%) as a colorless oil. The 1H NMR is in accordance to
the literature.13
Diethyl 2-(3-Methylbut-2-en-1-yl)-2-(3-oxo-3-phenylpropyl)-
malonate (1l). Prepared according to a similar procedure.18 To a
suspension of NaH (0.2400 g, 6.0 mmol) in THF/DMF (1:1, 6 mL)
was added diethyl 2-(3-methylbut-2-en-1-yl)malonate (1.1506 g, 5.04
mmol) dropwise at 0 °C under N2 atmosphere and stirred for another
10 min. Then the reaction mixture was warmed to room temperature
and stirred for 1 h. Then 3-chloropropiophenone (1.0211g, 6 mmol)
and NaI (0.0750 g, 0.5 mmol) was added and the mixture was refluxed
at 80 °C for 18 h. The resulting suspension was diluted with ether, and
quenched with saturated aqueous NH4Cl. The organic layer was
washed with saturated aqueous NH4Cl. The aqueous was extracted
with Et2O. The combined organic layers were dried over MgSO4,
filtered, concentrated and purified by flash column chromatography on
silica gel (PE/EtOAc 30:1) to afford the title compound (1.0989 g, 3.0
mmol, 61% yield) as a colorless oil. IR ν 2978, 2926, 1730, 1688, 1449,
1182 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7.6 Hz, 2H),
7.54 (t, J = 7.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 2H), 5.00 (t, J = 7.2 Hz,
1H), 4.17 (q, J = 7.2 Hz, 4H), 3.01−2.94 (m, 2H), 2.66 (d, J = 7.2 Hz,
2H), 2.32−2.26 (m, 2H), 1.68 (s, 3H), 1.62 (s, 3H), 1.22 (t, J = 6.8
Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 199.0, 171.3, 136.7, 135.6,
133.0, 128.5, 128.0, 117.6, 61.2, 57.0, 33.8, 32.2, 27.1, 25.9, 17.9, 14.0;
HRMS (EI-TOF) Calcd for C21H28O5 [M]+: 360.1937, found
360.1938.
6-Bromo-2-methylhex-2-ene. Prepared by a procedure smiliar to
synthesis of 1-bromo-6-methyl-hept-5-ene using 4-bromobutanal
(7.6560 g, 50.7 mmol), isopropyl triphenyl phosphonium bromide
(28.9500 g, 75.1 mmol), n-BuLi (2.4 M in hexane, 27.5 mL, 66.0
mmol) and THF (250 mL) as starting materials to afford the title
1
compound (2.2179 g, 12.5 mmol, 25% yield) as a colorless oil. H
NMR (400 MHz, CDCl3) δ 5.10−5.03 (m, 1H), 3.40 (t, J = 6.8 Hz,
2H), 2.13 (q, J = 7.2 Hz, 2H), 1.93−1.84 (m, 2H), 1.69 (s, 3H), 1.63
(s, 3H).
6-Methyl-1-phenylhept-5-en-1-one (1o). Prepared according to
the general procedure A using benzoyl chloride (1.4 mL, 12.0 mmol),
1-bromo5-methyl-hept-5-ene (2.0895 g, 11.8 mmol), Mg turnings
(0.4893 g, 20.0 mmol), CuI (0.1169 g, 0.6 mmol) and THF (50 mL)
as starting materials to afford 1o (1.2412 g, 6.1 mmol, 52% yield) as a
colorless oil. IR ν 2926, 2856, 1687, 1450 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.95 (d, J = 6.8 Hz, 2H), 7.58−7.52 (m, 1H), 7.49−7.43 (m,
2H), 5.17−5.10 (m, 1H), 2.99−2.93 (m, 2H), 2.08 (q, J = 7.6 Hz,
2H), 1.84−1.74 (m, 2H), 1.69 (s, 3H), 1.60 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 200.6, 137.1, 132.8, 132.5, 128.5, 128.0, 123.8, 37.9,
27.5, 25.7, 24.5, 17.7; HRMS (EI-TOF) Calcd for C14H18O [M]+:
202.1358, found 202.1355.
3,7-Dimethyl-1-phenyloct-6-en-1-one (1m). Prepared according to
the general procedure B using phenylmagnesium bromide (1 M in
THF, 20 mL), 2,6-dimethyl-5-heptena (2.7 mL, 15.0 mmol), PCC
(6.8200 g, 31.6 mmol) and DCM (80 mL) as starting materials to
afford 1m (1.9110 g, 8.3 mmol, 55% yield) as a colorless oil. IR ν
3060, 2962, 2854, 1729, 1686, 1450 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.94 (d, J = 7.2 Hz, 2H), 7.55 (dd, J = 7.2, 7.2 Hz, 1H), 7.45
(Z/E)-1-Phenylnon-6-en-1-one (1p).13 Prepared according to the
general procedure A using benzoyl chloride (1.4244 g, 10.1 mmol), 1-
bromo5-methyl-hex-4-ene (Z/E mixture) (1.9603 g, 10.2 mmol), Mg
turnings (0.3703 g, 15.4 mmol), CuI (0.1055 g, 0.5 mmol) and THF
(35 mL) as starting materials to afford 1p (1.5983 g, 7.4 mmol, 74%
G
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7.2
Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.46 (dd, J = 7.2, 7.2 Hz, 2H), 5.51−
5.26 (m, 2H), 2.97 (t, J = 7.2 Hz, 2H), 2.14−1.97 (m, 4H), 1.81−1.70
(m, 2H), 1.50−1.40 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H). Anal. Calcd
C15H20O for C, 83.28; H, 9.32. Found C, 82.84; H, 9.01.
General Procedure C for Synthesis of Silyl Enol Ethers. To a
50 mL flame-dried Schlenk flask cooled under N2, LDA (2 M in THF)
and THF (3 mL) was added. The Schlenk was placed at −78 °C and 1
(5 mmol, in 6 mL THF) was added dropwise via syringe. The mixture
was stirred for another 30 min at −78 °C, and then TBDMSOTf (7.5
mmol, 1.5 equiv) was added via syringe and stirred for 30 min at −78
°C and stirred overnight at 0 °C. The reaction mixture was diluted
with Et2O, quenched with saturated aqueous NaHCO3 and separated.
The aqueous layer was extracted with Et2O (3 × 20 mL). The
combined organic layers were dried over Na2SO4, concentrated and
purified by flash column chromatography on silica gel to afford the silyl
enol ethers.
(Z)-tert-Butyldimethyl((7-methyl-1-phenylocta-1,6-dien-1-yl)-
oxy)silane (2a). Prepared according the general procedure C
employing 1a (0.7775 g, 3.6 mmol), LDA (2 M in THF, 2.4 mL,
4.7 mmol), TBDMSOTf (1.26 mL, 5.4 mmol) and THF (6 mL) as
starting materials to afford 2a (0.9745 g, 2.9 mmol, 82% yield) as a
colorless oil. IR ν 3031, 2957, 2929, 1649, 1447, 1283 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.42 (d, J = 7.2 Hz, 2H), 7.30−7.19 (m, 3H),
5.14 (t, J = 7.2 Hz, 1H), 5.10 (t, J = 7.2 Hz, 1H), 2.23−2.15 (m, 2H),
2.08−1.98 (m, 2H), 1.69 (s, 3H), 1.61 (s, 3H), 1.50−1.39 (m, 2H),
0.98 (s, 9H), −0.06 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 149.3,
139.9, 131.5, 127.9, 127.3, 125.9, 124.6, 111.9, 29.9, 27.9, 25.9, 25.8,
25.7, 18.3, 17.7, −4.1; HRMS (EI-TOF) Calcd for C21H34OSi
[M]+:330.2379, found 330.2382.
(Z)-tert-Butyl((1-(4-methoxyphenyl)-7-methylocta-1,6-dien-1-yl)-
oxy)dimethylsilane (2b). Prepared according to the general procedure
C employing 1b (0.9722 g, 3.95 mmol), LDA (2 M in THF, 2.4 mL),
TBDMSOTf (1.3 mL, 5.5 mmol) as starting materials to afford 2b
(1.0615 g, 2.9 mmol, 75% yield) as a colorless oil. IR ν 2930, 2857,
1650, 1609, 1510, 1248 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.36 (d,
J = 8.8 Hz, 2H), 6.82 (d, J = 8.8 Hz, 2H), 5.16 (t, J = 7.2 Hz, 1H), 5.00
(t, J = 7.1 Hz, 1H), 3.81 (s, 3H), 2.21−2.16 (m, 2H), 2.07−2.01(m,
2H), 1.71 (s, 3H), 1.62 (s, 3H), 1.49−1.41 (m, 2H), 0.99 (s, 9H),
−0.04 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 159.0, 148.9, 132.6,
131.4, 127.1, 124.7, 113.2, 110.4, 55.2, 30.0, 27.9, 25.9, 25.8, 25.7, 18.3,
17.6, −4.1; HRMS (EI-TOF) Calcd for C22H36O2Si [M]+:360.2485,
found 360.2484.
mmol), TBDMSOTf (1.1 mL, 4.6 mmol) as starting materials to
afford 2e (0.6498 g, 2.7 mmol, 86% yield) as a colorless oil. IR ν 2931,
1
2858, 1603, 1283 cm−1; H NMR (400 MHz, CDCl3) δ 7.34 (d, J =
8.4 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 5.17−5.12 (m, 1H), 5.06 (t, J =
7.2 Hz, 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.2−2.16 (m, 2H), 2.06−2.01
(m, 2H), 1.70 (s, 3H), 1.61 (s, 3H), 1.48−1.40 (m, 2H), 1.23 (t, J =
7.6 Hz, 3H), 0.98 (s, 9H), −0.05 (s, 6H); 13C NMR (101 MHz,
CDCl3) δ 149.3, 143.3, 137.3, 131.4, 127.3, 125.8, 124.7, 111.2, 29.9,
28.5, 27.9, 25.9, 25.8, 25.7, 18.3, 17.7, 15.5, −4.0; HRMS (EI-TOF)
Calcd for C23H38OSi [M]+: 358.2692, found 358.2690.
(Z)-Triethyl((1-(4-ethylphenyl)-7-methylocta-1,6-dien-1-yl)oxy)-
silane (2ea). Prepared according to the general procedure C
employing 1e (0.5732 g, 2.3 mmol), LDA (2 M in THF, 2.0
mmol), chlorotriethylsilane (0.67 mL, 4.0 mmol) as starting materials
to afford 2ea (0.4440 g, 1.2 mmol, 41% yield) as a colorless oil. IR ν
3028, 2960, 2878, 1686, 1649, 1458 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 5.16 (t, J
= 6.8 Hz, 1H), 5.10 (t, J = 7.2 Hz, 1H), 2.64 (q, J = 7.6 Hz, 2H),
2.24−2.18 (m, 2H), 2.08−2.02 (m, 2H), 1.71 (s, 3H), 1.63 (s, 3H),
1.48−1.42 (m, 2H), 1.24 (t, J = 7.6 Hz, 3H), 0.94 (t, J = 7.9 Hz, 9H),
0.62 (q, J = 8.0 Hz, 6H); 13C NMR (101 MHz, CDCl3) δ 149.4, 143.4,
137.1, 131.5, 127.4, 125.5, 124.6, 110.6, 30.0, 28.5, 27.9, 25.8, 25.7,
17.7, 15.4, 6.7, 5.4; HRMS (EI-TOF) Calcd for C23H38OSi [M]+:
358.2692, found 358.2690.
(Z)-((1-(4-Ethylphenyl)-7-methylocta-1,6-dien-1-yl)oxy)-
triisopropylsilane (2eb). Prepared according to the general procedure
C employing 1e (0.7360 g, 3.0 mmol), HMDS (2 M in THF, 2.0 mL,
4.0 mmol) instead of LDA, triisopropylsilyl chloride (0.85 mL, 4.0
mmol) and THF (8 mL) as starting materials to afford 2eb (0.8925 g,
2.2 mmol, 74% yield) as a colorless oil. IR ν 2926, 1648, 1462, 1329
1
cm−1; H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.0 Hz, 2H), 7.11
(d, J = 8.0 Hz, 2H), 5.15 (t, J = 7.2 Hz, 1H), 4.94 (t, J = 7.2 Hz, 1H),
2.64 (q, J = 7.6 Hz, 2H), 2.25−2.20 (m, 2H), 2.07−2.02 (m, 2H), 1.70
(s, 3H), 1.62 (s, 3H), 1.49−1.42 (m, 2H), 1.24 (t, J = 7.6 Hz, 3H),
1.11−1.02 (m, 21H); 13C NMR (101 MHz, CDCl3) δ 150.2, 143.4,
137.8, 131.4, 127.3, 126.0, 124.7, 110.6, 29.9, 28.5, 27.9, 25.9, 25.8,
17.9, 17.6, 15.5, 13.5; HRMS (EI-TOF) Calcd for C26H44OSi [M]+:
400.3161, found 400.3163.
(Z)-tert-Butyl((1-(4-fluorophenyl)-7-methylocta-1,6-dien-1-yl)-
oxy)dimethylsilane (2f). Prepared according to the general procedure
C employing 1f (1.1885 g, 5.0 mmol), LDA (2 M in THF, 3 mL, 6.0
mmol), TBDMSOTf (1.73 mL, 7.5 mmol) and THF (8 mL) as
starting materials to afford 2f (1.6154 g, 4.6 mmol, 91% yield) as a
colorless oil. IR ν 2930, 2857, 1651, 1507, 1228 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.43−7.36 (m, 2H), 7.01−6.93 (m, 2H), 5.14 (t, J =
7.2 Hz, 1H), 5.04 (t, J = 7.2 Hz, 1H), 2.21−2.16 (m, 2H), 2.07−2.01
(m, 2H), 1.70 (s, 3H), 1.62 (s, 3H), 1.49−1.41 (m, 2H), 0.98 (s, 9H),
−0.05 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 162.2 (d, J = 247.5
Hz), 148.4, 136.1 (d, J = 3.0 Hz), 131.6, 127.5 (d, J = 7.1 Hz), 124.5,
114.7 (d, J = 21.2 Hz), 111.8, 29.8, 27.9, 25.83, 25.80, 25.75, 18.3, 17.7,
−4.1; 19F NMR (376 MHz, CDCl3) δ −115.2; HRMS (EI-TOF)
Calcd for C21H33OSiF [M]+: 348.2285, found 348.2289.
(Z)-tert-Butyl((1-(4-bromophenyl)-7-methylocta-1,6-dien-1-yl)-
oxy)dimethylsilane (2g). Prepared according to the general procedure
C employing 1g (0.8827 g, 3.0 mmol), LDA (2 M in THF, 1.6 mL, 3.3
mmol), TBDMSOTf (1.0 mml, 4.5 mmol) and THF (6 mL) as
starting materials to afford 2g (0.5298 g, 1.3 mmol, 43% yield) as a
colorless oil. IR ν 2956, 2857, 1647, 1483, 1256 cm−1; 1H NMR (400
MHz, CDCl3) δ 7.37 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.8 Hz, 2H),
5.13−5.06 (m, 2H), 2.18−2.12 (m, 2H), 2.03−1.98 (m, 2H), 1.67 (s,
3H), 1.58 (s, 3H), 1.49−1.38 (m, 2H), 0.96 (s, 9H), −0.07 (s, 6H);
13C NMR (101 MHz, CDCl3) δ 148.3, 138.8, 131.5, 131.0, 127.4,
(Z)-tert-Butyl((1-(3-methoxyphenyl)-7-methylocta-1,6-dien-1-yl)-
oxy)dimethylsilane (2c). Prepared according to the general procedure
C employing 1c (0.7427 g, 3.0 mmol), LDA (2 M in THF, 2 mL, 4.0
mmol), TBDMSOTf (1.1 mL, 4.5 mmol) and THF (7 mL) as starting
materials to afford 2c (0.7827 g, 2.2 mmol, 72% yield) as a colorless
1
oil.IR ν 2930, 2857, 1649, 1600, 1256 cm−1; H NMR (400 MHz,
CDCl3) δ 7.23−7.16 (m, 1H), 7.04 (d, J = 7.6 Hz, 1H), 7.00 (s, 1H),
6.79 (dd, J = 8.0, 2.4 Hz, 1H), 5.20−5.10 (m, 2H), 3.81 (s, 3H), 2.23−
2.18 (m, 2H), 2.08−2.02 (m, 2H), 1.71 (s, 3H), 1.63 (s, 3H), 1.50−
1.43 (m, 2H), 1.00 (s, 9H), −0.01 (s, 6H); 13C NMR (101 MHz,
CDCl3) δ 159.2, 149.0, 141.4, 131.5, 128.9, 124.6, 118.4, 113.1, 112.1,
111.1, 55.1, 29.8, 27.9, 25.9, 25.80, 25.76, 18.3, 17.7, −4.1; HRMS (EI-
TOF) Calcd for C22H36O2Si [M]+: 360.2485, found 360.2487.
(Z)-tert-Butyl((1-(2-methoxyphenyl)-7-methylocta-1,6-dien-1-yl)-
oxy)dimethylsilane (2d). Prepared according to the general procedure
C employing 1d (0.4611 g, 1.82 mmol), LDA (2 M in THF, 1.2 mL,
2.4 mmol), TBDMSOTf (0.66 mL, 2.8 mmol) and THF (5 mL) as
starting materials to afford 2d (0.5292 g, 1.47 mmol, 78% yield, 86%
1
purity) as a colorless oil. H NMR (400 MHz, CDCl3) δ 7.21−7.10
(m, 2H), 6.85−6.77 (m, 1H), 6.75 (d, J = 8.0 Hz, 1H), 5.08 (t, J = 7.2
Hz, 1H), 4.83 (t, J = 6.8 Hz, 1H), 3.74 (s, 3H), 2.18−2.12 (m, 2H),
1.99−1.94 (m, 2H), 1.62 (s, 3H), 1.54 (s, 3H), 1.42−1.31 (m, 2H),
0.83 (s, 9H), −0.21 (s, 6H). Anal. Calcd for C22H36O2Si: C, 73.28; H,
10.06. Found C, 72.89; H, 9.81.
(Z)-tert-Butyl((1-(4-ethylphenyl)-7-methylocta-1,6-dien-1-yl)oxy)-
dimethylsilane (2e). Prepared according to the general procedure C
employing 1e (0.7609 g, 3.1 mmol), LDA (2 M in THF, 1.9 mL, 3.7
124.5, 121.1, 112.6, 29.7, 27.9, 25.8, 25.7, 18.3, 17.7, −4.0; HRMS (EI-
TOF) Calcd for C21H33OSiBr [M]+: 408.1484, found 408.1486.
(Z)-tert-Butyl((1-(2,5-dimethoxyphenyl)-7-methylocta-1,6-dien-1-
yl)oxy)dimethylsilane (2h). Prepared according to the general
procedure C employing 1h (1.1886 g, 4.3 mmol), LDA (2 M in
THF, 4.0 mL, 8 mmol), TBDMSOTf (1.6 mL, 7.0 mmol) and THF (6
mL) as starting materials to afford 2h (1.4530 g, 3.7 mmol, 74% yield)
1
as a colorless oil. IR ν 2932, 2856, 1658, 1496, 1216, 1053 cm−1; H
H
DOI: 10.1021/acs.joc.6b01016
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
NMR (400 MHz, CDCl3) δ 6.88 (dd, J = 2.0, 1.6 Hz 1H), 6.76 (d, J =
2.0 Hz, 2H), 5.18−5.17 (m, 1H), 4.98 (t, J = 7.2 Hz, 1H), 3.78 (s,
3H), 3.76 (s, 3H), 2.22−2.19 (m, 2H), 2.07−2.01 (m, 2H), 1.70 (s,
3H), 1.62 (s, 3H), 1.4−1.10 (m, 2H), 0.93 (s, 9H), −0.10 (s, 6H); 13C
NMR (101 MHz, CDCl3) δ 153.0, 151.2, 146.2, 131.3, 130.0, 124.8,
115.9, 114.2, 113.4, 112.1, 55.9, 55.7, 29.9, 27.9, 25.7, 25.9, 25.5, 18.3,
17.6, −4.5; HRMS (EI-TOF) Calcd for C23H38O3Si [M]+: 390.2590,
found 390.2592.
(Z)-tert-Butyldimethyl((7-methyl-1-(naphthalen-2-yl)octa-1,6-
dien-1-yl)oxy)silane (2i). Prepared according to the general procedure
C employing 1i (1.0964 g, 4.1 mmol), LDA (2 M in THF, 2.6 mL, 5.2
mmol), TBDMSOTf (1.4 mL, 6.0 mmol) and THF (8 mL) as starting
materials to afford 2i (0.9371 g, 2.4 mmol, 60% yield) as a colorless oil.
IR ν 2929, 2856, 1646, 1467, 1255 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.94 (s, 1H), 7.84 (dd, J = 6.8, 6.0 Hz, 2H), 7.79 (d, J = 8.6
Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.51−7.45 (m, 2H), 5.33 (t, J = 7.2
Hz, 1H), 5.22 (t, J = 6.8 Hz, 1H), 2.34−2.29 (m, 2H), 2.15−2.10 (m,
2H), 1.76 (s, 3H), 1.68 (s, 3H), 1.59−1.51 (m, 2H), 1.08 (s, 9H), 0.03
(s, 6H); 13C NMR (101 MHz, CDCl3) δ 149.2, 137.2, 133.2, 132.8,
131.5, 128.1, 127.6, 127.4, 126.0, 125.7, 124.6, 124.34, 124.33, 112.7,
29.9, 27.9, 26.0, 25.9, 25.8, 18.4, 17.7, −4.0; HRMS (EI-TOF) Calcd
for C25H36OSi [M]+: 380.2535, found 380.2531.
CDCl3) δ 7.43 (d, J = 8.0 Hz, 2H), 7.30−7.22 (m, 3H), 5.18−5.14 (m,
1H), 4.88 (d, J = 9.6 Hz, 1H), 2.77−2.66 (m, 1H), 2.06−2.00 (m,
2H), 1.70 (s, 3H), 1.62 (s, 3H), 1.41−1.31 (m, 2H), 1.03 (d, J = 6.8
Hz, 3H), 1.00 (s, 9H), −0.02 (s, 3H), −0.07 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 148.4, 140.1, 131.0, 127.8, 127.3, 126.2, 125.0, 118.4,
37.9, 30.0, 26.0, 25.9, 25.7, 20.8, 18.3, 17.6, −4.0, −4.1; HRMS (EI-
TOF) Calcd for C22H36OSi [M]+: 344.2535, found 344.2534.
(Z)-tert-Butyldimethyl((8-methyl-1-phenylnona-1,7-dien-1-yl)-
oxy)silane (2n). Prepared according to the general procedure C
employing 1n (0.5868 g, 2.5 mmol), LDA (2 M in THF, 1.5 mL, 3.0
mmol), TBDMSOTf (0.8 mL, 3.5 mmol) and THF (5 mL) as starting
materials to afford 2n (0.7785 g, 2.2 mmol, 89% yield) as a colorless
oil. IR ν 2928, 2856, 1689, 1256 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.44−7.41 (m, 2H), 7.29−7.19 (m, 3H), 5.15−5.08 (m, 2H), 2.22−
2.17 (m, 2H), 2.02−1.97 (m, 2H), 1.69 (s, 3H), 1.60 (s, 3H), 1.44−
1.36 (m, 4H), 0.98 (s, 9H), −0.05 (s, 6H); 13C NMR (101 MHz,
CDCl3) δ 149.2, 139.9, 131.2, 127.8, 127.3, 125.9, 124.8, 112.0, 29.8,
29.4, 28.0, 26.1, 25.9, 25.7, 18.3, 17.7, −4.1; HRMS (EI-TOF) Calcd
for C22H36OSi [M]+: 344.2535, found 344.2534.
(Z)-tert-Butyldimethyl((6-methyl-1-phenylhepta-1,5-dien-1-yl)-
oxy)silane (2o). Prepared according to the general procedure C
employing 1o (1.0135 g, 5.0 mmol), LDA (2 M in THF, 2.2 mL, 4.5
mmol), TBDMSOTf (1.05 mL, 4.5 mmol) and THF (6 mL) as
starting materials to afford 2o (1.0713g, 3.0 mmol, 66% yield) as a
colorless oil. IR ν 2929, 2857, 1650, 1255 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.49−7.45 (m, 2H), 7.31−7.21 (m, 3H), 5.19 (t, J = 6.8 Hz,
1H), 5.12 (t, J = 7.2 Hz, 1H), 2.27−2.22 (m, 2H), 2.14−2.08 (m 2H),
1.72 (s, 3H), 1.64 (s, 3H), 0.99 (s, 9H), −0.04 (s, 6H); 13C NMR
(101 MHz, CDCl3) δ 149.3, 139.9, 131.7, 127.9, 127.3, 125.9, 124.3,
111.6, 28.2, 26.5, 25.9, 25.8, 18.3, 17.8, −4.0; HRMS (EI-TOF) Calcd
for C20H32OSi [M]+: 316.2222, found 316.2222.
(Z)-2-(1-((tert-Butyldimethylsilyl)oxy)-7-methylocta-1,6-dien-1-
yl)-1-methyl-1H-indole (2j). Prepared according to the general
procedure C employing 1j (1.1314 g, 4.2 mmol), LDA (2 M in
THF, 2.3 mL, 5.5 mmol), TBDMSOTf (1.4 mL, 6.3 mmol) and THF
(8 mL) as starting materials to afford 2j (1.1184 g, 2.9 mmol, 69%
1
yield) as a colorless oil. IR ν 2929, 2857, 1661, 1465, 1254 cm−1; H
NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.0 Hz, 1H), 7.33−7.21 (m,
2H), 7.21 (t, J = 7.6 Hz, 1H), 6.44 (s, 1H), 5.20 (t, J = 7.2 Hz, 1H),
5.12 (t, J = 7.2 Hz, 1H), 3.74 (s, 3H), 2.29−2.23 (m, 2H), 2.-2.06 (m,
2H), 1.74 (s, 3H), 1.66 (s, 3H), 1.54−1.46 (m, 2H), 0.97 (s, 9H),
−0.13 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 141.9, 139.7, 137.6,
131.6, 127.5, 124.5, 121.7, 120.6, 119.5, 116.8, 109.2, 101.4, 30.9, 29.7,
27.8, 25.8, 25.7, 25.3, 18.1, 17.7, −5.1; HRMS (EI-TOF) Calcd for
C24H37NOSi [M]+: 383.2644, found 383.2643.
tert-Butyldimethyl(((1Z,5E/Z)-1-phenylocta-1,5-dien-1-yl)oxy)-
silane13 (2p). Prepared according to the general procedure C
employing(Z/E)-1-phenylnon-6-en-1-one (1.0166 g, 4.7 mmol),
LDA (2 M in THF, 3.1 mL, 6.2 mmol), TBDMSOTf (1.5 mL, 7.0
mmol) and THF (9 mL) as starting materials to afford the title
compound (1.1343 g, 3.4 mmol, 73% yield) as a colorless oil. 1H NMR
(400 MHz, CDCl3) δ 7.44 (d, J = 7.0 Hz, 2H), 7.32−7.25 (m, 3H),
5.49−5.32 (m, 2H), 5.12 (t, J = 7.2 Hz, 1H), 2.29−2.20 (m, 2H),
2.15−1.98 (m, 4H), 1.56−1.46 (m, 2H), 1.03−0.95 (m, 12H), −0.04
(s, 6H). Anal. Calcd for C21H34OSi: C, 76.30; H, 10.37. Found C,
76.15; H, 10.04.
(Z)-2-(1-((tert-Butyldimethylsilyl)oxy)-7-methylocta-1,6-dien-1-
yl)-1,5-dimethyl-1H-indole (2k). Prepared according to the general
procedure C employing 1k (0.4757 g, 1.24 mmol), LDA (2 M in THF,
0.8 mL, 1.6 mmol), TBDMSOTf (0.5 mL, 1.9 mmol) and THF (6
mL) as starting materials to afford 2k (0.4091 g, 1.0 mmol, 83% yield)
1
as a colorless oil. IR ν 2928, 2856, 1661, 1253 cm−1; H NMR (400
MHz, CDCl3) δ 7.38 (s, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.06 (dd, J =
8.4, 1.2 Hz, 1H), 6.36 (s, 1H), 5.23−5.19 (m, 1H), 5.11 (t, J = 7.4 Hz,
1H), 3.72 (s, 3H), 2.47 (s, 3H), 2.29−2.23 (m, 2H), 2.012−2.06 (m,
2H), 1.75 (s, 3H), 1.66 (s, 3H), 1.54−1.47 (m, 2H), 0.98 (s, 9H),
−0.12 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 142.0, 139.7, 136.1,
131.5, 128.6, 127.7, 124.6, 123.3, 120.3, 116.5, 108.9, 100. 9, 30.9, 29.7,
27.8, 25.8, 25.7, 25.3, 21.4, 18.1, 17.7, −5.1; HRMS (EI-TOF) Calcd
for C25H39NOSi [M]+: 397.2801, found 397.2807.
(Z)-Diethyl-2-(3-((tert-butyldimethylsilyl)oxy)-3-phenylallyl)-2-(3-
methylbut-2-en-1-yl)malonate (2l). Prepared according to the
general procedure C employing 1l (0.9682 g, 2.7 mmol), LDA (2 M
in THF, 1.6 mL, 3.2 mmol), TBDMSOTf (0.87 mL, 3.8 mmol) and
THF (6 mL) as starting materials to afford 2l (1.1175 g, 2.4 mmol,
88% yield) as a colorless oil. IR ν 2931, 2859, 1731, 1648, 1253 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.42 (dd, J = 8.0, 1.6 Hz, 2H), 7.28−
7.26 (m, 3H), 5.10−5.07 (m, 1H), 5.00 (t, J = 7.2 Hz, 1H), 4.21 (q, J =
6.4 Hz, 4H), 2.85 (d, J = 7.2 Hz, 2H), 2.66 (d, J = 7.6 Hz, 2H), 1.74 (s,
3H), 1.65 (s, 3H), 1.27 (t, J = 7.2 Hz, 6H), 1.04 (s, 9H), −0.00 (s,
6H); 13C NMR (101 MHz, CDCl3) δ 171.4, 151.8, 139.4, 135.2,
127.8, 127.6, 125.9, 118.1, 105.0, 61.0, 57.6, 31.4, 29.4, 27.0, 25.8, 18.2,
17.8, 14.0, −4.1; HRMS (EI-TOF) Calcd for C27H42O5Si [M]+:
474.2802, found 474.2804.
(Z)-tert-Butyl((3,7-dimethyl-1-phenylocta-1,6-dien-1-yl)oxy)-
dimethylsilane13 (2m). Prepared according to the general procedure
C employing 1m (0.9192 g, 4.0 mmol), LDA (2 M in THF, 2.6 mL,
5.2 mmol), TBDMSOTf (1.4 mL, 6.0 mmol) and THF (6 mL) as
starting materials to afford 2m (1.1077 g, 3.2 mmol, 81% yield) as a
colorless oil. IR ν 2957, 2858, 1648, 1255 cm−1; 1H NMR (400 MHz,
General Procedure for Oxidative [4 + 2] Cycloaddition of
Aryl Silyl Enol Ethers. To a 50 mL flame-dried Schlenk flask
containing 4 Å MS (100 wt %) cooled under N2, (NH4)2S2O8 (3
equiv), Ru(bpy)3(PF6)2 (1.5 mol %), 2 (0.3 mmol) and MeOH (6
mL) were added. The mixture was degassed through three freeze−
pump−thaw cycles under N2. The reaction was placed at room
temperature and stirred in front of a 18W compact fluorescent lamp at
a distance of 15 cm for 17 h. The reaction was diluted with Et2O and
filtered through a short pad of silica using Et2O. The filtrate was
concentrated in vacuo before it was purified by flash chromatography
on silica gel to afford 3.
To a 50 mL flame-dried Schlenk flask cooled under N2, 2,4-
dinitrofenylhydrazin, Cat.H2SO4 (con.) (two drops), MeOH (3 mL)
was added. The mixture was stirred at 50 °C for 15 min. Then 3
(without purification) dissolved in MeOH (6 mL) was added via
syringe. The mixture was stirred for another 4 h at 50 °C. After cooled
to room temperature, the solid was filtered and washed by small
amount of MeOH, dried in vacuo, affording the title compound 4.
(E)-1-(9,9-Dimethyl-3,3a,9,9a-tetrahydro-1H-cyclopenta[b]-
naphthalen-4(2H)-ylidene)-2-(2,4-dinitrophenyl)hydrazine (4a).
Prepared according to the general procedure employing (NH4)2S2O8
(0.2122 g, 0.92 mmol), 4 Å MS (0.0902 g), Ru(bpy)3(PF6)2 (0.0043 g,
0.005 mmol), 2a (0.0866 g, 0.29 mmol) and MeOH (6 mL). After 17
h, the reaction was diluted with Et2O and passed through a short pad
of silica using Et2O. The filtrate was concentrated in vacuo. The crude
1
mixture was monitored by H NMR (dr = 5:1), and then condensed
with DNP (0.1123 g, 0.57 mmol) in MeOH (9 mL) affording 4a as a
red solid (0.6557 g, 0.164 mmol, 57% yield) by filtration and washed
I
DOI: 10.1021/acs.joc.6b01016
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
by MeOH. mp = 206−208 °C; IR ν 3331, 3109, 1615, 1589, 1335
(d, J = 8.4 Hz, 1H), 3.86 (s, 3H), 2.77−2.65 (m, 1H), 2.17−2.06 (m,
1H), 2.06−1.96 (m, 1H), 1.91−1.81 (m, 2H), 1.80−1.61 (m, 2H),
1.60−1.49 (m, 1H), 1.39 (s, 3H), 1.25 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 199.7, 159.4, 156.0, 133.3, 122.7, 118.8, 109.5, 56.0, 53.8,
50.6, 38.4, 29.9, 27.0, 23.9, 23.2, 22.4; HRMS (EI-TOF) Calcd for
C16H20O2 [M]+: 244.1463, found 244.1459.
(3a*R,9aR)-7-Ethyl-9,9-dimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3e). Prepared according to the
general procedure employing (NH4)2S2O8 (0.2108 g, 0.88 mmol), 4 Å
MS (0.1132 g), Ru(bpy)3(PF6)2 (0.0048 g, 0.005 mmol), 2eb (0.1132
g, 0.28 mmol) and MeOH (6 mL). After 17 h, the reaction was diluted
with Et2O and passed through a short pad of silica using Et2O. The
filtrate was concentrated in vacuo. The crude mixture was monitored
by 1H NMR (dr = 10:1), and then purified by flash column
chromatography using 60:1 PE/EtOAc as the eluent to give 3e
(0.0649 g, 0.268 mmol, 95% yield, dr = 10:1) as a white solid.
When employing (NH4)2S2O8 (0.2021 g, 0.88 mmol), 4 Å MS
(0.1013 g), Ru(bpy)3(PF6)2 (0.0040 g, 0.005 mmol), 2ea (0.1013 g,
0.28 mmol) and MeOH (6 mL) as starting materials, affording 3e
(0.0441 g, 0.18 mmol, 64% yield, dr = 4:1).
1
cm−1; H NMR (400 MHz, CDCl3) δ 11.49 (s, 1H), 9.14 (d, J = 2.4
Hz, 1H), 8.34 (dd, J = 9.6, 2.4 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.15
(d, J = 9.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.39 (dd, J = 7.6, 7.6 Hz,
1H), 7.29 (t, J = 7.6 Hz, 1H), 2.97−2.91 (m, 1H), 2.75−2.67 (m, 1H),
2.09−1.75 (m, 6H), 1.45 (s, 3H), 1.13 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 155.2, 150.4, 145.0, 137.9, 132.2, 130.1, 129.9, 129.6, 126.2,
126.1, 125.0, 123.5, 116.8, 53.2, 40.5, 36.3, 27.3, 23.9, 22.9, 22.1;
HRMS (EI-TOF) Calcd for C21H22N4O4 [M]+: 394.1641, found
394.1642.
(E)-1-(2,4-Dinitrophenyl)-2-(7-methoxy-9,9-dimethyl-3,3a,9,9a-
tetrahydro-1H-cyclopenta[b]naphthalen-4(2H)-ylidene)hydrazine
(4b). Prepared according to the general procedure employing
(NH4)2S2O8 (0.2065g, 0.90 mmol), 4 Å MS (0.1132 g), Ru-
(bpy)3(PF6)2 (0.0042 g, 0.005 mmol), 2b (0.1023 g, 0.28 mmol)
and MeOH (6 mL). After 17 h, the reaction was diluted with Et2O and
passed through a short pad of silica using Et2O. The filtrate was
concentrated in vacuo. The crude mixture was monitored by 1H NMR
(dr = 7:1) and then condensed with DNP (0.1123 g, 0.57 mmol) in
MeOH (9 mL) to afford the red solid (0.0754 g, 0.172 mmol, 61%
yield) by filtration and washed by MeOH. mp = 156−157 °C; IR ν
When employing (NH4)2S2O8 (0.2104 g, 0.88 mmol), 4 Å MS
(0.1113 g), Ru(bpy)3(PF6)2 (0.0042 g, 0.005 mmol), 2 (0.1007 g, 0.28
mmol) and MeOH (6 mL) as starting materials, affording 3e (0.0608
g, dr = 10:1, 0.25 mmol, 89% yield).
1
3314, 2958, 1614, 1589, 1334 cm−1; H NMR (400 MHz, CDCl3) δ
11.49 (s, 1H), 9.15 (s, 1H), 8.31 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 9.2
Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 6.95−6.75 (m, 2H), 3.88 (s, 3H),
3.56−3.36 (m, 1H), 2.73−2.55 (m, 1H), 2.41−2.25 (m, 1H), 1.87−
1.72 (m, 1H), 1.70−1.50 (m, 3H), 1.44 (s, 3H), 1.18 (s, 3H), 1.06−
0.85 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 161.7, 157.9, 148.5,
144.8, 137.6, 129.9, 129.3, 128.2, 124.0, 123.6, 116.7, 111.5, 111.1,
55.3, 51.9, 37.3, 36.6, 32.3, 31.1, 29.4, 26.3, 25.8; HRMS (EI-TOF)
Calcd for C22H24N4O5 [M]+: 424.1747, found 424.1743.
1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.0 Hz, 1H), 7.28 (d, J
= 1.2 Hz, 1H), 7.13 (dd, J = 8.0, 1.6 Hz, 1H), 2.73−2.63 (m, 3H),
2.09−1.99 (m, 2H), 1.98−1.84 (m, 2H), 1.83−1.63 (m, 2H), 1.61−
1.48 (m, 1H), 1.42 (s, 3H), 1.30−1.22 (m, 6H). Anal. Calcd for
C17H22O: C, 84.25; H, 9.15. Found C, 83.90; H, 8.91.
(E)-1-(2,4-Dinitrophenyl)-2-(7-fluoro-9,9-dimethyl-3,3a,9,9a-tet-
rahydro-1H-cyclopenta[b]naphthalen-4(2H)-ylidene)hydrazine (4f).
Prepared according to the general procedure employing (NH4)2S2O8
(0.2063g, 0.90 mmol), 4 Å MS (0.1050 g), Ru(bpy)3(PF6)2 (0.0044 g,
0.005 mmol), 2f (0.1002 g, 0.288 mmol) and MeOH (6 mL). After 17
h, the reaction was diluted with Et2O and passed through a short pad
of silica using Et2O. The filtrate was concentrated in vacuo. The crude
(3a*R,9a*R)-8-Methoxy-9,9-dimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3c). Prepared according to the
general procedure employing (NH4)2S2O8 (0.2002 g, 0.88 mmol), 4 Å
MS (0.0912 g), Ru(bpy)3(PF6)2 (0.0046 g, 0.005 mmol), 2c (0.1039 g,
0.29 mmol) and MeOH (6 mL). After 17 h, the reaction was diluted
with Et2O and passed through a short pad of silica using Et2O. The
filtrate was concentrated in vacuo. The crude mixture was monitored
by 1H NMR (dr > 20:1), and then purified by flash column
chromatography using 50:1 PE/EtOAc as the eluent to give 3c
(0.0161 g, 0.066 mmol, 23% yield) as a white solid and 3c′ (0.0467 g,
0.191 mmol, 66% yield) as a white solid. mp = 108−110 °C; IR ν
1
mixture was monitored by H NMR (dr = 5:1), and then condensed
with DNP (0.1181 g, 0.60 mmol) in MeOH (9 mL) affording the red
solid (0.0601 g, 0.146 mmol, 49% yield) by filtration and washed by
MeOH. mp = 241−243 °C; IR ν 3335, 2963, 1617, 1589, 1337 cm−1
;
1H NMR (400 MHz, CDCl3) δ 11.47 (s, 1H), 9.15 (s, 1H), 8.36 (d, J
= 9.2 Hz, 1H), 8.27 (dd, J = 8.8, 6.4 Hz, 1H), 8.11 (d, J = 9.6 Hz, 1H),
7.11 (d, J = 8.4 Hz, 1H), 7.04−6.94 (m, 1H), 3.02−2.86 (m, 1H),
2.77−2.61 (m, 1H), 2.08−1.71 (m, 6H), 1.43 (s, 3H), 1.12 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 164.1 (d, J = 251.5 Hz), 154.3, 153.2
1
2959, 2874, 1694, 1664, 1260 cm−1; H NMR (400 MHz, CDCl3) δ
7.66 (d, J = 7.6 Hz, 1H), 7.27 (dd, J = 8.0, 8.0 Hz, 1H), 7.07 (d, J = 8.0
Hz, 1H), 3.88 (s, 3H), 2.74−2.60 (m, 1H), 2.10−1.85 (s, 5H), 1.84−
1.73 (m, 1H), 1.72−1.64 (m, 1H), 1.53 (s, 3H), 1.36 (s, 3H); 13C
NMR (101 MHz, CDCl3) δ 200.4, 158.5, 140.8, 134.7, 127.1, 119.6,
116.2, 55.4, 54.2, 48.3, 38.0, 27.5, 26.4, 23.4, 22.6, 17.8; HRMS (EI-
TOF) Calcd for C16H20O2 [M]+: 244.1463, found 244.1467.
(3a*R,9a*R)-6-Methoxy-9,9-dimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3c′). mp = 102−104 °C; IR ν
2874, 2839, 1691, 1251 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.49 (d,
J = 2.8 Hz, 1H), 7.38 (d, J = 8.8 Hz, 1H), 7.09 (dd, J = 8.8, 2.8 Hz,
1H), 3.84 (s, 3H), 2.76−2.63 (m, 1H), 2.11−1.85 (m, 4H), 1.84−1.75
(m, 1H), 1.74−1.62 (m, 1H), 1.55−1.47 (m, 1H), 1.40 (s, 3H), 1.23
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 200.1, 157.8, 146.4, 133.4,
127.6, 121.4, 109.1, 55.4, 53.2, 49.3, 37.1, 29.1, 26.5, 24.0, 23.1, 22.2;
HRMS (EI-TOF) Calcd for C16H20O2 [M]+: 244.1463, found
244.1468.
(d, J = 7.1 Hz), 145.0, 138.0, 130.0, 129.6, 128.5, 128.4, 123.6, 116.7,
113.7 (d, J = 22.2 Hz), 111.7 (d, J = 22.2 Hz), 53.1, 40.5, 36.6, 30.9,
27.2, 23.9, 22.8 22.1; 19F NMR (376 MHz, CDCl3) δ −110.2; HRMS
(EI-TOF) Calcd for C21H21O4N4F [M]+: 412.1547, found 412.1549.
(E)-1-(7-Bromo-9,9-dimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-ylidene)-2-(2,4-dinitrophenyl)-
hydrazine (4g). Prepared according to the general procedure
employing (NH4)2S2O8 (0.2038 g, 0.90 mmol), 4 Å MS (0.1161 g),
Ru(bpy)3(PF6)2 (0.0044 g, 0.005 mmol), 2g (0.1262 g, 0.308 mmol)
and MeOH (6 mL). After 17 h, the reaction was diluted with Et2O and
passed through a short pad of silica using Et2O. The filtrate was
concentrated in vacuo. The crude mixture was monitored by 1H NMR
(dr = 3:1), and then condensed with DNP (0.1179 g, 0.60 mmol) in
MeOH (9 mL) affording 4g (0.0582 g, 0.123 mmol, 40% yield) as a
red solid by filtration and washed by MeOH. mp = 195−198 °C; IR ν
3329, 2923, 2855, 1724, 1614, 1589, 1334 cm−1; 1H NMR (400 MHz,
CDCl3) δ 11.48 (s, 1H), 9.15 (s, 1H), 8.37 (d, J = 8.4 Hz, 1H), 8.12
(dd, J = 9.6, 8.0 Hz, 2H), 7.56 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 3.03−
2.85 (m, 1H), 2.77−2.58 (m, 1H), 2.10−1.72 (m, 6H), 1.44 (s, 3H),
1.12 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 154.1, 152.2, 144.8,
138.1, 131.3, 130.0, 129.7, 129.5, 128.3, 127.8, 124.7, 123.5, 116.8,
53.0, 40.4, 36.6, 27.3, 27.2, 23.9, 22.8, 22.0; HRMS (EI-TOF) Calcd
for C21H21O4N4Br [M]+: 472.0746, found 472.0744.
(3a*R,9a*R)-5-Methoxy-9,9-dimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3d). Prepared according to the
general procedure employing (NH4)2S2O8 (0.1999 g, 0.88 mmol), 4 Å
MS (0.1073 g), Ru(bpy)3(PF6)2 (0.0041 g, 0.005 mmol), 2d (0.1068
g, 0.30 mmol) and MeOH (6 mL). After 17 h, the reaction was diluted
with Et2O and passed through a short pad of silica using Et2O. The
filtrate was concentrated in vacuo. The crude mixture was monitored
by 1H NMR (dr = 20:1), and then purified by flash column
chromatography using 10:1 PE/EtOAc as the eluent to give 3d
(0.0399 g, 0.1633 mmol, 55% yield) as a white solid. mp = 106−108
1
°C; IR ν 2962, 2874, 1693, 1592, 1467 cm−1; H NMR (400 MHz,
(3a*R,9a*R)-5,8-Dimethoxy-9,9-dimethyl-3,3a,9,9a-tetrahydro-
1H-cyclopenta[b]naphthalen-4(2H)-one (3h). Prepared according to
CDCl3) δ 7.41 (dd, J = 8.0, 8.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 6.80
J
DOI: 10.1021/acs.joc.6b01016
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
the general procedure employing (NH4)2S2O8 (0.2101 g, 0.92 mmol),
4 Å MS (0.1073 g), Ru(bpy)3(PF6)2 (0.0042 g, 0.005 mmol), 2h
(0.1038 g, 0.266 mmol) and MeOH (6 mL). After 17 h, the reaction
was diluted with Et2O and passed through a short pad of silica using
Et2O. The filtrate was concentrated in vacuo. The crude mixture was
monitored by 1H NMR (dr > 20:1), and then purified by flash column
chromatography using 5:1 PE/EtOAc as the eluent to give 3h (0.0676
g, 0.246 mmol, 93% yield) as a white solid. mp = 159−160 °C; IR ν
2957, 2924, 1700, 1465, 1262 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.00 (d, J = 9.2 Hz, 1H), 6.83 (d, J = 9.2 Hz, 1H), 3.828 (s, 3H), 3.825
(s, 3H), 2.79−2.69 (m, 1H), 2.25−2.16 (m, 1H), 2.01−1.91 (m, 1H),
1.91−1.82 (m, 1H), 1.81−1.70 (m, 2H), 1.68−1.55 (m, 2H), 1.50 (s,
3H), 1.36 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 200.0, 153.1,
152.2, 142.1, 125.0, 116.8, 111.4, 56.8, 55.84, 55.78, 50.1, 38.6, 27.8,
26.9, 23.1, 22.5, 18.6; HRMS (EI-TOF) Calcd for C17H22O3 [M]+:
274.1569, found 274.1571.
(3a*R,9a*R)-Diethyl-4,4-dimethyl-9-oxo-3a,4,9,9a-tetrahydro-
1H-cyclopenta[b]naphthalene-2,2(3H)-dicarboxylate (3l). Prepared
according to the general procedure employing (NH4)2S2O8 (0.2077 g,
0.90 mmol), 4 Å MS (0.1470 g), Ru(bpy)3(PF6)2 (0.0042 g, 0.005
mmol), 2l (0.1393 g, 0.293 mmol) and MeOH (6 mL). After 17 h, the
reaction was diluted with Et2O and passed through a short pad of silica
using Et2O. The filtrate was concentrated in vacuo. The crude mixture
1
was monitored by H NMR (dr = 1:2), and then purified by flash
column chromatography using PE/EtOAc (20:1) as the eluent to give
3l and 3l′ (0.0351 g, 0.10 mmol, 33% yield, dr = 1:2) as a colorless oil.
IR ν 2977, 2900, 1731, 1681, 1264 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.96 (dd, J = 8.0, 1.2 Hz, 1H), 7.54 (td, J = 8.0, 1.6 Hz, 1H),
7.38 (d, J = 7.2 Hz, 1H), 7.35−7.27 (m, 1H), 4.27−4.15 (m, 2H),
4.12−4.01 (m, 2H), 3.19−3.12 (m, 1H), 2.79−2.73 (m, 2H), 2.53−
2.41 (m, 1H), 2.40−2.30 (m, 1H), 1.84 (t, J = 13.2 Hz, 1H), 1.46 (s,
3H), 1.33 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 199.5, 172.4, 171.5, 149.6, 134.1,
(3a*R,11a*R)-11,11-Dimethyl-3,3a,11,11a-tetrahydro-1H-
cyclopenta[b]anthracen-4(2H)-one (3i). Prepared according to the
general procedure employing (NH4)2S2O8 (0.2120 g, 0.93 mmol), 4 Å
MS (0.1060 g), Ru(bpy)3(PF6)2 (0.0042 g, 0.005 mmol), 2i (0.1059 g,
0.278 mmol) and MeOH (6 mL). After 17 h, the reaction was diluted
with Et2O and passed through a short pad of silica using Et2O. The
filtrate was concentrated in vacuo. The crude mixture was monitored
by 1H NMR (dr > 20:1), and then purified by flash column
chromatography using 60:1 PE/EtOAc as the eluent to give 3i (0.0234
g, 0.088 mmol, 32% yield) as a white solid. mp = 113−115 °C; IR ν
130.4, 127.8, 126.7, 125.8, 61.7, 61.5, 58.9, 50.6, 47.6, 37.2, 36.6, 35.5,
34.1, 26.7, 14.0, 13.9; HRMS (EI-TOF) Calcd for C21H26O5 [M]+:
358.1780, found 358.1771.
(3a*S,9a*R)-Diethyl-4,4-dimethyl-9-oxo-3a,4,9,9a-tetrahydro-
1H-cyclopenta[b]naphthalene-2,2(3H)-dicarboxylate (3l′). IR ν
2970, 2934, 1730, 1693, 1258, 1063 cm−1; 1H NMR (400 MHz,
CDCl3) δ 8.01 (dd, J = 8.0, 1.6 Hz, 1H), 7.57−7.50 (m, 1H), 7.47 (d, J
= 7.2 Hz, 1H), 7.34−7.27 (m, 1H), 4.29−4.12 (m, 4H), 2.97−2.79 (m,
2H), 2.65 (dd, J = 12.8, 6.8 Hz, 1H), 2.45 (dd, J = 14.0, 10.4 Hz, 1H),
2.36−2.25 (m, 1H), 2.14−2.05 (m, 1H), 1.44 (s, 3H), 1.31−1.22 (m,
9H); 13C NMR (101 MHz, CDCl3) δ 198.4, 172.5, 172.1, 153.2,
133.7, 131.8, 127.2, 126.4, 126.2, 61.7, 61.6, 57.5, 51.50, 48.4, 37.5,
35.2, 33.6, 28.7, 23.2, 14.04, 14.00; HRMS (EI-TOF) Calcd for
C21H26O5 [M]+: 358.1780, found 358.1771.
1
2960, 2875, 1689, 1463, 1221 cm−1; H NMR (400 MHz, CDCl3) δ
8.59 (d, J = 9.2 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 7.90−7.83 (m, 1H),
7.75 (d, J = 8.8 Hz, 1H), 7.57−7.50 (m, 2H), 2.85−2.74 (m, 1H),
2.20−1.92 (m, 4H), 1.91−1.79 (m, 1H), 1.76 (s, 3H), 1.74 (s, 3H),
1.73−1.66 (m, 1H), 1.62−1.56 (m, 1H); 13C NMR (101 MHz,
CDCl3) δ 200.2, 151.3, 137.2, 131.14, 131.12, 129.6, 127.9, 127.5,
127.2, 125.3, 123.3, 55.7, 47.5, 39.1, 30.6, 26.6, 23.6, 22.7, 20.1; HRMS
(EI-TOF) Calcd for C19H20O [M]+: 264.1514, found 264.1513.
(3a*R, 10a*R)-5, 10, 10-Trimethyl-1, 2, 3, 3a, 10, 10a-
hexahydrocyclopenta[b]carbazol-4(5H)-one (3j). Prepared accord-
ing to the general procedure employing (NH4)2S2O8 (0.2091 g, 0.92
mmol), 4 Å MS (0.1082 g), Ru(bpy)3(PF6)2 (0.0040 g, 0.005 mmol),
2j (0.1061 g, 0.277 mmol) and MeOH (6 mL). After 17 h, the
reaction was diluted with Et2O and passed through a short pad of silica
using Et2O. The filtrate was concentrated in vacuo. The crude mixture
(3a*R,9a*R)-3,9,9-Trimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3m).2 Prepared according to
the general procedure employing (NH4)2S2O8 (0.2068 g, 0.90 mmol),
4 Å MS (0.1042 g), Ru(bpy)3(PF6)2 (0.0041g, 0.005 mmol), 2m
(0.1013 g, 0.294 mmol) and MeOH (6 mL). After 17 h, the reaction
was diluted with Et2O and passed through a short pad of silica using
Et2O. The filtrate was concentrated in vacuo. The crude mixture was
monitored by 1H NMR (dr = 2.5:1), and then purified by flash column
chromatography using 50:1 PE/EtOAc as the eluent to give 3m and
3m′ (0.0477 g, 0.209 mmol, 71% yield) as a white solid. IR ν 2962,
1
1
2871, 1691, 1604, 1462, 1227 cm−1; H NMR (400 MHz, CDCl3) δ
was monitored by H NMR (dr > 50:1), and then purified by flash
column chromatography using 50:1 PE/EtOAc as the eluent to give 3j
7.99 (dd, J = 7.6, 1.2 Hz, 1H), 7.54−7.48 (m, 1H), 7.46 (dd, J = 8.0,
1.2 Hz, 1H), 7.31−7.24 (m, 1H), 2.45−2.30 (m, 1H), 2.25 (dd, J =
14.0, 8.8 Hz, 1H), 2.21−2.11 (m, 1H), 2.02−1.90 (m, 1H), 1.86−1.76
(m, 1H), 1.69−1.56 (m, 1H), 1.39 (s, 3H), 1.38−1.30 (m, 1H), 1.26
(s, 3H), 1.24 (d, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
200.1, 153.7, 133.3, 132.5, 127.0, 126.3, 126.1, 55.8, 53.3, 37.7, 33.4,
31.7, 28.6, 24.7, 23.2, 21.5; HRMS (EI-TOF) Calcd for C16H20O
[M]+: 228.1514, found 228.1516.
(3a*R,9a*S)-3,9,9-Trimethyl-3,3a,9,9a-tetrahydro-1H-
cyclopenta[b]naphthalen-4(2H)-one (3m′).13 IR ν 2958, 2870, 1678,
1600, 1455, 1248 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.86 (dd, J =
7.6, 1.2 Hz, 1H), 7.51 (td, J = 8.0, 1.6 Hz, 1H), 7.36 (d, J = 7.2 Hz,
1H), 7.30 (td, J = 7.6, 1.2 Hz, 1H), 2.66 (dd, J = 8.4, 5.2 Hz, 1H),
2.47−2.36 (m, 1H), 2.24−2.11 (m, 1H), 1.87−1.80 (m, 1H), 1.77−
1.70 (m, 1H), 1.43 (s, 3H), 1.25 (s, 3H), 1.20 (d, J = 8.0 Hz, 3H),
1.17- 1.01 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 201.9, 150.2,
133.4, 132.0, 127.4, 126.3, 125.3, 55.7, 50.4, 40.6, 36.0, 34.6, 34.1, 29.4,
26.1, 21.4; HRMS (EI-TOF) Calcd for C16H20O [M]+: 228.1514,
found 228.1512.
(4a*R,9a*R)-10,10-Dimethyl-1,3,4,4a,9a,10-hexahydroanthra-
cen-9(2H)-one (3n). Prepared according to the general procedure
employing (NH4)2S2O8 (0.2129 g, 0.93 mmol), 4 Å MS (0.1059 g),
Ru(bpy)3(PF6)2 (0.0042 g, 0.005 mmol), 2n (0.0957 g, 0.278 mmol)
and MeOH (6 mL). After 17 h, the reaction was diluted with Et2O and
passed through a short pad of silica using Et2O. The filtrate was
concentrated in vacuo. The crude mixture was monitored by 1H NMR
(dr unknown), and then purified by flash column chromatography
using 60:1 PE/EtOAc as the eluent to give 3n (0.0075 g, 0.033 mmol,
(0.0733 g, 0.274 mmol, 99% yield) as a white solid. mp = 174−176
1
°C; H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 1H), 7.40−
7.33 (m, 2H), 7.15−7.10 (m, 1H), 4.06 (s, 3H), 2.84−2.74 (m, 1H),
2.25 (ddd, J = 13.6, 12.0, 6.4 Hz, 1H), 2.11−1.99 (m, 1H), 1.98−1.68
(m, 4H), 1.64 (s, 3H), 1.62−1.54 (m, 1H), 1.39 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 194.9, 138.9, 136.8, 130.3, 128.9, 127.5, 123.6,
121.9, 110.3, 56.0, 50.4, 35.5, 31.3, 28.7, 25.4, 23.6, 22.2, 21.6, 20.9;
HRMS (EI-TOF) Calcd for C18H21NO [M]+: 267.1623, found
267.1624.
(3a*R,10a*R)-5,8,10,10-Tetramethyl-1,2,3,3a,10,10a-
hexahydrocyclopenta[b]carbazol-4(5H)-one (3k). Prepared accord-
ing to the general procedure employing (NH4)2S2O8 (0.2057 g, 0.90
mmol), 4 Å MS (0.1061 g), Ru(bpy)3(PF6)2 (0.0040 g, 0.005 mmol),
2k (0.1151 g, 0.29 mmol) and MeOH (6 mL). After 17 h, the reaction
was diluted with Et2O and passed through a short pad of silica using
Et2O. The filtrate was concentrated in vacuo. The crude mixture was
monitored by 1H NMR (dr > 50:1), and then purified by flash column
chromatography using 50:1 PE/EtOAc as the eluent to give 3k
(0.0734 g, 0.261 mmol, 90% yield) as a white solid. mp = 128−129
1
°C; IR ν 2958, 2929, 1666, 1512, 1460 cm−1; H NMR (400 MHz,
CDCl3) δ 7.67 (s, 1H), 7.26 (d, J = 8.6 Hz, 1H), 7.20 (d, J = 8.8 Hz,
1H), 4.03 (s, 3H), 2.82−2.72 (m, 1H), 2.48 (s, 3H), 2.23 (ddd, J =
13.6, 12.0, 6.4 Hz, 1H), 2.10−1.99 (m, 1H), 1.97−1.70 (m, 4H), 1.64
(s, 3H), 1.61−1.51 (m, 1H), 1.39 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 194.9, 138.9, 136.8, 130.3, 128.9, 127.5, 123.6, 121.9, 110.3,
55.9, 50.4, 35.5, 31.3, 28.7, 25.4, 23.6, 22.2, 21.6, 20.9; HRMS (EI-
TOF) Calcd for C19H23NO [M]+: 281.1780, found 281.1782.
K
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
13% yield) as a white solid. IR ν 2925, 2856, 1679, 1598, 1314 cm−1;
1H NMR (400 MHz, CDCl3) δ 8.05−7.99 (m, 1H), 7.55−7.48 (m,
2H), 7.31−7.26 (m, 1H), 2.54−2.45 (m, 1H), 2.41−2.32 m, 1H),
2.07−1.98 (m, 1H), 1.92−1.81 (m, 2H), 1.80−1.71 (m, 1H), 1.42 (s,
3H), 1.31−1.22 (m, 4H), 1.21 (s, 3H); 13C NMR (101 MHz, CDCl3)
δ 199.8, 153.2, 133.6, 130.7, 127.3, 126.2, 125.8, 47.5, 46.2, 37.0, 27.1,
26.9, 26.5, 26.0, 25.7, 25.0; HRMS (EI-TOF) Calcd for C16H20O
[M]+: 228.1514, found 228.1518.
2-Methoxy-6-methyl-1-phenylhept-5-en-1-one (5o). Prepared
according to the general procedure employing (NH4)2S2O8 (0.2042
g, 0.90 mmol), 4 Å MS (0.0972 g), Ru(bpy)3(PF6)2 (0.0040 g, 0.005
mmol), 2o (0.0914 g, 0.289 mmol) and MeOH (6 mL). After 17 h,
the reaction was diluted with Et2O and passed through a short pad of
silica using Et2O. The filtrate was concentrated in vacuo and purified
by flash column chromatography using 50:1 PE/EtOAc as the eluent
to give 5o (0.0188 g, 0.093 mmol, 32% yield) as a colorless oil. IR ν
2925, 1694, 1449, 1122 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.03 (d,
J = 7.2 Hz, 2H), 7.60−7.54 (m, 1H), 7.46 (dd, J = 7.6, 7.6 Hz, 2H),
5.11 (t, J = 8.0 Hz, 1H), 4.44 (dd, J = 7.6, 5.2 Hz, 1H), 3.36 (s, 3H),
2.28−2.06 (m, 2H), 1.85−1.77 (m, 2H), 1.70 (s, 3H), 1.60 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 200.8, 135.2, 133.3, 133.1, 128.63,
(3 × 20 mL). The combined organic layers were dried over Na2SO4,
filtered, concentrated and purified by flash column chromatography
using PE/EtOAc (50:1) as eluent to afford 7 (0.0830 g, 99% yield) as
1
a slight yellow oil. IR ν 2963, 2844, 1468, 1368 cm−1; H NMR (400
MHz, CDCl3) δ 7.80 (dd, J = 7.6, 5.6 Hz, 1H), 7.37−7.31 (m, 1H),
7.25−7.18 (m, 1H), 7.17−7.09 (m, 1H), 3.73 (d, J = 3.2 Hz, 3H),
3.61−3.48 (m, 1H), 2.76−2.62 (m, 1H), 2.61−2.48 (m, 2H), 2.44−
2.29 (m, 1H), 2.09−1.95 (m, 2H), 1.63−1.52 (m, 6H), 1.41−1.34 (m,
3H); 13C NMR (101 MHz, CDCl3) δ 142.8, 138.2, 134.1, 125.1,
120.3, 120.0, 118.41, 118.40, 116.7, 108.9, 35.1, 33.7, 30.5, 29.7, 28.6,
27.3, 22.7, 20.9; HRMS (EI-TOF) Calcd for C19H23N [M]+: 265.1830,
found 265.1831.
(3a*S,10a*R)-5,10,10-Trimethyl-1,2,3,3a,4,5,10,10a-
octahydrocyclopenta[b]carbazole (8). According to a known
procedure.24 To a 50 mL flame-dried Schlenk flask cooled under N2,
NaBH4 (40.5 mg, 1.07 mmol) and 3j (0.0613 g, 0.23 mmol), AlCl3
(0.0800 g, 0.60 mmol), and THF (6 mL) was added, respectively. The
mixture was refluxed for 2 h. When cooled to room temperature, the
mixture was quenched by water and extracted by ethyl acetate. The
combined organic layers were dried by sodium sulfate, filtered,
concentrated and purified by flash chromatography through silica gel
to afford 8 (0.0569 g, 1.0 mmol, 98% yield) as a white solid. mp =
130−131 °C; IR ν 3412, 2957, 2925, 1466, 1090, 736 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.81−7.74 (m, 1H), 7.30 (d, J = 8.0 Hz, 1H),
7.23−7.15 (m, 1H), 7.15−7.07 (m, 1H), 3.63 (d, J = 1.6 Hz, 3H), 3.02
(ddd, J = 15.6, 5.2, 2.0 Hz, 1H), 2.48−2.36 (m, 1H), 2.18−2.05 (m,
1H), 2.05−1.94 (m, 1H), 1.94−1.77 (m, 3H), 1.78−1.66 (m, 1H),
1.59 (s, 3H), 1.51−1.38 (m, 2H), 1.34 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 137.6, 135.4, 125.5, 120.0, 119.7, 119.5, 118.3, 108.8, 55.3,
37.7, 34.1, 31.6, 29.5, 29.0, 28.9, 24.1, 23.2, 23.1; HRMS (EI-TOF)
Calcd for C18H23N [M]+: 253.1830, found 253.1831.
7-Methyl-1-phenyl-2-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)oct-
6-en-1-one (9). To a 50 mL flame-dried Schlenk flask containing 4 Å
MS (100 wt %) cooled under N2, (NH4)2S2O8 (0.2101 g, 0.90 mmol),
Ru(bpy)3(PF6)2 (0.0045 g, 0.0045 mmol), 2a (0.0993 g, 0.30 mmol),
TEMPO (0.0469 g, 0.30 mmol) and MeOH (6 mL) were added. The
mixture was degassed through three freeze−pump−thaw cycles under
N2. The reaction was placed at room temperature and stirred in front
of a 18W compact fluorescent lamp at a distance of 15 cm for 17 h.
The reaction was diluted with Et2O and filtered through a short pad of
silica using Et2O. The filtrate was concentrated in vacuo and purified
by flash chromatography on silica gel using PE/EtOAc (50:1) as
eluent to afford 9 (0.0221 g, 0.06 mmol, 20% yield) as a yellow oil. IR
ν 2927, 2860, 1685, 1457, 1376 cm−1; 1H NMR (400 MHz, CDCl3) δ
8.09 (d, J = 7.3 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.46 (dd, J = 8.0, 7.2
Hz, 2H), 4.98 (t, J = 7.2 Hz, 1H), 4.87 (dd, J = 9.2, 5.2 Hz, 1H), 2.07−
1.83 (m, 4H), 1.61 (s, 3H), 1.60−1.54 (m, 1H), 1.52 (s, 3H), 1.51−
1.44 (m, 2H), 1.43−13.4 (m, 2H), 1.33−1.14 (m, 9H), 1.03 (s, 3H),
0.84 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 201.6, 136.1, 132.9,
131.8, 129.3, 128.4, 124.0, 89.7, 59.8, 40.4, 33.9, 32.6, 27.8, 25.6, 24.9,
20.3, 17.6, 17.1; HRMS (EI-TOF) Calcd for C15H18O [M-
C9H19NO]+: 214.1358, found 214.1363.
128.59, 123.1, 84.1, 57.8, 33.2, 25.7, 24.0, 17.6; HRMS (EI-TOF)
Calcd for C15H20O2 [M]+: 232.1463, found 232.1459.
(3a*R,9*R,9a*S)-9-ethyl-3,3a,9,9a-tetrahydro-1H-cyclopenta[b]-
naphthalen-4(2H)-one (3p).13 Prepared according to the general
procedure employing (NH4)2S2O8 (0.2102 g, 0.93 mmol), 4 Å MS
(0.1009 g), Ru(bpy)3(PF6)2 (0.0041 g, 0.005 mmol), 2p (0.0913g,
0.276 mmol) and MeOH (6 mL). After 17 h, the reaction was diluted
with Et2O and passed through a short pad of silica using Et2O. The
filtrate was concentrated in vacuo. The crude mixture was monitored
by 1H NMR (dr = 12:1), and then purified by flash column
chromatography using 60:1 PE/EtOAc as the eluent to give 3p
1
(0.0229 g, 0.107 mmol, 39% yield) as a white solid. H NMR (400
MHz, CDCl3) δ 8.05 (dd, J = 7.6, 1.2 Hz, 1H), 7.54−7.49 (m, 1H),
7.42 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H), 2.99−2.92 (m, 1H),
2.51 (ddd, J = 13.63, 10.0, 8.0 Hz, 1H), 2.30−1.66 (m, 8H), 1.48 (q, J
= 10.0 Hz, 1H), 0.76 (t, J = 7.6 Hz, 3H).
( 3 a * R , 1 0 a * R ) - 5 , 1 0 , 1 0 - T r i m e t h y l - 4 - m e t h y l e n e -
1,2,3,3a,4,5,10,10a-octahydrocyclopenta[b]carbazole (6). Accord-
ing to a known procedure.22 To a 50 mL flame-dried Schlenk flask
cooled under N2, methyltriphenylphosphonium bromide (0.4307 g,
1.2 mmol) THF (10 mL) and NaH (60%) (0.0502 g, 1.2 mmol) was
added. The mixture was refluxed for 30 mim and then 3j dissolved in
THF (5 mL) was added dropwise. The mixture was refluxed for
another 13 h. Petroleum ether was added and passed through a short
pad of silica with Et2O as eluent. The filtrate was concentrated and in
vacuo and purified by flash column chromatography using PE/EtOAc
(100:1) as the eluent to afford 6 (0.0843 g, 0.3 mmol, 82% yield). mp
1
= 104−106 °C; IR ν 2958, 2870, 1625, 1464, 1241 cm−1; H NMR
(400 MHz, CDCl3) δ 7.89−7.81 (m, 1H), 7.35 (d, J = 6.8 Hz, 1H),
7.31−7.23 (m, 1H), 7.17−7.09 (m, 1H), 5.31 (s, 1H), 5.14 (s, 1H),
3.88 (d, J = 1.6 Hz, 3H), 2.61−2.48 (m, 1H), 2.11−1.99 (m, 1H),
1.98−1.74 (m, 5H), 1.73−1.65 (m, 1H), 1.62 (d, J = 3.2 Hz, 3H), 1.37
(d, J = 3.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 142.2, 139.9,
134.4, 125.0, 124.1, 121.9, 120.8, 118.8, 109.5, 105.6, 56.5, 44.7, 34.7,
32.2, 29.1, 27.5, 24.3, 22.9, 22.8; HRMS (EI-TOF) Calcd for C19H23N
[M]+: 265.1830, found 265.1829.
(Z)-tert-Butyldimethyl((1-(4-(trifluoromethyl)phenyl)prop-1-en-1-
yl)oxy)silane (10). To a 50 mL flame-dried Schlenk flask cooled under
N2, KH (0.2092 g, 5.0 mmol), 1-(4-(trifluoromethyl)phenyl)propan-1-
one (0.9680 g, 5.0 mmol) and THF (10 mL) was added. The mixture
was stirred for 1 h at room temperature and then TBSCl (0.9123 g, 6.0
mmol) was added. The mixture was stirred overnight and filtered
through a short pad of silica gel, concentrated and purified by flash
column chromatography using petroleum ether as eluent to afford 10
(1.4131 g, 4.47 mmol, 93% yield) as a colorless oil. IR ν 2934, 2861,
4,5,10,10-Tetramethyl-1,2,3,5,10,10a-hexahydrocyclopenta[b]-
carbazole (7). According to a known procedure.23 To a 50 mL flame-
dried Schlenk flask cooled under N2, methylmagnesium bromide (3 M
in THF) (0.6 mmol) was added dropwise to a solution of 3j in THF
(5 mL) at 0 °C. The mixture was stirred at room temperature
overnight. The mixture was treated with saturated NH4Cl, The two
layers were separated and the aqueous one was extracted with Et2O (3
× 20 mL). The combined organic layers were dried over Na2SO4,
filtered and concentrated to afford the crude product. The crude
product was dissoloved in toluene (10 mL), and p-toluenesulfonic acid
monohydrate (0.0104 g, 0.06 mmol) was added under N2. The
mixture was refluxed overnight. The mixture was treated with saturated
NaHCO3 and separated. The aqueous layers was extracted with EtOAc
1
1324, 1127, 1067, 841 cm−1; H NMR (400 MHz, CDCl3) δ 7.54 (s,
4H), 5.32 (q, J = 6.9 Hz, 1H), 1.76 (d, J = 6.9 Hz, 3H), 1.00 (s, 9H),
−0.03 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 149.0, 143.3, 129.3 (q,
J = 32.4 Hz), 125.7, 125.0 (q, J = 3.7 Hz), 123.0, 108.1, 25.8, 18.3,
11.8, −4.0; 19F NMR (376 MHz, CDCl3) δ −62.4; HRMS (EI-TOF)
Calcd for C16H23OSiF3 [M]+: 316.1470, found 316.1467.
2-((tert-butyldimethylsilyl)peroxy)-1-(4-(trifluoromethyl)phenyl)-
propan-1-one (11). To a 50 mL flame-dried Schlenk flask cooled
under O2 balloon, (Z)-tert-butyldimethyl((1-(4-(trifluoromethyl)-
L
DOI: 10.1021/acs.joc.6b01016
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The Journal of Organic Chemistry
Note
phenyl)prop-1-en-1-yl)oxy)silane (0.1264 g, 0.4 mmol), Ru-
(bpy)3(PF6)2 (0.0037 g, 0.004 mmol) and MeCN (8 mL) was
added. The reaction was placed at room temperature and stirred in
front of a 18W compact fluorescent lamp at a distance of 15 cm for 8
h. The reaction was diluted with Et2O and passed through a short pad
of silica using Et2O. The filtrate was concentrated and in vacuo and
purified by flash chromatography on silica gel to afford 11 (0.1136 g,
(3) For selected reviews on visible light photocatalysis in organic
transformations, see: (a) Yoon, T. P.; Ischay, M. A.; Du, J. Nat. Chem.
2010, 2, 527. (b) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc.
Rev. 2011, 40, 102. (c) Teply, F. Collect. Czech. Chem. Commun. 2011,
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76, 859. (d) Xuan, J.; Xiao, W. Angew. Chem., Int. Ed. 2012, 51, 6828.
(e) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013,
113, 5322. (f) Schultz, D. M.; Yoon, T. P. Science 2014, 343, 985.
(g) Wang, C.; Lu, Z. Org. Chem. Front. 2015, 2, 179.
(4) For reviews on visible light-promoted cycloadditions, see:
(a) Yoon, T. P. ACS Catal. 2013, 3, 895. (b) Xuan, J.; Lu, L.; Chen,
J.; Xiao, W. Eur. J. Org. Chem. 2013, 6755. For examples on visible
light-promoted [4 + 2] cycloaddition reactions, see: (c) Lemieux, V.;
Branda, N. R. Org. Lett. 2005, 7, 2969. (d) Chen, Y.; Steinmetz, M. G.
J. Org. Chem. 2006, 71, 6053. (e) Hurtley, A. E.; Cismesia, M. A.;
Ischay, M. A.; Yoon, T. P. Tetrahedron 2011, 67, 4442. (f) Lin, S.;
Ischay, M. A.; Fry, C. G.; Yoon, T. P. J. Am. Chem. Soc. 2011, 133,
19350. (g) Lin, S.; Padilla, C. E.; Ischay, M. A.; Yoon, T. P.
Tetrahedron Lett. 2012, 53, 3073. (h) Yuan, Z.; Wang, Q.; Zheng, A.;
Zhang, K.; Lu, L.-Q.; Tang, Z.; Xiao, W. Chem. Commun. 2016, 52,
5128.
1
82% yield) as a colorless oil. IR ν 2934, 2860, 1323, 1133 cm−1; H
NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.0
Hz, 2H), 5.14 (d, J = 6.8 Hz, 1H), 1.47 (d, J = 6.8 Hz, 3H), 0.85 (s,
9H), 0.10 (s, 6H); 13C NMR (101 MHz, CDCl3) δ 198.5, 138.1, 134.2
(d, J = 32.6 Hz), 129.3, 125.4 (q, J = 3.7 Hz), 84.0, 26.0, 25.7, 18.1,
15.5, −6.0; 19F NMR (376 MHz, CDCl3) δ −63.2; HRMS (ESI)
Calcd for C16H23F3O3Si [M-H]−: 347.1290, found 347.1288.
(3a*R, 10a*S)-5, 10, 10-Trimethyl-1, 2, 3, 3a, 10, 10a-
hexahydrocyclopenta[b]carbazol-4(5H)-one (3j′). Prepared accord-
ing to a general procedure using 2j (Z/E 4:1, 0.0963 g, 0.25 mmol),
(NH4)2S2O8 (0.2102 g, 0.92 mmol), 4 Å MS (0.0963 g),
Ru(bpy)3(PF6)2 (0.0041 g, 0.005 mmol), MeOH (6 mL). After 17
h, the reaction was diluted with Et2O and passed through a short pad
of silica using Et2O. The filtrate was concentrated in vacuo. The crude
(5) Wang, C.; Ren, X.; Xie, H.; Lu, Z. Chem. - Eur. J. 2015, 21, 9676.
(6) For examples on visible light photocatalytic reactions using silyl
enols as radical trappers, see: (a) Pham, P. V.; Nagib, D. A.;
MacMillan, D. W. C. Angew. Chem., Int. Ed. 2011, 50, 6119. (b) Zhao,
G.; Yang, C.; Guo, L.; Sun, H.; Chen, C.; Xia, W. Chem. Commun.
2012, 48, 2337. (c) Yasu, Y.; Koike, T.; Akita, M. Chem. Commun.
2012, 48, 5355.
1
mixture was monitored by H NMR (dr = 4:1) and then purified by
flash column chromatography using PE/EtOAc (50:1) as the eluent to
give 3j and 3j′ (total: 0.0681 g, 0.25 mmol, 99% yield, 4/1 dr) as white
solids.
3j′: mp = 86−88 °C; IR ν 2957, 2926, 1653, 1467, 1053, 742 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 8.4 Hz, 1H), 7.40−7.33
(m, 2H), 7.11 (ddd, J = 8.1, 6.0, 1.6 Hz, 1H), 4.06 (s, 3H), 3.06−3.01
(m, 1H), 2.53 (ddd, J = 13.2, 7.6, 1.2 Hz, 1H), 2.26−2.18 (m, 1H),
1.89−1.75 (m, 2H), 1.68 (s, 3H), 1.66−1.60 (m, 2H), 1.54 (s, 3H),
1.46−1.37 (m, 1H); 13C NMR (101 MHz, CDCl3) δ 194.0, 140.4,
133.9, 128.1, 126.0, 124.3, 123.1, 119.7, 110.5, 55.0, 49.5, 34.8, 32.5,
31.5, 28.0, 27.5, 26.7, 22.4; HRMS (EI-TOF) Calcd for C18H21NO
[M]+: 267.1623, found 267.1626.
(7) Pearson, W. H.; Lin, K. C.; Poon, Y. F. J. Org. Chem. 1989, 54,
5814.
(8) Lin, M.; Das, A.; Liu, R. S. J. Am. Chem. Soc. 2006, 128, 9340.
(9) For an example on using (NH4)2S2O8 as an oxidant to oxidize the
excited state of Ru(bpy)32+, see: Dai, C.; Meschini, F.; Narayanam, J.
M. R.; Stephenson, C. R. J. J. Org. Chem. 2012, 77, 4425.
(10) For an example on alkylation of aldehydes using iron-based
visible light photosensitizer, see: Gualandi, A.; Marchini, M.;
Mengozzi, L.; Natali, M.; Lucarini, M.; Ceroni, P.; Cozzi, P. G. ACS
Catal. 2015, 5, 5927.
(11) (a) Fagnoni, M.; Dondi, D.; Ravelli, D.; Albini, A. Chem. Rev.
2007, 107, 2725. For an example on visible light-promoted Saegusa-
type reaction by using oxygen as a terminal oxidant, see: (b) Zhang, J.;
Wang, L.; Liu, Q.; Yang, Z.; Huang, Y. Chem. Commun. 2013, 49,
11662.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01016.
Characterization data for all new compounds. (PDF)
(12) Tzirakis, M. D.; Alberti, M. N.; Orfanopoulos, M. Org. Lett.
2011, 13, 3364.
(13) Gribkov, D. V.; Hultzsch, K. C.; Hampel, F. J. Am. Chem. Soc.
2006, 128, 3748.
AUTHOR INFORMATION
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Corresponding Author
*E-mail: luzhan@zju.edu.cn.
Notes
(14) Ganton, M. D.; Kerr, M. A. Org. Lett. 2005, 7, 4777.
(15) Sechi, M.; Derudas, M.; Dallocchio, R.; Dessì, A.; Bacchi, A.;
Sannia, L.; Carta, F.; Palomba, M.; Ragab, O.; Chan, C.; Shoemaker,
R.; Sei, S.; Dayam, R.; Neamati, N. J. Med. Chem. 2004, 47, 5298.
(16) Shang, R.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2015, 137,
7660.
(17) Qiu, Y.; Zhu, X.; Li, Y.; He, Y.; Yang, F.; Wang, J.; Hua, H.;
Zheng, L.; Wang, L.; Liu, X.; Liang, Y. Org. Lett. 2015, 17, 3694.
(18) Ito, H.; Ohmiya, H.; Sawamura, M. Org. Lett. 2010, 12, 4380.
(19) Chen, B.; Metera, K.; Sleiman, H. F. Macromolecules 2005, 38,
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(20) Crooks, P. A.; Dwoshin, L.; Xu, R.; Ayers, J. T. U.S. Pat. Appl.
Publ., 20030225142.
(21) Wu, B.; Li, K.; Toy, P. H. Synlett 2012, 23, 2564.
(22) Hu, G.; Xu, J.; Li, P. Org. Lett. 2014, 16, 6036.
(23) Friedfeld, M. R.; Shevlin, M.; Margulieux, G. W.; Campeau, L.
C.; Chirik, P. J. J. Am. Chem. Soc. 2016, 138, 3314.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We are grateful for the financial support from the National 973
Program (2015CB856600), NSFC (21472162), the “Thousand
Youth Talents Plan”.
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DOI: 10.1021/acs.joc.6b01016
J. Org. Chem. XXXX, XXX, XXX−XXX