Synthesis of 9-aryl-9,10-dihydrophenanthrenes by domino [3+3] annulation/ring-opening/Friedel-Crafts alkylation reactions of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-aroyl-5-aryl-4,5-dihydrofurans

Article abstract of DOI:10.1002/ejoc.201000451

The reaction of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with 3-benzoyl-5-aryl-4,5-dihydrofurans, available by CANmediated reaction of styrenes with benzoylacetones, af-forded functionalized 9,10- dihydrophenanthrenes. These reactions proceed by a novel domino [3+3] cyclization/ringopening/ Friedel-Crafts alkylation process.

Full text of DOI:10.1002/ejoc.201000451

FULL PAPER
DOI: 10.1002/ejoc.201000451
Synthesis of 9-Aryl-9,10-dihydrophenanthrenes by Domino [3+3] Annulation/
Ring-Opening/Friedel–Crafts Alkylation Reactions of 1,3-
Bis(trimethylsilyloxy)-1,3-butadienes with 3-Aroyl-5-aryl-4,5-dihydrofurans
Matthias Lau,[a] Muhammad Sher,[a,b,c] Alexander Villinger,[a] Christine Fischer,[b] and
Peter Langer*[a,b]
Keywords: Arenes / Cyclization / Regioselectivity / Domino reactions / Enols
The reaction of 1,3-bis(trimethylsilyloxy)-1,3-butadienes
with 3-benzoyl-5-aryl-4,5-dihydrofurans, available by CAN-
mediated reaction of styrenes with benzoylacetones, af-
forded functionalized 9,10-dihydrophenanthrenes. These re-
actions proceed by a novel domino [3+3] cyclization/ring-
opening/Friedel–Crafts alkylation process.
For example, the natural product juncusol,[11] isolated
from the plant Juncus roemerianus, has been reported to
possess anticancer activity (Figure 1).[12,13] The first synthe-
sis of this compound was reported by Kende and Cur-
ran.[11] Combrestatin A-4 and several related molecules are
naturally occurring cis-stilbenes isolated from the South Af-
rican willow tree Combretum caffrum.[14] They are promis-
ing candidates for the development of anticancer drugs, be-
cause they act as inhibitors of tubulin polymerization. A
number of structurally related oxygenated phenanthrenes
have been isolated from the same tree.[15] In addition, vari-
ous other phenanthrene natural products are potentially
interesting as cytotoxic agents or tubulin-binding molecules.
Introduction
Domino reactions provide a versatile tool for the facile
assembly of complex molecules from simple starting materi-
als.[1] 1,3-Bis(trimethylsilyloxy)-1,3-butadienes represent
versatile building blocks for one-pot cyclizations and dom-
ino reactions.[2] We have reported cyclizations of these
building blocks with oxalyl chloride,[3] 3-silyloxy- and 3-alk-
oxy-2-en-1-ones,[4] iminium salts,[5] benzopyrylium tri-
flates,[6] fluorinated substrates,[7] and various other electro-
philes.[8] Some years ago, we reported[9] the TiCl4-mediated
cyclization of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with
1,1-diacylcyclopropanes. These reactions provide conve-
nient access to 5-(2-haloethyl)salicylates and proceed by a
domino [3+3] cyclization/cyclopropane opening process.
Recently, we reported[10] the synthesis of 5-(2-aryl-2-halo-
ethyl)salicylates by domino reactions of 1,3-bis(trimethyl-
silyloxy)-1,3-butadienes with 3-acetyl-5-aryl-4,5-dihydro-
furans.
Herein, we report, for the first time, the synthesis of func-
tionalized 9,10-dihydrophenanthrenes and phenanthrenes
on the basis of the reaction of 1,3-bis(trimethylsilyloxy)-1,3-
butadienes with 3-benzoyl-5-aryl-4,5-dihydrofurans. These
reactions proceed by an unprecedented domino [3+3] cycli-
zation/ring-opening/Friedel–Crafts alkylation process. All
products reported herein, highly functionalized phen-
anthrenes, are not readily available by other methods. They
represent useful synthetic intermediates, are pharmacologi-
cally relevant, and represent core structures of several natu-
ral products.
Figure 1. Structure of juncusol.
Classic synthetic approaches to phenanthrenes were de-
veloped, for example, by Pschorr and Haworth.[16] Phen-
anthrenes have been also prepared by oxidative cyclizations of
cis-stilbene derivatives.[17] For example, vanadium trifluo-
ride mediated oxidation was employed for the synthesis of
the natural product (Ϯ)-tylophorine. Chan reported the
synthesis of dihydrophenanthrenes by [3+3] cyclocondensa-
tion of tetralone-derived 3-silyloxy-2-alk-1-ones with 1,3-
bis(silyloxy)-1,3-butadienes.[18] We reported the synthesis of
cyclopenta[def]phenanthren-4-ones on the basis of a related
approach.[19] Fürstner and co-workers developed a versatile
approach to phenanthrenes that is based on transition-
metal-catalyzed cycloisomerization reactions of 2-alkynylbi-
aryls.[20]
[a] Institut für Chemie der Universität Rostock,
Albert-Einstein-Straße 3a, 18059 Rostock, Germany
Fax: +49-381-498-6411
E-mail: peter.langer@uni-rostock.de
[b] Leibniz Institut für Katalyse e.V. an der Universität Rostock,
Albert-Einstein-Straße 29a, 18059 Rostock, Germany
[c] Department of Chemistry, Allama Iqbal Open University,
Islamabad, Pakistan
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Domino “[3+3] Annulation/Ring-Opening/Friedel–Crafts Alkylation
4a (1.5–1.7 equiv.) in the presence of TiCl4 (2.0 equiv.) af-
forded unexpected 9-aryl-9,10-dihydrophenanthrene 5a in
67% yield (Scheme 3).
Results and Discussion
3-Aroyl-5-aryl-4,5-dihydrofurans 3a–e were prepared by
ceric ammonium nitrate (CAN)-mediated cyclization of
benzoylacetones 1a–d with styrenes 2a,b (Scheme 1,
Table 1). The reactions were carried out following the con-
ditions reported for the synthesis of 3-acetyl-4,5-dihydro-
furans.[21] The synthesis of 3-aroyl-5-aryl-4,5-dihydrofurans
has, to the best of our knowledge, not been previously re-
ported.
Scheme 1. Synthesis of 3a–e. Reagents and conditions: (i) CAN
(2.0 equiv.), CH3CN, 20 °C, 0.5–2 h.
Table 1. Synthesis of 3a–e.
1
2
3
R1
R2
% Yield of 3[a]
a
a
b
c
a
b
a
a
a
a
b
c
d
e
H
Br
H
H
H
H
H
Cl
Br
OMe
37
44
45
30
46
d
[a] Yield of isolated product.
The cyclization of benzoylacetones 1 with styrenes 2 can
theoretically not only result in the formation of the 3-benz-
oyl-5-aryl-2-methyl-4,5-dihydrofurans 3, but also of the
isomeric products, that is, 3-acetyl-2,5-diaryl-5-phenyl-4,5-
dihydrofurans. The structures of 3a and 3c were unambigu-
ously proved by 2D NMR experiments (Scheme 2). The
correlation of the methyl protons with carbon atom C2 and
the correlation of the aromatic protons with the carbon
atom of the carbonyl group (1H–13C HMBC) are proof of
structure 3a (Scheme 2). Similar correlations are observed
for 3c. In addition, a 1H–1H NOESY correlation is ob-
served between the ortho-phenyl protons and the methylene
protons located at carbon C4 of 3c.
Scheme 3. Possible mechanism for the formation of 5a. Reagents
and conditions: (i) TiCl4 (2.0 equiv.), CH2Cl2, –78Ǟ20 °C.
The formation of this product can be explained by TiCl4-
mediated attack of the terminal carbon atom of 4a to 3a to
give intermediate A, ring cleavage (intermediate B), recycli-
zation (intermediate C), and subsequent intramolecular
Friedel–Crafts alkylation to give intermediate D. The ad-
dition of hydrochloric acid (aqueous workup) afforded 5a.
The cyclization of dihydrofurans 3a–e with dienes 4a–
i afforded 9-aryl-9,10dihydrophenanthrenes 5a–q (Table 2).
The best yields were obtained in the reactions of the simple,
unsubstituted dienes 4a,b,e with 3a. The yields decrease for
dienes containing a substituent located at carbon C4 and
for dihydrofurans containing substituents attached to the
phenyl groups.
1,3-Bis(trimethylsilyloxy)-1,3-butadienes 4a–i are readily
available in one or two steps from the corresponding β-keto
esters.[18,22–24] The cyclization of dihydrofuran 3a with diene
The cyclization of dienes 4 with dihydrofurans 3 can
theoretically result in the formation of two regioisomeric
products. The regioselectivity depends on whether the first
attack of the diene occurs at the double bond or at the
benzoyl group of 3. The structure of 9,10-dihydrophenan-
threne 5b was established by 2D NMR studies (Scheme 4).
A
1H–1H NOESY correlation was observed between the
aromatic proton adjacent to the hydroxy group and the pro-
1
Scheme 2. HMBC and NOESY correlations of 3a and 3c.
tons of the methyl group. In addition, a diagnostic H–13C
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M. Lau, M. Sher, A. Villinger, C. Fischer, P. Langer
Table 2. (Continued).
FULL PAPER
Table 2. Synthesis of 5a–q.
[a] Yield of isolated product.
HMBC correlation was observed between the carbon atom
of the methyl group and the neighboring aromatic proton.
Therefore, the regioisomeric product iso-5b is not present.
Similar correlations were observed for 5i and 5l. The re-
gioselectivity follows a general pattern, which is observed
for the reaction of 1,3-bis(silyloxy)-1,3-butadienes with sim-
ple 3-alkoxy-2-alken-1-ones.[4,18,25] These cyclizations pro-
ceed by regioselective conjugate addition of the terminal
carbon atom of the diene to the C=C of the enone. In con-
trast, the cyclizations of 1,3-bis(silyloxy)-1,3-butadienes
with simple 3,3-(alkylthio)-2-alken-1-ones proceed by at-
tack of the diene to the carbonyl group.[26] The exact expla-
nation for the regioselectivity is unclear at present. It can
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Domino “[3+3] Annulation/Ring-Opening/Friedel–Crafts Alkylation
be anticipated that the reaction of the enone with TiCl4
results in the formation of an allylic cation. The regioselec-
tivity is influenced by the substitution pattern of this cation
by steric and electronic effects (electron density of the dif-
ferent carbon atoms of the allylic system).
Scheme 5. Synthesis of 6.
Scheme 4. NOESY and HMBC correlation of observed product 5b
and structure of its regioisomer iso-5b, which is not observed.
The structure of 5a was independently confirmed by X-
ray crystal structure analysis (Figure 2).[27] The biaryl unit
is twisted out of plane. The hydrogen atoms located at car-
bon atoms C11 and C12 adopt an ap orientation to each
other.
Figure 3. Crystal structure analysis of 6.
Scheme 6. Synthesis of 8. Reagents and conditions: (i) pyridine,
Tf2O, CH2Cl2, –78Ǟ0 °C 4 h; (ii) PhB(OH)2, Pd(PPh3)4 (3–5 mol-
%), K3PO4 (1.6 equiv.), 1,4dioxane, 101 °C, 4–20 h.
Figure 2. Crystal structure of 5a.
Some key synthetic transformations of 9,10-dihy-
drophenanthrenes 5 were next studied. Compound 5a could
be successfully transformed into phenanthrene 6 by treat-
ment with DDQ (55%; Scheme 5). The structure of 6 was
independently confirmed by X-ray crystal structure analysis
(Figure 3).[27] As expected, the molecule is flat.
Dihydrophenanthrene 5a was transformed into its triflate
7, which was converted into derivative 8 by Suzuki–Mi-
yaura reaction (Scheme 6).
Dihydrophenanthrene 5k, containing a chloroethyl group
located at carbon atom C3, was transformed into chromane
9 by base-mediated intramolecular Williamson reaction
(Scheme 7).
Scheme 7. Synthesis of 9. Reagents and conditions: (i) NaH
(1.5 equiv.), NBu4I (2.2 equiv.), DMF, 20 °C, 20 h.
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M. Lau, M. Sher, A. Villinger, C. Fischer, P. Langer
FULL PAPER
(300 mL), dried (Na2SO4), and filtered. The solvent of the filtrate
was removed in vacuo. The residue was purified by chromatography
(silica gel, heptanes/EtOAc).
Conclusions
In conclusion, we have reported a new synthesis of func-
tionalized 9,10-dihydrophenanthrenes by reaction of 1,3-
bis(trimethylsilyloxy)-1,3-butadienes with 3-benzoyl-5-aryl-
4,5-dihydrofurans. These reactions proceed by a novel dom-
ino [3+3] cyclization/ring-opening/Friedel–Crafts alkylation
process.
(2-Methyl-5-phenyl-4,5-dihydro-furan-3-yl)phenylmethanone
(3a):
Starting with 1a (0.800 g, 4.93 mmol), 2a (2.49 mL, 21.70 mmol),
and CAN (5.408 g, 9.87 mmol) in acetonitrile (100 mL), 3a was
isolated by chromatography (heptane/EtOAc, 50:1) as a yellow oil
(0.480 g, 37%). Rf
=
0.46 (heptane/EtOAc, 1:1). 1H NMR
(250 MHz, CDCl3): δ = 1.89–1.96 (m, 3 H, CH3), 3.07–3.23 (m, 1
H, Ha), 3.42–3.58 (m, 1 H, Hb), 5.54–5.74 (m, 1 H, Hx), 7.31–7.49
(m, 8 H, Ph), 7.56–7.64 (m, 2 H, Ph) ppm. 13C NMR (62.9 MHz,
CDCl3): δ = 15.5 (CH3), 39.4 (CH2), 83.4 (CHCH2), 112.3, 140.8,
141.0, 168.3 (CPh,olefin), 125.7, 127.8, 128.4, 128.7, 131.0 (CHAr),
Experimental Section
193.0 (CO) ppm. IR (ATR): ν = 1597 (m), 1447 (m), 1386 (m),
˜
General Methods: 1H NMR: Bruker: AM 250, Bruker ARX 300,
Bruker ARX 500; δ = 0.00 ppm for tetramethylsilane; δ = 2.04 ppm
for [D6]acetone; δ = 7.26 ppm for (CDCl3); δ = 2.50 ppm for [D6]
DMSO; characterization of the signal multiplicities: s = singlet, d
= doublet, dd = double of doublet, ddd = doublet of a double
doublet,t = triplet, q = quartet, quint = quintet, sext = sextet, sept
= septet, m = multiplet, br. = broad. Spectra were evaluated ac-
cording to first-order rule. All coupling constants are indicated as
J. 13C NMR: Bruker AM 250 (62.9 MHz), Bruker ARX 300
(75 MHz), Bruker ARX 500 (125 MHz); δ = 29.84Ϯ0.01 ppm and
206.26Ϯ0.13 ppm for (CD3)2CO; δ = 128.00 ppm for [D6]benzene;
δ = 77.00 ppm for CDCl3. The multiplicity of the carbon atoms
was determined by the DEPT 135 and APT techniques (APT =
attached-proton test) and quoted as CH3, CH2, CH and C for pri-
mary, secondary, tertiary and quaternary carbon atoms, respec-
tively. Characterization of the signal multiplicities: q = quartet; the
multiplicity of the signals was determined by the DEPT recording
technology and/or the APT recording technology. MS: AMD
MS40, AMD 402 (AMD Intectra), Varian MAT CH 7, MAT 731.
HRMS: Finnigan MAT 95 or Varian MAT 311; Bruker FT CIR,
AMD 402 (AMD Intectra). IR: Bruker IFS 66 (FT IR), Nicolet
205 FT IR; Nicolet Protege 460, Nicolet 360 Smart Orbit (ATR);
KBr, KAP, Nujol, and ATR; abbreviations for signals: w = weak,
m = medium, s = strong, br. = broad. Elementary analysis: LECO
CHNS-932, Thermoquest Flash EA 1112. X-ray crystal structure
analysis: Bruker X8Apex diffractometer with CCD camera (Mo-
Kα und graphite monochromator, λ = 0.71073 Å). Melting points:
Micro heating table HMK 67/1825 Kuestner (Büchi apparatus).
Column chromatography: Chromatography was performed on
Merck silica gel 60 (0.063–0.200 mm, 70–230 mesh) as normal and/
or on mesh silica gel 60 (0.040–0.063 mm, 200–400 mesh) as flash
chromatography. All solvents were distilled before use. TLC: Merck
DC finished foils silica gel 60 F254 on aluminum foil and Macherey
finished foils Alugram® Sil G/UV254. Detection under UV light
with 254 nm and/or 366 nm without dipping reagent, as well as
with anisaldehyde/sulfuric acid reagent (1 mL anisaldehyde in
100 mL of stock solution of 85% methanol, 14% acetic acid and
1% sulfuric acid). Chemicals and workup technique: All solvents
for were distilled according to standard methods. All reactions were
carried out under an inert gas with oxygen and humidity exclusion.
All of the chemicals are standard, commercially available from
Merck®, Aldrich®, Arcos® and others.
1360 (m), 1266 (m), 1217 (s), 1106 (m), 1071 (m), 968 (m), 888 (s)
cm–1. MS (EI, 70 eV): m/z (%) = 264 (41) [M]+, 221 (20), 105 (100),
77 (52). HRMS (EI): calcd. for C18H16O2 [M]+ 264.11427; found
264.11448.
[5-(4-Bromophenyl)-2-methyl-4,5-dihydrofuran-3-yl]phenylmethan-
one (3b): Starting with 1a (1.000 g, 6.16 mmol), 2d (3.55 mL,
27.13 mmol), and CAN (6.760 g, 12.33 mmol) in acetonitrile
(100 mL), 3b was isolated by chromatography (heptane/EtOAc,
200:1) as a yellow oil (0.931 g, 44%). Rf = 0.60 (heptane/EtOAc,
1
1:1). H NMR (250 MHz, CDCl3): δ = 1.91–1.96 (m, 3 H, CH3),
3.05–3.18 (m, 1 H, Ha), 3.45–3.60 (m, 1 H, Hb), 5.57–5.69 (m, 1 H,
Hx), 7.237.31 (m, 2 H, Ph/Ar), 7.41–7.66 (m, 7 H, Ph/Ar) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 15.4 (CH3), 39.3 (CH2), 82.6
(CHCH2), 112.2, 122.2, 140.1, 140.6, 168.3 (CAr,olefin), 127.4, 127.8,
128.3, 131.2, 131.8 (CHPh,Ar), 192.9 (CO) ppm. IR (ATR): ν = 2926
˜
(w), 1720 (m), 1595 (s), 1488 (m), 1446 (m), 1385 (m), 1270 (m),
1216 (s), 1070 (m), 966 (m) cm–1. MS (EI, 70 eV): m/z (%) = 344
(6) [M+, 81Br], 342 (8) [M+, 79Br], 183 (8), 105 (100), 77 (35).
HRMS (EI): calcd. for C18H15BrO2 [M+, 79Br] 342.02449; found
342.02499.
(4-Chlorophenyl)(2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)methan-
one (3c): Starting with 1b (1.200 g, 6.10 mmol), 2a (3.09 mL,
26.85 mmol), and CAN (6.691 g, 12.21 mmol) in acetonitrile
(100 mL), 3c was isolated by chromatography(heptane/EtOAc,
200:1) as a yellow oil (0.828 g, 45%). Rf = 0.54 (heptane/EtOAc,
1
1:1). H NMR (300 MHz, CDCl3): δ = 1.94–1.99 (m, 3 H, CH3),
3.07–3.19 (m, 1 H, Ha), 3.41–3.54 (m, 1 H, Hb), 5.60–5.70 (m, 1 H,
Hx), 7.327.43 (m, 7 H, Ph/Ar), 7.50–7.58 (m, 2 H, Ph/Ar) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 15.6 (CH3), 39.3 (CH2), 83.5
(CHCH2), 112.1, 137.3, 139.1, 140.8, 168.9 (CAr,olefin), 125.7, 128.3,
128.6, 128.7, 129.3 (CHAr), 191.5 (CO) ppm. IR (ATR): ν = 3032
˜
(w), 2922 (w), 1587 (s), 1487 (m), 1383 (m), 1266 (m), 1217 (s),
1087 (s), 967 (m), 890 (s) cm–1. MS (EI, 70 eV): m/z (%) = 300 (21)
[M+, 37Cl], 298 (63) [M+, 35Cl], 255 (20), 139 (100), 111 (46).
HRMS (EI): calcd. for C18H15ClO2 [M+, 35Cl] 298.07485; found
298.07551.
(4-Bromophenyl)(2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)methan-
one (3d): Starting with 1c (1.500 g, 6.22 mmol), 2a (3.15 mL,
27.38 mmol), and CAN (6.822 g, 12.44 mmol) in acetonitrile
(100 mL), 3a was isolated by chromatography(heptane/EtOAc,
200:1) as a yellow oil (0.631 g, 30%). Rf = 0.63 (heptane/EtOAc,
1
General Procedure for the Synthesis of Dihydrofurans 3: Ceric am-
monium nitrate (2.0 equiv.) was dissolved in acetonitrile. To the
mixture was added an acetonitrile solution (10 mL) of 1 (1.0 equiv.)
and 2 (4.4 equiv.), and the solution was stirred at 20 °C until the
reaction was complete (TLC control). To the mixture was added
1:1). H NMR (300 MHz, CDCl3): δ = 1.93–1.99 (m, 3 H, CH3),
3.07–3.18 (m, 1 H, Ha), 3.41–3.53 (m, 1 H, Hb), 5.60–5.71 (m, 1 H,
Hx), 7.327.41 (m, 5 H, Ph/Ar), 7.44–7.50 (m, 2 H, Ph/Ar) 7.52–
7.60 (m, 2 H, Ph/Ar) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
15.6 (CH3), 39.3 (CH2), 83.5 (CHCH2), 112.0, 139.5, 140.8, 169.0
water (250 mL), and the mixture was extracted with diethyl ether (CAr,olefin), 125.7, 128.3, 128.7, 129.4, 131.5 (CHAr), 191.5 (CO)
(3ϫ100 mL). The combined organic layer was washed with water ppm. IR (ATR): ν = 1583 (s), 1482 (m), 1393 (m), 1359 (m), 1265
˜
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Domino “[3+3] Annulation/Ring-Opening/Friedel–Crafts Alkylation
(m), 1217 (s), 1067 (m), 1010 (m), 888 (s), 750 (s) cm–1. MS (EI, 1311 (m), 1224 (s), 1205 (m), 1064 (m), 1005 (m) cm–1. MS (EI,
70 eV): m/z (%) = 344 (26) [M+, 81Br], 342 (30) [M+, 79Br], 220 (40),
185 (95), 43 (100). HRMS (EI): calcd. for C18H15BrO2 [M+, 79Br]
342.02404; found 342.02499.
70 eV): m/z (%) = 358 (44) [M]+, 312 (100), 284 (10), 269 (10).
HRMS (EI): calcd. for C24H22O3 [M]+ 358.15604; found 358.15635.
Methyl 3-Hydroxy-1,2-dimethyl-9-phenyl-9,10-dihydrophen-
(4-Methoxyphenyl)(2-methyl-5-phenyl-4,5-dihydrofuran-3-yl)- anthrene-4-carboxylate (5c): Starting with 3a (0.131 g, 0.50 mmol),
methanone (3e): Starting with 1d (1.500 g, 7.80 mmol), 2a (3.95 mL, 4c (0.204 g, 0.74 mmol), and TiCl4 (0.11 mL, 0.99 mmol), 5c was
34.34 mmol), and CAN (8.557 g, 15.61 mmol) in acetonitrile
(100 mL), 3a was isolated by chromatography (heptane/EtOAc,
isolated by chromatography (heptane/EtOAc, 50:1) as a yellow so-
lid (0.051 g, 30%). M.p. 136–138 °C. Rf = 0.85 (heptane/EtOAc,
1:1). 1H NMR (250 MHz, CDCl3): δ = 2.22, 2.24 (s, 3 H, CH3),
100:1) as a yellow oil (1.051 g, 46%). Rf = 0.27 (heptane/EtOAc,
1
1:1). H NMR (300 MHz, CDCl3): δ = 1.94–1.99 (m, 3 H, CH3), 2.87–3.10 (m, 2 H, CH2CH), 3.67 (s, 3 H, OCH3), 4.07–4.17 (m, 1
3.10–3.23 (m, 1 H, Ha), 3.43–3.55 (m, 1 H, Hb), 3.85 (s, 3 H,
OCH3), 5.58–5.68 (m, 1 H, Hx), 6.86–6.96 (m, 2 H, Ar), 7.33–7.43
(m, 5 H, Ph) 7.59–7.67 (m, 2 H, Ar) ppm. 13C NMR (75.5 MHz,
H, CH2CH), 6.83–6.93 (m, 1 H, Ph/Ar), 7.07–7.38 (m, 8 H, Ph/
Ar), 9.86 (s, 1 H, OH) ppm. 13C NMR (75.5 MHz, CDCl3): δ =
12.3, 16.3 (CH3), 33.5 (CH2), 44.7 (CHCH2), 51.7 (OCH3), 108.5,
CDCl3): δ = 15.5 (CH3), 39.8 (CH2), 55.5 (OCH3), 83.2 (CHCH2), 124.2, 128.6, 133.8, 134.9, 140.0, 140.2, 142.6, 156.4 (CPh,Ar), 125.5,
112.0, 133.2, 141.2, 162.2, 167.2 (CAr,olefin), 113.5, 125.8, 128.2, 126.5, 126.6, 127.1, 128.4, 128.7, 128.9 (CHPh,Ar), 172.7 (COOCH3)
128.7, 130.3 (CHAr,Ph), 191.8 (CO) ppm. IR (ATR): ν = 2956 (w),
ppm. IR (ATR): ν = 2961 (w), 2928 (w), 1652 (m), 1597 (m), 1434
˜
˜
2930 (w), 1596 (s), 1508 (m), 1344 (m), 1247 (s), 1209 (s), 1155 (m), (m), 1322 (m), 1260 (m), 1078 (m), 1011 (s), 907 (m) cm–1. MS (EI,
1025 (m), 976 (m) cm–1. MS (EI, 70 eV): m/z (%) = 294 (50) [M]+,
186 (21), 171 (51), 135 (100). HRMS (EI): calcd. for C19H18O3
[M]+ 294.12535; found 294.12505.
70 eV): m/z (%) = 358 (75) [M]+, 326 (100), 298 (42), 235 (66), 105
(49). HRMS (EI): calcd. for C24H22O3 [M+, 35Cl] 358.155854;
found 358.15635.
General Procedure for the Synthesis of 5a–q: To a dichloromethane
solution (50 mL) of 3 (1.0 equiv.) was added 4a–i (1.5–1.7 equiv.)
at –78 °C under an argon atmosphere. To the mixture was added
TiCl4 (2.0 equiv.). The temperature of the solution was warmed to
20 °C over 16 h with stirring. To the mixture was added hydrochlo-
ric acid (10%, 50 mL). The mixture was stirred for 10 min and
subsequently extracted with dichloromethane (3 ϫ50 mL). The
combined organic layer was dried (Na2SO4) and filtered, and the
filtrate was concentrated in vacuo. The residue was purified by
chromatography (silica gel, heptanes/EtOAc).
Methyl 2-Ethyl-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen-
anthrene-4-carboxylate (5d): Starting with 3a (0.158 g, 0.60 mmol),
4d (0.259 g, 0.90 mmol), and TiCl4 (0.13 mL, 1.20 mmol), 5d was
isolated by chromatography (heptane/EtOAc, 50:1) as a colorless
solid (0.068 g, 31%). M.p. 134–135 °C. Rf = 0.80 (heptane/EtOAc,
1:1). H NMR (250 MHz, CDCl3): δ = 1.14 (t, J = 7.5 Hz, 3 H,
CH3CH2), 2.25 (s, 3 H, CH3), 2.69–2.84 (m, 3J = 7.5 Hz, 2 H,
CH3CH2), 2.85–3.10 (m, 2 H, CH2CH), 3.66 (s, 3 H, OCH3), 4.06–
4.18 (m, 1 H, CH2CH), 6.81–6.90 (m, 1 H, Ph/Ar), 7.07–7.39 (m,
8 H, Ph/Ar), 9.82 (s, 1 H, OH) ppm. 13C NMR (75.5 MHz, CDCl3):
δ = 13.5, 15.7 (CH3), 19.9, 33.5 (CH2), 44.8 (CHCH2), 51.7
(OCH3), 108.6, 129.0, 130.2, 133.9, 134.9, 139.5, 140.0, 142.6, 156.3
(CPh,Ar), 125.5, 126.5, 126.6, 127.1, 128.5, 128.7, 128.9 (CHPh,Ar),
1
3
Methyl 3-Hydroxy-1-methyl-9-phenyl-9,10-dihydrophenanthrene-4-
carboxylate (5a): Starting with 3a (0.159 g, 0.60 mmol), 4a (0.235 g,
0.90 mmol), and TiCl4 (0.13 mL, 1.20 mmol), 5a was isolated by
chromatography (heptane/EtOAc, 50:1) as a colorless solid
(0.139 g, 67%). M.p. 149–150 °C. Rf = 0.62 (heptane/EtOAc, 1:1).
1H NMR (300 MHz, CDCl3): δ = 2.25 (br. s, 3 H, CH3), 2.84–3.04
(m, 2 H, CH2CH), 3.67 (s, 3 H, OCH3), 4.08–4.18 (m, 1 H,
CH2CH), 6.78 (s, 1 H, Ar), 6.85–6.94 (m, 1 H, Ph/Ar), 7.10–7.38
(m, 8 H, Ph/Ar), 9.53 (s, 1 H, OH) ppm. 13C NMR (75.5 MHz,
172.7 (COOCH ) ppm. IR (ATR): ν = 2972 (w), 2878 (w), 1668
˜
3
(s), 1592 (m), 1434 (m), 1400 (m), 1302 (m), 1202 (s), 1102 (m), 942
(m) cm–1. MS (EI, 70 eV): m/z (%) = 372 (79) [M]+, 340 (100), 325
(48), 312 (41), 249 (28). HRMS (ESI): calcd. for C25H23O3 [M –
H]– 371.16527; found 371.16485.
Isopropyl 3-Hydroxy-1-methyl-9-phenyl-9,10-dihydrophenanthrene-
CDCl3): δ = 20.3 (CH3), 32.6, (CH2), 44.5 (CHCH2), 51.7 (OCH3), 4-carboxylate (5e): Starting with 3a (0.142 g, 0.54 mmol), 4i
109.1, 128.9, 134.5, 136.4, 140.3, 142.1, 142.4, 158.3 (CPh,Ar), 117.7, (0.233 g, 0.81 mmol), and TiCl4 (0.12 mL, 1.08 mmol), 5e was iso-
125.6, 126.7, 126.7, 127.5, 128.5, 128.6, 129.1 (CHPh,Ar), 172.0 (CO-
lated by chromatography (heptane/EtOAc, 50:1) as a yellow solid
OCH ) ppm. IR (ATR): ν = 3031 (w), 2950 (w), 1659 (s), 1604 (m),
(0.161 g, 80%). M.p. 132–134 °C. Rf = 0.70 (heptane/EtOAc, 1:1).
˜
3
1434 (m), 1320 (m), 1225 (m), 1068 (m), 974 (m), 862 (m) cm–1. 1H NMR (250 MHz, CDCl3): δ = 1.09 (d, 3J = 6.2 Hz, 3 H,
MS (EI, 70 eV): m/z (%) = 344 (69) [M]+, 312 (100), 284 (24), 269
(31), 241 (22). HRMS (EI): calcd. for C23H20O3 [M]+ 344.14026;
found 344.14070. C23H20O3 (344.14): calcd. C 80.21, H 5.85; found
C 80.10, H 5.83.
CH3CH), 1.13 (d, J = 6.2 Hz, 3 H, CH3CH), 2.23 (s, 3 H, CH3),
2.87–3.09 (m, 2 H, CH2CH), 4.11–4.27 (m, 1 H, CH2CH), 5.13
3
3
(sept., J = 6.2 Hz, CH3CHCH3), 6.74 (s, 1 H, Ar), 6.92–7.05 (m,
1 H, Ph/Ar), 7.14–7.33 (m, 8 H, Ph/Ar), 9.75 (s, 1 H, OH) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 20.2, 21.3, 21.3 (CH3), 32.8,
(CH2), 44.1 (CHCH2), 69.4 (CH), 109.7, 128.3, 134.9, 136.9, 139.6,
141.8, 144.5, 158.4 (CPh,Ar), 117.5, 125.9, 126.4, 126.9, 127.5, 128.2,
Ethyl 3-Hydroxy-1-methyl-9-phenyl-9,10-dihydrophenanthrene-4-
carboxylate (5b): Starting with 3a (0.160 g, 0.61 mmol), 4b (0.282 g,
1.03 mmol) and TiCl4 (0.13 mL, 1.21 mmol), 5b was isolated by
chromatography (heptane/EtOAc, 50:1) as a colorless solid
(0.115 g, 53%). M.p. 130–131 °C. Rf = 0.48 (heptane/EtOAc, 1:1).
1H NMR (250 MHz, CDCl3): δ = 1.03 (t, 3J = 7.2 Hz, 3 H,
128.5, 130.1 (CHPh,Ar), 170.9 (COO) ppm. IR (ATR): ν = 2981 (w),
˜
2964 (w), 1651 (s), 1568 (m), 1447 (m), 1369 (m), 1309 (s), 1177 (s),
1101 (s), 1061 (s) cm–1. MS (EI, 70 eV): m/z (%) = 372 (46) [M]+,
312 (100), 284 (21), 269 (23), 241 (17). HRMS (ESI): calcd. for
C25H24NaO3 [M + Na]+ 395.16177; found 395.16141. C25H24O3
(372.17): calcd. C 80.62, H 6.49; found C 79.72, H 6.49.
CH3CH2), 2.24 (s, 3 H, CH3), 2.96 (d, 3JHab
= 7.0 Hz, 2 H,
,Hx
3
Ha,Hb), 4.07–4.29 (m, JHab = 7.0 Hz, 1 H, Hx, 2 H, CH3CH2),
,Hx
6.75 (s, 1 H, Ar), 6.90–6.99 (m, 1 H, Ph/Ar), 7.13–7.35 (m, 8 H,
Ph/Ar), 9.62 (s, 1 H, OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ
Methyl 3-Hydroxy-1-methyl-9-phenyl-2-propyl-9,10-dihydrophen-
= 13.5, 20.3 (CH3), 32.7, 61.2 (CH2), 44.3 (CHCH2), 109.3, 134.8, anthrene-4-carboxylate (5f): Starting with 3a (0.130 g, 0.49 mmol),
136.9, 140.0, 142.0, 142.5, 158.3 (CPh,Ar), 117.6, 125.5, 126.5, 126.8, 4j (0.223 g, 0.74 mmol), and TiCl4 (0.11 mL, 0.98 mmol), 5f was
127.5, 128.3, 128.5, 129.6 (CHPh,Ar), 171.5 (COOCH2CH3) ppm.
isolated by chromatography (heptane/EtOAc, 100:1) as a colorless
IR (ATR): ν = 2963 (w), 2886 (w), 1659 (s), 1452 (m), 1371 (m),
oil (0.078 g, 41 %). Rf = 0.69 (heptane/EtOAc, 1:1). 1H NMR
˜
Eur. J. Org. Chem. 2010, 5118–5127
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5123

M. Lau, M. Sher, A. Villinger, C. Fischer, P. Langer
FULL PAPER
(250 MHz, CDCl3): δ = 1.00 (t, J = 7.3 Hz, 3 H, CH3), 1.49–1.60
(48) [M+, 81Br], 422 (39) [M+, 79Br], 390 (100), 283 (39), 239 (25).
3
(m, 2 H, CH2), 2.24 (s, 3 H, CH3), 2.64–2.78 (m, 2 H, CH2), 2.83– HRMS (ESI): calcd. for C23H18BrO3 [M – H]– 421.04448; found
3.10 (m, 2 H, CH2CH), 3.66 (s, 3 H, OCH3), 4.05–4.18 (m, 1 H,
CH2CH), 6.82–6.89 (m, 1 H, Ph/Ar), 7.06–7.38 (m, 8 H, Ph/Ar),
9.81 (s, 1 H, OH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 14.4,
16.0 (CH3), 22.5, 28.7, 33.5 (CH2), 44.7 (CHCH2), 51.7 (OCH3),
108.5, 128.9, 133.9, 134.9, 139.8, 140.0, 142.6, 156.5 (CPh,Ar), 125.5,
126.4, 126.6, 127.1, 128.4, 128.7, 128.8 (CHPh,Ar), 172.7 (COOCH3)
421.04412.
Isopropyl 9-(4-Bromophenyl)-3-hydroxy-1-methyl-9,10-dihydrophen-
anthrene-4-carboxylate (5j): Starting with 3b (0.131 g, 0.38 mmol),
4i (0.143 g, 0.50 mmol), and TiCl4 (0.08 mL, 0.76 mmol), 5j was
isolated by chromatography (heptane/EtOAc, 100:1) as a colorless
solid (0.076 g, 44%). M.p. 162–164 °C. Rf = 0.67 (heptane/EtOAc,
ppm. IR (ATR): ν = 2954 (m), 2870 (m), 1662 (s), 1595 (m), 1434
˜
1
3
1:1). H NMR (250 MHz, CDCl3): δ = 1.09 (d, J = 6.2 Hz, 3 H,
CH3CH), 1.11 (d, 3J = 6.2 Hz, 3 H, CH3CH), 2.21 (br. s, 3 H,
CH3), 2.85–3.04 (m, 2 H, CH2CH), 4.07–4.24 (m, 1 H, CH2CH),
(m), 1314 (m), 1205 (s), 1108 (m), 1040 (m), 980 (m) cm–1. MS (EI,
70 eV): m/z (%) = 386 (11) [M]+, 358 (18), 183 (75), 79 (100).
HRMS (EI): calcd. for C26H26O3 [M]+ 386.18718; found 386.18765.
3
5.12 (sept., J = 6.2 Hz, 1 H, CH3CHCH3), 6.72 (br. s, 1 H, Ar),
Ethyl 3-Hydroxy-1-methyl-9-phenyl-9,10-dihydrophenanthrene-4-
carboxylate (5g): Starting with 3a (0.160 g, 0.61 mmol), 4l (0.277 g,
0.91 mmol), and TiCl4 (0.13 mL, 1.21 mmol), 5g was isolated by
chromatography (heptane/EtOAc, 100:1) as a yellow oil (0.043 g,
18 %). Rf = 0.54 (heptane/EtOAc, 1:1). 1H NMR (250 MHz,
CDCl3): δ = 2.22 (s, 3 H, CH3), 2.95 (d, 3J = 6.9 Hz, 2 H, CH2CH),
6.97–7.12 (m, 3 H, Ph/Ar), 7.17–7.39 (m, 5 H, Ph/Ar), 9.72 (s, 1 H,
OH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 20.2, 21.2, 21.4
(CH3), 32.8 (CH2), 43.4, 69.5 (CH), 109.6, 120.2, 134.9, 136.8,
138.8, 141.6, 141.8, 158.4 (CPh,Ar), 117.7, 126.2, 126.9, 127.6, 130.1,
130.2, 131.2 (CHPh,Ar), 170.8 (COO) ppm. IR (ATR): ν = 2980 (w),
˜
2934 (w), 1657 (s), 1569 (m), 1487 (m), 1450 (m), 1366 (m), 1221
(m), 1101 (s), 1009 (m) cm–1. MS (EI, 70 eV): m/z (%) = 452 (25)
[M+, 81Br], 450 (25) [M+, 79Br], 392 (100), 312 (7), 283 (16). HRMS
(EI): calcd. for C25H23BrO3 [M+, 79Br] 450.08138; found 450.08251.
3
3.13 (s, 3 H, OCH3), 3.33 (t, J = 4.8 Hz, 2 H, CH2), 4.11–4.37 (m,
3
3J = 6.9 Hz, 1 H, CH2CH, J = 4.8 Hz, 2 H, CH2), 6.74 (br. s, 1
H, Ar), 6.89–7.00 (m, 1 H, Ph/Ar), 7.11–7.34 (m, 8 H, Ph/Ar), 9.46
(s, 1 H, OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 20.2 (CH3),
32.6, 64.0, 69.5 (CH2), 44.2 (CHCH2), 58.7 (OCH3), 109.2, 128.6,
134.7, 136.9, 140.0, 142.1, 142.4, 158.2 (CPh,Ar), 117.6, 125.7, 126.5
126.9, 127.5, 128.3, 128.5, 129.4 (CHPh,Ar), 171.1 (COO) ppm. IR
Methyl 9-(4-Bromophenyl)-2-(3-chloropropyl)-3-hydroxy-9,10-dihy-
drophenanthrene-4-carboxylate (5k): Starting with 3b (0.185 g,
0.54 mmol), 4k (0.309 g, 0.92 mmol), and TiCl4 (0.12 mL,
1.08 mmol), 5k was isolated by chromatography (heptane/EtOAc,
100:1) as a colorless solid (0.055 g, 20%). M.p. 172–174 °C. Rf =
0.60 (heptane/EtOAc, 1:1). 1H NMR (300 MHz, CDCl3): δ = 1.93–
2.06 (m, 2 H, CH2), 2.25 (s, 3 H, CH3), 2.82–3.04 (m, 4 H, 2CH2),
3.61 (t, 3J = 6.6 Hz, 2 H, CH2), 3.66 (s, OCH3), 4.05–4.15 (m, 1 H,
(ATR): ν = 2923 (w), 2880 (w), 1661 (s), 1601 (m), 1569 (m), 1447
˜
(m), 1375 (m), 1197 (s), 1125 (s), 1064 (s) cm–1. MS (EI, 70 eV):
m/z (%) = 388 (26) [M]+, 312 (100), 269 (8), 241 (8). HRMS (EI):
calcd. for C25H24O4 [M]+ 388.16606; found 388.16691. C25H24O4
(388.17): calcd. C 77.30, H 6.23; found C 77.16, H 6.48.
3
CH), 6.87–6.96 (m, 1 H, Ar), 7.07–7.23 (m, J = 8.4 Hz, 5 H, Ar),
7.38–7.45 (m, 3J = 8.4 Hz, 2 H, CH2), 9.84 (s, OH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 15.9 (CH3), 24.2, 32.2, 33.5, 45.1 (CH2),
44.2 (CHCH2) 51.8 (OCH3), 108.6, 120.4, 127.2, 128.4, 134.4,
134.7, 139.2, 140.0, 141.5, 156.2 (CAr), 125.8, 126.6, 127.4, 129.0,
Ethyl 2-Chloro-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen-
anthrene-4-carboxylate (5h): Starting with 3a (0.178 g, 0.67 mmol),
4m (0.353 g, 1.15 mmol), and TiCl4 (0.15 mL, 1.35 mmol), 5h was
isolated by chromatography (heptane/EtOAc, 200:1) as a yellow so-
lid (0.048 g, 18%). M.p. 54–54 °C. Rf = 0.53 (heptane/EtOAc, 1:1).
1H NMR (300 MHz, CDCl3): δ = 1.05 (t, 3J = 7.2 Hz, 3 H,
CH3CH2), 2.37 (s, 3 H, CH3), 2.96–3.12 (m, 2 H, CH2CH), 4.09–
4.32 (m, 2 H, CH3CH2, 1 H CH2CH), 6.92–7.04 (m, 1 H, Ph/Ar),
7.13–7.35 (m, 8 H, Ph/Ar), 9.96 (s, 1 H, OH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 13.4, 17.1 (CH3), 33.8, 61.6 (CH2), 44.1
(CHCH2), 110.6, 121.7, 129.1, 34.3, 135.0, 139.2, 139.7, 142.1,
153.9 (CPh,Ar), 125.9, 126.6, 127.0, 127.9 128.4, 128.4, 129.3,
130.3, 131.3 (CHAr), 172.4 (COOCH ) ppm. IR (ATR): ν = 2954
˜
3
(w), 2915 (w), 1658 (m), 1485 (m), 1434 (m), 1324 (m), 1210 (m),
1010 (m), 988 (m), 767 (m) cm–1. MS (EI, 70 eV): m/z (%) = 500
(27) [M+, 37Cl/79Br,35Cl/81Br], 462 (76), 433 (100), 405 (47). HRMS
(EI): calcd. for C18H18BrClO3 [M+, 35Cl, 81Br] 500.05714; found
500.05790.
Methyl 7-Chloro-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen-
anthrene-4-carboxylate (5l): Starting with 3c (0.195 g, 0.65 mmol),
4a (0.255 g, 0.98 mmol), and TiCl4 (0.14 mL, 1.31 mmol), 5l was
isolated by chromatography (heptane/EtOAc, 200:1) as a colorless
solid (0.125 g, 51%). M.p. 166–167 °C. Rf = 0.54 (heptane/EtOAc,
(CHPh,Ar), 171.2 (COOCH CH ) ppm. IR (ATR): ν = 2980 (w),
˜
2
3
2936 (w), 1660 (s), 1594 (m), 1445 (m), 1371 (m), 1293 (m), 1219
(s), 1193 (s), 1012 (m) cm–1. MS (EI, 70 eV): m/z (%) = 394 (6)
[M+, 37Cl], 392 (19) [M+, 35Cl], 346 (100), 239 (21), 44 (26). HRMS
(EI): calcd. for C24H21ClO3 [M+, 35Cl] 392.11804; found 392.11737.
1
1:1). H NMR (500 MHz, CDCl3): δ = 2.25 (s, 3 H, CH3), 2.85–
2.99 (m, 2 H, CH2CH), 3.69 (s, 3 H, OCH3), 4.05–4.12 (m, 1 H,
CH2CH), 6.79 (s, 1 H, Ar),6.87 (br. s, 1 H, Ar), 7.06 (d, 3J = 8.4 Hz,
1 H, Ph/Ar), 7.16–7.19 (m, 3J = 8.4 Hz, 1 H, Ph/Ar), 7.22–7.37 (m,
5 H, Ph/Ar), 9.60 (s, 1 H, OH) ppm. 13C NMR (125.8 MHz,
CDCl3): δ = 20.3 (CH3), 32.5 (CH2), 44.5 (CHCH2), 51.8 (OCH3),
108.9, 128.8, 133.1, 133.4, 135.6, 141.4, 142.2, 142.3, 158.6 (CPh,Ar),
118.1, 125.7, 126.8, 127.0, 128.5, 128.7, 130.4 (CHPh,Ar), 171.7 (CO-
Methyl 9-(4-Bromophenyl)-3-hydroxy-1-methyl-9,10-dihydrophen-
anthrene-4-carboxylate (5i): Starting with 3b (0.164 g, 0.48 mmol),
4a (0.187 g, 0.72 mmol), and TiCl4 (0.10 mL, 0.96 mmol), 5i was
isolated by chromatography (heptane/EtOAc, 100:1) as a yellow so-
lid (0.079 g, 39%). M.p. 193–194 °C. Rf = 0.56 (heptane/EtOAc,
1:1). 1H NMR (250 MHz, CDCl3): δ = 2.24 (br. s, 3 H, CH3), 2.81–
3.00 (m, 2 H, CH2CH), 3.67 (s, 3 H, OCH3), 4.04–4.16 (m, 1 H,
CH2CH), 6.77 (br. s, 1 H, Ar), 6.88–6.95 (m, 1 H, Ph/Ar), 7.07–
7.27 (m, 5 H, Ph/Ar), 7.37–7.45 (m, 2 H, Ph/Ar), 9.51 (s, 1 H, OH)
ppm. 13C NMR (62.9 MHz, CDCl3): δ = 20.3 (CH3), 32.6 (CH2),
43.8 (CHCH2), 51.7 (OCH3), 109.1, 120.4, 128.3, 134.6, 136.6,
139.4, 141.4, 142.1, 158.3 (CPh,Ar), 117.8, 125.9, 126.8, 127.7, 129.3,
OCH ) ppm. IR (ATR): ν = 2947 (w), 2884 (w), 1658 (s), 1599 (m),
˜
3
1433 (m), 1348 (m), 1219 (s), 1132 (m), 1063 (m), 949 (m) cm–1.
MS (EI, 70 eV): m/z (%) = 380 (13) [M+, 37Cl], 378 (37) [M+, 35Cl],
346 (100), 255 (12). HRMS (EI): calcd. for C23H19ClO3 [M+, 35Cl]
378.10286; found 378.10172. C23H19ClO3 (378.10): calcd. C 72.92,
H 5.06; found C 72.63, H 5.20.
130.2, 131.5 (CHPh,Ar), 171.9 (COOCH ) ppm. IR (ATR): ν = 2947
˜
3
(w), 2884 (w), 1668 (s), 1568 (m), 1486 (m), 1433 (s), 1312 (m),
Ethyl 7-Chloro-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen-
anthrene-4-carboxylate (5m): Starting with 3c (0.168 g, 0.56 mmol),
1177 (s), 1064 (s), 1008 (s) cm–1. MS (EI, 70 eV): m/z (%) = 424
5124
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5118–5127

Domino “[3+3] Annulation/Ring-Opening/Friedel–Crafts Alkylation
4b (0.231 g, 0.84 mmol), and TiCl4 (0.12 mL, 1.13 mmol), 5a was
isolated by chromatography (heptane/EtOAc, 200:1) as a colorless
solid (0.115 g, 52%). M.p. 143–145 °C. Rf = 0.63 (heptane/EtOAc,
8 H, Ph/Ar), 9.80 (s, 1 H, OH) ppm. 13C NMR (62.9 MHz, CDCl3):
δ = 20.2, 21.3, (CH3), 32.6, (CH2), 44.0 (CHCH2), 69.7 (CH), 109.4,
121.4, 128.2, 133.9, 135.8, 141.5, 141.9, 142.0, 158.7 (CPh,Ar), 118.0,
1
3
1:1). H NMR (300 MHz, CDCl3): δ = 1.09 (t, J = 7.2 Hz, 3 H, 126.7, 128.3, 128.4, 128.8, 129.8, 131.6, (CHPh,Ar), 170.6 (COO)
CH3CH2), 2.24 (s, 3 H, CH3), 2.91–2.97 (m, 2 H, CH2CH), 4.07– ppm. IR (ATR): ν = 2978 (w), 2921 (w), 1657 (s), 1572 (m), 1451
˜
4.29 (m, 1 H, CH2CH, 2 H, CH3CH2), 6.77 (br. s, 1 H, Ar), 6.92 (m), 1370 (m), 1307 (m), 1221 (s), 1101 (s), 1060 (s) cm–1. MS (EI,
(br. s, 1 H, Ar), 7.087.37 (m, 7 H, Ph/Ar), 9.71 (s, 1 H, OH) ppm. 70 eV): m/z (%) = 452 (21) [M+, 81Br], 450 (21) [M+, 79Br], 390
13C NMR (62.9 MHz, CDCl3): δ = 13.6, 20.2 (CH3), 32.5, 61.3
(CH2), 44.2 (CHCH2), 109.0, 128.5, 133.3, 133.3, 135.7, 141.5,
141.9, 142.1, 158.6 (CPh,Ar), 118.0, 125.7, 126.8, 126.9, 128.4, 128.5,
(100), 283 (23), 239 (32). C25H23BrO3 (450.08): calcd. C 66.53, H
5.14; found C 66.31, H 5.29.
Methyl 3-Hydroxy-7-methoxy-1-methyl-9-phenyl-9,10-dihydrophen-
anthrene-4-carboxylate (5q): Starting with 3e (0.152 g, 0.52 mmol),
4a (0.202 g, 0.75 mmol), and TiCl4 (0.11 mL, 1.03 mmol), 5q was
isolated by chromatography (heptane/EtOAc, 100:1) as a colorless
solid (0.041 g, 21%). M.p. 70–71 °C. Rf = 0.79 (heptane/EtOAc,
130.8 (CHPh,Ar), 171.2 (COOCH CH ) ppm. IR (ATR): ν = 2980
˜
3
2
(w), 2882 (w), 1657 (s), 1573 (m), 1452 (m), 1371 (m), 1313 (m),
1222 (s), 1193 (s), 1066 (m) cm–1. MS (EI, 70 eV): m/z (%) = 394
(11) [M+, 37Cl], 392 (31) [M+, 35Cl], 346 (100), 255 (10). HRMS
(EI): calcd. for C24H21ClO3 [M+, 35Cl] 392.11749; found 392.11737.
1
1:1). H NMR (300 MHz, CDCl3): δ = 2.24 (s, 3 H, CH3), 2.81–
Methyl 7-Bromo-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen- 3.03 (m, 2 H, CH2CH), 3.70, 3.72 (s, 3 H, OCH3), 4.05–4.15 (m, 1
4
anthrene-4-carboxylate (5n): Starting with 3d (0.190 g, 0.55 mmol),
4a (0.216 g, 0.83 mmol), and TiCl4 (0.12 mL, 1.11 mmol), 5n was
isolated by chromatography (heptane/EtOAc, 200:1) as a colorless
solid (0.112 g, 48%). M.p. 81–82 °C. Rf = 0.57 (heptane/EtOAc,
1:1). 1H NMR (300 MHz, CDCl3): δ = 2.25 (br. s, 3 H, CH3), 2.81–
3.01 (m, 2 H, CH2CH), 3.69 (s, 3 H, OCH3), 4.04–4.13 (m, 1 H,
H, CH2CH), 6.45 (d, J = 2.6 Hz, 1 H, Ar), 6.72 (br. s, 1 H, Ar),
4
3
3
6.76 (dd, J = 2.6 Hz, J = 8.6 Hz, 1 H, Ar), 7.08 (d, J = 8.6 Hz,
1 H, Ar), 7.20–7.38 (m, 5 H, Ph), 9.52 (s, 1 H, OH) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 20.3 (CH3), 32.6 (CH2), 44.8 (CHCH2),
51.7, 55.1 (OCH3), 108.7, 127.5, 128.1, 136.6, 141.9, 142.1, 142.3,
158.2, 159.2 (CPh,Ar), 111.2, 112.2, 116.8, 126.7, 128.5, 128.6, 130.5
3
CH2CH), 6.79 (br. s, 1 H, Ar), 6.99 (d, J = 8.3 Hz, 1 H, Ph/Ar),
(CHPh,Ar), 172.1 (COOCH ) ppm. IR (ATR): ν = 2947 (w), 2836
˜
3
3
7.03 (br. s, 1 H, Ar), 7.20–7.38 (m, J = 8.3 Hz, 6 H, Ph/Ar), 9.61 (w), 1661 (m), 1604 (m), 1573 (m), 1494 (m), 1434 (m), 1300 (m),
(s, 1 H, OH) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 20.3 (CH3), 1228 (s), 1034 (m) cm–1. MS (EI, 70 eV): m/z (%) = 374 (36) [M]+,
32.5 (CH2), 44.4 (CHCH2), 51.8 (OCH3), 108.1, 121.7 128.8, 133.6, 342 (100), 314 (16), 44 (36). HRMS (EI): calcd. for C24H22O4
135.6, 141.4, 142.3, 142.5, 158.6 (CPh,Ar), 118.2, 127.0, 128.5, 128.7, [M]+ 374.15149; found 374.15126. C24H22O4 (374.15): calcd. C
129.7, 130.7 (CHPh,Ar), 171.7 (COOCH ) ppm. IR (ATR): ν = 3026
76.99, H 5.92; found C 76.78, H 5.85.
˜
3
(w), 2947 (w), 1662 (s), 1573 (m), 1434 (s), 1316 (m), 1221 (s), 1196
(s), 163 (s), 949 (m) cm–1. MS (EI, 70 eV): m/z (%) = 424 (26) [M+,
81Br], 422 (26) [M+, 79Br], 390 (100), 283 (27), 239 (34). HRMS
(EI): calcd. for C23H19BrO3 [M+, 79Br] 422.05080; found 422.05121.
C23H19BrO3 (422.05): calcd. C 65.26, H 4.52; found C 64.85, H
4.29.
Methyl 3-Hydroxy-1-methyl-9-phenylphenanthrene-4-carboxylate
(6): To a 1,4-dioxane solution (7 mL per 1 mmol 5a) of 5a
(1.0 equiv.) was added DDQ (2.0 equiv.), and the solution was
stirred for 48 h at 101 °C. To the mixture was added diethyl ether
(50 mL), and the mixture was filtered. The solvent of the filtrate
was removed in vacuo. The residue was purified by chromatography
(silica gel, heptanes/EtOAc). Starting with 5a (0.254 g, 0.74 mmol)
and DDQ (0.335 g, 1.48 mmol), 6 was isolated by chromatography
Methyl 7-Bromo-3-hydroxy-1,2-dimethyl-9-phenyl-9,10-dihy-
drophenanthren-4-carboxylate (5o): Starting with 3d (0.170 g,
0.50 mmol), 4c (0.204 g, 0.74 mmol), and TiCl4 (0.11 mL, (heptane/EtOAc, 30:1) as a yellow solid (0.139 g, 55%). M.p. 55–
0.99 mmol), 5a was isolated by chromatography (heptane/EtOAc,
200:1) as a colorless solid (0.080 g, 37%). M.p. 204–205 °C. Rf =
0.64 (heptane/EtOAc, 1:1). 1H NMR (300 MHz, CDCl3): δ = 2.21,
57 °C. Rf = 0.59 (heptane/EtOAc, 1:1). 1H NMR (300 MHz,
4
CDCl3): δ = 2.70 (d, J = 0.8 Hz, 3 H, CH3), 3.84 (s, 3 H, OCH3),
7.15 (d, 4J = 0.8 Hz, 1 H, Ar), 7.42–7.61 (m, 8 H, Ph/Ar), 7.85–
2.23 (s, 3 H, CH3), 2.84–3.08 (m, 2 H, CH2CH), 3.68 (s, 3 H, 7.93 (m, 1 H, Ph/Ar), 7.95–8.03 (m, 1 H, Ph/Ar), 9.87 (s, 1 H, OH)
OCH3), 4.02–4.13 (m, 1 H, CH2CH), 6.96 (d, 3J = 8.3 Hz, 1 H,
Ar), 7.01 (br. s, 1 H, Ar), 7.217.38 (m, 6 H, Ph/Ar), 9.93 (s, 1 H,
OH) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 12.3, 16.3 (CH3),
33.4 (CH2), 44.6 (CHCH2), 51.8 (OCH3), 108.2, 121.2, 124.8, 128.4,
ppm. 13C NMR (75.5 MHz, CDCl3): δ = 20.2 (CH3), 51.3 (OCH3),
106.5, 125.7, 129.5, 130.2, 132.0, 137.2, 140.7, 142.5, 159.2 (CPh,Ar),
119.1, 122.5, 124.3, 126.2, 126.7, 127.4, 128.4, 129.2, 130.1
(CHPh,Ar), 172.5 (COOCH ) ppm. IR (ATR): ν = 2954 (w), 2916
˜
3
132.8, 134.0, 140.5, 141.6, 142.2, 156.8 (CPh,Ar), 127.0, 128.5, 128.6, (w), 1659 (m), 1574 (m), 1429 (m), 1333 (m), 1220 (s), 1072 (m),
128.6, 129.5, 130.4 (CHPh,Ar), 172.4 (COOCH ) ppm. IR (ATR): ν
1009 (m), 976 (m) cm–1. MS (EI, 70 eV): m/z (%) = 342 (15) [M]+,
˜
3
= 2922 (w), 1651 (s), 1588 (m), 1481 (m), 1450 (m), 1429 (m), 1316
310 (100), 284 (30), 252 (36), 239 (14). HRMS (EI): calcd. for
(s), 1209 (s), 1090 (s), 1009 (s) cm–1. MS (EI, 70 eV): m/z (%) = 438 C23H18O3 [M]+ 342.12556; found 342.12505.
(50) [M+, 81Br], 436 (50) [M+, 79Br], 406 (100), 378 (24), 325 (94).
Methyl 1-Methyl-9-phenyl-3-trifluoromethansulfonyloxy-9,10-dihy-
HRMS (EI): calcd. for C24H21BrO3 [M+, 79Br] 436.06650; found
436.06686. C24H21BrO3 (436.07): calcd. C 65.91, H 4.84; found C
65.80, H 5.10.
drophenanthrene-4-carboxylate (7): To a dichloromethane solution
(10 mL per 1 mmol of 5a) of 5a (1.0 equiv.) was added pyridine
(2.0 equiv.) at –78 °C and Tf2O (1.2 equiv.). The temperature of the
Isopropyl 7-Bromo-3-hydroxy-1-methyl-9-phenyl-9,10-dihydrophen- solution was warmed to 0 °C over 4 h with stirring. The mixture
anthrene-4-carboxylate (5p): Starting with 3d (0.170 g, 0.50 mmol), was purified by chromatography (dichloromethane) without aque-
4i (0.214 g, 0.74 mmol), and TiCl4 (0.11 mL, 0.99 mmol), 5p was ous workup. Starting with 5a (0.300 g, 0.87 mmol), Tf2O (0.17 mL,
isolated by chromatography (heptane/EtOAc, 200:1) as a colorless
solid (0.086 g, 40%). M.p. 74–55 °C. Rf = 0.66 (heptane/EtOAc,
1.05 mmol), and pyridine (0.14 mL, 1.74 mmol), 7 was isolated by
chromatography (CH2Cl2) as a colorless solid (0.409 g, 99%). M.p.
238–240 °C. Rf = 0.95 (CH2Cl2). 1H NMR (300 MHz, CDCl3): δ
1
3
1:1). H NMR (300 MHz, CDCl3): δ = 1.11 (d, J = 6.2 Hz, 3 H,
3
CH3CH), 1.14 (d, J = 6.2 Hz, 3 H, CH3CH), 2.22 (s, 3 H, CH3), = 2.33 (s, 3 H, CH3), 2.96–3.15 (m, 2 H, CH2CH), 3.86 (s, 3 H,
2.85–3.04 (m, 2 H, CH2CH), 4.07–4.20 (m, 1 H, CH2CH), 5.13
(sept., J = 6.2 Hz, CH3CHCH3), 6.75 (s, 1 H, Ar), 7.04–7.42 (m,
OCH3), 4.08–4.19 (m, 1 H, CH2CH), 6.85–6.95 (m, 1 H, Ph/Ar),
7.06 (s, 1 H, Ar), 7.15–7.39 (m, 7 H, Ph/Ar), 7.41–7.50 (m, 1 H,
3
Eur. J. Org. Chem. 2010, 5118–5127
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5125

M. Lau, M. Sher, A. Villinger, C. Fischer, P. Langer
FULL PAPER
Ph/Ar) ppm. 13C NMR (75.5 MHz, CDCl3): δ = 20.2 (CH3), 33.1
(CH2), 44.1 (CHCH2), 52.7 (OCH3), 118.5 (1J = 320.1 Hz, CF3),
121.5, 126.6, 126.8, 126.9, 127.5, 128.5, 128.7, 128.8 (CHPh,Ar),
122.4, 132.6, 135.7, 137.0, 139.4, 141.0, 141.7, 145.3 (CPh,Ar), 166.8
(COOCH3) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.8 (CF3)
[1]
[2]
For reviews of domino reactions, see: a) L. F. Tietze, U. Beifuss,
Angew. Chem. 1993, 105, 137; Angew. Chem. Int. Ed. Engl.
1993, 32, 131; b) L. F. Tietze, Chem. Rev. 1996, 96, 115.
For a review of 1,3-bis(silyl enol ethers) in general, see: P.
Langer, Synthesis 2002, 441.
ppm. IR (ATR): ν = 1730 (s), 1603 (w), 1658 (s), 1421 (s), 1277
˜
(m), 1203 (s), 1137 (s), 1025 (m), 973 (m), 903 (m) cm–1. MS (EI,
70 eV): m/z (%) = 476 (100) [M]+, 445 (12), 311 (92), 283 (74), 239
(21). HRMS (EI): calcd. for C24H19F3SO5 [M]+ 476.08978; found
476.08998.
[3]
[4]
[5]
[6]
[7]
[8]
Review: P. Langer, Synlett 2006, 3369.
Review: H. Feist, P. Langer, Synthesis 2007, 327.
Review: P. Langer, Eur. J. Org. Chem. 2007, 2233.
Review: P. Langer, Synlett 2007, 1016.
Review: P. Langer, Synlett 2009, 2205.
Review: E. Bellur, H. Feist, P. Langer, Tetrahedron 2007, 63,
10865.
1-Methyl-3,9-diphenyl-9,10-dihydrophenanthrene-4-carboxylate (8):
To a 1,4-dioxane solution (2.5 mL/mmol 7) of 7 (1.0 equiv.) was
added phenylboronic acid (1.3 equiv.), K3PO4 (1.6 equiv.), and the
catalyst (3 mol-%). The mixture was heated for 21 h at 101 °C. The
mixture was allowed to cool to 20 °C and an aqueous solution of
NH4Cl (20 mL) was added. The organic and the aqueous layer
were separated, and the latter was extracted with diethyl ether
(3ϫ20 mL). The combined organic layer was dried (Na2SO4), fil-
tered, and concentrated in vacuo. Starting with 7 (0.190 g,
0.40 mmol), phenylboronic acid (0.063 g, 0.52 mmol), K3PO4
(0.135 g, 0.64 mmol), and Pd(PPh3)4 (0.014 mL, 0.01 mmol), 8 was
isolated by chromatography (heptane/EtOAc, 100:1) as a colorless
solid (0.150 g, 96%). M.p. 83–84 °C. Rf = 0.74 (heptane/EtOAc,
[9]
a) P. Langer, G. Bose, Angew. Chem. Int. Ed. 2003, 42, 4033;
b) G. Bose, V. T. H. Nguyen, E. Ullah, S. Lahiri, H. Görls, P.
Langer, J. Org. Chem. 2004, 69, 9128.
a) M. Lau, P. Langer, Tetrahedron Lett. 2008, 49, 5618; b) M.
Lau, M. Sher, A. Villinger, C. Fischer, P. Langer, Eur. J. Org.
Chem. 2010, 3743–3753.
A. S. Kende, D. P. Curran, J. Am. Chem. Soc. 1979, 101, 1857.
a) A. S. Kende, D. P. Curran, J. Am. Chem. Soc. 1979, 101,
1857; b) D. H. Miles, J. Bhattacharyya, N. V. Mody, J. L. At-
wood, S. Black, P. A. Hedin, J. Am. Chem. Soc. 1977, 99, 618.
B. Fugmann (Ed.), Römpp-Lexikon Naturstoffe, Thieme, Stutt-
gart, 1997.
a) G. R. Pettit, S. B. Singh, M. R. Boyd, E. Hamel, R. K. Pettit,
J. M. Schmidt, F. Hogan, J. Med. Chem. 1995, 38, 1666; b) D. J.
Chaplin, G. R. Pettit, S. A. Hall, Anticancer Res. 1999, 19, 189;
c) A. Cirla, J. Mann, Nat. Prod. Rep. 2003, 20, 558; d) K. Gau-
kroger, J. A. Hadfield, N. J. Lawrence, S. Nolan, A. T.
McGown, Org. Biomol. Chem. 2003, 1, 3033; e) G. M. Cragg,
D. J. Newman, J. Nat. Prod. 2004, 67, 232.
[10]
[11]
[12]
[13]
[14]
1
1:1). H NMR (300 MHz, CDCl3): δ = 2.34 (s, 3 H, CH3), 2.97–
3.20 (m, 2 H, CH2CH), 3.55 (s, 3 H, OCH3), 4.12–4.20 (m, 1 H,
CH2CH), 6.81–6.89 (m, 1 H, Ph/Ar), 7.09–7.45 (m, 13 H, Ph/Ar),
7.55 (m, 1 H, Ph/Ar) ppm. 13C NMR (62.9 MHz, CDCl3): δ =
20.0 (CH3), 33.3, (CH2), 44.6 (CHCH2), 51.9 (OCH3), 126.4, 126.5,
126.7, 127.1, 127.2, 127.7, 128.1, 128.3, 128.6, 128.7, 131.0
(CHPh,Ar), 128.5, 132.9, 133.9, 135.9, 134.4, 139.1, 140.9, 141.4,
[15]
142.5 (CPh,Ar), 171.2 (COOCH ) ppm. IR (ATR): ν = 3026 (w),
a) R. M. Letcher, L. R. M. Nhamo, J. Chem. Soc. C 1971,
3070; b) R. M. Letcher, L. R. M. Nhamo, I. T. Gumiro, J.
Chem. Soc. Perkin Trans. 1 1972, 206; c) R. M. Letcher,
L. R. M. Nhamo, J. Chem. Soc. Perkin Trans. 1 1972, 2941;
d) T. Hashimoto, K. Hasegawa, H. Yamaguchi, M. Saito, S.
Ishimoto, Phytochemistry 1974, 13, 2849; e) T. T. Lee, G. L.
Rock, A. Stoessl, Phytochemistry 1978, 17, 1721; f) M. Yamaki,
T. Kato, L. Bai, K. Inoue, S. Takagi, Phytochemistry 1991, 30,
2759; g) M. Tori, A. Hashimoto, K. Hirose, Y. Asakawa, Phy-
tochemistry 1995, 40, 1263; h) Y.-W. Leong, L. J. Harrison,
A. D. Powell, Phytochemistry 1999, 50, 1237; i) S. Estrada,
R. A. Toscano, R. Mata, J. Nat. Prod. 1999, 62, 1175; j) T.
Hattori, Y. Shimazumi, H. Goto, O. Yamabe, N. Morohashi,
W. Kawai, S. Miyano, J. Org. Chem. 2003, 68, 2099; k) Y.
Hernández-Romero, J.-I. Rojas, R. Castillo, A. Rojas, R. Mata,
J. Nat. Prod. 2004, 67, 160.
For an early review of phenanthrene derivatives, see: G. Rie-
veschl, F. E. Ray, Chem. Rev. 1938, 23, 278.
A. J. Liepa, R. E. Summons, J. Chem. Soc., Chem. Commun.
1977, 826 and references cited therein.
T.-H. Chan, P. Brownbridge, J. Am. Chem. Soc. 1980, 102,
3534.
S. Reim, M. Lau, M. Adeel, I. Hussain, M. A. Yawer, A. Riahi,
Z. Ahmed, C. Fischer, H. Reinke, P. Langer, Synthesis 2009,
445.
˜
3
2945 (w), 1725 (s), 1598 (m), 1494 (m), 1447 (m), 1267 (m), 1238
(m), 1195 (m), 1129 (m) cm–1. MS (EI, 70 eV): m/z (%) = 404 (100)
[M]+, 373 (23), 345 (13), 295 (10), 252 (20). HRMS (EI): calcd. for
C29H24O2 [M]+ 404.17745; found 404.17708.
Methyl 5-(4-Bromophenyl)-5,7a,8,9,10,11a-hexahydro-6H-11-oxa-
benzo[a]anthracene-12-carboxylate (9): To
a solution of 5k
(1.0 equiv.) in DMF (20 mL per 1 mmol of 5k) was added TBAI
(2.2 equiv.) under an argon atmosphere. The mixture was cooled to
–78 °C and NaH (60% dispersion in mineral oil, 1.5 equiv.) was
added at 0 °C. After stirring for 20 h at 20 °C, ethyl acetate (5 mL)
and ice-cold water (5 mL) were added, and the mixture was sub-
sequently neutralized by addition of hydrochloric acid (10%). The
mixture was extracted with EtOAc (3ϫ20 mL). The combined or-
ganic layer was dried (Na2SO4) and filtered, and the filtrate was
concentrated in vacuo. The residue was purified by chromatog-
raphy. Starting with 5k (0.050 g, 0.10 mmol), sodium hydride
(0.006 g, 0.15 mmol), and TBAI (0.081 g, 0.22 mmol), 9 was ob-
tained as a colorless solid (0.025 g, 54%). M.p. 88–90 °C. Rf = 0.74
[16]
[17]
[18]
[19]
1
(heptane/EtOAc, 1:1). H NMR (300 MHz, CDCl3): δ = 2.002.10
3
(m, 2 H, CH2), 2.12 (s, 3 H, CH3), 2.68 (t, J = 6.6 Hz, 2 H, CH2),
2.88–3.08 (m, 2 H, CH2), 3.79 (s, 3 H, OCH3), 4.00–4.08 (m, 1 H,
CH), 4.10–4.23 (m, 2 H, CH2), 6.83–6.90 (m, 1 H, Ar), 7.02–7.10
[20]
a) A. Fürstner, V. Mamane, J. Org. Chem. 2002, 67, 6264; b)
V. Mamane, P. Hannen, A. Fürstner, Chem. Eur. J. 2004, 10,
4556.
3
(m, J = 8.4 Hz, 2 H, Ar), 7.12–7.27 (m, 2 H, Ar), 7.37–7.44 (m,
3J = 8.4 Hz, 2 H, Ar), 7.52–7.58 (m, 1 H, Ar) ppm. 13C NMR
(75.5 MHz, CDCl3): δ = 15.1 (CH3), 22.3, 23.4, 33.3, 66.1 (CH2),
44.4 (CHCH2), 52.4 (OCH3), 118.0, 120.3, 121.2, 127.2, 131.2,
134.2, 136.1, 140.2, 141.9, 151.3 (CAr), 126.1, 126.9, 127.1, 127.6,
[21]
[22]
E. Baciocchi, R. Ruzziconi, J. Org. Chem. 1991, 56, 4772.
a) P. Brownbridge, T.-H. Chan, M. A. Brook, G. J. Kang, Can.
J. Chem. 1983, 61, 688; b) G. A. Molander, K. O. Cameron, J.
Am. Chem. Soc. 1993, 115, 830.
For recent methods, see: a) T. Okabayashi, A. Iida, K. Takai,
Y. Nawate, T. Misaki, Y. Tanabe, J. Org. Chem. 2007, 72, 8142;
b) K. Takai, Y. Nawate, T. Okabayashi, H. Nakatsuji, A. Iida,
Y. Tanabe, Tetrahedron 2009, 65, 5596.
130.3, 131.5 (CHAr), 170.1 (COOCH ) ppm. IR (ATR): ν = 2946
˜
3
(w), 2874 (w), 1727 (s), 1562 (w), 1485 (m), 1408 (m), 1282 (s), 1203
(s), 1068 (s), 1009 (s) cm–1. MS (EI, 70 eV): m/z (%) = 464 (97)
[M+, 81Br], 462 (100) [M+, 79Br], 431 (16), 403 (42), 252 (9). HRMS
(EI): calcd. for C23H19BrO3 [M+, 81Br] 464.08046; found 464.08104.
[23]
5126
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5118–5127

Domino “[3+3] Annulation/Ring-Opening/Friedel–Crafts Alkylation
[24] a) V. T. H. Nguyen, E. Bellur, B. Appel, Synthesis 2006, 2865;
b) V. T. H. Nguyen, B. Appel, P. Langer, Tetrahedron 2006, 62,
7674.
[25] G. Mroß, S. Ladzik, H. Reinke, A. Spannenberg, C. Fischer, P.
Langer, Synthesis 2009, 2236.
[26] M. Lubbe, R. Klassen, T. Trabhardt, A. Villinger, P. Langer,
Synlett 2008, 2331.
[27]
CCDC-767218 (for 5a) and -767219 (for 6) contain the supple-
mentary crystallographic data for this paper. These data can
be obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Received: April 4, 2010
Published Online: July 20, 2010
Eur. J. Org. Chem. 2010, 5118–5127
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5127