Synthesis of spiro[5.4]decenones and their transformation into bicyclo[4.4]deca-1,4-dien-3-ones by domino "elimination-double-Wagner- Meerwein-rearrangement" reactions

Article abstract of DOI:10.1002/chem.200400707

The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopentanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these compounds with trifluoroacetic acid (TFA) afforded a great variety of bicyclo[4.4.0]deca-1,4-dien-3-on

Full text of DOI:10.1002/chem.200400707

FULL PAPER
Synthesis of Spiro[5.4]decenones and Their Transformation into
Bicyclo[4.4]deca-1,4-dien-3-ones by Domino “Elimination–
Double-Wagner–Meerwein-Rearrangement” Reactions
Gopal Bose, Ehsan Ullah, and Peter Langer*[a]
Abstract: The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-diacylcyclopen-
tanes allows a convenient synthesis of spiro[5.4]decenones. Treatment of these
compounds with trifluoroacetic acid (TFA) afforded a great variety of bicy-
clo[4.4.0]deca-1,4-dien-3-ones containing an angular alkyl group. This core struc-
ture occurs in a number of pharmacologically relevant natural products.
Keywords: cyclization
·
domino
silyl
reactions
·
rearrangement ·
enol ethers · spiro compounds
Introduction
vetivone; Scheme 1), which are biosynthetically derived
from the eudesmanes.[10] The biosynthetic pathways for the
interconversion of eudesmane, eremophilane, and the spiro-
vetivane sesquiterpenes involve Wagner–Meerwein rear-
rangements.[12–14]
1,3-Bis-silyl enol ethers can be regarded as electroneutral
1,3-dicarbonyl dianion equivalents (masked dianions).[1,2]
They represent useful synthetic building blocks in Lewis
acid mediated transformations. In cyclization reactions, 1,3-
bis-silyl enol ethers can react as 1,3-dinucleophiles or, simi-
larly to the well-known Danishefsky diene,[3] as functional-
ized 1,3-butadienes. Chan and co-workers have reported
TiCl4-mediated [3+3] cyclizations of 1,3-bis-silyl enol ethers
with 3-silyloxyalk-2-en-1-ones and with ketals of b-ketoalde-
hydes, b-ketoesters, and b-ketocarboxylic chlorides to give
benzene derivatives.[4] In addition, the synthesis of aromatic
products by cyclization of free 1,3-dicarbonyl compounds
with 1,3-dielectrophiles has been reported.[5,6]
We have recently reported the TiCl4-mediated cyclization
of 1,3-bis-silyl enol ethers with 1,1-diacetylcyclopentane to
give spiro[5.4]decenones.[7] Treatment of these compounds
with trifluoroacetic acid (TFA) resulted in a domino rear-
rangement[8] and formation of bicyclo[4.4.0]deca-1,4-dien-3-
ones containing an angular methyl group. This type of rear-
rangement has been previously reported by Hagenbruch
and Hünig[9a] and by others.[9b–g] The bicyclo[4.4.0]decane
core structure is present in a variety of natural products,
such as steroids and the eudesmane and eremophilane ses-
quiterpenes (for example, nootkaton; Scheme 1).[10,11] The
spiro[5.4]decane skeleton also occurs in nature. This in-
cludes the spirovetivane sesquiterpenes (for example, sola-
Scheme 1. Spiro[5.4]decanes and bicyclo[4.4.0]decanes in nature.
We have significantly extended the preparative scope of
the methodology, with regard to our preliminary communi-
cation.[7] We have successfully developed regioselective cy-
clizations of unsymmetrical 1,1-diacylcyclopentanes, such as
1-acetyl-1-formylcyclopentane, and also studied cyclizations
of 2,2-diacetylindane, 1,1-diacetylcyclopent-3-ene, and 3,3-
dimethylpentane-2,4-dione. In addition, the mechanism of
the domino process was studied.
Results and Discussion
Our starting point was the development of conditions for
the cyclization of 3,3-dimethylpentane-2,4-dione (2) with
1,3-bis-silyl enol ether 1a. Treatment of a CH Cl2 solution of
2
the starting materials with TiCl4 (2 equiv) resulted in the for-
mation of 3-hydroxycyclohex-5-en-1-one 3a (Scheme 2). The
product was formed by cyclization and subsequent extrusion
of water. The use of other Lewis acids, such as BF3·OEt2,
Me3SiOTf, or ZnCl2, was unsuccessful. Optimal yields were
obtained when the reaction was carried out at ꢀ78!208C.
[a] Dr. G. Bose, E. Ullah, Prof. Dr. P. Langer
Institut für Chemie und Biochemie
der Ernst-Moritz-Arndt Universität Greifswald
Soldmannstrasse 16, 17487 Greifswald (Germany)
Fax : (+49)3834-864-373
E-mail: peter.langer@uni-greifswald.de
Chem. Eur. J. 2004, 10, 6015 – 6028
DOI: 10.1002/chem.200400707
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6015

FULL PAPER
Scheme 2. Cyclization of 1,3-bis-silyl enol ethers with 3,3-dimethylpen-
tane-2,4-dione: a) 1. TiCl4 (2.0 equiv), CH2Cl2, 4 Š molecular sieves
(MS), ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2, 72 h.
The use of molecular sieves (4 Š) proved to be mandatory.
Treatment of a CH Cl2 solution of 3a with TFA afforded,
2
after optimization of the reaction conditions, the cyclohexa-
2,5-dien-1-one 4a in 88% yield. A number of related prod-
ucts (3b–e and 4b–e) were prepared by variation of the 1,3-
bis-silyl enol ether (Table 1).
Table 1. Products and yields.
3,4
R
% 3[a]
% 4[a]
a
b
c
d
e
Me
OMe
OEt
OiPr
47
61
63
56
61
88
95
96
90
92
O(CH2)2Me
Scheme 3. Cyclization of 1,3-bis-silyl enol ether 1a with 1,1-diacetylcyclo-
pentane: a) 1. TiCl4 (2.0 equiv), CH2Cl2, 4 Š MS, ꢀ78!208C; 2. H+,
H2O; b) TFA, CH2Cl2, 72 h.
[a] Yield of isolated products.
The TiCl4-mediated cyclization of 1a with 1,1-diacetylcy-
clopentane (5a), prepared by K2CO3-mediated cyclization of
acetylacetone with 1,4-dibromobutane,[9,15] afforded the hy-
droxyspiro[5.4]decenone 6a in good yield (Scheme 3). The
following parameters proved to be important during the op-
timization of this reaction: a) the choice of the Lewis acid,
b) the temperature (ꢀ78!208C), and c) the presence of
molecular sieves (4 Š). Stirring of a TFA/CH2Cl2 solution of
6a for 72 h afforded the bicyclo[4.4.0]deca-1,4-dien-3-one 7a
in high yield. The formation of 7a can be explained as fol-
lows (Scheme 3): acid-mediated elimination of water gave
the spiroannulated cyclohexa-2,5-dien-1-one A, which was
protonated to give intermediate B. Ring enlargement by
[1,2] rearrangement gave intermediate C. Rearrangement of
the methyl group gave intermediate D and subsequent ex-
trusion of a proton afforded 7a. The rearrangement pro-
ceeded with very good regioselectivity. The formation of the
regioisomer iso-7a was not observed. The regioselectivity of
the ring enlargement (B!C) can be explained by the fact
that carbon atom C-5 of the delocalized carbocation B is
more electron-poor than carbon atom C-3, due to the prox-
imity of two electron-withdrawing carbonyl groups.
The preparative scope of our methodology was studied.
The reaction of 5a with ester-derived 1,3-bis-silyl enol
ethers 1b–e gave the spiro compounds 6b–e, which were
successfully transformed into the bicyclo[4.4.0]deca-1,4-dien-
3-ones 7b–e (Scheme 4, Table 2). The cyclization of 5a with
1,3-bis-silyl enol ethers 1 f and 1g, which contain either a
methyl or an ethyl group at the terminal carbon atom, af-
forded the spiro compounds 6 f and 6g, respectively. Treat-
ment of these compounds with TFA resulted in formation of
the bicyclo[4.4.0]decadienones 7 f and 7g containing
a
Abstract in German: Die [3+3] Cyclisierung von 1,3-Bis-Si-
lylenolethern mit 1,1-Diacylcyclopentanen ermçglicht eine ef-
fiziente Synthese von Spiro[5.4]decenonen. Durch Behand-
lung dieser Verbindungen mit Trifluoressigsäure (TFA)
konnte eine große Bandbreite von Bicyclo[4.4.0]deca-1,4-
dien-3-onen mit angularer Alkylgruppe hergestellt werden.
Dieses Gerüstsystem tritt in einer Reihe pharmakologisch
relevanter Naturstoffe auf.
methyl and an ethyl substituent, respectively. Variation of
the 1,1-diacylcyclopentane was studied next. The reaction of
1b–d with novel 1,1-dipropionylcyclopentane (5b), prepared
by cyclization of heptane-3,5-dione with 1,4-dibromobutane,
resulted in formation of spiro compounds 6h–j, which were
successfully transformed into 7h–j. The cyclization of 1,3-
bis-silyl enol ether 1c with (unsymmetrical) 1-acetyl-1-ben-
zoylcyclopentane (5c)[15d] gave the spiro[5.4]decenone 6k.
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Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
transformed into an aldehyde by application of the Swern
oxidation. This straightforward synthesis of 5d is related to
the procedure reported for the preparation of 1-acetyl-1-for-
mylcyclopropane.[16]
The cyclization of 1,3-bis-silyl enol ether 1c with 1-acetyl-
1-formylcyclopentane (5d) gave the spiro compound 13a,
which was formed by regioselective attack of the terminal
carbon atom of 1c onto the aldehyde group (Scheme 6,
Scheme 4. Synthesis of 6a–k and 7a–k: a) 1. TiCl4 (2.0 equiv), CH2Cl2,
4 Š MS, ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2, 72 h.
Table 2. Products and yields.
6,7
R1
R2
R3
R4
% 6[a]
% 7[a]
a
b
c
d
e
f
g
h
i
H
H
H
H
H
Me
Et
H
H
H
H
Me
OMe
OEt
Me
Me
Me
Me
Me
Me
Me
Et
Me
Me
Me
Me
Me
Me
Me
Et
67
72
78
66
95
98
96
97
97
92
88
83
85
89
91
OiPr
O(CH2)2OMe
OMe
OEt
OMe
OEt
53
23[b]
41[b]
58
Et
Et
Me
Et
Et
Ph
53
38
20
j
k
OiPr
OEt
[a] Yields of isolated products. [b] Diastereomeric mixture.
The TFA-mediated rearrangement of 6k selectively afford-
ed the bicyclo[4.4.0]decadienone 7k.
Treatment of hydroxyspiro[5.4]decenone 6c with TFA for
only 3 h (rather than for 72 h) afforded the spiro[5.4]deca-
dienone 8 in 56% yield (Scheme 5). This experiment sup-
Scheme 6. Synthesis of 13a, 13b, 14a, 15a, and 15b: a) 1. TiCl4
(2.0 equiv), CH2Cl2, 4 Š MS, ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2,
72 h.
Table 3. Products and yields.
13,14,15
R
% 13[a]
% 14[a]
% 15[a]
a
b
OEt
Me
20
27
43
0
22
52
[a] Yields of isolated products.
Scheme 5. Synthesis of 8: a) T FA, CHCl2, 3 h.
2
Table 3). Treatment of 13a with TFA afforded a separable
mixture of the expected bicyclo[4.4.0]decadienone 14a
(43%, mechanism path B) and of the tetraline 15a (22%,
mechanism path A). The formation of 15a can be explained
by elimination of water and protonation to give intermedi-
ate E and subsequent ring enlargement and aromatization.
The regioselectivity of the ring enlargement can be ex-
plained by the higher reactivity of the secondary carbocat-
ion located at C-3 (with respect to the tertiary carbocation
located at C-5). The product 15a is formed by a rapid ring
enlargement (mechanism path A) and irreversible formation
of a stable aromatic product. The cyclization of 5d with 1,3-
bis-silyl enol ether 1a afforded 13b. Treatment of the latter
with TFA resulted in exclusive formation of the tetraline
15b in 52% yield (mechanism path A).
ports the intermediacy of spiro[5.4]decadienone A in the
mechanism suggested (Scheme 3). The formation of a carbo-
cation by extrusion of water and subsequent ring enlarge-
ment (without protonation of the carbonyl group) appears
to be less likely.
Cyclization reactions of 1-acetyl-1-formylcyclopentane
(5d) were studied next. The synthesis of novel compound
5d was accomplished as follows (see the Experimental Sec-
tion). The cyclization of ethyl acetoacetate with 1,4-dibro-
mobutane afforded ethyl 1-acetylcyclopentane-1-carboxylate
(9). The keto group of 9 was protected by transformation
into a ketal (10). The ester group was reduced to an alcohol
(11), the acetal was hydrolyzed, and the alcohol (12) was
Chem. Eur. J. 2004, 10, 6015 – 6028
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P. Langer et al.
FULL PAPER
The reaction of 5d with 1g afforded the spiro compound
13c (Scheme 7). Treatment of the latter with TFA exclusive-
ly afforded the bicyclo[4.4.0]decadienone 14c in 60% yield
(mechanism path B). The formation of an aromatic product
7. Despite the acidic conditions, no migration of the double
bond was observed during the reaction.
The reaction of 1,3-bis-silyl enol ethers with 2,2-diacetyl-
indane (5 f), prepared by base-mediated cyclization of acetyl-
acetone with 1,2-bis(bromomethyl)benzene,[19] was studied
next (Scheme 9, Table 5). The cyclization of 1,3-bis-silyl enol
Scheme 7. Synthesis of 13c and 14c: a) 1. TiCl4 (2.0 equiv), CH2Cl2, 4 Š
MS, ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2, 72 h.
15 by mechanism path A is disfavored, due to the presence
of the ethyl group at carbon atom C-2 and steric repulsion
during the ring enlargement.
Cyclization reactions of 1,1-diacetylcyclopent-3-ene (5e)
were studied next. Direct base-mediated cyclization of ace-
tylacetone with 1,4-dichlorobut-2-ene has been reported to
give mixtures of regioisomeric products.[17] Therefore, we
have developed a new synthesis of 5e. The reaction of ace-
tylacetone with allyl bromide afforded the known 3,3-dial-
lylacetylacetone, which was subsequently transformed into
5e by ring-closing metathesis (RCM) with the Grubbs cata-
lyst and Ti(OiPr)4 (Fürstner conditions).[18] The reaction of
1,3-bis-silyl enol ethers 1b–d with 5e afforded the spiro
compounds 16a–c (Scheme 8, Table 4). Treatment of 16a–c
with TFA afforded the bicyclo[4.4.0]deca-1,4,6-trien-3-ones
17a–c. The formation of the latter can be explained by a
double Wagner–Meerwein rearrangement, as described for
Scheme 9. Synthesis of 18a–m and 19a–l: a) 1. TiCl4 (2.0 equiv), CH2Cl2,
4 Š MS, ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2, 72 h.
Table 5. Products and yields.
18,19
R1
R2
R3
R4
% 18[a]
% 19[a]
a
b
c
d
e
f
g
h
i
H
H
H
H
H
Et
H
H
H
H
H
H
H
Me
OMe
OEt
OiPr
O(CH2)2OMe
OEt
OMe
OMe
OEt
Me
Me
Me
Me
Me
Me
Me
Ph
Me
Ph
Me
Ph
Me
Me
Me
Me
Me
Me
Ph
Me
Ph
Me
Ph
82
86
86
82
61
31[b]
23
21
22
17
21
15
43
82
79
86
76
85
[c]
–
73
84
84
83
83
73
j
k
l
OEt
OiBu
OiBu
OiPr
Me
Et
[c]
m
Et
–
[a] Yields of isolated products. [b] Diastereomeric mixture. [c] The prod-
uct could not be isolated in pure form.
ether 1a with 5 f afforded the benzo-annulated spiro[5.4]de-
cenone 18a in good yield. Treatment of 18a with TFA af-
forded the tricyclic product 19a, which can be regarded as a
9,9a-dihydroanthracene. Due to conjugation of the enol
moiety with the aryl group, this compound resides in the
enol tautomeric form. The reaction of 1,3-bis-silyl enol
ethers 1b–e with 5 f afforded the spiro[5.4]decenones 18b–e,
which were transformed into the 9,9a-dihydroanthracenes
19b–e. The reaction of 1g with 5 f afforded 18 f. Treatment
of the latter resulted in the formation of the ethyl-substitut-
ed 9,9a-dihydroanthracene 19 f; however, this could not be
isolated in pure form. The reaction of 1,3-bis-silyl enol ether
1b with novel 2-acetyl-2-benzoylindane (5g) afforded a sep-
arable mixture of the regioisomeric spiro[5.4]decenones 18g
(23%) and 18h (21%). These products were transformed
Scheme 8. Synthesis of 16a–c and 17a–c: a) 1. TiCl4 (2.0 equiv), CH2Cl2,
4 Š MS, ꢀ78!208C; 2. H+, H2O; b) TFA, CH2Cl2, 72 h.
Table 4. Products and yields.
16,17
R
% 16[a]
% 17[a]
a
b
c
OMe
OEt
OiPr
83
64
59
76
76
73
[a] Yields of isolated products.
6018
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Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
(CH2), 44.49 (C), 24.40, 22.09, 20.66, 17.68 ppm (CH3); IR (KBr): n˜ =
3411 (br), 2987 (m), 1728 (s), 1661 (s), 1618 (m), 1436 (m), 1340 (m),
1225 (s), 1091 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=226.3 (5) [M+], 211.1
(11), 194.2 (35), 179.2 (16), 151.5 (29), 136.1 (100), 107.2 (20), 43.0 (16);
elemental analysis calcd (%) for C12H18O4: C 63.70, H 8.31; found: C
63.64, H 8.39.
into the corresponding 9,9a-dihydroanthracenes 19g and
19h, respectively. The reaction of ethoxy- and isobutoxy-
substituted 1,3-bis-silyl enol ethers with 5g afforded separa-
ble mixtures of the regioisomers 18i and 18j and of the re-
gioisomers 18k and 18l, respectively. These products were
transformed into the 9,9a-dihydroanthracenes 19i–l. T he
cyclization of 1d with novel 2,2-dipropionylindane (5h) af-
forded 18m. Treatment of the latter with TFA afforded
19m; however, this could not be isolated in pure form.
4-Hydroxy-2,3,3,4-tetramethyl-6-oxocyclohex-1-ene carboxylic acid ethyl
ester (3c): From 1-ethoxy-1,3-bis(trimethysilyloxy)buta-1,3-diene (1c;
0.375 g,
1.37 mmol),
3,3-dimethylpentane-2,4-dione
(2;
0.135 g,
1.05 mmol), and TiCl4 (0.23 mL, 2.09 mmol), 3c was obtained as a color-
less solid (0.159 g, 63%). M.p. 116–1178C; Rf =0.12 (hexane/ethyl acetate
7:3); 1H NMR (200 MHz, CDCl3): d=4.31 (d, 2H, J=7.2 Hz; OCH2),
2.64 (s, 2H; CH2), 2.27 (s, 1H; OH), 1.95 (s, 3H; CH3), 1.33 (t, 3H, J=
7.2 Hz; CH3), 1.31 (s, 3H; CH3), 1.26 (s, 3H; CH3), 1.21 ppm (s, 3H;
CH3); 13C NMR (50 MHz, CDCl3): d=193.44, 167.19, 164.08, 132.39 (C),
Conclusion
ꢀ
74.99 (C OH), 61.29 (OCH2), 48.71 (CH2), 44.35 (C), 24.34, 22.10, 20.59,
The [3+3] cyclization of 1,3-bis-silyl enol ethers with 1,1-di-
acylcyclopentanes allows a convenient synthesis of spi-
ro[5.4]decenones. Treatment of these compounds with TFA
afforded a great variety of bicyclo[4.4.0]deca-1,4-dien-3-ones
containing an angular alkyl group.
17.66, 14.11 ppm (CH3); IR (KBr): n˜ =3424 (br), 2986 (m), 1719 (s), 1663
(s), 1621 (m), 1384 (m), 1243 (s), 129 (s), 1092 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%)=240.5 (7) [M+], 211.3 (10), 195.3 (34), 179.3 (14), 151.5 (30),
136.2 (100), 108.5 (22), 43.1 (14); elemental analysis calcd (%) for
C13H20O4: C 64.98, H 8.39; found: C 64.80, H 8.24.
4-Hydroxy-2,3,3,4-tetramethyl-6-oxocyclohex-1-ene carboxylic acid iso-
propyl ester (3d): From 1-isopropyloxy-1,3-bis(trimethysilyloxy)buta-1,3-
diene (1d; 0.380 g, 1.32 mmol), 3,3-dimethylpentane-2,4-dione (2; 0.130 g,
1.01 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 3d was obtained as a color-
less solid (0.144 g, 56%). M.p. 68–698C; Rf =0.11 (hexane/ethyl acetate
3:2); 1H NMR (300 MHz, CDCl3): d=5.15 (sep, 1H, J=6.2 Hz; OCH),
2.62 (s, 2H; CH2), 2.30 (s, 1H; OH), 1.93 (s, 3H; CH3), 1.31 (s, 3H;
CH3), 1.25 (d, 6H, J=6.2 Hz; CH3), 1.22 (s, 3H; CH3), 1.16 ppm (s, 3H;
CH3); 13C NMR (75 MHz, CDCl3): d=193.41, 166.75, 163.45, 132.58 (C),
Experimental Section
General: All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For the 1H and 13C NMR
spectra (1H NMR: 300, 600 MHz; 13C NMR: 75, 150 MHz), the deuterat-
ed solvents indicated were used. Mass spectrometry (MS) data were ob-
tained by using the electron ionization (70 eV), chemical ionization (CI,
H2O), or electrospray ionization (ESI) techniques. For preparative scale
chromatography, silica gel (60–200 mesh) was used. Melting points are
uncorrected.
ꢀ
75.01 (C OH), 68.93 (OCH), 48.75 (CH2), 44.30 (C), 24.33, 22.13, 21.70
(2C), 20.60, 17.45 ppm (CH3); IR (KBr): n˜ =3415 (br), 2982 (m), 1723
(s), 1658 (s), 1619 (m), 1461 (m), 1356 (s), 1226 (s), 1096 cmꢀ1 (s); MS
(EI, 70 eV): m/z (%)=254.6 (17) [M+], 211.4 (77), 195.3 (69), 169.2 (65),
151.8 (44), 136.3 (100), 108.5 (24), 43.1 (52); elemental analysis calcd (%)
for C14H22O4 (254.33): C 66.11, H 6.81; found: C 65.93, H 9.38.
Typical procedure for the preparation of 3-hydroxycyclohex-5-en-1-ones
of 3: TiCl4 (0.22 mL, 2.00 mmol) was added dropwise to a stirred CH2Cl2
solution (100 mL) of 3,3-dimethylpentane-2,4-dione (2; 0.133 g,
1.04 mmol) and 1,3-bis(trimethylsilyloxy)-1,3-butadiene 1a (0.330 g,
1.35 mmol) at ꢀ788C under an argon atmosphere in the presence of mo-
lecular sieves (4 Š; 1.0 g). The temperature of the reaction mixture was
allowed to rise to 208C over 6 h. The solution was stirred for an addition-
al 6 h at 208C. The reaction mixture was filtered and the filtrate was
poured into an aqueous solution of HCl (10%, 100 mL). The organic
layer was separated and the aqueous layer was extracted with CH2Cl2
(3”100 mL). The combined organic layers were dried (Na2SO4) and fil-
tered and the filtrate was concentrated in vacuo. The residue was purified
by column chromatography (silica gel; hexane/ethyl acetate 3:2) to give
3a as a colorless oil (0.102 g, 47%).
4-Hydroxy-2,3,3,4-tetramethyl-6-oxocyclohex-1-ene carboxylic acid 2-me-
thoxyethyl ester (3e): From 1-(2-methoxy)ethoxy-1,3-bis(trimethysilyl-
oxy)buta-1,3-diene (1e; 0.401 g, 1.32 mmol), 3,3-dimethylpentane-2,4-
dione (2; 0.135 g, 1.05 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 3e was ob-
tained as
a colorless solid (0.164 g, 61%). M.p. 78–888C; Rf =0.11
(hexane/ethyl acetate 1:1); 1H NMR (300 MHz, CDCl3): d=4.39 (t, 2H,
J=4.8 Hz; OCH2), 3.64 (t, 2H, J=4.8 Hz; OCH2), 3.38 (s, 3H; OCH3),
2.61 (s, 2H; CH2), 2.29 (s, 1H; OH), 1.96 (s, 3H; CH3), 1.29 (s, 3H;
CH3), 1.26 (s, 3H; CH3), 1.19 ppm (s, 3H; CH3); 13C NMR (50 MHz,
ꢀ
CDCl3): d=193.31, 167.07, 164.57, 132.08 (C), 74.92 (C OH), 70.22,
63.92 (OCH2), 58.75 (OCH3), 48.72 (CH2), 44.42 (C), 24.33, 22.02, 20.62,
17.66 ppm (CH3); IR (KBr): n˜ =3402 (br), 2987 (m), 1727 (s), 1660 (s),
1619 (m), 1456 (m), 1382 (s), 1245 (s), 1091 cmꢀ1 (s); MS (EI, 70 eV):
m/z (%)=270.5 (18) [M+], 211.3 (40), 194.5 (79), 179.2 (41), 151.8 (68),
136.6 (100), 108.5 (32), 43.1 (37); elemental analysis calcd (%) for
C14H22O5 (270.33): C 62.20, H 8.20; found: C 62.35, H 8.59.
2-Acetyl-5-hydroxy-3,4,4,5-tetramethylcyclohex-2-enone (3a): From 1-
methyl-1,3-bis(trimethysilyloxy)buta-1,3-diene (1a; 0.330 g, 1.35 mmol),
3,3-dimethylpentane-2,4-dione (2; 0.133 g, 1.04 mmol), and TiCl4
(0.22 mL, 2.00 mmol), 3a was obtained as a colorless oil (0.102 g, 47%).
1
Typical procedure for the preparation of cyclohexa-2,5-dien-1-ones of 4:
TFA (0.4 mL, 5.2 mmol) was added dropwise to a stirred CH2Cl2 solution
(0.4 mL) of 3a (0.065 g, 0.31 mmol) at 208C. The solution was stirred for
72 h until all starting material disappeared (TLC control). The solvent
and TFA were removed in vacuo and the residue was purified by column
chromatography (silica gel; hexane/ethyl acetate 7:3) to give 4a as a col-
orless oil (0.052 g, 88%).
Rf =0.08 (hexane/ethyl acetate 7:3); H NMR (200 MHz, CDCl3): d=2.65
(s, 2H; CH2), 2.33 (s, 3H; CH3), 2.05 (br, 1H; OH), 1.89 (s, 3H; CH3),
1.30 (s, 3H; CH3), 1.26 (s, 3H; CH3), 1.20 ppm (s, 3H; CH3); 13C NMR
ꢀ
(50 MHz, CDCl3): d=205.19, 195.06, 163.03, 138.77 (C), 75.09 (C OH),
49.06 (CH2), 44.51 (C), 31.81, 24.51, 22.24, 20.61, 16.95 ppm (CH3); IR
(KBr): n˜ =3424 (br), 2986 (m), 1719 (s), 1663 (s), 1621 (m), 1384 (m),
1243 (s), 129 (s), 1092 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=240.5 (7)
[M+], 211.3 (10), 195.3 (34), 179.3 (14), 151.5 (30), 136.2 (100), 108.5
(22), 43.1 (14).
2-Acetyl-3,4,4,5-tetramethylcyclohexa-2,5-dienone
(4a):
From
3a
(0.065 g, 0.31 mmol), 4a was obtained as a colorless oil (0.052 g, 88%).
1
Rf =0.23 (hexane/ethyl acetate 7:3); H NMR (300 MHz, CDCl3): d=6.12
4-Hydroxy-2,3,3,4-tetramethyl-6-oxocyclohex-1-ene
carboxylic
acid
(d, 1H, J=1.2 Hz; =CH), 2.37 (s, 3H; CH3), 2.05 (d, 3H, J=1.2 Hz;
CH3), 1.96 (s, 3H; CH3), 1.29 ppm (s, 6H; CH3); 13C NMR (75 MHz,
CDCl3): d=205.32, 183.14, 165.71, 160.60, 139.12 (C), 126.40 (CH), 42.96
(C), 31.72, 24.51 (2C), 19.93, 16.17 ppm (CH3); IR (KBr): n˜ =1734 (s),
1664 (s), 1623 (s), 1386 (m), 1250 (s), 1048 (m), 888 cmꢀ1 (w); MS (EI,
70 eV): m/z (%)=192.2 (2) [M+], 177.1 (100), 162.1 (5), 149.1 (11), 135.1
(9), 121.1 (8), 91.1 (7), 43.1 (13). The exact molecular mass for C12H16O2:
m/z=192.1150ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
methyl ester (3b): From 1-methoxy-1,3-bis(trimethysilyloxy)buta-1,3-
diene (1b; 0.386 g, 1.48 mmol), 3,3-dimethylpentane-2,4-dione (2; 0.152 g,
1.18 mmol), and TiCl4 (0.24 mL, 2.18 mmol), 3b was obtained as a color-
less solid (0.164 g, 61%). M.p. 114–1158C; Rf =0.12 (hexane/ethyl acetate
7:3); 1H NMR (200 MHz, CDCl3): d=3.78 (s, 3H; OCH3), 2.62 (s, 2H;
CH2), 2.15 (s, 1H; OH), 1.90 (s, 3H; CH3), 1.26 (s, 3H; CH3), 1.22 (s,
3H; CH3), 1.16 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3): d=
ꢀ
193.18, 167.47, 164.33, 132.34 (C), 74.96 (C OH), 52.05 (OCH3), 48.83
Chem. Eur. J. 2004, 10, 6015 – 6028 www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6019

P. Langer et al.
FULL PAPER
ꢀ
2,3,3,4-Tetramethyl-6-oxocyclohexa-1,4-dienecarboxylic acid methyl ester
(4b): From 3b (0.075 g, 0.33 mmol), 4b was obtained as a colorless oil
(0.065 g, 95%). Rf =0.18 (hexane/ethyl acetate 7:3); 1H NMR (300 MHz,
CDCl3): d=6.07 (d, 1H, J=1.2 Hz; =CH), 3.79 (s, 3H; OCH3), 1.99 (d,
3H, J=1.2 Hz; CH3), 1.97 (s, 3H; CH3), 1.23 ppm (s, 6H; CH3);
13C NMR (75 MHz, CDCl3): d=181.43, 167.55, 165.32, 161.73, 132.72 (C),
125.92 (CH), 52.05 (CH3), 42.69 (C), 24.33 (2C), 19.80, 16.82 ppm (CH3);
IR (KBr): n˜ =1739 (s), 1662 (s), 1627 (s), 1390 (m), 1250 (s), 1048 (m),
870 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=208.2 (100) [M+], 193.1, 177.1,
149.1, 121.1, 91.1. The exact molecular mass for C12H16O3: m/z=
208.1099ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
2,3,3,4-Tetramethyl-6-oxocyclohexa-1,4-dienecarboxylic acid ethyl ester
(4c): From 3c (0.070 g, 0.29 mmol), 4c was obtained as a colorless oil
(0.062 g, 96%). Rf =0.22 (hexane/ethyl acetate 7:3); 1H NMR (300 MHz,
CDCl3): d=6.11 (d, 1H, J=1.3 Hz; =CH), 4.32 (d, 2H, J=7.1 Hz;
OCH2), 2.03 (d, 3H, J=1.3 Hz; CH3), 2.01 (s, 3H; CH3), 1.32 (t, 3H, J=
7.1 Hz; CH3), 1.28 ppm (s, 6H; CH3); 13C NMR (75 MHz, CDCl3): d=
181.59, 167.18, 165.27, 161.30, 132.99 (C), 126.07 (CH), 61.18 (OCH2),
42.69 (C), 24.40 (2C), 19.86, 16.71, 14.11 ppm (CH3); IR (neat): n˜ =2982
(w), 1733 (s), 1665 (s), 1632 (s), 1389 (m), 1244 (s), 1048 (s), 878 cmꢀ1
(w); MS (EI, 70 eV): m/z (%)=222.2 (98) [M+], 207.2 (34), 177.1 (100),
149.1 (87), 135.1 (45), 121.1 (65), 105.5 (41), 91.1 (35). The exact molecu-
lar mass for C13H18O3: m/z=222.1256ꢁ2 mD was confirmed by HRMS
(EI, 70 eV).
(50 MHz, CDCl3): d=205.44, 195.65, 163.68, 137.63 (C), 75.40 (C OH),
56.26 (C), 49.95, 32.93 (2C, CH2), 31.75 (CH3), 28.22 (2C, CH2), 24.89,
17.04 ppm (CH3); IR (KBr): n˜ =3414 (s), 2959 (m), 1704 (s), 1652 (s),
1603 (m), 1383 (m), 1344 (m), 1191 cmꢀ1 (m); MS (EI; 70 eV): m/z (%)=
236.2 (26) [M+], 218.0 (64), 193.1 (60), 149.1 (100), 43.0 (89); elemental
analysis calcd (%) for C14H20O3: C 71.15, H 8.53; found: C 71.31, H 8.53.
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic
acid
methyl ester (6b): From 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1b; 0.390 g, 1.5 mmol), 1,1-diacetylcyclopentane (5a; 0.156 g,
1.0 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6b was obtained as colorless
crystals (0.184 g, 72%). M.p. 106–1078C; Rf =0.23 (hexane/ethyl acetate
3:2); 1H NMR (300 MHz, CDCl3): d=3.82 (s, 3H; OCH3), 2.65 (br, 2H;
CH2), 2.22 (br, 1H; OH), 1.99 (br, 2H; CH2), 1.98 (s, 3H; CH3), 1.76 (br,
6H; CH2), 1.27 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
ꢀ
193.83, 167.66, 164.91, 131.25 (C), 75.34 (C OH), 56.13 (C), 52.20
(OCH3), 49.64, 32.98 (2C), 28.23 (2C, CH2), 24.86, 17.88 ppm (CH3); IR
(KBr): n˜ =3431 (s), 2961 (s), 1730 (s), 1663 (s), 1620 (s), 1344 (m), 1385
(s), 1231 (s), 1203 (s), 863 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=252.3 (4)
[M+], 220.2 (16), 162.1 (100), 134.1 (52), 91.1 (54), 43.0 (72); elemental
analysis calcd (%) for C14H20O4: C 66.64, H 7.99; found: C 66.58, H 8.23.
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic
acid
ethyl ester (6c): From 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1c; 0.415 g, 1.5 mmol), 1,1-diacetylcyclopentane (5a; 0.154 g, 1.0 mmol),
and TiCl4 (0.22 mL, 2.00 mmol), 6c was obtained as colorless crystals
(0.208 g, 78%). M.p. 107–1088C; Rf =0.35 (hexane/ethyl acetate 1:1);
1H NMR (300 MHz, CDCl3): d=4.29 (q, 2H, J=7.2 Hz; OCH2), 2.64 (br,
2H; CH2), 2.16 (br, 2H; CH2), 1.98 (s, 3H; CH3), 1.88 (br, 1H; OH),
1.76 (br, 6H; CH2), 1.32 (t, 3H, J=7.2 Hz; CH3), 1.26 ppm (s, 3H; CH3);
13C NMR (75 MHz, CDCl3): d=194.15, 167.54, 164.61, 131.72 (C), 75.68
2,3,3,4-Tetramethyl-6-oxocyclohex-1,4-dienecarboxylic acid isopropyl
ester (4d): From 3d (0.066 g, 0.26 mmol), 4d was obtained as a colorless
oil (0.055 g, 90%). Rf =0.23 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=6.12 (d, 1H, J=1.2 Hz; =CH), 5.23 (sep, 1H, J=
6.3 Hz; OCH), 2.05 (d, 3H, J=1.2 Hz; CH3), 2.04 (s, 3H; CH3), 1.32 (d,
6H, J=6.3 Hz; CH3), 1.27 ppm (s, 6H; CH3); 13C NMR (75 MHz,
CDCl3): d=181.43, 166.56, 165.14, 160.69, 132.99 (C), 125.91 (CH), 68.57
(OCH), 42.49 (C), 24.23 (2C), 21.55 (2C), 19.65, 16.32 ppm (CH3); IR
(neat): n˜ =2982 (w), 1731 (s), 1667 (s), 1627 (s), 1386 (m), 1249 (s),
1039 cmꢀ1 (s); MS (EI, 70 eV): m/z (%)=236.0 (42) [M+], 220.9 (10),
177.1 (100), 149.1 (56), 135.1 (44), 121.1 (29), 91.0 (31), 43.1 (87). The
exact molecular mass for C14H20O3: m/z=236.1412ꢁ2 mD was confirmed
by HRMS (EI, 70 eV).
ꢀ
(C OH), 61.53 (OCH2), 56.35 (C), 49.95, 33.54 (2C), 28.50 (2C, CH2),
25.11, 17.98, 14.40 ppm (CH3); IR (KBr): n˜ =3410 (s), 2966 (s), 1724 (s),
1663 (s), 1619 (s), 1470 (m), 1385 (s), 1342 (s), 1237 (s), 1205 (s), 1089 (s),
1026 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=266.3 (9) [M+], 220.2 (52),
162.2 (100), 134.1 (33); elemental analysis calcd (%) for C15H22O4: C
67.64, H 8.32; found: C 67.38, H 8.45.
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic
acid
isopropyl ester (6d): From 1-isopropoxy-1,3-bis(trimethylsilyloxy)buta-
1,3-diene (1d; 0.430 g, 1.5 mmol) and 1,1-diacetylcyclopentane (5a;
0.154 g, 1.0 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6d was obtained as a
colorless oil (0.185 g, 66%). Rf =0.17 (hexane/ethyl acetate 7:3);
1H NMR (300 MHz, CDCl3): d=5.18 (sep, 1H, J=6.3 Hz; OCH), 2.63
(br, 2H; CH2), 2.37 (br, 2H; CH2), 1.97 (s, 3H; CH3), 1.95 (br, 1H; OH),
1.75 (br, 6H; CH2), 1.32 (s, 3H; CH3), 1.28 ppm (d, 6H, J=6.3 Hz; CH3);
13C NMR (75 MHz, CDCl3): d=193.97, 166.88, 163.89, 131.55 (C), 75.29
2,3,3,4-Tetramethyl-6-oxocyclohex-1,4-dienecarboxylic acid 2-methoxy-
ethyl ester (4e): From 3e (0.080 g, 0.29 mmol), 4e was obtained as a col-
orless oil (0.068 g, 92%). Rf =0.18 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=6.13 (d, 1H, J=1.2 Hz; =CH), 4.44 (m, 2H;
OCH2), 3.67 (m, 2H; OCH2), 3.39 (s, 3H; OCH3), 1.31 (s, 6H; CH3),
1.05 ppm (s, 6H; CH3); 13C NMR (75 MHz, CDCl3): d=181.31, 167.10,
165.08, 161.53, 132.77 (C), 126.05 (CH), 70.26, 63.84 (OCH2), 58.76
(OCH3), 42.68 (C), 24.36 (2C), 19.80, 16.69 ppm (CH3); IR (KBr): n˜ =
1734 (s), 1664 (s), 1623 (s), 1386 (m), 1250 (s), 1048 (m), 888 cmꢀ1 (w);
MS (EI, 70 eV): m/z (%)=252.0 (26) [M+], 237.0 (12), 195.0 (27), 177.0
(100), 148.3 (29), 58.5 (44), 28.1 (29). The exact molecular mass for
C14H20O4: m/z=252.1362ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Typical procedure for the preparation of spiro[5.4]decenones 6, 13, 16,
and 18: TiCl4 (0.22 mL, 2.00 mmol) was added dropwise to a stirred
CH2Cl2 solution (100 mL) of 1,1-diacetylcyclopentane (5a; 0.160 g,
1.04 mmol) and 1,3-bis(trimethylsilyloxy)-1,3-butadiene (1a; 0.380 g,
1.54 mmol) at ꢀ788C under an argon atmosphere in the presence of mo-
lecular sieves (4 Š; 1.0 g). The temperature of the reaction mixture was
allowed to rise to 208C over 6 h. The solution was stirred for additional
6 h at 208C. The reaction mixture was filtered and the filtrate was
poured into an aqueous solution of HCl (10%, 100 mL). The organic
layer was separated and the aqueous layer was extracted with CH2Cl2
(3”100 mL). The combined organic layers were dried (Na2SO4) and fil-
tered and the filtrate was concentrated in vacuo. The residue was purified
by column chromatography (silica gel; hexane/ethyl acetate 7:3) to give
6a as colorless crystals (0.164 g, 67%).
ꢀ
(C OH), 68.84 (OCH), 56.01 (C), 49.66, 32.77 (2C), 28.19 (2C, CH2),
24.75, 21.67 (2C), 17.47 ppm (CH3); IR (KBr): n˜ =3460 (br), 2977 (s),
1728 (s), 1671 (s), 1619 (m), 1379 (m), 1248 (s), 1108 cmꢀ1 (m); MS (EI,
70 eV): m/z (%)=280.3 (5) [M+], 237.2 (22), 220.2 (20), 195.2 (12), 178.2
(11), 162.1 (100), 134.1 (17), 43.0 (16); elemental analysis calcd (%) for
C16H24O4: C 68.54, H 8.62; found: C 67.38 H 8.97. The exact molecular
mass for C16H24O4: m/z=280.1675ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic acid 2-
methoxyethyl ester (6e): From 1-(2-methoxy)ethoxy-1,3-bis(trimethylsi-
lyloxy)buta-1,3-diene (1e; 0.455 g, 1.5 mmol), 1,1-diacetylcyclopentane
(5a; 0.154 g, 1.0 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6e was obtained
as a colorless oil (0.156 g, 53%). Rf =0.21 (hexane/ethyl acetate 1:1);
1H NMR (300 MHz, CDCl3): d=4.37 (t, 2H, J=6.0 Hz; OCH2), 3.62 (t,
2H, J=6.0 Hz; OCH2), 3.36 (s, 3H; OCH3), 2.62 (br, 2H; CH2), 2.09 (br,
2H; CH2), 2.00 (s, 3H; CH3), 1.95 (br, 1H; OH), 1.73 (br, 6H; CH2),
1.22 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=193.76, 167.16,
ꢀ
164.91, 134.13 (C), 75.38 (C OH), 70.23, 63.90 (OCH2), 58.76 (OCH3),
56.12 (C), 49.26, 32.82 (2C), 28.25 (2C, CH2), 24.81, 17.71 ppm (CH3); IR
(neat): n˜ =3462 (br), 2973 (s), 1733 (s), 1666 (s), 1621 (m), 1382 (s), 1253
(s), 1108 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=295.6 (8) [M+], 219.7 (77),
177.9 (46), 162.0 (100), 133.9 (76), 90.9 (28), 43.1 (28). The exact molecu-
lar mass for C16H24O5: m/z=296.1624ꢁ2 mD was confirmed by HRMS
(EI, 70 eV).
7-Acetyl-10-hydroxy-6,10-dimethylspiro[5,4]dec-6-en-8-one (6a): From 1-
methyl-1,3-bis(trimethylsilyloxy)buta-1,3-diene (1a; 0.380 g, 1.54 mmol),
1,1-diacetylcyclopentane (5a; 0.160 g, 1.04 mmol), and TiCl4 (0.22 mL,
2.00 mmol), 6a was obtained as colorless crystals (0.164 g, 67%). M.p.
80–818C; Rf =0.11 (hexane/ethyl acetate 7:3); 1H NMR (200 MHz,
CDCl3): d=2.60 (br, 2H; CH2), 2.30 (br, 1H; OH), 2.25 (s, 3H; CH3),
1.86 (s, 3H; CH3), 1.73 (br, 8H; CH2), 1.21 ppm (s, 3H; CH3); 13C NMR
10-Hydroxy-6,9,10-trimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic acid
methyl ester (6 f) (major isomer): From 1-methoxy-1,3-bis(trimethylsi-
6020
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
lyloxy)penta-1,3-diene (1 f; 0.410 g, 1.5 mmol), 1,1-diacetylcyclopentane
(5a; 0.157 g, 1.0 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6 f was obtained
as a colorless oil (0.061 g, 23%). Rf =0.23 (hexane/ethyl acetate 3:2);
1H NMR (300 MHz, CDCl3): d=3.36 (s, 3H; OCH3), 2.88 (q, 1H, J=
6.9 Hz; CH), 2.08 (s, 3H; CH3), 1.96–1.92 (m, 3H; OH, CH2), 1.41–1.21
(m, 6H; CH2), 1.20 (d, 3H, J=7.2 Hz; CH3), 1.08 ppm (s, 3H; CH3);
13C NMR (75 MHz, CDCl3): d=196.32, 168.60, 163.67, 131.13 (C), 75.38
27.36, 24.64 (CH2), 21.85 (2C), 14.72, 7.63 ppm (CH3); IR (neat): n˜ =
3462 (br), 2975 (s), 1725 (s), 1698 (s), 1667 (s), 1612 (m), 1450 (m), 1102
(s), 827 cmꢀ1 (m); MS (EI; 70 eV): m/z (%)=308.1 (10) [M+], 265.2
(19), 248.1 (22), 192.1 (22), 176.1 (100), 43.1 (14); elemental analysis
calcd (%) for C18H28O4: C 70.10, H 9.19; found: C 69.92, H 9.68.
10-Hydroxy-10-methyl-8-oxo-6-phenylspiro[4,5]dec-6-ene-7-carboxylic
acid ethyl ester (6k): From 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1b; 0.415 g, 1.50 mmol), 1-acetyl-1-benzoylcyclopentane (5c;
0.216 mg, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6k was obtained
as a colorless oil (0.125 g, 38%). Rf =0.28 (hexane/ethyl acetate 3:2);
1H NMR (300 MHz, CDCl3): d=7.38–7.18 (m, 5H; ArH), 3.85 (q, 2H,
J=7.2 Hz; OCH2), 2.90–2.70 (m, 4H; CH2), 2.07 (br, 1H; OH), 1.98–1.86
(m, 4H; CH2), 1.55–1.42 (m, 2H; CH2), 1.39 (s, 3H; CH3), 0.81 ppm (t,
3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=194.63, 166.16
ꢀ
(C OH), 57.23 (C), 52.42 (OCH3), 49.48 (CH), 33.37 (2C), 28.60 (2C,
CH2), 17.71, 16.88, 14.09 ppm (CH3); IR (neat): n˜ =3462 (br), 2973 (s),
1733 (s), 1666 (s), 1621 (m), 1382 (s), 1253 (s), 1108 cmꢀ1 (m); MS (EI,
70 eV): m/z (%)=266.5 (2) [M+], 234.4 (15), 192.3 (23), 162.2 (100),
134.2 (60), 91.2 (28), 43.0 (58). The exact molecular mass for C15H22O4:
m/z=266.1519ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
9-Ethyl-10-hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic
acid ethyl ester (6g): From 1-ethoxy-1,3-bis(trimethylsilyloxy)hexa-1,3-
diene (1g; 0.380 g, 1.56 mmol), 1,1-diacetylcyclopentane (5a; 0.160 g,
1.04 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6g was obtained as a color-
less oil (0.100 g, 41%). Rf =0.23 (hexane/ethyl acetate 3:2); 1H NMR
(300 MHz, CDCl3): d=4.27 (q, 2H, J=7.2 Hz; OCH2), 2.60–2.40 (m, 1H;
CH), 2.10 (br, 1H; OH), 1.94 (s, 3H; CH3), 1.92–1.40 (m, 10H; CH2),
1.31 (t, 3H, J=7.2 Hz; CH3), 1.08 (t, 3H, J=7.5 Hz; CH3), 1.06 ppm (s,
3H; CH3); 13C NMR (75 MHz, CDCl3): d=196.43, 167.44, 162.37, 131.58
(C), 61.13 (CH), 57.44 (C), 57.10 (CH2), 33.36, 31.89, 28.72, 27.20, 19.55,
17.42, 16.44, 14.63, 14.10, 11.01 ppm; IR (neat): n˜ =3515 (s), 2976 (s),
2875 (m), 1732 (s), 1670 (s), 1622 (m), 1457 (m), 1382 (m), 1257 (m),
1210 (m), 1112 (s), 1023 cmꢀ1 (m); MS (EI; 70 eV): m/z (%)=294.5 (6)
[M+], 265.5 (76), 219.3 (45), 162.2 (100), 134.2 (75), 43.0 (52). The exact
molecular mass for C17H26O4: m/z=294.1831ꢁ2 mD was confirmed by
HRMS (EI, 70 eV).
ꢀ
(2C), 136.50, 132.25 (C), 128.03 (2C), 127.83, 127.55 (2C, CH), 75.72 (C
OH), 60.88 (OCH2), 57.17 (C), 50.07, 33.15 (2C), 27.25, 27.03 (CH2),
24.83, 13.58 ppm (CH3); IR (neat): n˜ =3542 (m), 2953 (m), 1727 (s), 1677
(s), 1612 (m), 1341 (m), 1234 (s), 704 cmꢀ1 (w); MS (EI, 70 eV): m/z
(%)=328.4 (6) [M+], 282.8 (33), 224.6 (100), 104.8 (40), 43.1 (76), 28.1
(53). The exact molecular mass for C20H24O4: m/z=328.1675ꢁ2 mD was
confirmed by HRMS (EI, 70 eV).
10-Hydroxy-6-methyl-8-oxospiro[4.5]dec-6-en-7-carboxylic acid ethyl
ester (13a): From 1-acetyl-1-formylcyclopentane (5d; 0.200 g,
1.42 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (0.585 g,
2.13 mmol), and TiCl4 (0.31 mL, 2.84 mmol), 13a was obtained as a
yellow oil (0.068 g, 20%). 1H NMR (300 MHz, CDCl3): d=4.30 (q, 2H,
J=7.2 Hz; OCH2), 3.49 (br, 1H, J=6.9 Hz; CHOH), 2.79 (dd, 1H, J=
16.8, 3.7 Hz; CH2), 2.63 (dd, 1H, J=16.8, 7.2 Hz; CH2), 2.04 (s, 1H;
OH), 1.96 (s, 3H; CH3), 1.81–1.77 (m, 8H; CH2), 1.32 ppm (t, 3H, J=
7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=193.0, 167.12, 162.55,
132.54 (C), 72.85 (CH), 61.30 (CH2), 52.57 (C), 43.04, 35.36, 32.48, 27.36,
27.01 (CH2), 17.69, 14.16 ppm (CH3); IR (neat): n˜ =3430 (br), 2959 (m),
1729.2 (s), 1666 (s), 1614 (m), 1378 (m), 1239 (m), 1090 cmꢀ1 (m); MS
(EI, 70 eV): m/z (%)=252.0 (7) [M++1], 206.0 (19), 161.9 (83), 134.1
(30), 82.1 (33), 68.0 (67), 43.1 (53), 28.1 (100); elemental analysis calcd
(%) for C14H19O4: C 66.93, H 7.5; found: C 66.05, H 8.53.
6,10-Diethyl-10-hydroxy-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic
acid
methyl ester (6h): From 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1b; 0.180 g, 0.69 mmol), 1,1-dipropionylcyclopentane (5b; 0.097 g,
0.53 mmol), and TiCl4 (0.12 mL, 1.09 mmol), 6h was obtained as a color-
less oil (0.086 g, 58%). Rf =0.22 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=3.77 (s, 3H; OCH3), 2.63 (br, 2H; CH2), 2.30–2.22
(br, 2H; CH2), 2.12 (br, 1H; OH), 1.93–1.53 (br, 10H; CH2), 1.13 (t, 3H,
J=7.5 Hz; CH3), 0.87 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz,
7-Acetyl-10-hydroxy-10-methylspiro[5,4]dec-6-en-8-one (13b): From 1-
acetyl-1-formylcyclopentane (5d; 0.150 g, 1.07 mmol), 2,4-bis-trimethylsi-
lyloxypenta-1,3-diene (0.391 g, 1.60 mmol), and TiCl4 (0.23 mL,
2.14 mmol), 13b was obtained as a yellow oil (0.064 g, 27%). 1H NMR
(300 MHz, CDCl3): d=3.96 (br, 1H; CHOH), 2.78 (dd, 1H, J=16.5,
3.6 Hz; CH2), 2.61 (dd, 1H, J=16.8, 6.9 Hz; CH2), 2.32 (s, 3H; CH3),
2.09–2.01 (m, 3H; CH2, OH), 1.90 (s, 3H; CH3), 1.85–1.75 ppm (m, 6H;
CH2); 13C NMR (75 MHz, CDCl3); d=205.48, 195.08, 161.81, 138.68 (C),
72.74 (CH), 52.72 (C), 43.25, 33.41, 32.65 (CH2), 31.77 (CH3), 27.30, 26.81
(CH2), 17.05 ppm (CH3); IR (neat): n˜ =3461 (br), 2960 (m), 1703 (s),
1664 (s), 1355 (s), 1215 (m), 1074 cmꢀ1 (m); MS (EI, 70 eV): m/z (%):
223.0 (9) [M++1], 222.0 (51) [M+], 181.0 (100), 163 (38), 149.1 (81), 122
(40), 43.1 (97), 29.0 (7); elemental analysis calcd (%) for C13H18O3: C
70.27, H 8.62; found: C 69.00, H 8.10.
ꢀ
CDCl3): d=194.20, 170.99, 167.75, 131.39 (C), 75.33 (C OH), 57.53 (C),
52.08 (OCH3), 44.08, 40.62 (CH2), 29.63 (2C), 27.20 (2C), 24.62 (CH2),
14.48, 7.38 ppm (CH3); IR (neat): n˜ =3496 (br), 2971 (s), 2875 (m), 1735
(s), 1666 (s), 1606 (w), 1436 (m), 1342 (m), 1228 (m), 1082 cmꢀ1 (m); MS
(EI; 70 eV): m/z (%)=280.4 (10) [M+], 248.4 (50), 192.2 (62), 176.3
(100), 147.6 (41), 120.5 (48), 91.1 (41), 29.0 (44). The exact molecular
mass for C16H24O4: m/z=280.1675ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
6,10-Diethyl-10-hydroxy-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic acid ethyl
ester (6i): From 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (1b;
0.415 g,
1.60 mmol),
1,1-dipropionylcyclopentane
(5b;
0.193 g,
1.06 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 6i was obtained as a color-
less oil (0.167 g, 56%). Rf =0.28 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=4.30 (dq, 2H, J=7.2, 1.5 Hz; OCH2), 2.67 (br,
2H; CH2), 2.40–2.30 (br, 4H; CH2), 2.04 (br, 1H; OH), 1.94–1.59 (br,
8H; CH2), 1.31 (t, 3H, J=7.2 Hz; CH3), 1.17 (t, 3H, J=7.5 Hz; CH3),
0.91 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
9-Ethyl-10-methyl-8-oxospiro[5,4,0]deca-6,9-diene-7-carboxylic
acid
(13c): From 1-acetyl-1-formylcyclopentane (5d; 0.150 g, 1.07 mmol), 1,3-
bis(trimethylsilyloxy)buta-1,3-diene (0.485 g, 1.60 mmol), and TiCl4
(0.23 mL, 2.14 mmol), 13c was obtained as a colorless oil (56 mg, 20%).
1H NMR (300 MHz, CDCl3): d=6.47 (s, 1H; =CH), 4.33 (q, 2H, J=
7.2 Hz; OCH2), 2.54–2.42 (m, 1H; CH2), 2.38–2.37 (m, 3H; CH2), 2.05–
1.95 (m, 1H; CH2), 1.87–1.81 (m, 1H; CH2), 1.73–1.67 (m, 2H; CH2),
1.43–1.35 (m, 2H; CH2), 1.34 (t, 3H, J=7.2 Hz; CH3), 1.28 (s, 3H; CH3),
1.07 ppm (t, 3H, J=7.5 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
182.98, 167.35, 162.83 (C), 151.30 (CH), 137.64, 130.67 (C) 61.14 (CH2),
40.02 (C), 38.72, 29.40, 27.59 (CH2) 23.16 (CH3), 21.75, 20.70 (CH2),
14.18, 12.36 ppm (CH3); IR (neat): n˜ =3440 (br), 2960 (m); 1730 (s), 1670
(s), 1365 (s), 1237 (m), 1092 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=262.1
(25) [M+], 217.1 (29), 201.1 (55), 189.1 (100), 161.1 (21), 29.0 (10). The
exact molecular mass for C16H22O3: m/z=262.1570ꢁ2 mD was confirmed
by HRMS (EI, 70 eV).
ꢀ
194.20, 170.99, 167.75, 131.39 (C), 75.33 (C OH), 57.53 (C), 52.08
(OCH3), 44.08, 40.62 (CH2), 29.63 (2C), 27.20 (2C), 24.62 (CH2), 14.48,
7.38 ppm (CH3); IR (neat): n˜ =3496 (br), 2971 (s), 2875 (m), 1735 (s),
1666 (s), 1606 (w), 1436 (m), 1342 (m), 1228 (m), 1082 cmꢀ1 (m); MS (EI;
70 eV): m/z (%)=294.2 (10) [M+], 248.2 (25), 219.0 (16), 192.1 (26),
176.1 (100), 91.0 (14), 29.0 (35). The exact molecular mass for C17H26O4:
m/z=294.1813ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
6,10-Diethyl-10-hydroxy-8-oxo-spiro[4,5]dec-6-ene-7-carboxylic acid iso-
propyl ester (6j): From 1-isopropoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1d; 0.475 g, 1.65 mmol), 1,1-dipropionylcyclopentane (5b; 0.200 g,
1.10 mmol), and TiCl4 (0.24 mL, 2.20 mmol), 6j was obtained as a color-
less solid (0.179 g, 53%). M.p. 96–978C; Rf =0.34 (hexane/ethyl acetate
7:3); 1H NMR (300 MHz, CDCl3): d=5.18 (sep, 1H, J=6.3 Hz; OCH),
2.65 (br, 2H; CH2), 2.36–1.56 (m, 13H; OH, CH2), 1.30 (d, 6H, J=
6.3 Hz; CH3), 1.19 (t, 3H, J=7.5 Hz; CH3), 0.88 ppm (t, 3H, J=7.2 Hz;
CH3); 13C NMR (75 MHz, CDCl3): d=194.39, 169.99, 167.06, 132.11 (C),
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]deca-2,6-diene-7-carboxylic
acid methyl ester (16a): From 1-(1-acetylcyclopent-3-enyl)ethanone (5e;
0.155 g, 1.02 mmol), 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1b; 0.400 g, 1.53 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 16a was ob-
ꢀ
75.33 (C OH), 68.95 (OCH), 57.72 (C), 45.19, 28.07, 36.48 (2C), 28.48,
Chem. Eur. J. 2004, 10, 6015 – 6028
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6021

P. Langer et al.
FULL PAPER
tained as a colorless solid (0.211 g, 83%). M.p. 123–1248C; Rf =0.22
(hexane/ethyl acetate 7:3); 1H NMR (300 MHz, CDCl3): d=5.76 (br, 1H;
=CH), 5.70 (br, 1H; =CH), 3.81 (s, 3H; OCH3), 2.74–2.64 (m, 6H; CH2),
2.38 (br, 1H; OH), 1.88 (s, 3H; CH3), 1.23 ppm (s, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=193.61, 167.13, 163.45, 130.57 (C), 129.80, 128.39
CH2), 24.96, 18.31 ppm (CH3); IR (KBr): n˜ =3398 (s), 2960 (w), 1732 (s),
1668 (s), 1629 (w), 1381 (m), 1241 (m), 1114 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%)=300.2 (2) [M+], 282.1 (61), 267.1 (21), 210.1 (27), 182.1 (100),
153.1 (47), 142.1 (40), 115.1 (26), 43.1 (58); elemental analysis calcd (%)
for C18H20O4: C 71.98, H 6.71; found: C 71.78, H 6.50.
ꢀ
(CH), 75.22 (C OH), 52.34 (OCH3), 49.13 (CH2), 42.70 (C), 38.73, 31.03
Compound 18c: From 1-ethoxy-1,3-bis(trimethysilyloxy)buta-1,3-diene
(1c; 0.415 g, 1.51 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f; 0.202 g,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18c was obtained as color-
less crystals (0.270 g, 86%). M.p. 132–1338C; Rf =0.31 (hexane/ethyl ace-
tate 3:2); 1H NMR (200 MHz, CDCl3): d=7.19 (s, 4H; ArH), 4.28 (q,
2H, J=7.2 Hz; OCH2), 3.90–3.65 (br, 1H; CH2), 3.39 (d, 1H, J=17.1 Hz;
CH2), 3.04 (d, 2H, J=17.1 Hz; CH2), 2.70 (br, 2H; CH2), 2.45 (br, 1H;
OH), 1.81 (s, 3H; CH3), 1.30 (s, 3H; CH3), 1.28 ppm (t, 3H, J=7.2 Hz;
CH3); 13C NMR (CDCl3, 75 MHz): d=193.68, 167.07, 163.74, 141.81,
(CH2), 24.75, 17.74 ppm (CH3); IR (neat): n˜ =3442 (br), 2977 (m), 1784
(m), 1734 (s), 1653 (s), 1609 (m), 1435 (m), 1246 (s), 1159 (s), 875 cmꢀ1
(w); MS (EI, 70 eV): m/z (%)=250.1 (3) [M+], 232.1 (18), 218.1 (53),
200.0 (24), 185.1 (23), 160.0 (100), 132.0 (91), 91.0 (23), 43.1 (31); elemen-
tal analysis calcd (%) for C14H18O4: C 67.18, H 7.24; found: C 67.00, H
7.22. The exact molecular mass for C14H18O4: m/z=250.1205ꢁ2 mD was
confirmed by HRMS (EI, 70 eV).
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-2,6-diene-7-carboxylic acid
ethyl ester (16b): From 1-(1-acetylcyclopent-3-enyl)ethanone (5e;
0.149 g, 0.98 mmol), 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1c; 0.400 g, 1.47 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 16b was ob-
ꢀ
141.21, 131.14 (C), 126.95, 126.84, 124.24, 12.94 (CH), 74.44 (C OH),
61.36 (OCH2), 56.28 (C), 49.59, 39.33 (2C, CH2), 24.87, 18.11, 14.10 ppm
(CH3); IR (KBr): n˜ =3421 (s), 2975 (w), 2947 (w), 2904 (w), 1727 (s),
1665 (s), 1619 (m), 1445 (w), 1381 (m), 1239 (m), 1129 (m), 1030 (m), 866
(w), 745 cmꢀ1 (w); MS (EI; 70 eV): m/z (%)=314.2 (5) [M+], 296.2 (88),
210.1 (37), 182.1 (100), 142.1 (38), 115.1 (23), 43.1 (20); elemental analy-
sis calcd (%) for C19H22O4: C 72.59, H 7.05; found: C 72.75, H 6.94.
tained as
a colorless solid (0.165 g, 64%). M.p. 89–908C; Rf =0.26
(hexane/ethyl acetate 7:3); 1H NMR (300 MHz, CDCl3): d=5.75 (br, 1H;
=CH), 5.70 (br, 1H; =CH), 4.29 (q, 2H, J=7.2 Hz; OCH2), 2.74–2.32 (m,
7H; CH2, OH), 1.95 (s, 3H; CH3), 1.31 (t, 3H, J=7.2 Hz; CH3),
1.24 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=193.73, 167.13,
Compound 18d: From 1-isopropoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1d; 0.430 g, 1.50 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f;
0.202 g, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18d was obtained as
a colorless solid (0.269 g, 82%). M.p. 185–1868C; Rf =0.33 (hexane/ethyl
acetate 3:2); 1H NMR (300 MHz, CDCl3): d=7.20 (s, 4H; ArH), 5.18
(sep, 1H, J=6.3 Hz; OCH), 3.90–3.60 (br, 1H; CH2), 3.38 (d, 1H, J=
17.1 Hz; CH2), 3.02 (d, 2H, J=17.1 Hz; CH2), 2.65 (br, 2H; CH2), 2.38
(br, 1H; OH), 1.76 (s, 3H; CH3), 1.31 (s, 3H; CH3), 1.27 ppm (d, 6H, J=
6.3 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=193.58, 166.62, 163.70,
ꢀ
163.16, 130.57 (C), 129.87, 128.39 (CH), 75.27 (C OH), 61.24 (OCH2),
54.59 (C), 48.71, 39.49, 38.21 (CH2), 24.38, 17.38, 14.08 ppm (CH3); IR
(neat): n˜ =3442 (br), 2977 (m), 1784 (m), 1734 (s), 1653 (s), 1609 (m),
1435 (m), 1246 (s), 1159 (s), 875 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=
264.2 (3) [M+], 246.1 (14), 218.1 (51), 200.1 (21), 185.1 (19), 160.1 (100),
132.0 (89), 91.0 (21), 43.1 (33); elemental analysis calcd (%) for
C15H20O4: C 68.16, H 7.63; found: C 68.62, H 7.38.
10-Hydroxy-6,10-dimethyl-8-oxo-spiro[4,5]dec-2,6-diene-7-carboxylic acid
isospropyl ester (16c): From 1-(1-acetylcyclopent-3-enyl)ethanone (5e;
0.200 g, 1.31 mmol), 1-isopropoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1c; 0.512 g, 1.97 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 16c was ob-
ꢀ
141.84, 141.24, 131.39 (C), 126.96, 126.86, 124.26, 123.96 (CH), 74.61 (C
OH), 69.04 (OCH), 56.25 (C), 49.52, 39.72 (2C, CH2), 24.93, 21.71 (2C),
17.93 ppm (CH3); IR (KBr): n˜ =3383 (s), 2978 (w), 1723 (s), 1655 (s),
1622 (w), 1381 (m), 1251 (m), 1104 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=
328.8 (2) [M+], 310.8 (64), 269.7 (32), 250.7 (36), 210.6 (66), 182.5 (96),
153.0 (65), 142.3 (53), 115.8 (38), 43.1 (100), 28.1 (38); elemental analysis
calcd (%) for C20H24O4: C 73.15, H 7.15; found: C 73.17, H 6.97.
tained as
a colorless solid (0.216 g, 59%). M.p. 90–918C; Rf =0.27
(hexane/ethyl acetate 7:3); 1H NMR (300 MHz, CDCl3): d=5.75 (br, 1H;
=CH), 5.70 (br, 1H; =CH), 5.18 (sep, 1H, J=6.3 Hz; OCH), 2.74–2.30
(m, 7H; CH2, OH), 1.94 (s, 3H; CH3), 1.31 (d, 6H, J=6.3 Hz; CH3),
1.24 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=193.72, 166.70,
Compound 18e: From 1-(2-methoxy)ethoxy-1,3-bis(trimethylsilyloxy)bu-
ta-1,3-diene (1e; 0.455 g, 1.50 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f;
0.205 g, 1.01 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18e was obtained as
a colorless solid (0.213 g, 61%). M.p. 115–1168C; Rf =0.17 (hexane/ethyl
acetate 3:2); 1H NMR (200 MHz, CDCl3): d=7.18 (s, 4H; ArH), 4.81 (t,
2H, J=4.5 Hz; OCH2), 3.90–3.65 (br, 1H; CH2), 3.62 (t, 2H, J=4.5 Hz;
OCH2), 3.46 (d, 1H, J=17.1 Hz; CH2), 3.35 (s, 3H; OCH3), 3.03 (d, 2H,
J=17.1 Hz; CH2), 2.68 (brs, 2H; CH2), 2.26 (brs, 1H; OH), 1.82 (s, 3H;
CH3), 1.28 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3): d=195.28,
166.90, 163.63, 141.76, 141.13, 137.36 (C), 127.02, 126.92, 124.28, 123.98
ꢀ
165.98, 130.82 (C), 128.75 (2C, CH), 69.54 (C OH), 68.91 (OCH), 54.51
(C), 48.81, 42.35, 38.18 (CH2), 24.38, 21.58 (2C), 14.11 ppm (CH3); IR
(neat): n˜ =3392 (br), 2982 (w), 1719 (s), 1664 (s), 1618 (m), 1379 (m),
1249 (s), 1105 cmꢀ1 (m); MS (EI, 70 eV): m/z (%): 278.3 (3) [M+], 260.3
(7), 218.2 (51), 200.2 (19), 186.2 (15), 160.1 (100), 132.2 (61), 91.1 (20),
43.1 (38); elemental analysis calcd (%) for C16H22O4: C 69.04, H 7.97;
found: C 69.09, H 8.70. The exact molecular mass for C16H22O4: m/z=
278.1518ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 18a: From 1-methyl-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1a; 0.368 g, 1.51 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f; 0.202 g,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18a was obtained as color-
less crystals (0.230 g, 82%). M.p. 168–1698C; Rf =0.31 (hexane/ethyl ace-
tate 3:2); 1H NMR (200 MHz, CDCl3): d=7.20 (s, 4H; ArH), 3.90–3.65
(br, 1H; CH2), 3.39 (d, 1H, J=17.1 Hz; CH2), 3.02 (d, 2H, J=17.1 Hz;
CH2), 2.32 (br, 2H; CH2), 2.28 (s, 3H; CH3), 2.21 (br, 1H; OH), 1.67 (s,
3H; CH3), 1.22 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3): d=
204.96, 195.26, 163.60, 141.80, 141.14, 137.37 (C), 127.03, 126.94, 124.25,
ꢀ
(CH), 74.51 (C OH), 70.28, 64.04 (OCH2), 58.82 (OCH3), 56.35 (C),
49.85, 39.29 (2C, CH2), 25.01, 18.19 ppm (CH3); IR (KBr): n˜ =3421 (s),
2946 (w), 1727 (s), 1665 (s), 1619 (m), 1381 (m), 1239 (s), 1129 (s), 866
(w), 745 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=344.9 (4) [M+], 326.9 (45),
268.7 (42), 250.7 (44), 210.5 (43), 182.5 (100), 153.0 (43), 114.6 (31), 59.6
(36), 43.1 (45); elemental analysis calcd (%) for C20H24O5 (344.41): C
69.74, H 7.02; found: C 69.48, H 6.86.
ꢀ
123.98 (CH), 74.54 (C OH), 56.39 (C), 49.88, 39.24 (2C, CH2), 31.77,
Compound 18 f: From 1-ethoxy-1,3-bis(trimethylsilyloxy)hexa-1,3-diene
(1g; 0.453 g, 1.50 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f; 0.202 g,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18 f was obtained as a color-
less solid (0.106 g, 31%). Rf =0.27 (hexane/ethyl acetate 3:2); 1H NMR
(300 MHz, CDCl3): d=7.16 (br, 4H; ArH), 4.26 (q, 2H, J=7.2 Hz;
OCH2), 4.02 (d, 1H, J=16.8 Hz; CH2), 3.47 (d, 1H, J=16.5 Hz; CH2),
3.03 (d, 1H, J=16.8 Hz; CH2), 2.92 (d, 1H, J=16.5 Hz; CH2), 2.51 (br,
1H; CH), 1.95 (br, 1H; OH), 1.90–1.75 (m, 1H; CH2), 1.69 (s, 3H; CH3),
1.65–1.58 (m, 1H; CH2), 1.29 (t, 3H, J=7.2 Hz; CH3), 1.20 (s, 3H; CH3),
1.11 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
196.16, 167.25, 162.43, 142.05, 141.23, 131.03 (C), 126.98, 126.79, 124.30,
25.02, 17.49 ppm (CH3); IR (KBr): n˜ =3396 (s), 2970 (w), 1700 (s), 1662
(s), 1612 (m), 1485 (w), 1380 (m), 1336 (m), 1192 (m), 742 cmꢀ1 (m); MS
(EI; 70 eV): m/z (%)=284.2 (32) [M+], 266.1 (71), 251.2 (33), 223.1 (60),
183.1 (64), 155.1 (46), 115.1 (90), 43.1 (100); elemental analysis calcd (%)
for C18H20O3: C 76.03, H 6.97; found: C 75.94, H 6.97.
Compound 18b: From 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1b; 0.390 g, 1.50 mmol), 1-(2-acetylindan-2-yl)ethanone (5 f; 0.202 g,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18b was obtained as a color-
less solid (0.258 g, 86%). M.p. 164–1658C; Rf =0.24 (hexane/ethyl acetate
3:2); 1H NMR (300 MHz, CDCl3): d=7.19 (s, 4H; ArH), 3.81 (s, 3H;
OCH3), 3.90–3.65 (br, 1H; CH2), 3.40 (d, 1H, J=16.8 Hz; CH2), 3.05 (d,
2H, J=16.8 Hz; CH2), 2.71 (br, 2H; CH2), 2.20 (br, 1H; OH), 1.81 (s,
3H; CH3), 1.28 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
193.55, 167.43, 164.00, 141.21, 141.09, 131.01 (C), 127.03, 126.92, 124.27,
ꢀ
123.72 (CH), 74.55 (C OH), 61.24 (OCH2), 57.69 (CH), 56.09 (C), 40.13,
37.47, 19.99 (CH2), 17.54, 16.13, 14.52, 14.02 ppm (CH3); IR (KBr): n˜ =
3504 (s), 2983 (w), 1706 (s), 1676 (m), 1630 (w), 1380 (m), 1216 (m), 1129
(s), 760 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=342.3 (4) [M+], 324.3 (53),
296.3 (42), 278.2 (24), 256.2 (30), 210.1 (57), 182.1 (100), 142.1 (70), 71.1
ꢀ
123.98 (CH), 74.40 (C OH), 56.52 (C), 52.29 (OCH3), 49.56, 39.39 (2C,
6022
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
(38), 43.1 (54); elemental analysis calcd (%) for C21H26O4: C 73.65, H
7.65; found: C 73.42, H 7.86.
0.264 mg, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18k was obtained
as a colorless solid (0.085 g, 21%). M.p. 121–1228C; Rf =0.49 (hexane/
ethyl acetate 7:3); 1H NMR (300 MHz, CDCl3): d=7.54–7.00 (m, 9H;
ArH), 4.03 (d, 2H, J=6.7 Hz; OCH2), 3.97–3.92 (br, 1H; CH2), 3.49–3.42
(br, 1H; CH2), 3.30–3.22 (br, 1H; CH2), 3.16 (d, 1H, J=17.1 Hz; CH2),
3.08 (d, 1H, J=17.1 Hz; CH2), 2.92–2.86 (br, 1H; CH2), 2.24 (brs, 1H;
OH), 2.03 (sep, 1H, J=6.6 Hz; CH2), 1.87 (s, 3H; CH3), 0.94 ppm (d,
6H, J=6.6 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=193.23, 167.09,
163.61, 142.88, 141.90, 140.76, 131.82 (C), 128.69 (2C), 127.85, 127.16
(2C), 126.83, 126.59, 123.96, 123.85 (CH), 78.86 (C), 71.47 (CH2), 56.80
(C), 52.25 (OCH2), 49.32, 40.77, 39.36 (CH2), 27.72 (CH), 19.11 (2C),
18.56 ppm (CH3); IR (KBr): n˜ =3368 (m), 2963 (w), 1719 (s), 1657 (s),
1616 (w), 1379 (m), 1240 (m), 1073 (w), 770 cmꢀ1 (w); MS (EI, 70 eV):
m/z (%): 404.0 (9) [M+], 386.1 (12), 330.0 (34), 311.9 (35), 210.1 (45),
182.0 (90), 142.1 (93), 104.7 (100), 77.4 (25), 41.2 (25); elemental analysis
calcd (%) for C26H28O4: C 77.20, H 6.98; found: C 77.58, H 7.49. The
exact molecular mass for C26H28O4: m/z=404.1988ꢁ2 mD was confirmed
by HRMS (EI, 70 eV).
Compound 18g: From 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1b; 0.390 g, 1.50 mmol), 1-(2-benzoylindan-2-yl)ethanone (5 f; 0.264 mg,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18g was obtained as a color-
less solid (0.084 g, 23%). Rf =0.36 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=7.54–6.97 (m, 9H; ArH), 3.87 (s, 3H; OCH3),
3.81–3.63 (br, 1H; CH2), 3.45 (d, 1H, J=19.2 Hz; CH2), 3.40–3.25 (br,
1H; CH2), 3.15 (d, 1H, J=17.1 Hz; CH2), 3.06 (d, 1H, J=17.1 Hz; CH2),
2.95–2.70 (br, 1H; CH2), 2.46 (brs, 1H; OH), 1.85 ppm (s, 3H; CH3);
13C NMR (75 MHz, CDCl3): d=193.33, 167.38, 164.24, 142.74, 141.86,
140.61, 132.63 (C), 131.36, 128.63, 128.03, 127.77, 127.10, 127.05, 126.75,
126.50, 123.79 (CH), 78.76, 56.74 (C), 52.25 (OCH3), 49.11, 45.45, 40.74
(CH2), 18.60 ppm (CH3); IR (KBr): n˜ =3556 (s), 1739 (s), 1665 (s), 1656
(s), 1623 (m), 1349 (m), 1241 (m), 1072 (w), 768 cmꢀ1 (w); MS (EI,
70 eV): m/z (%)=362.4 (7) [M+], 330.4 (49), 312.3 (32), 210.2 (62), 182.2
(95), 142.2 (100), 104.7 (99), 77.4 (70), 43.2 (17), 28.1 (13); elemental
analysis calcd (%) for C23H22O4: C 76.22, H 5.96; found: C 75.40, H 5.96.
Compound 18l: From 1-isobutoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1c; 0.455 g, 1.50 mmol), 1-(2-benzoylindan-2-yl)ethanone (5 f;
0.264 mg, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18l was obtained
as a colorless solid (0.060 g, 15%). M.p. 89–908C; Rf =0.33 (hexane/ethyl
acetate 7:3); 1H NMR (300 MHz, CDCl3): d=7.14–6.89 (m, 9H; ArH),
3.58 (d, 2H, J=6.7 Hz; OCH2), 3.36 (d, 1H, J=17.1 Hz; CH2), 3.17 (d,
1H, J=16.8 Hz; CH2), 2.85 (brs, 2H; CH2), 2.69 (brs, 1H; OH), 2.07–
2.03 (m, 1H; CH2), 1.57 (sep, 1H, J=6.9 Hz; CH2), 1.36 (brs, 3H; CH3),
0.95–0.85 (m, 1H; CH2), 0.68 ppm (d, 6H, J=6.7 Hz; CH3); 13C NMR
(75 MHz, CDCl3): d=194.03, 166.24 (2C), 141.91, 140.92, 136.22, 133.01
(C), 128.63, 127.99, 127.35, 127.03, 126.80, 126.63, 126.47, 123.62 (2C,
CH), 75.19, 71.30 (CH2), 56.72 (C), 49.45, 40.70, 39.06 (CH2), 27.27 (CH),
25.00, 18.88 ppm (2C, CH3); IR (KBr): n˜ =3472 (s), 1740 (s), 1656 (s),
1612 (w), 1351 (m), 1232 (m), 1068 (w), 773 cmꢀ1 (w); MS (EI, 70 eV):
m/z (%)=403.9 (12) [M+], 386.0 (75), 311.9 (53), 244.0 (100), 214.9 (77),
43.1 (25), 28.1 (54). The exact molecular mass for C26H28O4: m/z=
404.1988ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 18m: From 1-isopropoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (0.453 g, 2.11 mmol), 1-(2-propylindan-2-yl)propan-1-one (5 f;
0.230 mg, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18m was obtained
as a colorless oil (0.160 g, 43%). Rf =0.50 (hexane/ethyl acetate 7:3);
1H NMR (300 MHz, CDCl3): d=7.18 (s, 4H; ArH), 4.00 (d, 2H, J=
6.6 Hz; OCH2), 3.37 (d, 1H, J=16.5 Hz; CH2), 3.07 (d, 1H, J=16.8 Hz;
CH2), 2.69 (br, 2H; CH2), 2.69 (br, 2H; CH2), 2.17–2.03 (m, 2H; CH2),
2.01–1.97 (m, 1H; CH), 1.95 (br, 1H; OH), 1.67–1.54 (m, 2H; CH2),
0.99–0.81 ppm (m, 12H; CH3); IR (KBr): n˜ =3466 (br), 2970 (m), 1279
(s), 1670 (s), 1609 (m), 1465 (m), 1230 (m), 785 cmꢀ1 (w); MS (EI,
70 eV): m/z (%)=370.0 (4) [M+], 352.1 (24), 322.9 (65), 297.0 (58), 223.9
(60), 196.0 (63), 181.9 (78), 101.9 (100), 57.4 (78), 28.4 (70). The exact
molecular mass for C23H30O4: m/z=370.2144ꢁ2 mD was confirmed by
HRMS (EI, 70 eV).
Compound 18h: From 1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1b; 0.390 g, 1.50 mmol), 1-(2-benzoylindan-2-yl)ethanone (5 f; 0.264 mg,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18h was obtained as a color-
less solid (0.076 g, 21%). M.p. 139–1408C; Rf =0.28 (hexane/ethyl acetate
7:3); 1H NMR (300 MHz, CDCl3): d=7.16–6.80 (m, 9H; ArH), 3.38 (s,
3H; OCH3), 3.90–3.65 (br, 1H; CH2), 3.33 (br, 1H; CH2), 3.17 (d, 2H,
J=18.0 Hz; CH2), 2.85 (br, 2H; CH2), 2.45 (brs, 1H; OH), 1.85 ppm (s,
3H; CH3); 13C NMR (75 MHz, CDCl3): d=194.01, 166.56 (2C), 141.91,
140.88, 136.24 (C), 132.87 (CH), 132.70 (C), 127.13, 128.70, 128.08,
127.39, 126.72 (2C), 126.57, 123.69 (CH), 75.20, 56.85 (C), 52.91 (OCH3),
49.51, 40.22 (2C, CH2), 25.10 ppm (CH3); IR (KBr): n˜ =3537 (s), 1736
(s), 1661 (s), 1615 (w), 1344 (m), 1233 (m), 1074 (w), 734 cmꢀ1 (w); MS
(EI, 70 eV): m/z (%)=362.0 (17) [M+], 344.0 (89), 311.9 (39), 244.0 (86),
214.9 (71), 104.6 (100), 77.4 (52), 43.2 (77), 28.1 (34). The exact molecular
mass for C23H22O4: m/z=362.1518ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
Compound 18i: From 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1c; 0.410 g, 1.50 mmol), 1-(2-benzoylindan-2-yl)ethanone (5 f; 0.263 mg,
1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18i was obtained as a color-
less solid (0.083 g, 22%). M.p. 177–1788C; Rf =0.39 (hexane/ethyl acetate
7:3); 1H NMR (300 MHz, CDCl3): d=7.29–6.97 (m, 9H; ArH), 4.29 (q,
2H, J=7.2 Hz; OCH2), 3.95–3.80 (br, 1H; CH2), 3.48–3.25 (m, 2H;
CH2), 3.16 (d, 1H, J=17.1 Hz; CH2), 3.06 (d, 1H, J=17.1 Hz; CH2),
2.95–2.75 (m, 1H; CH2), 2.56 (brs, 1H; OH), 1.85 (s, 3H; CH3), 1.29 ppm
(t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=193.24, 166.95
(2C), 142.77, 141.91, 140.66, 131.66 (C), 128.66, 128.14, 127.83, 127.16
(2C), 126.79, 126.54, 123.89, 123.83 (CH), 78.86 (C), 61.36 (OCH2), 56.76
(C), 49.21, 40.90, 39.50 (CH2), 18.42, 14.15 ppm (CH3); IR (KBr): n˜ =
3400 (m), 1728 (s), 1656 (s), 1621 (m), 1447 (m), 1377 (m), 1240 (m),
1071 (w), 7660 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=376.0 (3) [M+],
358.0 (3), 329.9 (12), 209.9 (23), 181.9 (66), 142.0 (68), 104.6 (58), 87.0
(100), 43.1 (63), 28.1 (77). The exact molecular mass for C24H24O4: m/z=
376.1675ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 18j: From 1-ethoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene
(1c; 0.410 g, 1.50 mmol) and 1-(2-benzoylindan-2-yl)ethanone (5 f;
0.263 mg, 1.00 mmol), and TiCl4 (0.22 mL, 2.00 mmol), 18j was obtained
as a colorless solid (0.064 g, 17%). M.p. 133–1348C; Rf =0.33 (hexane/
ethyl acetate 7:3); 1H NMR (300 MHz, CDCl3): d=7.15–6.87 (m, 9H;
ArH), 3.87 (q, 2H, J=7.2 Hz; OCH2), 3.36 (d, 1H, J=16.8 Hz; CH2),
3.18 (d, 1H, J=16.8 Hz; CH2), 2.80 (br, 2H; CH2), 2.43 (br, 1H; OH),
1.87 (br, 1H; CH2), 1.37 (br, 3H; CH3), 1.24 (br, 1H; CH2), 0.80 ppm (t,
3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=193.96, 166.95
(2C), 141.95, 141.91, 136.25, 133.00 (C), 128.71, 128.03, 127.34, 127.12,
Typical procedure for the preparation of bicyclo[4.4.0]deca-1,4-dien-3-
ones 7, 14, 15, 17, and 19: TFA (0.4 mL, 5.2 mmol) was added dropwise
to a stirred CH2Cl2 solution (0.4 mL) of 6a (0.100 g, 0.42 mmol) at 208C.
The solution was stirred for 72 h until all starting material disappeared
(TLC control). The solvent and TFA were removed in vacuo and the resi-
due was purified by column chromatography (silica gel; hexane/ethyl ace-
tate 7:3) to give 7a as a colorless solid (0.088 g, 95%).
1-Acetyl-4,10-dimethyl-5,6,7,8-tetrahydro-10H-naphthalen-2-one
(7a):
From 6a (0.100 g, 0.42 mmol), 7a was obtained as a colorless solid
(0.088 g, 95%). M.p. 56–578C; Rf =0.16 (hexane/ethyl acetate 7:3);
1H NMR (200 MHz, CDCl3): d=6.10 (d, 1H, J=1.2 Hz; =CH), 2.45–2.30
(m, 2H; CH2), 2.34 (s, 3H; CH3), 2.10–1.95 (m, 2H; CH2), 1.98 (d, 3H,
J=1.2 Hz; CH3), 1.75–1.62 (m, 2H; CH2), 1.35–1.20 (m, 2H; CH2),
1.32 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3): d=205.22, 183.45,
166.72, 163.20, 137.41 (C), 126.22 (CH), 43.32, 37.62 (CH2), 32.14 (CH3),
28.62, 28.31 (CH2), 22.63 (CH3) 21.03 (CH2), 18.98 ppm (CH3); IR (KBr):
n˜ =2944 (m), 1704 (s), 1654 (s), 1610 (s), 1446 (m), 1391 (m), 1142 (w),
958 (w), 880 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=218.5 (65), 203.5 (68),
189.5 (100), 175.5 (33), 161.4 (36), 43.1 (85) [M+]; elemental analysis
calcd (%) for C14H18O2: C 77.03, H 8.31; found: C 76.89, H 9.26. The
exact molecular mass for C14H18O2 m/z=218.1307ꢁ2 mD was confirmed
by HRMS (EI, 70 eV).
ꢀ
126.94, 126.72, 126.57, 123.70 (2C, CH), 75.21 (C OH), 61.04 (OCH2),
56.92 (C), 49.56, 40.00 (2C, CH2), 25.17, 13.61 ppm (CH3); IR (KBr): n˜ =
3447 (s), 1735 (s), 1664 (s), 1613 (w), 1373 (m), 1234 (s), 1026 (w),
763 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=376.9 (8) [M+], 358.0 (6), 243.9
(42), 214.9 (28), 142.0 (43), 104.7 (100), 77.4 (41), 43.1 (89), 28.1 (63).
The exact molecular mass for C24H24O4: m/z=376.1675ꢁ2 mD was con-
firmed by HRMS (EI, 70 eV).
Compound 18k: From 1-isobutoxy-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1c; 0.455 g, 1.50 mmol), 1-(2-benzoylindan-2-yl)ethanone (5 f;
Chem. Eur. J. 2004, 10, 6015 – 6028
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6023

P. Langer et al.
FULL PAPER
4,10-Dimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic acid
methyl ester (7b): From 6b (0.071 g, 0.28 mmol), 7b was obtained as a
colorless solid (0.064 g, 98%). M.p. 82–838C; Rf =0.28 (hexane/ethyl ace-
mass for C15H20O3 m/z=248.1412ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
3-Ethyl-4,10-dimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carbox-
ylic acid ethyl ester (7g): From 6g (0.060 g, 0.22 mmol), 7g was obtained
as a colorless oil (0.049 g, 88%). Rf =0.31 (hexane/ethyl acetate 3:2);
1H NMR (300 MHz, CDCl3): d=4.35 (q, 2H, J=7.2 Hz; OCH2), 2.45–
2.38 (m, 4H; CH2), 2.16–2.11 (m, 1H; CH2), 2.05–1.95 (m, 1H; CH2),
1.98 (s, 3H; CH3), 1.74–1.68 (m, 2H; CH2), 1.45–1.22 (m, 2H; CH2), 1.34
(t, 3H, J=7.2 Hz; CH3), 1.31 (s, 3H; CH3), 0.98 ppm (t, 3H, J=7.2 Hz;
CH3); 13C NMR (75 MHz, CDCl3): d=181.42, 167.68, 162.67, 159.24,
136.23, 130.55 (C), 61.18 (OCH2), 42.92 (C), 37.41, 29.73, 27.95 (CH2),
22.17 (CH3), 21.21, 18.63 (CH2), 14.79, 14.19, 12.69 ppm (CH3); IR
(neat): n˜ =2936 (s), 2870 (w), 1733 (s), 1656 (m), 1629 (s), 1447 (m), 1393
(m), 1268 (m), 1149 (m), 1028 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=276.1
(63) [M+], 230.1 (77), 215.0 (100), 203.1 (37), 28.0 (60). The exact molec-
ular mass for C17H24O3 m/z=276.1725ꢁ2 mD was confirmed by HRMS
(EI, 70 eV).
1
tate 3:2); H NMR (200 MHz, CDCl3): d=6.15 (d, 1H, J=1.2 Hz; =CH),
3.86 (s, 3H; OCH3), 2.47–2.41 (m, 2H; CH2), 2.14–2.04 (m, 2H; CH2),
2.01 (d, 3H, J=1.2 Hz; CH3), 1.80–1.68 (m, 2H; CH2), 1.46–1.28 (m, 2H;
CH2), 1.36 ppm (s, 3H; CH3); 13C NMR (50 MHz, CDCl3): d=181.91,
167.60, 166.06, 164.21, 130.79 (C), 126.04 (CH), 52.19 (OCH3), 43.22,
37.49, 29.91, 28.10 (CH2), 22.58 (CH3), 21.09 (CH2), 18.98 ppm (CH3); IR
(KBr): n˜ =2951 (m), 1732 (s), 1660 (s), 1630 (m), 1608 (m), 1389 (m),
1268 (s), 1048 (m), 958 (w), 868 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=
234.2 (31) [M+], 203.1 (20), 187.1 (45), 175.1 (100), 147.1 (21), 91.1 (23);
elemental analysis calcd (%) for C14H18O3: C 71.77, H 7.14; found: C
71.90, H 7.12.
4,10-Dimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic acid
ethyl ester (7c): From 6c (0.134 g, 0.5 mmol), 7c was obtained as color-
less crystals (0.120 g, 96%). M.p. 79–808C; Rf =0.30 (hexane/ethyl ace-
1
tate 3:2); H NMR (300 MHz, CDCl3): d=6.14 (q, 1H, J=1.2 Hz; =CH),
4,10-Diethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic acid
methyl ester (7h): From 6,10-diethyl-10-hydroxy-8-oxo-spiro[4,5]dec-6-
ene-7-carboxylic acid methyl ester (6h; 0.080 g, 0.28 mmol), 7h was ob-
tained as a colorless oil (0.062 g, 83%). Rf =0.32 (hexane/ethyl acetate
7:3); 1H NMR (300 MHz, CDCl3): d=6.34 (s, 1H; =CH), 3.85 (s, 3H;
OCH3), 2.42–2.13 (m, 6H; CH2), 2.04–1.98 (m, 1H; CH2), 1.83–1.67 (m,
3H; CH2), 1.48–1.35 (m, 2H; CH2), 1.15 (t, 3H, J=7.2 Hz; CH3),
0.53 ppm (t, 3H, J=7.1 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
182.76, 169.75, 167.62, 163.44, 132.86 (C), 125.85 (CH), 52.21 (OCH3),
48.52 (C), 37.74, 29.92, 28.12, 27.50, 23.02, 20.95 (CH2), 12.15, 7.96 ppm
(CH3); IR (neat): n˜ =2951 (m), 1729 (s), 1656 (m), 1623 (s), 1438 (m),
1275 (m), 1007 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=248.1 (45) [M+],
201.1 (51), 189.1 (100), 173.0 (41), 144.8 (34), 91.0 (57), 77.4 (36), 41.2
(46); elemental analysis calcd (%) for C16H22O3: C 73.25, H 8.45; found:
C 73.20, H 8.68.
4.33 (q, 2H, J=7.2 Hz; OCH2), 2.47–2.41 (m, 2H; CH2), 2.12–1.98 (m,
2H; CH2), 2.01 (d, 3H, J=1.2 Hz; CH3), 1.78–1.71 (m, 2H; CH2), 1.44–
1.37 (m, 2H; CH2), 1.36 (s, 3H; CH3), 1.34 ppm (t, 3H, J=7.2 Hz; CH3);
13C NMR (75 MHz, CDCl3): d=182.02, 167.23, 165.95, 163.77, 131.08 (C),
126.26 (CH), 61.27 (OCH2), 43.23 (C), 37.60, 29.83, 28.13 (CH2), 22.60
(CH3), 21.19 (CH2), 19.00, 14.24 ppm (CH3); IR (KBr): n˜ =2941 (s), 1730
(s), 1658 (s), 1630 (m), 1447 (m), 1390 (m), 1324 (w), 1265 (s), 1245 (s),
1050 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=248.1 (71) [M+], 233.1 (46),
203.1 (72), 178.1 (100); elemental analysis calcd (%) for C15H20O3: C
72.55, H 8.11; found: C 72.59, H 8.39.
4,10-Dimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic acid
isopropyl ester (7d): From 6d (0.054 g, 0.19 mmol), 7d was obtained as
colorless crystals (0.049 g, 97%). M.p. 62–638C; Rf =0.34 (hexane/ethyl
acetate 3:2); 1H NMR (300 MHz, CDCl3): d=6.19 (q, 1H, J=1.2 Hz; =
CH), 5.23 (sep, 1H, J=6.3 Hz; OCH), 2.53–2.37 (m, 2H; CH2), 2.14–2.04
(m, 2H; CH2), 2.02 (d, 3H, J=1.2 Hz; CH3), 1.80–1.70 (m, 2H; CH2),
1.54–1.38 (m, 2H; CH2), 1.36 (s, 3H; CH3), 1.32 ppm (dd, 6H, J=1.2,
6.3 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=182.55, 167.13, 166.72,
164.49, 131.08 (C), 125.95 (CH), 69.06 (OCH), 43.44 (C), 37.68, 29.75,
28.14 (CH2), 22.54, 21.83 (2C, CH3), 21.15 (CH2), 19.09 ppm (CH3); IR
(KBr): n˜ =2939 (s), 1727 (s), 1660 (s), 1633 (m), 1450 (m), 1239 (m),
876 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=262.3 (51) [M+], 203.2 (80),
187.2 (100), 175.2 (63), 161.2 (57), 91.1 (32), 43.1 (85); elemental analysis
calcd (%) for C16H22O3: C 73.25, H 8.45; found: C 73.38, H 8.71.
4,10-Diethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalen-1-carboxylic
acid
ethyl ester (7i): From 6i (0.060 g, 0.22 mmol), 7i was obtained as a color-
less oil (0.048 g, 85%). Rf =0.36 (hexane/ethyl acetate 7:3); 1H NMR
(300 MHz, CDCl3): d=6.29 (s, 1H; =CH), 4.29 (q, 2H, J=7.2 Hz;
OCH2), 2.41–2.09 (m, 6H; CH2), 2.00–1.95 (m, 1H; CH2), 1.79–1.60 (m,
3H; CH2), 1.58–1.33 (m, 2H; CH2), 1.30 (t, 3H, J=7.1 Hz; CH3), 1.12 (t,
3H, J=7.5 Hz; CH3), 0.50 ppm (t, 3H, J=7.1 Hz; CH3); 13C NMR
(75 MHz, CDCl3): d=182.67, 169.31, 167.20, 162.26, 133.11 (C), 125.97
(CH), 61.17 (OCH2), 48.38 (C), 37.72, 29.71, 28.06, 27.42, 22.96, 20.96
(CH2), 14.25, 12.15, 7.99 ppm (CH3); IR (neat): n˜ =1733 (s), 1658 (s),
1632 (m), 1448 (m), 1236 (m), 1044 (w), 887 cmꢀ1 (w); MS (EI, 70 eV):
m/z (%)=276.1 (32) [M+], 247.1 (55), 203.0 (100), 175.1 (46), 231.0 (30),
91.0 (24), 28.0 (35).
4,10-Dimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic acid
2-methoxyethyl ester (7e): From 6e (0.078 g, 0.26 mmol), 7e was ob-
tained as colorless crystals (0.071 g, 97%). M.p. 64–658C; Rf =0.23
(hexane/ethyl acetate 3:2); 1H NMR (300 MHz, CDCl3): d=6.14 (q, 1H,
J=1.2 Hz; =CH), 4.50–4.36 (m, 2H; OCH2), 3.66 (t, 2H, J=4.8 Hz;
OCH2), 3.38 (s, 3H; OCH3), 2.55–2.37 (m, 2H; CH2), 2.13–1.98 (m, 2H;
CH2), 2.01 (d, 3H, J=1.2 Hz; CH3), 1.79–1.70 (m, 2H; CH2), 1.52–1.38
(m, 2H; CH2), 1.35 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
181.95, 167.13, 166.16, 164.37, 130.77 (C), 126.13 (CH), 70.39, 63.99
(OCH2), 58.90 (OCH3), 43.31 (C), 37.65, 29.87, 28.14 (CH2), 22.55 (CH3),
21.17 (CH2), 19.04 ppm (CH3); IR (KBr): n˜ =2944 (s), 1733 (s), 1659 (s),
1630 (m), 1449 (m), 1268 (m), 1053 (m), 876 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%)=277.7 (54) [M+], 220.9 (53), 203.2 (100), 187.9 (82), 175.7 (67),
161.0 (43), 90.9 (22); elemental analysis calcd (%) for C16H22O4: C 69.04,
H 7.97; found: C 68.83, H 7.95.
4,10-Diethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalen-1-carboxylic
acid
isopropyl ester (7j): From 6j (0.066 g, 0.21 mmol), 7j was obtained as a
colorless oil (0.055 g, 89%). Rf =0.44 (hexane/ethyl acetate 7:3);
1H NMR (300 MHz, CDCl3): d=6.32 (d, 1H, J=1.2 Hz; =CH), 5.22 (sep,
1H, J=6.3 Hz; OCH), 2.45–2.13 (m, 7H; CH2), 1.79–1.62 (m, 3H; CH2),
1.46–1.35 (m, 2H; CH2), 1.32 (d, 6H, J=6.3 Hz; CH3), 1.15 (t, 3H, J=
7.2 Hz; CH3), 0.53 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz,
CDCl3): d=182.61, 169.40, 166.52, 162.30, 133.01 (C), 48.20 (C), 37.54,
29.38, 27.82, 27.22, 22.79 (CH2), 21.66, 21.64 (CH3), 20.77 (CH2), 11.96,
7.81 ppm (CH3); IR (neat): n˜ =2933 (m), 1732 (s), 1659 (s), 1629 (m),
1439 (m), 1241 (m), 1044 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=290.0 (19)
[M+], 261.0 (19), 231.0 (46), 218.9 (85), 202.9 (96), 175.0 (62), 43.1 (78),
28.0 (100). The exact molecular mass for C18H26O3: m/z=290.1882ꢁ
2 mD was confirmed by HRMS (EI, 70 eV).
3,4,10-Trimethyl-2-oxo-2,5,6,7,8,10-hexahydronaphthalene-1-carboxylic
acid methyl ester (7 f): From 6 f (0.135 g, 0.5 mmol), 7 f was obtained as
colorless crystals (0.114 g, 92%). M.p. 110–1118C; Rf =0.28 (hexane/ethyl
acetate 3:2); 1H NMR (300 MHz, CDCl3): d=3.86 (s, 3H; OCH3), 2.43–
2.38 (m, 2H; CH2), 2.18–2.11 (m, 1H; CH2), 2.03–1.98 (m, 1H; CH2),
1.96 (s, 3H; CH3), 1.89 (s, 3H; CH3), 1.77–1.67 (m, 2H; CH2), 1.44–1.34
(m, 1H; CH2), 1.31 (s, 3H; CH3), 1.29–1.22 ppm (m, 1H; CH2); 13C NMR
(75 MHz, CDCl3): d=182.82, 168.09, 163.05, 159.57, 130.45, 130.19 (C),
52.19 (OCH3), 43.21 (C), 37.37, 29.90, 28.06 (CH2), 22.13 (CH3), 21.21
(CH2), 15.78, 11.01 ppm (CH3); IR (KBr): n˜ =2951 (m), 1729 (s), 1656
(m), 1623 (s), 1438 (m), 1275 (m), 1219 (m), 1007 cmꢀ1 (m); MS (EI,
70 eV): m/z (%)=248.1 (45) [M+], 201.0 (51), 189.1 (100), 173.0 (41),
144.8 (34), 91.0 (57), 41.2 (46); elemental analysis calcd (%) for
C15H20O3: C 72.55, H 8.11; found: C 72.59, H 8.39. The exact molecular
4-Methyl-2-oxo-10-phenyl-2,5,6,7,8,10-hexahydronaphthalen-1-carboxylic
acid ethyl ester (7k): From 6k (0.068 g, 0.22 mmol), 7k was obtained as a
colorless oil (0.088 g, 91%). Rf =0.28 (hexane/ethyl acetate 7:3);
1H NMR (300 MHz, CDCl3): d=7.38–7.16 (m, 5H; ArH), 6.09 (q, 1H,
J=1.2 Hz; =CH), 4.45–4.29 (m, 2H; OCH2), 3.00–2.94 (m, 1H; CH2),
2.44–2.39 (m, 1H; CH2), 1.95–1.79 (m, 3H; CH3), 1.71 (d, 3H, J=1.5 Hz;
CH3), 1.54–1.54 (m, 2H; CH2), 1.36 (t, 3H, J=7.2 Hz; CH3), 1.28–
1.23 ppm (m, 1H; CH2); 13C NMR (75 MHz, CDCl3): d=182.65, 166.90,
165.25, 164.05, 138.08, 131.87 (C), 129.21 (2C), 127.59 (2C), 127.45,
124.80 (CH), 61.37 (OCH2), 52.25 (C), 35.37, 31.22, 29.17, 21.61 (CH2),
19.39, 14.27 ppm (CH3); MS (EI, 70 eV): m/z (%)=310.9 (36) [M+],
6024
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
282.8 (100), 265.8 (39), 237.7 (60), 209.6 (63), 165.1 (43), 91.2 (30), 29.1
(57).
1H NMR (300 MHz, CDCl3): d=6.39–6.34 (ddd, 1H, J=1.5, 2.7, 9.9 Hz;
=CH), 6.27–6.22 (m, 1H; =CH), 6.17 (q, 1H, J=1.2 Hz; =CH), 4.35 (q,
2H, J=7.2 Hz; OCH2), 2.47–2.39 (m, 2H; CH2), 2.10–2.05 (m, 1H; CH2),
2.03 (d, 3H, J=1.2 Hz; CH3), 1.72–1.62 (m, 1H; CH2), 1.36 (t, 3H, J=
7.2 Hz; CH3), 1.35 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
182.29, 166.54, 164.34, 156.89 (C), 137.47 (CH), 128.99 (C), 126.66, 124.27
(CH), 61.42 (OCH2), 40.18 (C), 30.04 (CH2), 24.85 (CH3), 23.12 (CH2),
19.01, 14.18 ppm (CH3); IR (neat): n˜ =3440 (br), 2922 (m), 1784 (m),
1726 (s), 1657 (s), 1610 (m), 1449 (m), 1241 (s), 1160 (s), 732 cmꢀ1 (m);
MS (EI, 70 eV): m/z (%): 246.1 (70) [M+], 231.0 (25), 201.0 (79), 187.0
(100), 173.0 (62), 144.8 (79), 129.0 (50), 91.0 (21). The exact molecular
mass for C15H18O3: m/z=246.1256ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
Compound 14a: From 13a (0.050 g, 0.2 mmol) and TFA (0.15 mL,
2.00 mmol), 14a was obtained as a colorless oil (0.025 g, 43%). 1H NMR
(300 MHz, CDCl3): d=6.75 (d, 1H, J=9.9 Hz; CH), 6.24 (d, 1H, J=
9.9 Hz; CH), 4.33 (q, 2H, J=7.2 Hz; OCH2), 2.51–2.46 (m, 1H; CH2),
2.37 (dd, 1H, J=13.5, 5.1 Hz; CH2), 2.08–1.98 (m, 1H; CH2), 1.90–1.83
(m, 1H; CH2), 1.75–1.69 (m, 2H; CH2), 1.48–1.38 (m, 2H; CH2), 1.34 ( t,
3H, J=7.2 Hz; CH3), 1.31 ppm (s, 3H; CH3); 13C NMR (75 MHz,
CDCl3): d=182.77, 167.01, 163.57 (C), 157.14 (CH), 131.02 (C), 126.25
(CH), 61.33 (CH2), 40.62 (C), 38.46, 29.71, 27.65 (CH2), 23.01 (CH3),
20.68 (CH2), 14.29 ppm (CH3); IR (neat): n˜ =2936 (s); 1659 (s), 1233 (s),
1038 (s), 838 cmꢀ1 (w); MS (EI, 70 eV): m/z (%): 234.1 (21) [M+], 188.1
(100), 162.4 (19), 116.0 (6), 30.1 (7), 28.0 (5); elemental analysis calcd
(%) for C14H18O3: C 71.79, H 7.63; found: C 71.20, H 7.40.
4,10-Dimethyl-2-oxo-2,5,6,10-tetrahydronaphthalen-1-carboxylic acid iso-
propyl ester (17c): From 16c (0.058 g, 0.21 mmol), 17c was obtained as a
colorless oil (0.039 g, 73%). Rf =0.38 (hexane/ethyl acetate 7:3);
1H NMR (300 MHz, CDCl3): d=6.38 (ddd, 1H, J=1.5, 2.7, 9.9 Hz; =
CH), 6.26–6.21 (m, 1H; =CH), 6.15 (q, 1H, J=1.2 Hz; =CH), 5.25 (sep,
1H, J=6.3 Hz; OCH), 2.44–2.39 (m, 2H; CH2), 2.08–2.03 (m, 1H; CH2),
2.02 (d, 3H, J=1.2 Hz; CH3), 1.71–1.61 (m, 1H; CH2), 1.36 (d, 6H, J=
6.3 Hz; CH3), 1.35 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
182.52, 166.34, 164.33, 156.52 (C), 137.33 (CH), 129.56 (C), 127.01, 124.51
(CH), 69.32 (OCH), 40.36 (C), 30.31 (CH2), 25.05 (CH3), 23.38 (CH2),
22.07 (2C), 19.01 ppm (CH3); IR (neat): n˜ =3436 (br), 2982 (m), 1784
(m), 1722 (s), 1656 (s), 1610 (m), 1372 (s), 1246 (s), 732 cmꢀ1 (m); MS
(EI, 70 eV): m/z (%)=260.0 (26) [M+], 217.9 (37), 200.9 (57), 173.9
(100), 144.7 (28), 114.3 (23), 43.1 (48). The exact molecular mass for
C16H20O3: m/z=260.1412ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 19a: From 18a (0.110 g, 0.39 mmol), 19a was obtained as a
yellow oil (0.084 g, 82%). Rf =0.45 (hexane/ethyl acetate 3:2); 1H NMR
(300 MHz, CDCl3): d=16.55 (s, 1H; OH), 7.19–7.03 (m, 4H; ArH), 6.12
(s, 1H; =CH), 5.93 (q, 1H, J=1.2 Hz; =CH), 2.93 (d, 1H, J=15.0 Hz;
CH2), 2.85 (d, 1H, J=15.0 Hz; CH2), 2.38 (s, 3H; CH3), 2.04 (d, 3H, J=
1.2 Hz; CH3), 1.05 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
185.23, 182.27, 162.95, 138.40, 133.36, 131.57 (C), 128.17, 126.98, 126.65,
125.11 123.32, 122.53 (CH), 107.93, 43.53 (C), 38.19 (CH2), 23.67, 20.50,
19.08 ppm (CH3); IR (neat): n˜ =2974 (m), 1735 (m), 1657 (s), 1630 (m);
1601 (w), 1571 (m), 1441 (m), 1268 (m), 1235 (m), 1156 (w), 869 (m),
759 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=266.7 (96) [M+], 251.6 (100),
209.5 (47), 178.3 (19), 43.1 (79), 28.0 (73). The exact molecular mass for
C18H18O2: m/z=266.1307ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 19b: From 18b (0.097 g, 0.32 mmol), 19b was obtained as a
yellow oil (0.072 g, 79%). Rf =0.48 (hexane/ethyl acetate 3:2); 1H NMR
(300 MHz, CDCl3): d=13.28 (s, 1H; OH), 7.17–6.96 (m, 5H; ArH, =
CH), 5.86 (q, 1H, J=1.2 Hz; =CH), 3.88 (s, 3H; CH3), 3.01 (d, 1H, J=
15.3 Hz; CH2), 2.81 (d, 1H, J=15.3 Hz; CH2), 2.38 (s, 3H; CH3), 2.00 (d,
3H, J=1.2 Hz; CH3), 1.25 ppm (s, 3H; CH3); 13C NMR (75 MHz,
CDCl3): d=173.80, 168.60, 157.38, 136.69, 134.26, 130.60 (C), 127.89,
126.84, 126.24, 125.97, 121.39, 119.35 (CH), 96.05 (C), 51.82 (OCH3),
41.27 (C), 37.97 (CH2), 29.67, 21.88 (CH3); IR (neat): n˜ =3436 (br), 1736
(m), 1658 (s), 1626 (m), 1567 (m), 1441 (m), 1269 (s), 751 cmꢀ1 (w); MS
(EI, 70 eV): m/z (%)=281.9 (49) [M+], 267.0 (34), 249.9 (35), 234.9
(100), 179.0 (41), 57.4 (18), 28.1 (22). The exact molecular mass for
C18H18O3: m/z=282.1256ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 19c: From 18c (0.115 g, 0.36 mmol), 19c was obtained as
orange crystals (0.093 g, 86%). M.p. 126–1278C; Rf =0.45 (hexane/ethyl
acetate 3:2); 1H NMR (300 MHz, CDCl3): d=13.37 (s, 1H; OH), 7.10–
7.03 (m, 5H; ArH, =CH), 5.86 (q, 1H, J=1.4 Hz; =CH), 4.44–4.33 (m,
2H; OCH2), 3.02 (d, 1H, J=15.2 Hz; CH2), 2.80 (d, 1H, J=15.2 Hz;
CH2), 2.01 (d, 3H, J=1.4 Hz; CH3), 1.45 (t, 3H, J=7.2 Hz; CH3),
1.03 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=173.05, 168.59,
157.18, 136.89, 134.43, 130.66 (C), 127.92, 126.86, 126.21, 125.94, 121.45,
119.45 (CH), 96.06 (C), 61.11 (CH2), 41.31 (C), 38.04 (CH2), 21.98, 19.14,
14.21 ppm (CH3); IR (KBr): n˜ =2960 (m), 1725 (w), 1659 (s), 1613 (s),
1574 (s), 1408 (m), 1306 (s), 1272 (s), 1239 (s), 1073 (m), 1017 (w), 869
(m), 752 cmꢀ1 (m); MS (EI, 70 eV) m/z (%)=296.2 (43) [M+], 281.4
(28), 250.2 (41), 235.2 (100), 179.2 (43); elemental analysis calcd (%) for
C19H20O3: C 77.00, H 6.80; found: C 77.33, H 6.95.
Compound 15a: From 13a (0.050 g, 0.2 mmol) and TFA (0.15 mL,
2.00 mmol), 15a was obtained as a colorless solid (0.012 g, 22%). M.p.
216–2178C; 1H NMR (300 MHz, CDCl3): d=10.46 (s, 1H; OH), 6.58 (s,
1H; ArH), 4.41 (q, 2H, J=6.9 Hz; OCH2), 2.73 (t, 4H, J=6.3 Hz; CH2),
2.58 (t, 4H, J=6.3 Hz; CH2), 2.39 (s, 3H; CH3), 2.19–1.67 (m, 8H; CH2),
1.43 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
171.78, 158.82, 144.73, 139.24, 128.01 (C), 115.21 (CH), 112.09 (C), 61.53,
30.99, 27.13, 23.80, 22.44 (CH2), 18.07, 14.35 ppm (CH3); IR (neat): n˜ =
3410 (br), 2932 (s), 1727 (m), 1658 (s), 1237 (s), 1155 (m), 1080 (m),
802 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=233.9 (17) [M+], 187.9 (92),
160.9 (15), 86.9 (19), 43.0 (27), 28.0 (100); elemental analysis calcd (%)
for C14H18O3: C 71.79, H 7.63; found: C 71.38, H 7.23.
Compound 15b: From 13b (0.047 g, 0.21 mmol) and TFA (0.16 mL,
2.11 mmol), 15b was obtained as a colorless solid (0.022 g, 52%). M.p.
136–1378C; 1H NMR (300 MHz, CDCl3): d=10.72 (s, 1H; OH), 6.57 (s,
1H; ArH), 2.74 (t, 2H, J=6.3 Hz; CH2), 2.59 (s, 3H; CH3), 2.56 (t, 2H,
J=6.3 Hz; CH2), 2.35 (s, 3H; CH3), 1.85–1.82 (m, 2H; CH2), 1.76–
1.71 ppm (m, 2H; CH2); 13C NMR (75 MHz, CDCl3): d=206.40, 157.19,
144.80, 136.97, 127.86, 122.50 (C), 115.29 (CH), 32.71 (CH3), 30.79, 26.68,
23.50, 22.27 (CH2), 19.03 ppm (CH3); IR (neat): n˜ =3306 (br), 2933 (s),
1666 (s), 1599 (s), 1429 (s), 1302 (m), 1241 (m), 1149 (m), 855 cmꢀ1 (w);
MS (EI, 70 eV): m/z (%): 204.2 (41) [M+], 189.2 (100), 161.2 (9), 145.2
(5), 114.0 (7), 43.0 (8), 28.0 (12); elemental analysis calcd (%) for
C13H16O2: C 76.47, H 7.84; found: C 75.76, H 7.97.
Compound 14c: From 13c (0.040 g, 0.152 mmol) and TFA (0.12 mL,
1.52 mmol), 14c was obtained as a colorless oil (0.024 g, 60%). 1H NMR
(300 MHz, CDCl3): d=6.47 (s, 1H; =CH), 4.33 (q, 2H, J=7.2 Hz;
OCH2), 2.36 (q, 2H, J=7.1 Hz; CH2), 1.99 (t, 2H, J=3.0 Hz; CH2), 1.43–
1.38 (m, 4H; CH2), 1.34 (t, 3H, J=7.2 Hz; CH3), 1.32–1.28 (m, 2H;
CH2), 1.27 (s, 3H; CH3), 1.07 ppm (t, 3H, J=7.5 Hz; CH3); 13C NMR
(75 MHz, CDCl3): d=183.03, 167.40, 162.84 (C), 151.30 (CH), 137.71,
130.73 (C), 61.19, 38.76, 29.44, 27.63 (CH2), 23.21 (CH3), 21.79, 20.74
(CH2), 14.23, 12.40 ppm (CH3); IR (neat): n˜ =2936 (s), 1733 (s), 1663 (s),
1636 (s), 1440 (m), 1266 (s), 1184 (s), 1025 (m), 716 cmꢀ1 (m); MS (EI,
70 eV): m/z (%)=262.3 (22) [M+], 247.3 (13), 217.2 (28), 189.2 (100),
161.2 (28), 91.0 (20), 28.0 (78); elemental analysis calcd (%) for
C16H22O3: C 73.00, H 8.36; found: C 72.32, H 8.34.
4,10-Dimethyl-2-oxo-2,5,6,10-tetrahydronaphthalene-1-carboxylic
methyl ester (17a): From 16a (0.118 g, 0.48 mmol), 17a was obtained as
colorless oil (0.085 g, 76%). Rf =0.32 (hexane/ethyl acetate 7:3);
acid
a
1H NMR (300 MHz, CDCl3): d=6.38–6.33 (ddd, 1H, J=1.5, 2.4, 9.9 Hz;
=CH), 6.29–6.23 (m, 1H; =CH), 6.18 (q, 1H, J=1.2 Hz; =CH), 3.88 (s,
3H; OCH3), 2.47–2.39 (m, 2H; CH2), 2.10–2.05 (m, 1H; CH2), 2.04 (d,
3H, J=1.2 Hz; CH3), 1.71–1.61 (m, 1H; CH2), 1.26 ppm (s, 3H; CH3);
13C NMR (75 MHz, CDCl3): d=182.57, 167.12, 164.83, 157.79 (C), 137.99
(CH), 128.96 (C), 126.84, 124.60 (CH), 52.52 (OCH3), 40.56 (C), 30.32
(CH2), 25.12 (CH3), 23.38 (CH2), 19.23 ppm (CH3); IR (neat): n˜ =3442
(br), 2977 (m), 1784 (m), 1734 (s), 1653 (s), 1609 (m), 1435 (m), 1246 (s),
1159 (s), 875 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=232.1 (100) [M+],
217.1 (36), 201.0 (46), 173.0 (74), 144.8 (99), 129.0 (63), 91.0 (18). The
exact molecular mass for C14H16O3: m/z=232.1099ꢁ2 mD was confirmed
by HRMS (EI, 70 eV).
4,10-Dimethyl-2-oxo-2,5,6,10-tetrahydronaphthalen-1-carboxylic
acid
ethyl ester (17b): From 16b (0.118 g, 0.48 mmol), 17b was obtained as a
colorless oil (0.044 g, 76%). Rf =0.37 (hexane/ethyl acetate 7:3);
Compound 19d: From 18d (0.113 g, 0.34 mmol), 19d was obtained as a
yellow oil (0.081 g, 76%). Rf =0.54 (hexane/ethyl acetate 3:2); 1H NMR
Chem. Eur. J. 2004, 10, 6015 – 6028
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6025

P. Langer et al.
FULL PAPER
(300 MHz, CDCl3): d=13.44 (s, 1H; OH), 7.19–6.98 (m, 5H; ArH, =
CH), 5.85 (q, 1H, J=1.5 Hz; =CH), 5.25 (sep, 1H, J=6.0 Hz; CH), 3.00
(d, 1H, J=15.0 Hz; CH2), 2.80 (d, 1H, J=15.0 Hz; CH2), 2.00 (d, 3H,
J=1.5 Hz; CH3), 1.45 (d, 3H, J=6.0 Hz; CH3), 1.39 (d, 3H, J=6.0 Hz;
CH3), 1.03 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=172.57,
168.40, 156.96, 136.95, 134.37, 130.62 (C), 127.89, 126.80, 126.12, 125.86,
121.42, 119.44 (CH), 96.23 (C), 69.04 (OCH), 41.27 (C), 38.02 (CH2),
22.05, 21.19 (2C), 19.07 ppm (CH3); IR (neat): n˜ =2979 (w), 1733 (s),
1657 (s), 1630 (s), 1603 (w), 1569 (m), 1454 (w), 1269 (s), 1105 (s),
862 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=310.0 (36) [M+], 250.0 (53),
234.9 (100), 209.4 (24), 179.0 (45), 43.2 (44), 28.0 (23). The exact molecu-
lar mass for C20H22O3: m/z=310.1569ꢁ2 mD was confirmed by HRMS
(EI, 70 eV).
Compound 19j: From 18j (0.043 g, 0.11 mmol), 19j was obtained as a
yellow oil (0.040 g, 83%). Rf =0.40 (hexane/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3): d=7.37–7.27 (m, 9H; ArH), 6.27 (d, 1H, J=1.2 Hz;
=CH), 4.38 (d, 2H, J=7.2 Hz; OCH2), 3.88 (d, 1H, J=16.5 Hz; CH2),
3.64 (d, 1H, J=19.2 Hz; CH2), 3.32 (d, 1H, J=19.2 Hz; CH2), 3.08 (d,
1H, J=16.5 Hz; CH2), 1.78 (d, 3H, J=1.2 Hz; CH3), 1.35 ppm (t, 3H,
J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=182.26, 164.40, 163.65,
159.40, 137.73, 133.29, 132.25 (C), 128.97 (2C), 128.37, 128.00, 127.58,
127.12 (2C), 126.91, 126.81, 125.93 (CH), 61.52 (OCH2), 50.39 (C), 38.32,
33.61 (CH2), 19.48, 14.19 ppm (CH3); IR (neat): n˜ =3435 (s), 2977 (w),
1739 (s), 1655 (s), 1601 (m), 1562 (m), 1441 (m), 1275 (m), 763 cmꢀ1 (w);
MS (EI, 70 eV): m/z (%)=358.3 (45) [M+], 312.1 (100), 297.1 (19), 284.1
(18), 235.1 (47), 179.1 (20), 144.8 (9), 28.0 (8). The exact molecular mass
for C24H24O3: m/z=358.1569ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
Compound 19e: From 18e (0.113 g, 0.34 mmol), 19e was obtained as a
yellow oil (0.089 g, 85%). Rf =0.50 (hexane/ethyl acetate 3:2); 1H NMR
(300 MHz, CDCl3): d=13.12 (s, 1H; OH), 7.17–7.00 (m, 5H; ArH, =
CH), 5.86 (q, 1H, J=1.2 Hz; =CH), 4.57–4.51 (m, 1H; OCH2), 4.39–4.32
(m, 1H; OCH2), 3.77–3.73 (m, 2H; OCH2), 3.48 (s, 3H; OCH3), 3.00 (d,
1H, J=15.0 Hz; CH2), 2.80 (d, 1H, J=15.0 Hz; CH2), 2.00 (d, 3H, J=
1.2 Hz; CH3), 1.03 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=
173.05, 168.59, 157.18, 136.89, 134.43, 130.66 (C), 127.92, 126.86, 126.21,
125.94, 121.45, 119.45 (CH), 96.06 (C), 61.11 (CH2), 41.31 (C), 38.04
(CH2), 21.98, 19.14, 14.21 ppm (CH3); IR (neat): n˜ =2969 (w), 1714 (w),
1646 (s), 1621 (s), 1566 (s), 1454 (m), 1425 (s), 1283 (s), 962 cmꢀ1 (w);
MS (EI, 70 eV): m/z (%): 326.0 (39) [M+], 310.9 (20), 250.0 (51), 234.9
(100), 179.0 (32), 43.1 (55), 28.1 (48); elemental analysis calcd (%) for
C20H22O4: C 73.59, H 6.79; found: C 73.87, H 7.04. The exact molecular
mass for C20H22O4: m/z=326.1518ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
Compound 19k: From 18k (0.052 g, 0.13 mmol), 19k was obtained as a
yellow oil (0.041 g, 83%); a small amount of impurity could not be sepa-
rated. Rf =0.93 (hexane/ethyl acetate 3:1); 1H NMR (300 MHz, CDCl3):
d=13.32 (s, 1H; OH), 7.45–6.93 (m, 10H; ArH, =CH), 5.99 (s, 1H; =
CH), 4.24–4.09 (m, 2H; OCH2), 2.96 (d, 1H, J=15.6 Hz; CH2), 2.47 (d,
1H, J=15.6 Hz; CH2), 2.20–2.11 (m, 1H; CH), 1.27 (s, 3H; CH3),
1.10 ppm (d, 6H, J=6.7 Hz; CH3); IR (KBr): n˜ =2938 (s), 1736 (s), 1602
(m), 1453 (m), 1276 (s), 1115 (s), 706 cmꢀ1 (w); MS (EI, 70 eV): m/z
(%)=386.0 (51) [M+], 311.0 (100), 284.9 (15), 234.9 (38), 179.0 (18),
144.8 (9), 43.1 (10), 28.1 (41). The exact molecular mass for C26H26O3:
m/z=386.1882ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Compound 19l: From 18l (0.050 g, 0.12 mmol), 19l was obtained as a
yellow oil (0.035 g, 73%); a small amount of impurity could not be sepa-
rated. Rf =0.46 (hexane/ethyl acetate 3:1); 1H NMR (300 MHz, CDCl3):
d=7.30–6.90 (m, 9H; ArH), 6.27 (d, 1H, J=1.2 Hz; =CH), 4.16–4.05 (m,
2H; OCH2), 3.95–3.80 (br, 1H; CH2), 3.88 (d, 1H, J=16.7 Hz; CH2),
3.66 (d, 1H, J=19.1 Hz; CH2), 3.32 (d, 1H, J=17.2 Hz; CH2), 3.10 (d,
1H, J=16.7 Hz; CH2), 2.08–2.08 (m, 1H; CH), 1.78 (d, 3H, J=1.1 Hz;
CH3), 0.98 ppm (dd, 6H, J=12.6, 1.2 Hz; CH3); 13C NMR (75 MHz,
CDCl3): d=182.80, 166.94, 164.31, 160.07, 138.18, 133.69 (C), 132.66,
132.00, 129.44, 129.20, 128.85, 128.80, 128.39, 120.36, 127.77, 127.60,
Compound 19g: From 18g (0.046 g, 0.13 mmol), 19g was obtained as a
yellow oil (0.032 g, 73%). Rf =0.82 (hexane/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3): d=13.21 (s, 1H; OH), 7.30–6.92 (m, 10H; ArH, =
CH), 5.99 (s, 1H; =CH), 3.96 (s, 3H; OCH3), 2.97 (d, 1H, J=15.6 Hz;
CH2), 2.48 (d, 1H, J=15.6 Hz; CH2), 1.26 ppm (s, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=173.47, 167.80, 159.46, 139.55, 136.83, 134.10,
131.27 (C), 128.59 (2C), 128.25, 128.23 (2C), 127.93, 126.95, 126.61,
126.36, 122.16 (CH), 92.28 (C), 52.22 (CH3), 41.62 (C), 39.31 (CH2),
23.44 ppm (CH3); IR (neat): n˜ =3435 (s), 2977 (w), 1739 (s), 1655 (s),
1601 (m), 1562 (m), 1441 (m), 1275 (m), 763 cmꢀ1 (w); MS (EI, 70 eV):
m/z (%): 344.0 (47) [M+], 329.0 (35), 311.9 (29), 297.0 (100), 241.0 (34),
70.0 (34), 28.1 (32). The exact molecular mass for C23H20O3: m/z=
344.1412ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
ꢀ
127.48, 126.34 (CH), 72.07 (CH2), 50.90 (C OH), 38.70, 34.18 (CH2),
28.15 (CH), 20.00, 19.92, 19.57 ppm (CH3); IR (KBr): n˜ =2973 (m), 1736
(s), 1677 (m), 1657 (s), 1600 (m), 1450 (m), 1257 (m), 1115 (m), 759 cmꢀ1
(w); MS (EI, 70 eV): m/z (%): 386.0 (51) [M+], 311.0 (100), 284.9 (15),
234.9 (38), 179.0 (18), 144.8 (9), 43.1 (10), 28.1 (41). The exact molecular
mass for C26H26O3: m/z=386.1882ꢁ2 mD was confirmed by HRMS (EI,
70 eV).
6,10-Dimethyl-8-oxo-spiro[4,5]deca-6,9-dien-7-carboxylic acid ethyl ester
(8): TFA (0.40 mL, 5.30 mmol) was added to a well-stirred CH2Cl2 so-
lution (0.5 mL) of 7c (0.130 g, 0.49 mmol) at 208C and the mixture was
stirred for 1 h. The solvent and TFA were removed in vacuo and the resi-
due was purified by column chromatography (silica gel, ethyl acetate/
hexane 2:3) to give 8 as a colorless solid (0.068 g, 56%). M.p. 50–518C;
Rf =0.30 (ethyl acetate/hexane 2:3); 1H NMR (300 MHz, CDCl3): d=
6.06 (s, 1H; =CH), 4.35 (q, 2H, J=7.2 Hz; OCH2), 2.02 (s, 3H; CH3),
2.01 (s, 3H; CH3), 1.93–1.85 (m, 8H; cyclopentane CH2), 1.42 ppm (t,
3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=182.11, 167.45,
164.76, 161.00, 132.09 (C), 125.08 (CH), 61.23 (CH2), 53.40 (C), 37.33
(2C), 29.19 (2C, CH2), 20.79, 17.46, 14.19 ppm (CH3); IR (neat): n˜ =2959
(m), 1731 (s), 1657 (s), 1629 (m), 1607 (w), 1394 (m), 1243 (m), 1049 cmꢀ1
(m); MS (EI, 70 eV): m/z (%): 248.3 (20) [M+], 233.2 (6), 203.3 (37),
187.2 (20), 175.2 (100), 161.2 (30), 146.8 (30), 91.1 (11), 29.2 (17); elemen-
tal analysis calcd (%) for C15H20O3: C 72.55, H 8.11; found: C 72.61, H
8.29.
Compound 19h: From 18h (0.040 g, 0.11 mmol), 19h was obtained as a
yellow oil (0.032 g, 84%). Rf =0.39 (hexane/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3): d=7.29–7.05 (m, 9H; ArH), 6.27 (d, 1H, J=1.2 Hz;
=CH), 3.90 (s, 3H; OCH3), 3.88 (d, 1H, J=16.5 Hz; CH2), 3.63 (d, 1H,
J=19.2 Hz; CH2), 3.33 (d, 1H, J=19.2 Hz; CH2), 3.08 (d, 1H, J=
16.5 Hz; CH2), 1.79 ppm (d, 3H, J=1.1 Hz; CH3); 13C NMR (75 MHz,
CDCl3): d=182.18, 166.85, 163.71, 159.88, 137.69, 132.22, 132.19, 131.37
(C), 129.00 (2C), 128.41, 128.00, 127.63, 127.11 (2C), 126.93, 126.86,
125.00 (CH), 52.41 (OCH3), 50.47 (C), 38.36, 33.78 (CH2), 19.50 ppm
(CH3); IR (neat): n˜ =3435 (s), 2977 (w), 1739 (s), 1655 (s), 1601 (m),
1562 (m), 1441 (m), 1275 (m), 763 cmꢀ1 (w); MS (EI, 70 eV): m/z (%)=
344.4 (45) [M+], 312.6 (100), 285.1 (8), 253.0 (19), 179.0 (12), 104.8 (12),
28.0 (9). The exact molecular mass for C23H20O3: m/z=344.1412ꢁ2 mD
was confirmed by HRMS (EI, 70 eV).
Compound 19i: From 18i (0.050 g, 0.13 mmol), 19i was obtained as a
yellow oil (0.040 g, 84%). Rf =0.88 (hexane/ethyl acetate 3:1); 1H NMR
(300 MHz, CDCl3): d=13.31 (s, 1H; OH), 7.37–6.93 (m, 10H; ArH, =
CH), 5.98 (s, 1H; =CH), 4.51–4.34 (m, 2H; OCH2), 2.97 (d, 1H, J=
15.6 Hz; CH2), 2.48 (d, 1H, J=15.6 Hz; CH2), 1.47 (t, 3H, J=7.2 Hz;
CH3), 1.26 ppm (s, 3H; CH3); 13C NMR (75 MHz, CDCl3): d=172.87,
167.54, 159.10, 139.39, 136.77, 134.01, 131.08 (C), 128.40 (2C), 127.72
(3C), 126.72, 126.35, 126.09, 121.99 (2C, CH), 97.07 (C), 61.29 (CH3),
41.42 (C), 39.13 (CH2), 23.30, 14.18 ppm (CH3); IR (neat): n˜ =3435 (s),
2977 (w), 1739 (s), 1655 (s), 1601 (m), 1562 (m), 1441 (m), 1275 (m),
763 cmꢀ1 (w); MS (EI, 70 eV): m/z (%): 358.4 (41) [M+], 343.3 (28),
312.3 (33), 297.3 (100), 241.3 (39), 77.4 (3). The exact molecular mass for
C24H22O3: m/z=358.1569ꢁ2 mD was confirmed by HRMS (EI, 70 eV).
Synthesis of ethyl 1-acetylcyclopropanecarboxylate (9): 1,4-Dibromobu-
tane (46.6 mL, 395.3 mmol) was added dropwise through a dropping
funnel to a stirred solution of ethyl acetoacetate (51.4 g, 395.3 mmol) and
potassium carbonate (136.0 g, 987.5 mmol) in dimethyl sulfoxide
(120 mL) at 208C. After three days of stirring, the reaction mixture was
filtered and the residue was washed with Et2O (2”50 mL). The combined
organic layers were dried over anhydrous Na2SO4, filtered, and concen-
trated in vacuo. The crude reaction mixture was purified by column chro-
matography (hexane/ethyl acetate 9:1) to give 9 as a colorless oil (60.0 g,
83%). 1H NMR (300 MHz, CDCl3): d=4.19 (q, 2H, J=7.2 Hz; OCH2),
2.15 (s, 3H; CH3), 2.13–2.08 (m, 2H; CH2), 1.68–1.61 (m, 2H; CH2),
6026
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 6015 – 6028

Spiro[5.4]decenones and Bicyclo[4.4.]deca-1,4-dien-3-ones
6015 – 6028
1.26 ppm (t, 3H, J=7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
203.09, 172.87, 66.38 (C) 60.79, 32.50 (2C, CH2), 25.82 (CH3), 25.21 (2C,
CH2), 13.54 ppm (CH3); IR (neat): n˜ =2960 (s), 2874 (m), 1739 (s); 1710
(s), 1623 (m), 1448 (s), 1246 (s), 1171 (s), 858 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%): 184.0 (5) [M+], 139.0 (2), 84.9 (4), 55.3 (5), 43.1 (10), 28.0
(100).
(m), 1158 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=141 (3) [M++1], 125.0
(11), 111.1 (44), 98 (18), 81 (33), 67.9 (57), 43.1 (100), 28.1 (42).
1-(1-Propionylcyclopentyl)propan-1-one (5b): The reaction was carried
out by following the procedure as given for the synthesis of 9. From hep-
tane-3,5-dione
(3.20 g,
25.0 mmol),
1,4-dibromobutane
(5.40 g,
25.0 mmol), and potassium carbonate (7.60 g, 55.0 mmol), 5b was ob-
tained as a colorless oil (3.00 g, 66%). Rf =0.66 (hexane/ethyl acetate
9:1); 1H NMR (300 MHz, CDCl3): d=2.37 (q, 4H, J=7.2 Hz; CH2),
2.12–2.18 (m, 4H; CH2), 1.60–1.56 (m, 4H; CH2), 1.04 ppm (t, 6H, J=
7.2 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=208.26 (2C), 74.52 (C),
32.00 (2C), 31.26 (2C), 25.29 (2C, CH2), 8.11 ppm (2C, CH3); IR (neat):
n˜ =2973 (s), 1697 (s), 1456 (m), 1346 (m), 1139 (m), 1024 cmꢀ1 (w).
Synthesis of 10: 4-Methyl benzenesulfonic acid (PTSA; 0.028 g,
0.16 mmol) was added to a stirred benzene solution (200 mL) of 9
(30.4 g, 165.3 mmol) and ethane-1,2-diol (110.6 mL, 198.4 mmol) at 208C.
The reaction mixture was heated to reflux by using a Dean–Stark appara-
tus until water was completely removed from the reaction mixture (8 h).
The benzene was distilled off and the product was collected by fractional
distillation to give 10 as
a
colorless oil (32.0 g, 85%). 1H NMR
1-(2-Benzoylcyclopentyl)ethanone (5c): The reaction was carried out by
following the procedure as given for the synthesis of 9. From benzoylace-
tone (4.05 g, 25.0 mmol), 1,4-dibromobutane (5.40 g, 25.0 mmol), and po-
tassium carbonate (7.60 g, 55.0 mmol), 5c was obtained as a colorless oil
(3.95 g, 75%). Rf =0.68 (hexane/ethyl acetate 9:1); 1H NMR (300 MHz,
CDCl3): d=7.86–7.82 (m, 2H; ArH), 7.53–7.50 (m, 1H; ArH), 7.44–7.38
(m, 2H; ArH), 3.43 (m, 1H; CH2), 2.32–2.20 (m, 4H; CH2), 2.01 (s, 3H;
CH3), 1.66–1.61 ppm (m, 3H; CH2); 13C NMR (75 MHz, CDCl3): d=
205.75, 197.41, 135.21 (C), 132.95, 129.02 (2C), 128.50 (2C, CH), 72.32
(C), 33.09 (2C, CH2), 27.05 (CH3), 26.07 ppm (2C, CH2); IR (neat): n˜ =
2957 (m), 1713 (m), 1674 (s), 1598 (w), 1447 (m), 1243 (s), 710 cmꢀ1 (m);
MS (EI, 70 eV): m/z (%): 215.8 (1) [M+], 173.9 (5), 144.6 (2), 104.5
(100), 77.3 (36), 43.0 (7).
(300 MHz, CDCl3): d=4.15 (q, 2H, J=7.2 Hz; OCH2), 3.96 (s, 4H;
COCH2), 2.20–2.07 (m, 2H; CH2), 1.83–1.62 (m, 6H; CH2), 1.33 (s, 3H;
CH3), 1.26 ppm (t, 3H, J=6.9 Hz; CH3); 13C NMR (75 MHz, CDCl3): d=
174.26, 110.44 (C), 64.41 (2C, CH2), 62.91 (C), 59.91, 31.25 (2C), 24.48
(2C, CH2), 21.24, 13.44 ppm (CH3); IR (neat): n˜ =2982 (m), 2877 (m),
1719 (s), 1248 (s), 1043 (s), 890 cmꢀ1 (m); MS (EI, 70 eV): m/z (%): 229.0
(5) [M++1], 213.0 (46), 142.0 (24), 88.0 (22), 87.2 (100); elemental analy-
sis calcd (%) for C12H20O4: C 63.15, H 8.71; found: C 62.86, H 8.41.
Synthesis of 11: Lithium aluminium hydride (2.0 g, 52.6 mmol) was added
to a three-necked round-bottom flask containing Et2O (200 mL) under
argon at 208C. The suspension was cooled to 08C and an Et2O solution
(100 mL) of 10 (10.0 g, 43.8 mmol) was added dropwise over 0.5 h by
using a dropping funnel. After completion of addition, the reaction was
warmed to 208C and was stirred for additional 3 h. The reaction was
quenched by the slow addition of water (1.5 mL), followed by addition of
an aqueous solution of NaOH (4.0 mL, 1.0m) and water (4.0 mL). The re-
action mixture was filtered and the residue was washed with Et2O (2”
50 mL). The combined organic filtrates were dried over anhydrous
Na2SO4 and concentrated in vacuo to give 11 as a colorless oil (7.35 g,
90%). 1H NMR (300 MHz, CDCl3): d=4.01–3.96 (br, 4H; CH2), 3.49 (d,
2H, J=5.4 Hz; CH2OH), 3.12 (t, 1H, J=5.4 Hz; CH2OH), 1.68–1.52 (m,
6H; CH2), 1.48–1.44 (m, 2H; CH2), 1.36 ppm (s, 3H; CH3); 13C NMR
(75 MHz, CDCl3): d=114.66 (C), 67.31, 64.46 (2C, CH2), 54.29 (C), 30.65
(2C), 25.65 (2C, CH2), 20.03 ppm (CH3); IR (neat): n˜ =3453 (s), 2954 (s),
2873 (s), 1376 (s), 1126 (m), 1038 (s), 881.27 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%): 187.4 (2) [M++1], 171.4 (36), 87.2 (100), 82.2 (54), 68.1 (71),
43.1 (48), 31.1 (39); elemental analysis calcd (%) for C10H18O3: C 64.48,
H 9.74; found: C 63.95, H 9.45.
Preparation of 1-(1-acetylcyclopent-3-enyl)ethanone (5e): Ti(OiPr)4
(0.3 mL, 1.01 mmol) was added to a CH2Cl2 solution (degassed, 70 mL)
of 3,3-diallylpentane-2,4-dione (1.30 g, 7.22 mmol). After stirring for 1 h
at 358C, Grubbs catalyst (0.594 g, 0.7 mmol in 5 mL of CH2Cl2) was
added. The solution was stirred for 48 h at the same temperature. The
solvent was removed in vacuo and the residue was purified by column
chromatography (silica gel, ethyl acetate/hexane 1:9) to give 5e as an oil
(0.626 g, 57%). Rf =0.66 (ethyl acetate/hexane 1:9); 1H NMR (300 MHz,
CDCl3): d=5.59 (s, 2H; =CH), 2.90 (s, 4H; CH2), 2.15 ppm (s, 6H;
CH3); 13C NMR (75 MHz, CDCl3): d=204.99 (2C, C), 127.89 (2C, CH),
73.16 (C), 37.66 (2C, CH2), 26.37 ppm (2C, CH3); IR (neat): n˜ =1700 (s),
1433 (m), 1358 (m), 1216 (m), 1151 (m), 633 cmꢀ1 (m); MS (EI, 70 eV):
m/z (%): 151.3 (1) [M+], 138.1 (2), 124.1 (5), 108.4 (15), 97.0 (5), 81.0
(4), 43.1 (100), 28.0 (7).
1-(2-Acetylindan-2-yl)ethanone (5 f): The reaction was carried out by fol-
lowing the procedure as given for the synthesis of 9. From acetylacetone
(2.10 g, 25.0 mmol), 1,2-bis(bromomethyl)benzene (6.60 g, 25.0 mmol),
and potassium carbonate (7.60 g, 55.0 mmol), 5 f was obtained as a color-
less oil (4.10 g, 81%). Rf =0.66 (hexane/ethyl acetate 9:1); 1H NMR
(300 MHz, CDCl3): d=7.17–7.11 (m, 4H; ArH), 3.47 (s, 4H; CH2),
2.14 ppm (s, 6H; CH3); 13C NMR (75 MHz, CDCl3): d=214.56 (2C),
139.53 (2C, C), 126.84 (2C), 124.22 (2C, CH), 74.39 (C), 37.38 (2C,
CH2), 26.29 ppm (2C, CH3); IR (neat): n˜ =1695 (s), 1585 (s), 1430 (s),
1357 (s), 1032 (m), 771 cmꢀ1 (m); MS (EI, 70 eV): m/z (%): 201.9 (1)
[M+], 186.8 (1), 158.8 (80), 144.6 (6), 114.3 (21), 88.9 (4), 43.0 (100), 28.0
(16).
Synthesis of 12: An acetone solution (50 mL) of 11 (4.67 g, 25.10 mmol)
and PTSA (2.15 g, 12.55 mmol) was stirred for 24 h at 208C. The acetone
was removed in vacuo and the reaction mixture was extracted with Et2O
(50 mL). The organic layer was washed with water (50 mL), dried over
anhydrous Na2SO4, filtered, and and concentrated in vacuo to give 12 as
a colorless oil (3.09 g, 87%). 1H NMR (300 MHz, CDCl3): d=3.57 (s,
2H; CH2), 2.45 (s, 1H; OH), 2.18 (s, 3H; CH3), 1.91–1.62 ppm (m, 8H;
CH2); 13C NMR (75 MHz, CDCl3): d=214.14 (C), 66.92 (CH2), 60.89 (C),
32.08 (2C), 25.28 (2C, CH2), 20.40 ppm (CH3); IR (neat): n˜ =3431 (br),
2953 (s), 1700 (s), 1357 (m), 1041 cmꢀ1 (m); MS (EI, 70 eV): m/z (%)=
143.0 (12) [M++1], 125.0 (17), 108.4 (88), 81.1 (39), 68.0 (68), 43.1 (100),
28.1 (40).
1-(2-Propionylindan-2-yl)propan-1-one (5g): The reaction was carried
out by following the procedure as given for the synthesis of 9. From hep-
tane-3,5-dione (3.20 g, 25.0 mmol), 1,2-bis(bromomethyl)benzene (6.60 g,
25.0 mmol), and potassium carbonate (7.60 g, 55.0 mmol), 5g was ob-
tained as a colorless oil (3.91 g, 68%). 1H NMR (300 MHz, CDCl3): d=
7.20–7.13 (m, 4H; ArH), 3.51 (s, 4H; CH2), 2.44 (q, 4H, J=7.2 Hz;
CH2), 1.04 ppm (t, 6H, J=7.2 Hz; CH3); IR (neat): n˜ =2980 (m), 1697
(s), 1456 (m), 1348 (m), 1163 (m), 995 (w), 745 cmꢀ1 (m).
Synthesis of 5d:
A CH2Cl2 solution (2 mL) of dimethyl sulfoxide
(1.00 mL, 14.1 mmol) was added dropwise to a stirred CH2Cl2 solution
(7 mL) of oxalyl chloride (0.88 mL, 7.04 mmol) at ꢀ788C under an argon
atmosphere. After stirring for 10 min, a CH2Cl2 solution (3 mL) of 12
(1.00 g, 7.04 mmol) was added dropwise and the solution was stirred for
15 min. Triethylamine (3.9 mL, 28.2 mmol) was added slowly and the
temperature of the mixture was allowed to rise to 208C over 30 min.
Water (40 mL) was added to the reaction mixture and the latter was stir-
red for 10 min. The organic layer was separated and the aqueous layer
was washed with CH2Cl2 (2”25 mL). The combined organic layers were
washed with an aqueous solution of Na2CO3 (30 mL, 10%) and water
(30 mL), dried over anhydrous Na2SO4, filtered and concentrated in
vacuo to give 5d as a yellow oil (0.858 mg, 87%). 1H NMR (300 MHz,
CDCl3): d=9.57 (s, 1H; CHO), 2.20 (s, 3H; CH3), 2.15–2.06 (m, 4H;
CH2), 1.71–1.61 ppm (m, 4H; CH2); 13C NMR (75 MHz, CDCl3): d=
205.36 (C), 199.28 (CH), 72.23 (C), 30.05 (2C, CH2), 27.10 (CH3),
25.51 ppm (2C, CH2); IR (neat): n˜ =2952 (s), 2870 (m), 1702 (s), 1357
1-(2-Benzoylindan-2-yl)ethanone (5h): The reaction was carried out by
following the procedure as given for the synthesis of 9. From benzoylace-
tone (4.05 g, 25.0 mmol), 1,2-bis(bromomethyl)benzene (6.60 g,
25.0 mmol), and potassium carbonate (7.60 g, 55 mmol), 1 was obtained
as a colorless oil (4.50 g, 68%). Rf =0.59 (hexane/ethyl acetate 9:1);
1H NMR (300 MHz, CDCl3): d=7.89–7.84 (m, 2H; ArH), 7.56–7.51 (m,
1H; ArH), 7.45–7.39 (m, 2H; ArH), 7.18–7.11 (m, 4H; ArH), 3.78 (d,
2H, J=16.5 Hz; CH2), 3.68 (d, 2H, J=16.5 Hz; CH2), 2.11 ppm (s, 3H;
CH3); 13C NMR (75 MHz, CDCl3): d=204.51, 196.41, 139.43 (2C), 134.86
(C), 133.29, 129.14 (2C), 128.72 (2C), 126.84 (2C), 124.18 (2C, CH),
72.02 (C), 39.05 (2C, CH2), 26.75 ppm (CH3); IR (neat): n˜ =2944 (m),
Chem. Eur. J. 2004, 10, 6015 – 6028
www.chemeurj.org
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6027

P. Langer et al.
FULL PAPER
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Acknowledgement
We thank Sunanda Lahiri for an experimental contribution. This work
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Received: July 12, 2004
Published online: October 22, 2004
6028
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www.chemeurj.org
Chem. Eur. J. 2004, 10, 6015 – 6028