A new access to multifunctional linear triquinanes and their homologues via α,β-unsaturated fischer carbene complexes

Article abstract of DOI:10.1002/ejoc.200400858

Twelve differently substituted tricyclic hydroxy ketones 7, 8 with [5-5-x] (x = 5, 6, 7) combinations of ring sizes were prepared in a single step in 43-91% yields (10 examples with 74-91%) from the corresponding protected (2′-oxocycloalkyl)methyl-substituted cyclopentadienes 6, which were obtained by cocydization of the alkynes 5 with the β-dimethylamino-substituted α,β-unsaturated Fischer carbene complexes 4 in 38-81% yield (6 examples with 66-81%). In most cases, the cis,anti,cis-isomers anti-7 were the major products. While the twofold cis-fusion is favored by minimal ring strain, hydrogen bonding between the hydroxy and the carbonyl group probably favors the anti-configuration of the tricyclic skeletons. Acid-catalyzed dehydration of the hydroxy ketones anti-7aa, anti-7ba, anti-7ca afforded the corresponding tricyclic dienes 15aa/16aa, 15ba, and 15ca/16ca, respectively. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400858

FULL PAPER
A New Access to Multifunctional Linear Triquinanes and Their Homologues
via α,β-Unsaturated Fischer Carbene Complexes
Yao-Ting Wu,[a] Denis Vidovic,[a][‡] Jörg Magull,[a] and Armin de Meijere*[a]
Keywords: Template synthesis / Fused-ring systems / Ketones / Cycloaddition / Cyclization / Aldol reactions
Twelve differently substituted tricyclic hydroxy ketones 7, 8
with [5-5-x] (x = 5, 6, 7) combinations of ring sizes were pre-
pared in a single step in 43–91% yields (10 examples with
While the twofold cis-fusion is favored by minimal ring
strain, hydrogen bonding between the hydroxy and the car-
bonyl group probably favors the anti-configuration of the tri-
74–91%) from the corresponding protected (2Ј-oxocycloal- cyclic skeletons. Acid-catalyzed dehydration of the hydroxy
kyl)methyl-substituted cyclopentadienes 6, which were ob-
tained by cocyclization of the alkynes 5 with the β-dimeth-
ylamino-substituted α,β-unsaturated Fischer carbene com-
plexes 4 in 38–81% yield (6 examples with 66–81%). In most
cases, the cis,anti,cis-isomers anti-7 were the major products.
ketones anti-7aa, anti-7ba, anti-7ca afforded the correspond-
ing tricyclic dienes 15aa/16aa, 15ba, and 15ca/16ca, respec-
tively.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
(Scheme 1). According to the previously published one-pot
procedure,[2,3] the terminal acetylenes 3a–c were trans-
formed to the β-dimethylamino-substituted α,β-unsaturated
Fischer carbene complexes 4a–c containing acetal-protected
(2Ј-oxocycloalkyl)methyl substituents.
Introduction
Our recently published [3+2] cocyclization of β-dial-
kylamino-substituted α,β-unsaturated Fischer carbene
chromium complexes and alkynes to yield 5-dialkylamino-
3-ethoxycyclopentadienes, which essentially are protected
cyclopentenones,[1,2] also provided facile access to highly
substituted bicyclo[3.3.0]oct-2-en-4-ones (diquinanes) via
such cyclopentadienes with a carbonyl-protected oxoalkyl
side-chain, subsequent acid-catalyzed deprotection of both
carbonyl groups and intramolecular aldol reaction.[3] This
overall transformation can essentially be carried out in a
one-pot operation. As an extrapolation of this methodol-
ogy, linear triquinanes,[4] i.e. skeletons consisting of linearly
annelated five-membered carbocycles, should be accessible
from protected (2Ј-oxocycloalkyl)methyl-substituted Fi-
scher carbene complexes and alkynes. Therefore, we em-
barked on a study of the chemo- and stereoselectivities in
the formation of such tricycles as well as their homologues
by this approach.
Results and Discussion
Scheme 1. Synthesis of β-dimethylamino-substituted α,β-unsatu-
rated Fischer carbene complexes 4.
Adopting a published procedure,[5,6] 2-(trimethylsilylpro-
pargyl)cycloalkanones 2a–c were prepared from cycloalk-
anone N-cyclohexylimides 1a–c, and converted in two steps
into the 2-propargylcycloalkanone ethylene acetals 3a–c
Upon heating the complexes of type 4a–c with various
alkynes 5 in pyridine at 80 °C for 3 d, cyclopentadienes 6
were formed in 38–81% yields (Scheme 2). Alkynes with
bulky substituents like trimethylsilylethyne (5b) and 3,3-di-
methylbut-1-yne (5f), gave low yields (45 and 38%, respec-
tively). The cocyclizations occurred without any significant
diastereoselectivity. Upon treatment of these ethoxycyclop-
entadienes 6 with concd. hydrochloric acid in dioxane at
ambient temperature, cleavage of the enol ether as well as
[a] Institute für Organische und Biomolekulare as well as für Anor-
ganische Chemie, Georg-August-Universität Göttingen,
Tammannstrasse 2–4, 37077 Göttingen, Germany
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[‡]
Crystal structure analysis.
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
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DOI: 10.1002/ejoc.200400858
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Y.-T. Wu, D. Vidovic, J. Magull, A. de Meijere,
FULL PAPER
the dioxolane moieties and subsequent intramolecular aldol 11bh with a six-membered B-ring (Entry 10 in Table 1). Ob-
reactions occurred to give the tricyclic products anti-7 and viously, the tricycle of type 11 can only be formed, when
syn-7 as well as 8 in good to excellent yields (74–91% for the substituent RL can provide a methylene group towards
1
10 out of 13 examples). From the H, 13C, and even 2D- the ring closure. Thus, control experiments were carried out
NOESY NMR spectra, it was not possible to unambigu- with n-propyl-substituted cyclopentadienes 6ac and 6cc,
ously assign the relative configurations of the tricyclic mole- and indeed, cyclization products of type 11 were observed
cules 7 and 8 with their four stereogenic centers. Slow dif- besides 7/8 and the elimination products 10. Two dia-
fusion crystallization of syn-7aa and anti-7ba from benzene/ stereomers of the tricyclic molecules 11 with four ste-
dichloromethane afforded good quality single crystals for reogenic centers were isolated, but their relative configura-
X-ray structure analysis (Figure 1),[7] and their structures tions could not easily be assigned. The formation of the
were rigorously established as cis,syn,cis (syn-7aa), and cis,- elimination products 10 appeared to be enhanced upon use
anti,cis (anti-7ba). Thus, the third stereoisomer was as- of larger amounts of concd. hydrochloric acid.
signed as cis,anti,trans (8). Generally, the cis,anti,cis-stereo-
isomers (anti-7) were formed as the major products.
While the tricycles 7/8 are formed by intramolecular al-
dol reactions from the diketones 12 via the protonated keto
enols 13, the ring-enlarged tricycles 11 must arise by cycliza-
tion of the protonated isomeric keto enols 14 (Scheme 3).
This type of participation of an alkyl group attached at the
Scheme 2. Synthesis of triquinanes and homologous linearly annel-
ated tricyclic skeletons. For details see Table 1.
β-position of a cyclopentenone has previously been ob-
served.[3] Although such a participation would also be pos-
The starting materials 6 with a five-membered ring C sible with a methyl substituent in the β-position, it was only
gave only cis,anti,cis- (anti-7) and cis,syn,cis-isomer (syn-7), observed for the n-propyl-substituted cases. Such methyl-
but with a lower predominance of the anti-isomer than in substituted precursors 6 also reacted more slowly than
the case of the analogues with a six-membered ring C. As others and gave products anti- and syn-7 with lower diaster-
the size of the ring C increases, the amounts of the third eoselectivity.
isomers cis,anti,trans 8 also increase, and the anti/syn selec-
According to molecular-mechanics calculations, the cis,-
tivity decreases. This is an expression of the fact that trans- anti,cis-tricyclo[6.3.0.02,6]undecane is only slightly more
fusion of a five-membered to a larger ring does not cause a stable than the cis,syn,cis-isomer, but much more stable
severe increase in ring strain. The tricycles 7bb/8bb have than the third isomer with cis,anti,trans-configuration.[8] On
been prepared in a one-pot operation directly from the the other hand, Humbel et al. reported that the intramol-
complex 4b and the alkyne 5b. The derivative 6bh with the ecular aldol reaction of octane-2,7-dione under acidic con-
diethyl malonate moiety in the side chain gave, besides the ditions yielded predominantly cis-1-(2-hydroxy-2-methylcy-
tricyclic molecules 7bh/8bh, the elimination product 10bh in clopentynyl)ethanone due to a favorable hydrogen bonding
8% yield along with a trace of the new tricyclic structure in the transition structure leading to this stereoisomer in
Figure 1. The molecular structures of syn-7aa (left) and anti-7ba (right) in the crystals. syn-7aa: Monoclinic crystals of space group P21/
n, the distance between the hydroxy hydrogen and the carbonyl oxygen is 3.45 Å. anti-7ba: Monoclinic crystals of space group P21/c; the
distance between the hydroxy hydrogen and the carbonyl oxygen is 1.98 Å.[7]
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Triquinanes and Homologues via α,β-Unsaturated Fischer Carbene Complexes
FULL PAPER
Table 1. Cocyclizations of dioxolane-protected [1-ethoxy-3-dimethylamino-3-(oxocycloalkylmethyl)propenylidene]pentacarbonylchro-
mium complexes 4 with alkynes 5 and subsequent transformations of the resulting 3-ethoxycyclopentadienes 6 to tricyclic compounds 7/
8.
[a] All reactions were carried out at 80 °C for 4 d. The diastereomeric ratios are based on 1H NMR spectra. [b] A trace of the regioisomeric
cyclopentadiene 9ab was also detected. [c] Instead, 9% of the elimination product 10ac and 66% (59 + 7%) of the isomer 11ac were
isolated. [d] Traces of other stereoisomers were observed. [e] E = CO2Et. [f] In addition, 8% of the elimination product 10bh and 1% of
the isomer 11bh were isolated. [g] One-pot operation from complex 4b and trimethylsilylethyne (5b). [h] In addition, 22% of the elimination
product 10cc and 20% (17 + 3%) of the two diastereomers of 11cc were isolated.
Scheme 3. Mechanistic rationalization of the formation of tricycles 7/8 and 11.
which the hydroxy and the keto carbonyl group end up on veloping hydroxy and the remaining keto group in the tran-
the same side of the ring.[9] The stereochemical outcome of sition structure apparently favors the formation of the anti-
the intramolecular aldol reactions reported here is in agree- configured bicyclo[7.3.0.03,7]dodecanes.[10] The X-ray struc-
ment with the calculated relative stabilities of the stereoiso- ture of anti-7ba does indeed show a hydrogen bond between
meric triquinanes. Hydrogen bonding between the de- the keto carbonyl and hydroxy groups with a distance of
Eur. J. Org. Chem. 2005, 1625–1636
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Y.-T. Wu, D. Vidovic, J. Magull, A. de Meijere,
FULL PAPER
Scheme 4. Dehydration of tricyclic hydroxy ketones anti-7.
1.98 Å between them,[11] whereas the X-ray structure of syn-
7aa displays a distance of 3.45 Å between the hydroxy hy-
drogen and the carbonyl oxygen.
Upon heating the cyclization products anti-7 in the pres-
ence of a catalytic amount of p-toluenesulfonic acid in ben-
zene using a Dean–Stark apparatus, the dehydration prod-
ucts 15 and 16 were formed in excellent yields (Scheme 4).
The regioisomeric triquinadiene derivatives 15aa and 16aa
were obtained as an inseparable 1:1 mixture after 17 h,
reaction quenched with 250 mL of ice water, and the aqueous phase
is extracted with Et2O (3×200 mL). The solvents of the combined
organic phases are removed under reduced pressure. To the residue
is added at 0 °C a cold solution of 1 n hydrochloric acid (350 mL)
over a period of 10 min. The mixture is washed with pentane
(3×50 mL) in order to recover the propargyl bromide. The pH
value of the aqueous phase is adjusted to 5.5 to 6.0 by addition at
0 °C of a satd. aqueous solution of potassium carbonate, and the
mixture is heated under reflux at 70 °C for 1 h. The solution is
extracted with Et2O (3×200 mL), and the combined organic phases
while the homologous tricyclic diene with a fused six-mem- are dried with MgSO4. After evaporation of the solvent, the re-
maining liquid is distilled under reduced pressure to afford 2 as a
colorless oil.
bered C-ring, 15ba, was formed much more rapidly (within
2 h) and as a single isomer. Further heating for an ad-
ditional 36 h of the mixture of 15aa and 16aa in the pres-
ence of p-toluenesulfonic acid changed the ratio between
the two isomers from 1:1 to 2.1:1.
The tricyclic dienes 15ca and 16ca with a fused seven-
membered ring were formed in a ratio of 1.3:1, but could
be separated by column chromatography.
General Procedure for the Synthesis of Alkynyl-Substituted Acetals 3
(GP2): A mixture of 150 mmol of the respective alkynyl-substituted
cycloalkanone 2, ethylene glycol (10.0 mL, 179 mmol), a catalytic
amount of pTsOH (1.00 g) and benzene (250 mL) is heated under
reflux for 4–12 h using a Dean–Stark apparatus. After cooling to
ambient temperature, 100 mL of water is added to the mixture,
and the aqueous phase is extracted with Et2O (3×100 mL). The
combined organic extracts are dried with MgSO4, the solvent is
removed under reduced pressure, and the residue dissolved in
MeOH (300 mL). To this solution is added 20.0 g of potassium
carbonate, and the mixture stirred at ambient temperature for 12 h.
After filtration through Celite, washing with Et2O (3×50 mL) and
evaporation of the solvents, the residue is distilled under reduced
pressure to afford 3 as a colorless oil.
Experimental Section
1
General: H and 13C NMR: Bruker AM 250 (250 and 62.9 MHz)
and Bruker AMX 300 (300 and 75.5 MHz). IR: Bruker IFS 66
(FT-IR). EI-MS: Finnigan MAT 95 spectrometer (70 eV). High-
resolution mass data (HRMS) were obtained by preselected-ion
peak matching at R Ϸ 10000 to be within 2 ppm of the exact
mass. X-ray crystal structure determination: The data were col-
lected with a Stoe–Siemens-AED diffractometer. Melting points
were determined with a Büchi 510 capillary melting point appara-
tus and are uncorrected. Elemental analyses: Mikroanalytisches
Laboratorium des Instituts für Organische und Biomolekulare
Chemie der Georg-August-Universität Göttingen. Chromatog-
raphy: Merck silica gel 60 (230–400 mesh) or ICN neutral alumina
(Super I, Activity II). Solvents for chromatography were technical
grade and freshly distilled before use. Tetrahydrofuran was distilled
from sodium benzophenone ketyl and pyridine was distilled from
calcium hydride. p-Toluenesulfonic acid monohydrate is abbrevi-
ated as pTsOH.
2-(3Ј-Trimethylsilylprop-2Ј-ynyl)cyclopentanone (2a) and cis-/trans-
2,5-Bis(3Ј-trimethylsilylprop-2Ј-ynyl)cyclopentanone: According to
GP1, a solution of LDA (250 mmol) in 200 mL of THF was treated
with 49.5 g (299 mmol) of N-cyclohexylcyclopentylideneamine
(1a)[13] and then 60.0 g (314 mmol) of 1-bromo-3-trimethylsilyl-2-
propyne.[12] After hydrolysis and evaporation of the solvent, the
residue was distilled under reduced pressure to afford 26.8 g (55%)
of 2a as a colorless oil, b.p. 76 °C (0.5 Torr). The residue was sub-
jected to chromatography on silica gel (100 g). Elution with pen-
tane/Et2O (5:1) afforded a pale-yellow oil (Rf — 0.80), which was
distilled in a kugelrohr (0.5 Torr, 130 °C) to give 9.13 g (19%) of
cis-/trans-2,5-di(3Ј-trimethylsilylprop-2Ј-ynyl)cyclopentanone as a
colorless oil.
General Procedure for the Preparation of Alkynyl-Substituted Cyclo-
alkanones 2 (GP1):[5] To a solution of lithium diisopropylamide
2a: IR (film): ν = 2962 cm–1 (C–H), 2176 (CϵC), 1746 (C=O),
˜
(LDA) [250 mmol; from diisopropylamine (36.0 mL, 257 mmol) 1249, 1155, 839, 760. 1H NMR (250 MHz, CDCl3): δ = 0.08 [s,
and n-butyllithium (106 mL, 2.36 m in n-hexane, 250 mmol)] in
200 mL of THF at –78 °C is added dropwise 300 mmol of the
respective imine 1 within 15 min. The mixture is warmed to ambi-
ent temperature and stirred for an additional 1 h. 3-Trimethylsi-
lylpropargyl bromide[12] (300 mmol) is added to this solution at
–78 °C over a period of 10 min, and the mixture stirred at this tem-
perature for 30 min, at ambient temperature for 12 h and finally at
40 °C for 30 min. The mixture is cooled to room temperature, the
9 H, Si(CH3)3], 1.70–1.86 (m, 2 H) and 1.95–2.39 (m, 6 H) (total
8 H, 3,4,5,1Ј-H), 2.49–2.57 (m, 1 H, 2-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = –0.1 [+, Si(CH3)3], 19.9, 20.4,
28.6, 38.0 (–, C-3,4,5,1Ј), 47.6 (+, C-2), 85.7, 104.2 (Cquat, C-2Ј,3Ј),
218.7 (Cquat, C-1) ppm. MS (70 eV): m/z (%) = 194 (2) [M+], 179
(52), 149 (13), 97 (12), 83 (10), 75 (100), 73 (22) [Si(CH3)3+], 59
(10), 43 (13). C11H18OSi (194.4): calcd. C 67.98, H 9.34; found
C 67.68, H 9.09.
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Triquinanes and Homologues via α,β-Unsaturated Fischer Carbene Complexes
FULL PAPER
cis- and trans-2,5-Bis(3Ј-trimethylsilylprop-2Ј-ynyl)cyclopentanone: 2-(3Ј-Trimethylsilylprop-2Ј-ynyl)cycloheptanone (2c): According to
IR (film): ν = 2970 cm–1 (C–H), 2175 (CϵC), 1743 (C=O), 1246, GP1, to a solution of LDA (250 mmol) in THF (200 mL) was
˜
835, 759, 638. 1H NMR (250 MHz, CDCl3): δ = 0.12, 0.13 [s, 18 H,
Si(CH3)3, ratio = 2.2:1], 1.61–1.77 (m, 1 H) and 1.97–2.65 (m, 9 H)
(total 10 H, 2,3,4,5,1Ј-H). Major isomer: 13C NMR (62.9 MHz,
added 58.0 g (300 mmol) of cycloheptylidenecyclohexylamine
(2c),[13] and then 54.0 g (283 mmol) of 1-bromo-3-trimethylsilyl-2-
propyne. After aqueous work-up and hydrolysis, the residue was
CDCl3, plus DEPT): δ = 0.0 [+, Si(CH3)3], 20.1, 26.3 (–, C-3,4,1Ј), distilled under reduced pressure to afford 42.1 g (67%) 2c as a col-
48.1 (+, C-2,5), 86.1, 104.0 (Cquat, C-2Ј,3Ј), 217.3 (Cquat, C-1) ppm. orless oil, b.p. 105 °C (0.5 Torr). IR (KBr): ν = 2910 cm–1 (C–H),
˜
Minor isomer: 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 0.0
[+, Si(CH3)3], 20.1, 25.8 (–, C-3,4,1Ј), 46.7 (+, C-2,5), 85.7, 104.4
2853, 2177 (CϵC), 1700 (C=O), 1457, 1248, 837. 1H NMR
(250 MHz, CDCl3): δ = 0.02 [s, 9 H, Si(CH3)3], 1.19–1.93 (m, total
(Cquat, C-2Ј,3Ј), 217.8 (Cquat, C-1) ppm. MS (70 eV): m/z (%) = 304 8 H, 3,4,5,6-H), 2.11–2.19 (1 H), 2.21–2.47 (3 H), and 2.53–2.64
(11) [M+], 289 (20) [M+ – CH3], 192 (24), 177 (52), 147 (16), 83 (1 H) [m, 5 H, 2,7,1Ј-H] ppm. 13C NMR (62.9 MHz, CDCl3, plus
(12), 75 (26), 73 (100) [Si(CH3)3+], 59 (10). C17H28OSi2 (304.6):
calcd. C 67.04, H 9.27; found C 66.84, H 9.48.
DEPT): δ = –0.1 [+, Si(CH3)3], 22.0, 23.8, 28.6, 29.3, 30.0, 43.1
(–, C-3,4,5,6,7,1Ј), 50.7 (+, C-2), 85.5, 105.1 (Cquat, C-2Ј,3Ј), 213.7
(Cquat, C-1) ppm. MS (70 eV): m/z (%) = 222 (7) [M+], 207 (85),
189 (20), 179 (18), 170 (28), 149 (13), 131 (11), 83 (11), 75 (100),
73 (32) [Si(CH3)3+], 59 (10), 43 (12). C13H22OSi (222.4): calcd. C
70.21, H 9.97; found C 70.02, H 10.11.
6-(2Ј-Propynyl)-1,4-dioxaspiro[4.4]nonane (3a) and 6-[(2Ј-Methyl-
1Ј,3Ј-dioxolan-2Ј-yl)methyl]-1,4-dioxaspiro[4.4]nonane: According
to GP2, a mixture of 2a (25.0 g, 129 mmol), ethylene glycol (10 mL,
179 mmol), pTsOH (2.00 g) and benzene (250 mL) was heated un-
der reflux for 16 h. After aqueous work-up and evaporation of the
solvent, the residue was dissolved in 300 mL of MeOH. The solu-
tion was treated with K2CO3 (20.0 g) and stirred at ambient tem-
perature overnight (ca. 12 h). The organic extract was dried with
MgSO4, concentrated, and the product distilled under reduced
pressure to afford 10.3 g (48%) of 3a as a colorless oil, b.p. 57 °C
(0.5 Torr). The dark residue was distilled again in a kugelrohr appa-
ratus (0.5 Torr, oven temperature 110 °C) to give 6-[(2Ј-methyl-
6-(2Ј-Propynyl)-1,4-dioxaspiro[4.6]undecane (3c): According to
GP2, 40.7 g (183 mmol) of 2-(3Ј-trimethylsilyl-2Ј-propynyl)cyclo-
heptanone (2c) in benzene (250 mL) was heated under reflux with
ethylene glycol (15 mL, 269 mmol) and a catalytic amount of
pTsOH (2.0 g) for 8 h. After aqueous work-up and evaporation of
the solvent, the residue was dissolved in 300 mL of MeOH. The
solution was treated with K2CO3 (20.0 g) and stirred at ambient
temperature overnight (ca. 12 h). The organic extract was dried
with MgSO4 and distilled under reduced pressure to afford 29.2 g
1Ј,3Ј-dioxolan-2Ј-yl)methyl]-1,4-dioxaspiro[4.4]nonane
[8.76 g
(43%)] as a colorless oil.
(82%) of 3c as a colorless oil, b.p. 87 °C (0.5 Torr). IR (film): ν =
˜
3308 cm–1 (CϵC–H), 2929 (C–H), 2855, 2116 (CϵC), 1459, 1155,
1107. 1H NMR (250 MHz, CDCl3): δ = 1.23–2.07 (m, 13 H,
6,7,8,9,10,11,1Ј-H), 2.32 and 2.38 (t, 4J = 2.6 Hz, ratio = 1.5:1,
1 H, 3Ј-H), 3.73–3.96 (m, 4 H, 2,3-H) ppm. 13C NMR (62.9 MHz,
CDCl3, plus DEPT): δ = 19.2, 21.3, 27.0, 27.3, 28.5, 36.7 (–, C-
7,8,9,10,11,1Ј), 47.2 (+, C-6), 63.7, 64.9 (–, C-2,3), 68.1 (+, C-3Ј),
84.3 (Cquat, C-2Ј), 112.9 (Cquat, C-5) ppm. MS (70 eV): m/z (%) =
194 (1) [M+], 155 (20), 137 (70), 113 (18), 99 (100), 86 (11), 55 (17),
41 (18). C12H18O2 (194.3): calcd. C 74.19, H 9.34; found C 73.89,
H 9.12.
3a: IR (film): ν = 3286 cm–1 (CϵC–H), 2961 (C–H), 2875, 2117
˜
(CϵC), 1329, 1199, 1153, 1046, 1024, 649. 1H NMR (250 MHz,
CDCl3): δ = 1.33–1.73 (5 H) and 1.87–2.32 (3 H) [m, total 8 H,
4
7,8,9,1Ј-H], 2.17–2.33 (m, 1 H, 6-H), 1.86 and 1.87 (t, J = 2.5 Hz,
ratio = 2.1:1, 1 H, 3Ј-H), 3.74–3.96 (m, 4 H, 2,3-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = 18.2, 20.3, 29.1, 35.5 (–, C-
7,8,9,1Ј), 45.1 (+, C-6), 64.3, 64.6 (–, C-2,3), 68.0 (+, C-3Ј), 83.7
(Cquat, C-2Ј), 117.1 (Cquat, C-5) ppm.
6-[(2Ј-Methyl-1Ј,3Ј-dioxolan-2Ј-yl)methyl]-1,4-dioxaspiro[4.4]-
nonane: IR (film): ν = 2938 cm–1 (C–H), 1653, 1558, 1520, 1261.
˜
1H NMR (250 MHz, CDCl3): δ = 1.25 (s, 3 H, CH3), 1.31–2.07
(m, 9 H, CHCH2C, 6,7,8,9-H), 3.70–3.90 (m, 8 H, 2,3,4Ј,5Ј-H)
ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 20.4, 30.1,
34.7, 37.3 (–, CHCH2C, C-7,8,9), 24.1 (+, CH3), 41.2 (+, C-6), 64.1,
64.2, 64.4, 64.6 (–, C-2,3,4Ј,5Ј), 110.0, 118.2 (Cquat, C-5,2Ј) ppm.
MS (70 eV): m/z (%) = 213 (8) [M+ – CH3], 183 (12), 141 (16), 99
(52), 87 (100), 55 (10), 43 (26), 41 (11). C12H20O4 (228.3): calcd.
C 63.14, H 8.83; found C 62.94, H 8.60.
General Procedure for the Preparation of β-Amino-substituted α,β-
Unsaturated Fischer-Carbene Complexes 4 (GP3): To a solution of
the respective terminal alkyne 3 (20 mmol) in THF (100 mL) at
–78 °C is added a solution of n-butyllithium (20 mmol). The mixture
is stirred at this temperature for an additional 30 min. After ad-
dition of hexacarbonylchromium (4.40 g, 20.0 mmol), the solution
is warmed up to room temperature, stirred for another 30 min, and
20.5 mmol of triethyloxonium tetrafluoroborate (Et3OBF4) is
added at 0 °C. After an additional 10 min, gaseous dimethylamine
is added to the dark red solution in THF upon which the color
changes to yellow or orange as the reaction goes to completion.
After filtration through Celite and evaporation of the solvent, the
residue is purified by flash column chromatography.
6-(Prop-2Ј-ynyl)-1,4-dioxaspiro[4.5]decane (3b): 20.0 g (147 mmol)
of 2-(2Ј-propynyl)cyclohexanone in benzene (200 mL) was heated
under reflux with ethylene glycol (10 mL, 179 mmol) and pTsOH
(2.00 g) for 4 h. The mixture was cooled to ambient temperature
and washed with 100 mL water. The aqueous phases were extracted
with Et2O (3×50 mL). The combined organic extracts were dried
with MgSO4 and distilled under reduced pressure to afford 23.0 g
Pentacarbonyl[(2E)-4-(1Ј,4Ј-dioxaspiro[4.4]non-6Ј-yl)-3-dimethyl-
amino-1-ethoxy-2-buten-1-ylidene]chromium (4a): According to
GP3, 3.58 g (21.5 mmol) of 6-(2Ј-propynyl)-1,4-dioxaspiro[4.4]-
(87%) of 3b as a colorless oil, b.p. 78 °C (0.5 Torr). IR (film): ν =
˜
3300 cm–1 (CϵC–H), 2940 (C–H), 2854, 2116 (CϵC), 1440, 1336, nonane (3a) in THF (100 mL) was treated with n-butyllithium
1160, 1087, 1017, 952. 1H NMR (250 MHz, CDCl3): δ = 1.18–2.04 (13.5 mL, 1.56 m in n-hexane, 21.1 mmol), hexacarbonylchromium
4
(m, 11 H, 6,7,8,9,10,1Ј-H), 2.43, 2.50 (t, J = 3.2 Hz, ratio = 1.4:1, (4.73 g 21.5 mmol), Et3OBF4 (4.18 g, 22.0 mmol), and then, gas-
1 H, 3Ј-H), 3.84–3.97 (m, 4 H, 2,3-H) ppm. 13C NMR (62.9 MHz,
CDCl3, plus DEPT): δ = 17.9, 23.8, 24.5, 28.9, 34.6 (–, C-
7,8,9,10,1Ј), 44.0 (+, C-6), 64.6, 64.7 (–, C-2,3), 68.4 (+, C-3Ј), 83.9
eous dimethylamine. Flash chromatography on silica gel (120 g)
eluting with pentane/Et2O (from 5:1 to 0:1) gave 8.07 g (83%) of
4a [Rf — 0.63 (Et2O)] as a yellow solid, m.p. 93–94 °C (dec.). IR
(Cquat, C-2Ј), 109.8 (Cquat, C-5) ppm. MS (70 eV): m/z (%) = 180 (KBr): ν = 2960 cm–1 (C–H), 2043 (C=O), 1970 (C=O), 1920
˜
(6) [M+], 165 (12), 152 (33), 137 (70), 126 (16), 99 (100), 86 (19). (C=O), 1886 (C=O), 1538, 1281, 674, 650. 1H NMR (250 MHz,
3
C11H16O2 (180.2): calcd. C 73.30, H 8.95; found C 73.68, H 9.12.
CDCl3): δ = 1.48 (t, J = 7.0 Hz, 3 H, OCH2CH3), 1.41–1.82 (6 H)
Eur. J. Org. Chem. 2005, 1625–1636
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1629

Y.-T. Wu, D. Vidovic, J. Magull, A. de Meijere,
FULL PAPER
and 2.08–2.16 (1 H) [m, total 7 H, 4,7Ј,8Ј,9Ј-H], 2.59 (AB, dd, 2J = H), 7.11–7.35 (m, 8 H, Ph-H), 7.58–7.65 (m, 2 H, Ph-H) ppm. 13C
13.6, 3J = 4.3 Hz, 1 H, 4-H), 2.75–2.87 (m, 1 H, 6Ј-H), 3.16 [s, 6 H, NMR (62.9 MHz, CDCl3, plus DEPT): Major diastereomer: δ =
3
N(CH3)2], 3.85–3.94 (m, 4 H, 2Ј,3Ј-H), 4.72 (q, J = 7.0 Hz, 2 H, 14.1 (+, OCH2CH3), 20.1, 32.6, 34.2, 35.2 (–, CCH2CH, C-
OCH2CH3), 6.35 (s, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3,
plus DEPT): δ = 15.5 (+, OCH2CH3), 20.3, 28.1, 28.9, 35.0 (–, C-
7Ј,8Ј,9Ј), 39.9 [+, N(CH3)2], 41.0 (+, C-6Ј), 64.0, 64.3, 64.4 (–,
OCH2CH3, C-2Ј,3Ј), 75.8 (Cquat, C-5), 98.0 (+, C-4), 118.5 (Cquat
,
4,7Ј,8Ј,9Ј), 40.7, 41.9 [+, br., N(CH3)2], 45.5 (+, C-6Ј), 64.3, 64.6 (–, C-5Ј), 126.3, 126.8, 127.2, 127.7, 129.3, 129.5 (+, Ph-C), 134.2,
C-2Ј,3Ј), 73.8 (–, OCH2CH3), 117.5 (Cquat, C-5Ј), 118.1 (+, C-2), 135.3, 137.6 (Cquat, C-2, Ph-C), 145.7 (Cquat, C-1), 158.4 (Cquat, C-
159.3 (Cquat, C-3), 219.4, 224.5 (Cquat, CO), 285.4 (Cquat, C-1) ppm. 3). Minor diastereomer: δ = 14.2 (+, OCH2CH3), 20.9, 30.3, 34.2,
EI MS (70 eV): m/z (%) = 459 (5) [M+], 431 (21) [M+ – CO], 403
34.8 (–, CCH2CH, C-7Ј,8Ј,9Ј), 39.9 [+, N(CH3)2], 41.4. (+, C-6Ј),
(3) [M+ – 2 CO], 375 (11) [M+ – 3 CO], 347 (16) [M+ – 4 CO], 319 63.8, 64.0, 64.4 (–, OCH2CH3, C-2Ј,3Ј), 75.6 (Cquat, C-5), 97.7 (+,
(100) [M+ – 5 CO], 257 (95), 227 (10), 213 (11), 206 (49), 162 (31),
150 (78), 52 (17) [Cr+]. C20H25CrNO8 (459.4): calcd. C 52.29, H
5.48; found C 52.33, H 5.25.
C-4), 118.4 (Cquat, C-5Ј), 126.3, 126.8, 127.3, 127.6, 129.5, 129.7
(+, Ph-C), 133.8, 135.2, 137.6 (Cquat, C-2, Ph-C), 145.5 (Cquat, C-
1), 158.0 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 445 (18) [M+],
416 (26) [M+ – C2H5], 246 (16), 184 (13), 141 (36), 99 (100), 55
(17), 43 (20). HRMS (EI) calcd. for C29H35NO3: 445.2617 (correct
HRMS).
Pentacarbonyl[(2E)-4-(1Ј,4Ј-dioxaspiro[4.5]dec-6Ј-yl)-3-dimethyl-
amino-1-ethoxy-2-buten-1-ylidene]chromium (4b): According to
GP3, 6.43 g (35.7 mmol) of 6-(2Ј-propynyl)-1,4-dioxaspiro[4.5]dec-
ane (3b) in THF (175 mL) was treated with n-butyllithium
(22.0 mL, 1.56 m in n-hexane, 34.3 mmol), hexacarbonylchromium
(7.98 g, 36.3 mmol), Et3OBF4 (6.91 g, 36.4 mmol) and then gaseous
dimethylamine. Flash chromatography on silica gel (120 g) eluting
with pentane/Et2O (from 5:1 to 1:3) gave 14.1 g (87%) of 4b [Rf =
0.33 (pentane/Et2O, 1:1)] as a yellow solid, m.p. 91–92 °C (dec.).
5-Dimethylamino-5-[(1Ј,4Ј-dioxaspiro[4.4]non-6Ј-yl)methyl]-3-
ethoxy-1-trimethylsilyl-1,3-cyclopentadiene (6ab): According to
GP4, a solution of complex 4a (2.19 g, 4.76 mmol) in pyridine
(100 mL) was treated with 700 mg (7.13 mmol) of trimethylsilyl-
ethyne (5b), and the mixture was stirred at 80 °C for 4 d.
Chromatography on aluminum oxide (80 g) eluting with pentane/
Et2O (+1% NEt3, from 1:0 to 1:1) gave 230 mg of the first dia-
stereomer [Rf = 0.59 (pentane/Et2O, 1:1)] as a colorless oil, 353 mg
of a mixture of the first and the second diastereomer (ratio = 1.4:1)
as a colorless oil, and 201 mg of the second diastereomer [Rf =
0.51 (pentane/Et2O, 1:1)] as a pale yellow oil. The combined yields
were 784 mg (45%) and dr = 1.3:1. Major (first) diastereomer: IR
IR (KBr): ν = 2945 cmϪ1 (C–H), 2932, 2041 (C=O), 1912 (C=O),
˜
1898 (C=O), 1542, 1434, 1281, 1089, 668. 1H NMR (250 MHz,
CDCl3): δ = 1.13–1.86 (m, 10 H, 4,7Ј,8Ј,9Ј,10Ј-H), 1.51 (t, 3J =
7.1 Hz, 3 H, OCH2CH3), 2.75–2.87 (m, 1 H, 6Ј-H), 3.15 [s, 6 H,
3
N(CH3)2], 3.85–3.99 (m, 4 H, 2Ј,3Ј-H), 4.72 (q, J = 7.1 Hz, 1 H,
3
OCH2CH3), 4.73 (q, J = 7.1 Hz, 1 H, OCH2CH3), 6.40 (s, 1 H, 2-
(film): ν = 2952 cm–1 (C–H), 1615 (C=C), 1327, 1246, 1192, 1039,
H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 15.5 (+,
OCH2CH3), 23.7, 25.2, 28.2, 28.7, 34.8 (–, C-4,7Ј,8Ј,9Ј,10Ј), 40.7
[+, br., N(CH3)2], 44.6 (+, C-6Ј), 64.6, 64.7 (–, C-2Ј,3Ј), 73.9 (–,
OCH2CH3), 110.1 (Cquat, C-5Ј), 119.0 (+, C-2), 158.8 (Cquat, C-3),
219.5, 224.6 (Cquat, CO), 286.6 (Cquat, C-1) ppm. EI MS (70 eV):
m/z (%) = 473 (2) [M+], 445 (8) [M+ – CO], 417 (1) [M+ – 2 CO],
389 (13) [M+ – 3 CO], 361 (9) [M+/4 CO], 333 (100) [M+ – 5 CO],
271 (93), 220 (81), 176 (26), 164 (58), 52 (16) [Cr+]. C21H27CrNO8
(473.4): calcd. C 53.28, H 5.75; found C 53.43, H 5.53.
˜
1
838, 756. H NMR (250 MHz, CDCl3): δ = 0.15 [s, 9 H, Si(CH3)3],
1.31 [t, 3J = 7.1 Hz, 3 H, OCH2CH3], 1.00–1.09 (1 H), 1.34–
1.65 (6 H), and 1.80–2.22 (2 H) [m, total 9 H, CCH2CH, 6Ј,7Ј,8Ј,9Ј-
H], 2.16 [s, 6 H, N(CH3)2], 3.70–3.90 (m, 6 H, OCH2CH3, 2Ј,3Ј-
H), 4.96, (s, 1 H, 4-H), 6.25 (s, 1 H, 2-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = –0.4 [+, Si(CH3)3], 14.6 (+,
OCH2CH3), 20.7, 31.9, 34.5, 34.9 (–, CCH2CH, C-7Ј,8Ј,9Ј), 40.7
[+, N(CH3)2], 41.6 (+, C-6Ј), 64.4, 64.6, 64.7 (–, OCH2CH3, C-
2Ј,3Ј), 80.9 (Cquat, C-5), 103.0 (+, C-4), 118.9 (Cquat, C-5Ј), 138.9
(+, C-2), 157.2, 158.4 (Cquat, C-1,3) ppm. MS (70 eV): m/z (%) =
365 (37) [M+], 336 (100) [M+ – C2H5], 238 (34), 73 (12) [Si(CH3)3+].
HRMS (EI) calcd. for C2 0 H3 5 NO3 Si: 365.2386 (correct
General Procedure for Cocyclizations of Complexes 4 with Alkynes
5 (GP4): A thick-walled, screw-cap Pyrex bottle equipped with a
magnetic stirring bar is charged with a 0.05 m solution of the com-
plex 4 in anhydrous pyridine. Dry nitrogen is bubbled through the
solution for 2 min, and two equiv. of the respective alkyne 5 is
immediately added. The sealed bottle is kept in an oil bath at 80 °C
for 4 d. The solvent is removed under reduced pressure, the residue
is diluted with Et2O (100 mL), and the solution exposed to air for
2 h. The suspension is filtered through a 3 cm thick layer of Celite
and the solids rinsed well with Et2O (50 mL). The solvent of the
filtrate is evaporated, and the residue is subjected to chromatog-
raphy on aluminum oxide (activity grade II). Elution with pentane/
Et2O (from 1:0 to 3:1) affords the cocyclization products 6.
HRMS). Minor (second) diastereomer: IR (film): ν = 2952 cm–1
˜
(C–H), 1613 (C=C), 1328, 1247, 1193, 836, 764. 1H NMR
(250 MHz, CDCl3): δ = 0.15 [s, 9 H, Si(CH3)3], 1.30 [t, 3J = 7.1 Hz,
3 H, OCH2CH3], 1.26–1.39 (2 H), 1.42–1.90 (6 H), 2.15–2.30 (1 H),
[m, total 9 H, CCH2CH, 6Ј,7Ј,8Ј,9Ј-H], 2.22 [s, 6 H, N(CH3)2],
4
3.78–3.89 (m, 6 H, OCH2CH3, 2Ј,3Ј-H), 4.99 (d, J = 1.6 Hz, 1 H,
4
4-H), 6.25 (d, J = 1.6 Hz, 1 H, 2-H) ppm. 13C NMR (62.9 MHz,
CDCl3, plus DEPT): δ = 0.3 [+, Si(CH3)3], 14.5 (+, OCH2CH3),
20.1, 31.6, 33.8, 34.6 (–, CCH2CH, C-7Ј,8Ј,9Ј), 40.3 [+, N(CH3)2],
41.5 (+, C-6Ј), 64.3, 64.7, 64.8 (–, OCH2CH3, C-2Ј,3Ј), 81.0 (Cquat
,
C-5), 106.0 (+, C-4), 118.8 (Cquat, C-5Ј), 139.5 (+, C-2), 157.2, 158.0
(Cquat, C-1,3) ppm. MS (70 eV): m/z (%) = 365 (38) [M+], 336 (100)
[M+ – C2H5], 238 (53), 169 (12), 99 (11), 73 (34) [Si(CH3)3+].
HRMS (EI) calcd. for C20H35NO3Si: 365.2386 (correct HRMS).
5-Dimethylamino-5-[(1Ј,4Ј-dioxaspiro[4.4]non-6Ј-yl)methyl]-3-
ethoxy-1,2-diphenyl-1,3-cyclopentadiene (6aa): According to GP4, a
solution of complex 4a (2.30 g, 5.01 mmol) in pyridine (100 mL)
was treated with 1.34 g (7.52 mmol) 1,2-diphenylethyne (5a), and
the mixture was stirred at 80 °C for 4 d. Chromatography on alumi-
num oxide (80 g) eluting with pentane/Et2O (from 20:1 to 1:2) gave
1.11 g (50%) of 6aa [Rf = 0.38 (pentane/Et2O, 1:1); dr = 1.5:1] as
5-Dimethylamino-5-[(1Ј,4Ј-dioxaspiro[4.4]non-6Ј-yl)methyl]-3-
ethoxy-1-propyl-1,3-cyclopentadiene (6ac): According to GP4, a
solution of complex 4a (2.30 g, 5.01 mmol) in pyridine (100 mL)
was treated with 681 mg (10.0 mmol) of 1-pentyne (5c), and the
mixture was stirred at 80 °C for 4 d. Chromatography on aluminum
a pale-yellow oil. IR (film): ν = 2970 cm–1 (C–H), 2874 (C–H),
˜
1710, 1630 (C=C), 1347, 1194, 1031, 764, 700. 1H NMR (250 MHz,
CDCl3): δ = 1.20–2.20 (m, 11 H, OCH2CH3, CCH2CH, 7Ј,8Ј,9Ј- oxide (II, 80 g) eluting with pentane/Et2O (+ 1% NEt3, from 1:0
H), 2.35–2.45 (m, 1 H, 6Ј-H), 2.42 [s, 6 H, N(CH3)2], 3.24–3.70 (m, to 0:1) gave 1.15 g (68%) of 6ac [Rf = 0.48 (Et2O); dr = 1:1] as a
2 H, OCH2CH3), 3.80–4.12 (m, 4 H, 2Ј,3Ј-H), 5.10, 5.11 (s, 1 H, 4- pale-yellow oil. IR (film): ν = 2956 cm–1 (C–H), 1635 (C=C), 1584,
˜
1630
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1625–1636

Triquinanes and Homologues via α,β-Unsaturated Fischer Carbene Complexes
1339, 1196, 1151, 1107, 1040. 1H NMR (250 MHz, CDCl3): δ =
FULL PAPER
5-Dimethylamino-5-[(1ЈЈ,4ЈЈ-dioxaspiro[4.5]dec-6ЈЈ-yl)methyl]-3-
0.83 (t, 3J = 7.0 Hz, 3 H, CH2CH2CH3), 1.04–2.89 (m, 16 H, ethoxy-1-(3Ј-trifluoromethylphenyl)-1,3-cyclopentadiene (6bg): Ac-
CH2CH2CH3, CCH2C, OCH2CH3, 6Ј,7Ј,8Ј,9Ј-H), 2.02, 2.03 [s, cording to GP3, a solution of complex 4b (2.37 g, 5.01 mmol) in
6 H, N(CH3)3], 3.60–3.85 (m, 6 H, OCH2CH3, 2Ј,3Ј-H), 4.53, 4.55 pyridine (100 mL) was treated with 1.70 g (10.0 mmol) of 3Ј-(tri-
(s, 1 H, 4-H), 5.52, 5.57 (s, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, fluoromethyl)phenylethyne (5g),[14] and the mixture was stirred at
CDCl3, plus DEPT): δ = 13.96, 13.99, 14.2, 14.3 (+, CH2CH2CH3,
OCH2CH3), 19.27, 19.33, 19.9, 20.4, 28.2, 29.4, 30.4, 31.8, 32.8,
80 °C for 4 d. Chromatography on aluminum oxide (II, 80 g) elut-
ing with pentane/Et2O (from 20:1 to 1:1) gave 893 mg (40%) of 6bg
33.8, 34.1, 34.5 (–, CCH2CH, CH2CH2CH3, C-7Ј,8Ј,9Ј), 39.6, 39.7 [Rf = 0.56 (pentane/Et2O, 3:1); dr = 2:1] as a colorless oil. IR (film):
[+, N(CH2)2], 40.7, 40.9 (+, C-6Ј), 64.0, 64.10, 64.12, 64.17, 64.48, ν = 2938 cm–1 (C–H), 1699, 1624 (C=C), 1333, 1278, 924, 803, 701.
˜
64.51 (–, OCH2CH3, C-2Ј,3Ј), 75.7, 75.8 (Cquat, C-5), 94.5, 95.3 (+,
C-4), 118.4, 118.5 (Cquat, C-5Ј), 122.0, 122.3 (+, C-2), 155.7, 156.6,
1H NMR (250 MHz, CDCl3): δ = 0.76–1.87 (m, 10 H, CCH2CH,
7ЈЈ,8ЈЈ,9ЈЈ,10ЈЈ-H), 1.38 (t, 3J = 7.0 Hz, 3 H, OCH2CH3), 2.22 [s,
158.3, 158.4 (Cquat, C-1,3) ppm. MS (70 eV): m/z (%) = 335 (24) 6 H, N(CH3)2], 2.30–2.36 (m, 1 H, 6ЈЈ-H), 3.45–3.58 (m, 1 H,
[M+], 306 (100) [M+ – C2H5], 194 (14), 178 (15), 99 (14). HRMS
(EI) calcd. for C20H33NO3: 335.2460 (correct HRMS).
OCH2CH3), 3.85–3.99 (m, 5 H, OCH2CH3, 2ЈЈ,3ЈЈ-H), 5.04, 5.08
(d, 4J = 1.8 Hz, 1 H, 4-H), 6.55, 6.56 (d, 4J = 1.8 Hz, 1 H, 2-H),
3
7.39–7.44 (m, 2 H, Ar–H), 8.05 (d, J = 6.9 Hz, 1 H, Ar-H), 8.20
(d, 3J = 6.9 Hz, 1 H, Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3,
plus DEPT): Major diastereomer: δ = 14.4 (+, OCH2CH3), 23.56,
23.63, 30.7, 32.8, 33.5 (–, CCH2CH, C-7ЈЈ,8ЈЈ,9ЈЈ, 10ЈЈ), 39.0 (+, C-
6ЈЈ), 40.07 [+, N(CH3)2], 64.2, 64.5, 64.7 (–, OCH2CH3, C-2ЈЈ,3ЈЈ),
77.5 (Cquat, C-5), 100.5 (+, C-4), 111.0 (Cquat, C-5ЈЈ), 122.7 (+, q,
5-Dimethylamino-5-[(1Ј,4Ј-dioxaspiro[4.4]non-6Ј-yl)methyl]-3-
ethoxy-1-methyl-1,3-cyclopentadiene (6ad): According to GP4, a
solution of complex 4a (2.30 g, 5.01 mmol) in pyridine (100 mL)
was treated with 1-propyne (5d) (2 mL) at –78 °C, then the mixture
was stirred at 80 °C for 4 d. Chromatography on aluminum oxide
(80 g) eluting with pentane/Et2O (+ 1% NEt3, from 1:0 to 1:2) gave
1.15 g (75%) of 6ad [Rf = 0.13 (pentane/Et2O, 1:1); dr = 2:1] as a
3
3JC,F = 4.0 Hz, C-4Ј), 123.5 (+, q, JC,F = 3.7 Hz, C-2Ј), 124.3
1
(Cquat, q, JC,F = 272.3 Hz, CF3), 126.3, 128.6 (+, C-5Ј,6Ј), 129.1
colorless oil. IR (film): ν = 2948 cm–1 (C–H), 1638 (C=C), 1585,
2
˜
(+, C-2), 130.5 (Cquat, q, JC,F = 31.9 Hz, C-3Ј), 135.6 (Cquat, C-
1344, 1201, 1151, 1105, 1041. 1H NMR (250 MHz, CDCl3): δ =
1.13–1.88 (m, 8 H, CCH2CH, 7Ј,8Ј,9Ј-H), 1.27, 1.28 (t, 3J = 7.0 Hz,
1Ј), 148.7 (Cquat, C-1), 158.8 (Cquat, C-3). Minor diastereomer: δ =
14.4 (+, OCH2CH3), 23.4, 23.8, 33.2, 33.3, 34.1 (–, CCH2CH, C-
7ЈЈ,8ЈЈ,9ЈЈ,10ЈЈ), 39.8 (+, C-6ЈЈ), 40.14 [+, N(CH3)2], 63.9, 64.2, 64.7
(–, OCH2CH3, C-2ЈЈ,3ЈЈ), 77.5 (Cquat, C-5), 99.4 (+, C-4), 110.4
4
3 H, OCH2CH3), 1.69, 1.71 (d, J = 1.8 Hz, 3 H, CH3), 2.08–2.18
(m, 1 H, 6Ј-H), 2.12, 2.14 [s, 6 H, N(CH3)2], 3.74–3.90 (m, 6 H,
OCH2CH3, 2Ј,3Ј-H), 4.62, 4.64 (d, 4J = 1.8 Hz, 1 H, 4-H), 5.61,
3
(Cquat, C-5ЈЈ), 123.2, 123.3 (+, q, JC,F = 4.3 Hz, C-2Ј,4Ј), 124.4
4
4
5.66 (ЈЈquiЈЈ (dq), J = 1.8, J = 1.8 Hz, 1 H, 2-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): Major diastereomer: δ = 13.8,
14.4 (+, CH3, OCH2CH3), 20.0, 30.7, 32.7, 34.3 (–, CCH2CH, C-
7Ј,8Ј,9Ј), 39.8 [+, N(CH3)2], 40.8 (+, C-6Ј), 64.2, 64.4, 64.7 (–,
1
(Cquat, q, JC,F = 272.3 Hz, CF3), 126.0, 128.2 (+, C-5Ј,6Ј), 129.6
2
(+, C-2), 130.1 (Cquat, q, JC,F = 31.7 Hz, C-3Ј), 135.4 (Cquat, C-
1Ј), 149.3 (Cquat, C-1), 158.9 (Cquat, C-3) ppm. MS (70 eV): m/z (%)
= 451 (100) [M+], 422 (85) [M+/C2H5], 406 (14), 309 (24), 296 (18),
280 (34), 268 (12), 155 (14). HRMS (EI) calcd. for C25H32F3NO3:
451.2334 (correct HRMS).
OCH2CH3, C-2Ј,3Ј), 75.9 (Cquat, C-5), 95.7 (+, C-4), 118.6 (Cquat
,
C-5Ј), 124.5 (+, C-2), 151.9 (Cquat, C-1), 159.8 (Cquat, C-3). Minor
diastereomer: δ = 12.5, 14.5 (+, OCH2CH3, CH3), 20.5, 32.0, 33.7,
34.6 (–, CCH2CH, C-7Ј,8Ј,9Ј), 40.0 [+, N(CH3)2], 41.1 (+, C-6Ј),
64.3, 64.4, 64.8 (–, OCH2CH3, C-2Ј,3Ј), 75.7 (Cquat, C-5), 94.9 (+,
C-4), 118.7 (Cquat, C-5Ј), 124.7 (+, C-2), 151.0 (Cquat, C-1), 159.4
(Cquat, C-3) ppm. MS (70 eV): m/z (%) = 307 (36) [M+], 278 (100)
[M+ – C2H5], 150 (26), 41 (12). C18H29NO3 (307.4): calcd. C 70.32,
H 9.51; found C 69.97, H 9.36.
General Procedure for Intramolecular Adol Reactions (GP5): To a
solution of the respective ethoxycyclopentadiene 6 in dioxane (100–
150 mL) is added a concentrated or 3 n solution of hydrochloric
acid (5–10 mL), and the mixture is stirred at ambient temperature
for 2–4 d. The reaction is quenched by addition of a satd. aqueous
solution of potassium carbonate, until the gas evolution ceases. The
aqueous solution is extracted with CH2Cl2 (5×50 mL), and the
combined organic phases are dried with MgSO4. After removal of
the solvent, the residue is purified by column chromatography on
silica gel.
5-Dimethylamino-5-[(1Ј,4Ј-dioxaspiro[4.5]dec-6Ј-yl)methyl]-3-
ethoxy-1,2-dimethyl-1,3-cyclopentadiene (6be): According to GP4, a
solution of complex 4b (2.37 g, 5.01 mmol) in pyridine (100 mL)
was treated with 541 mg (10.0 mmol) of 2-butyne (5e), and the mix-
ture was stirred at 80 °C for 4 d. Chromatography on aluminum
oxide (80 g) eluting with pentane/Et2O (from 10:1 to 1:2) gave
1.11 g (66%) of 6be [Rf = 0.63 (Et2O); dr = 1:1] and traces of its
(3aS,3bR,6aS,7aR)/(3aR,3bS,6aR,7aS)-7a-Dimethyamino-3b-hy-
droxy-1,2-diphenyl-3a,3b,4,5,6,6a,7,7a-octahydrocyclopenta[a]pent-
alen-3-one (anti-7aa) and (syn-7aa): According to GP5, concd. hy-
drochloric acid (10 mL) was added to a solution of 6aa (623 mg,
1.40 mmol) in dioxane (150 mL), and the mixture was stirred for
2 d. After aqueous work-up, the residue was subjected to
chromatography on silica gel (60 g). Elution with pentane/Et2O (+
10% CH2Cl2, from 5:1 to 1:1) gave 283 mg (54%) of anti-7aa [Rf
= 0.57 (pentane/CH2Cl2, 1:1)] as colorless crystals (m.p. 156 °C)
and 136 mg (26%) of syn-7aa [Rf = 0.23 (pentane/CH2Cl2, 1:1)] as
pale-yellow crystals (m.p. 214–216 °C).
hydrolysis product as colorless oils. IR (film): ν = 2935 cm–1 (C–
˜
H), 1700, 1653 (C=C), 1446, 1382, 1155, 1088, 924. 1H NMR
(250 MHz, CDCl3): δ = 1.00–1.70 (m, 17 H, 2×CH3, CCH2CH,
3
6Ј,7Ј,8Ј,9Ј,10Ј-H), 1.29 (t, J = 7.0 Hz, 3 H, OCH2CH3), 2.09, 2.10
[s, 6 H, N(CH3)2], 3.70–3.90 (m, 6 H, OCH2CH3, 2Ј,3Ј-H), 4.58,
4.62 (s, 1 H, 4-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT):
δ = 8.7×2, 9.09, 11.1 (+, CH3), 14.4, 14.5 (+, OCH2CH3), 23.7×2,
23.8, 24.3, 30.8, 31.7, 32.7, 33.7 × 2, 34.3 (–, CCH2CH, C-
7Ј,8Ј,9Ј,10Ј), 39.2 (+, C-6Ј), 39.9, 40.0 [+, N(CH3)2], 64.3, 64.4, 64.5
anti-7aa: IR (KBr): ν = 3445 cm–1 (O–H), 2958 (C–H), 1693
˜
1
(–, OCH2CH3, C-2Ј,3Ј), 74.9, 75.0 (Cquat, C-5), 93.7, 94.6 (+, C-4), (C=O), 1340, 1175, 1122, 1009, 698. H NMR (250 MHz, CDCl3,
111.0, 111.1 (Cquat, C-5Ј), 130.8, 130.9 (Cquat, C-2), 142.2, 142.5
plus DEPT): δ = 1.39–1.44 (m, 1 H) and 1.63–1.99 (m, 7 H) [total
(Cquat, C-1), 160.3 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 335 8 H, 4,5,6,7-H], 2.17–2.35 (m, 1 H, 6a-H), 2.40 [s, 6 H, N(CH3)2],
(66) [M+], 306 (100) [M+ –C2H5], 291 (58) [M+ – N(CH3)2], 180 2.87 (s, 1 H, OH), 3.14 (s, 1 H, 3a-H), 7.17–7.32 (m, 8 H, Ph-H),
(55), 164 (18), 152 (32). HRMS (EI) calcd. for C20H33NO3: 7.55–7.60 (m, 2 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus
335.2460 (correct HRMS).
DEPT): δ = 23.6, 27.9, 26.5, 40.9 (–, C-4,5,6,7), 40.4 [+, N(CH3)2],
Eur. J. Org. Chem. 2005, 1625–1636
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1631

Y.-T. Wu, D. Vidovic, J. Magull, A. de Meijere,
FULL PAPER
4
47.1 (+, C-6a), 54.5 (+, C-3a), 80.2, 89.4 (Cquat, C-3b,7a), 127.8, 1Ј,3Ј-H), 1.88 (d, J = 1.2 Hz, 3 H, CH3), 1.98 [s, 6 H, N(CH3)2],
2
4
128.0, 128.1, 129.4, 129.8, 131.3 (+, Ph-C), 129.0, 134.2, 141.9 2.42 (AB, d, J = 18.8 Hz, 1 H, 5-H), 5.84 (d, J = 1.2 Hz, 1 H, 2-
(Cquat, C-2, Ph-C), 169.7 (Cquat, C-1), 207.3 (Cquat, C-3) ppm. MS
(70 eV): m/z (%) = 373 (100) [M+], 344 (18), 312 (18), 290 (24), 277
(65), 178 (12), 164 (34), 138 (17). C25H27NO2 (373.5): calcd. C
80.40, H 7.29; found C 80.75, H 7.10.
H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 14.1 (+,
CH3), 20.4, 32.0, 36.3, 36.6, 36.8 (–, CCH2CH, C-5,3Ј,4Ј,5Ј), 39.0
[+, N(CH3)2], 46.1 (+, C-1Ј), 70.2 (Cquat, C-4), 132.6 (+, C-2), 180.5
(Cquat, C-3), 205.7 (Cquat, C-1), 219.1 (Cquat, C-2Ј). Second dia-
stereomer: 1H NMR (250 MHz, CDCl3): δ = 1.18–1.70 (m, 4 H,
syn-7aa: IR (KBr): ν = 3254 cm–1 (O–H), 2783 (C–H), 1682 (C=O),
˜
2
4Ј,5Ј-H), 1.78–2.23 (m, 5 H, CCH2CH, 1Ј,3Ј-H), 1.82 (AB, d, J =
1342, 1216, 1170. 1H NMR (250 MHz, CDCl3, plus HH-, CH-
4
18.8 Hz, 1 H, 5-H), 1.87 (d, J = 1.2 Hz, 3 H, CH3), 1.98 [s, 6 H,
COSY and NOESY): δ = 1.36–1.48 (m, 1 H) and 1.79–2.00 (m,
N(CH3)2], 2.34 (AB, d, 2J = 18.8 Hz, 1 H, 5-H), 5.80 (d, 4J =
1.2 Hz, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT):
δ = 14.7 (+, CH3), 20.0, 31.6, 36.0, 36.4, 36.8 (–, CCH2CH, C-
5,3Ј,4Ј,5Ј), 39.1 [+, N(CH3)2], 45.4 (+, C-1Ј), 70.2 (Cquat, C-4),
3
5 H) [total 6 H, 4,5,6-H), 1.54 (dd, 2J = 14.7, J = 12.6 Hz, 1 H, 7-
3
exo-H), 2.28 (dd, 2J = 14.7, J = 8.5 Hz, 1 H, 7-endo-H), 2.38 [s,
6 H, N(CH3)2], 2.65–2.73 (m, 1 H, 6a-H), 3.32 (s, 1 H, 3a-H), 3.36
(s, 1 H, OH), 7.15–7.34 (m, 8 H, Ph-H), 7.61–7.66 (m, 2 H, Ph-H)
ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 24.0, 28.7,
36.0 (–, C-4,5,6), 40.1 [+, N(CH3)2], 41.2 (–, C-7), 54.2 (+, C-6a),
55.6 (+, C-3a), 79.8, 90.4 (Cquat, C-3b,7a), 127.97, 128.04, 128.3,
129.5, 129.7, 130.0 (+, Ph-C), 131.7, 134.0, 138.6 (Cquat, C-2, Ph-
C), 171.2 (Cquat, C-1), 206.1 (Cquat, C-3) ppm. MS (70 eV): m/z (%)
= 373 (100) [M+], 344 (12), 289 (26), 276 (89), 202 (14), 178 (14),
164 (24), 138 (18), 41 (21). C25H27NO2 (373.5): calcd. C 80.40,
H 7.29; found C 80.63, H 7.17.
132.6 (+, C-2), 180.3 (Cquat, C-3), 205.3 (Cquat, C-1), 219.2 (Cquat
,
C-2ЈЈ) ppm. MS (70 eV): m/z (%) = 235 (8) [M+], 205 (9), 191 (12),
138 (100), 59 (9).
(3aS,3bR,6aS,7aR)/(3aR,3bS,6aR,7aS)-7a-Dimethyamino-3b-hy-
droxy-1-methyl-3a,3b,4, 5,6,6a,7,7a-octahydrocyclopenta[a]pentalen-
3-one (anti-7ad) and (3aS,3bS,6aR,7aR)/(3aR,3bR,6aS,7aS)-7a-Di-
methyamino-3b-hydroxy-1-methyl-3a,3b,4,5,6,6a,7,7a-octahydrocy-
clopenta[a]pentalen-3-one (syn-7ad): According to GP5, concd. hy-
drochloric acid (10 mL) was added to a solution of 6ad (972 mg,
3.16 mmol) in dioxane (150 mL), and the mixture was stirred for
4 d. After aqueous work-up, the residue was subjected to
chromatography on aluminum oxide (II, 60 g). Elution with Et2O/
MeOH (from 20:1 to 10:1) gave 212 mg (29%) of syn-7ad [Rf =
0.67 (Et2O/MeOH, 10:1)] as a colorless solid (m.p. 121–122 °C),
249 mg (33%) of a mixture of (anti-/syn-7ad = 2.2:1) and 127 mg
(17%) of anti-7ad [Rf = 0.58 (Et2O/MeOH, 10:1)] as a colorless
solid (m.p. 102–103 °C).
(3aS,3bR,6aS,7aR)/(3aR,3bS,6aR,7aS)-7a-Dimethyamino-3b-hy-
droxy-1-trimethylsilyl-3a,3b,4,5,6,6a,7,7a-octahydrocyclopenta[a]-
pentalen-3-one (anti-7ab) and (3aS,3bS,6aR,7aR)/(3aR,3bR,6
aS,7aS)-7a-Dimethyamino-3b-hydroxy-1-trimethylsilyl-
3a,3b,4,5,6,6a,7,7a-octahydrocyclopenta[a]pentalen-3-one (syn-7ab):
According to GP5, a 3 n solution of hydrochloric acid (5 mL) was
added to a solution of 6ab (585 mg, 1.60 mmol) in dioxane
(150 mL), and the mixture was stirred for 2 d. After aqueous work-
up, the residue was subjected to chromatography on silica gel (60 g)
followed by chromatography on aluminum oxide (activity grade II,
50 g). Elution with CH2Cl2/Et2O (from 1:3 to 2:1) gave 347 mg
(74%) of a colorless oil [Rf = 0.17 (pentane/CH2Cl2, 1:1); anti-/syn-
anti-7ad: IR (KBr): ν = 3417 cm–1 (O–H), 2964 (C–H), 1685
˜
1
(C=O), 1627, 1282, 1191. H NMR (250 MHz, CDCl3): δ = 1.37–
1.59 (2 H) and 1.69–2.08 (7 H) [m, total 9 H, 4,5,6,6a,7-H], 1.95 (s,
3 H, CH3), 2.40 [s, 6 H, N(CH3)2], 2.64 (s, 1 H, 3a-H), 3.20 (br. s,
1 H, OH), 5.88 (s, 1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3,
plus DEPT): δ = 15.1 (+, CH3), 22.8, 27.5, 36.1, 40.0 (–, C-4,5,6,7),
7ab = 2:1]. IR (film): ν = 2953 cm–1 (C–H), 2780, 1700 (C=O),
˜
1464, 1249, 1124, 1025, 1000, 840. 1H NMR (250 MHz, CDCl3): δ
= 0.15 [s, 9 H, Si(CH3)3 of syn-7ab], 0.19 [s, 9 H, Si(CH3)3 of anti-
7ab], 1.27–1.45 and 1.60–2.20 (m, 18 H, 4,5,6,6a,7-H of anti-7ab,
4,5,6,7-H and OH of syn-7ab), 2.09 [s, 6 H, N(CH3)2 of anti-7ab],
2.10 [s, 6 H, N(CH3)2 of syn-7ab], 2.50–2.60 (m, 1 H, 6a-H of syn-
7ab), 2.69 (s, 1 H, 3a-H of anti-7ab), 2.88 (s, 1 H, 3a-H of syn-7ab),
3.38 (br. s, 1 H, OH of anti-7ab), 5.98 (s, 1 H, 2-H of syn-7ab), 6.32
(s, 1 H, 2-H of anti-7ab) ppm. 13C NMR (62.9 MHz, CDCl3, plus
DEPT): anti-7ab: δ = –0.53 ppm[+, Si(CH3)3], 22.9, 27.5, 37.5, 39.7
(–, C-4,5,6,7), 40.3 [+, N(CH3)2], 47.0 (+, C-6a), 54.3 (+, C-3a),
83.1, 88.5 (Cquat, C-3b,7a), 142.5 (+, C-2), 186.7 (Cquat, C-1), 209.6
(Cquat, C-3). syn-7ab: δ = –1.0 [+, Si(CH3)3], 24.2, 28.7, 36.1, 42.3
(–, C-4,5,6,7), 40.2 [+, N(CH3)2], 54.9, 55.0 (+, C-3a,6a), 84.2, 89.3
(Cquat, C-3b,7a), 138.0 (+, C-2), 189.2 (Cquat, C-1), 209.8 (Cquat, C-
3) ppm. MS (70 eV): m/z (%) = 293 (100) [M+], 378 (49) [M+ –
CH3], 264 (81), 251 (44), 220 (47), 197 (14), 138 (21), 73 (26).
HRMS (EI) calcd. for C16H27NO2Si: 293.1811 (correct HRMS).
39.9 [+, N(CH3)2], 47.2 (+, C-6a), 56.5 (+, C-3a), 79.6, 88.2 (Cquat
,
C-3b,7a), 132.4 (+, C-2), 179.1 (Cquat, C-1), 208.0 (Cquat, C-3) ppm.
MS (70 eV): m/z (%) = 235 (40) [M+], 206 (21), 193 (13), 164 (15),
152 (100), 138 (82), 124 (12). HRMS (EI) calcd. for C14H21NO2:
235.1572 (correct HRMS).
syn-7ad: IR (KBr): ν = 3235 cm–1 (O–H), 2956 (C–H), 1682 (C=O),
˜
1
1622 (C=C), 1457, 1324, 1141. H NMR (250 MHz, CDCl3): δ =
1.26–1.53 (3 H), 1.67–2.00 (4 H) and 2.12–2.22 (1 H) [m, total 8 H,
4,5,6,7-H], 1.99 (s, 3 H, CH3), 2.18 [s, 6 H, N(CH3)2], 2.62–2.71 (m,
1 H, 6a-H), 2.98 (s, 1 H, 3a-H), 3.58–3.65 (m, 1 H, OH), 5.68 (s,
1 H, 2-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ =
14.5 (+, CH3), 24.3, 29.0, 36.5, 40.7 (–, C-4, 5,6,7), 40.0 [+, N(CH3)
2], 54.4, 55.5 (+, C-3a,6a), 81.0, 89.8 (Cquat, C-3b,7a), 128.6 (+, C-
2), 182.0 (Cquat, C-1), 207.8 (Cquat, C-3) ppm. MS (70 eV): m/z (%)
= 235 (100) [M+], 192 (12), 164 (20), 152 (100), 138 (84), 124 (23),
108 (12), 91 (17), 77 (14), 55 (12), 41 (17). C14H21NO2 (235.3):
calcd. C 71.46, H 8.99; found C 71.31, H 8.72.
4-Dimethylamino-3-methyl-4-[(2Ј-oxo-1Ј-cyclopentyl)methyl]-
cyclopent-2-en-1-one (12ad): According to GP5, a 3 n solution of
hydrochloric acid (10 mL) was added to 6ad (985 mg, 3.20 mmol)
in dioxane (150 mL), and the mixture was stirred for 2 d. After
aqueous work-up, the residue was subjected to chromatography on
aluminum oxide (II, 60 g). Elution with Et2O/MeOH (from 20:1 to
10:1) gave 653 mg (87%) of 12ad [Rf = 0.58 and 0.49 (Et2O/MeOH,
(3aS,3bR,6aS,7aR)/(3aR,3bS,6aR,7aS)-7a-Dimethyamino-3b-hy-
droxy-1,2-dimethyl-3a,3b,4, 5,6,6a,7,7a-octahydrocyclopenta[a]pen-
talen-3-one (anti-7ae) and (3aS,3bS,6aR,7aR)/(3aR,3bR,6aS,7aS)-
7a-Dimethyamino-3b-hydroxy-1,2-dimethyl-3a,3b,4,5,6,6a,7,7a-
octahydrocyclopenta[a]pentalen-3-one (syn-7ae): According to GP5,
a solution of 3 n hydrochloric acid (10 mL) was added to a solution
10:1), dr = 1:1] as a colorless oil. IR (film): ν = 2952 cm–1 (C–H),
˜
1734 (C=O), 1684 (C=O), 1521, 1209, 1186. First diastereomer: 1H of 6ae (870 mg, 2.71 mmol) in dioxane (150 mL), and the mixture
NMR (250 MHz, CDCl3): δ = 1.21–1.62 (m, 4 H, 4Ј,5Ј-H), 1.77 was stirred for 2 d. After aqueous work-up, only the diketone 12ae
(AB, d, 2J = 18.8 Hz, 1 H, 5-H), 1.78–2.23 (m, 5 H, CCH2CH,
was detected. Then, the intermediate 12ae was taken-up again with
1632
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 1625–1636

Triquinanes and Homologues via α,β-Unsaturated Fischer Carbene Complexes
FULL PAPER
dioxane (150 mL), the solution treated with concd. hydrochloric
acid (20 mL), and the mixture kept at ambient temperature for an
additional 4 d. Chromatography on aluminum oxide (II, 60 g) elut-
ing with Et2O/MeOH (from 1:0 to 10:1) gave an inseparable mix-
ture of anti- and syn-7ae [520 mg (77%); Rf = 0.61 (Et2O/MeOH,
10:1); ratio = 1:1] as a colorless oil. This mixture was dissolved in
pentane/Et2O, (10:1, 100 mL), and this solution was slowly concen-
trated at 0 °C under reduced pressure. As a solid precipitated, the
mixture was kept at this temperature under normal pressure for
another 20 min. Separation from the remaining liquid (about
10 mL) and washing with pentane/Et2O, (10:1, 3×10 mL) afforded
210 mg of a colorless solid (m.p. 130–134 °C) of anti-/syn-7ae in
ratio 1:9.4. A colorless oil (310 mg; anti-/syn-7ae = 3.3:1) was col-
lected upon evaporation of the mother liquor and the washing solu-
(28), 164 (18), 138 (10). C26H29NO2 (387.5): calcd. C 80.59, H 7.54;
found C 80.41, H 7.25.
syn-7ba: IR (KBr): ν = 3345 cm–1 (O–H), 2929 (C–H), 1700 (C=O),
˜
1675, 1444, 1338, 1171. 1H NMR (250 MHz, CDCl3, plus HH-,
CH-COSY and NOESY): δ = 1.16–1.95 (m, 10 H, 4,5,6,7,8-H),
2.38 [s, 6 H, N(CH3)2], 2.40–2.55 (m, 1 H, 7a-H), 3.20 (s, 1 H, 3a-
H), 3.23–3.42 (m, 1 H, OH), 7.16–7.31 (m, 8 H, Ph-H), 7.67–7.71
(m, 2 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT):
δ = 19.9, 21.1, 23.4, 30.8, 34.9 (–, C-4,5,6,7,8), 40.0 [+, N(CH3)2],
46.6 (+, C-7a), 58.4 (+, C-3a), 76.5, 78.3 (Cquat, C-3b,8a), 127.9,
128.0, 128.2, 129.4, 129.70, 129.74 (+, Ph-C), 131.6, 134.1, 139.4
(Cquat, C-2, Ph-C), 170.0 (Cquat, C-1), 206.5 (Cquat, C-3) ppm. MS
(70 eV): m/z (%) = 387 (100) [M+], 370 (9) [M+ – OH], 344 (12), 290
(38), 277 (79), 164 (18), 138 (8). HRMS (EI) calcd. for C26H29NO2:
387.2198 (correct HRMS).
tion. IR (KBr): ν = 2959 cm–1 (C–H), 1692 (C=O), 1647 (C=C),
˜
1388, 1320, 1140, 1028. 1H NMR (250 MHz, CDCl3, plus DEPT):
δ = 1.13–1.26 (2 H of anti-7ae, 3 H of syn-7ae), 1.47–1.90 (6 H of
anti-7ae, 4 H of syn-7ae) and 1.97–2.10 (1 H of anti-7ae and 1 H
of syn-7ae) [m, total 17 H, 4,5,6,6a,7-H of anti-7ae, 4,5,6,7-H of
syn-7ae], 1.50 (s, 3 H, CH3 of syn-7ae), 1.56 (s, 3 H, CH3 of anti-
7ae), 1.78 (s, 3 H, CH3 of syn-7ae), 1.82 (s, 3 H, CH3 of anti-7ae),
2.02 [s, 12 H, N(CH3)2 of anti- and syn-7ae], 2.45–2.58 (m, 1 H, 6a
of syn-7ae), 2.62 (s, 1 H, 3a-H of anti-7ae), 2.84 (s, 1 H, 3a-H of
syn-7ae), 3.45 (br. s, 1 H, OH of anti-7ae), 4.43 (br. s, 1 H, OH of
syn-7ae) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): anti-
7ae: δ = 7.7, 12.9 (+, CH3), 22.9, 27.6, 36.0, 40.5 (–, C-4,5,6,7),
8ba: IR (film): ν = 2937 cm–1 (C–H), 1695 (C=O), 1444, 1343, 1173,
˜
1015, 775, 702. 1H NMR (250 MHz, CDCl3, plus HH-, CH-COSY
and NOESY): δ = 1.18–2.02 (m, 11 H, 4,5,6,7,8-H, OH), 2.20–2.30
(m, 1 H, 7a-H), 2.34 [s, 6 H, N(CH3)2], 2.90 (s, 1 H, 3a-H), 7.15–
7.28 (m, 8 H, Ph-H), 7.64–7.69 (m, 2 H, Ph-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = 20.9, 24.8, 25.4, 36.5, 37.5 (,
C-4,5,6,7,8), 40.2 [+, N(CH3)2], 50.0, 55.6 (+, C-3a,7a), 77.2, 78.8
(Cquat, C-3b,8a), 127.8, 127.9, 128.2, 129.2, 129.80, 129.84 (+, Ph-
C), 132.1, 134.8, 140.2 (Cquat, C-2, Ph-C), 169.9 (Cquat, C-1), 205.4
(Cquat, C-3) ppm. MS (70 eV): m/z (%) = 387 (78) [M+], 370 (18)
[M+/OH], 343 (10) [M+ – N(CH3)2], 290 (43), 277 (100), 178 (18),
164 (27). HRMS (EI) calcd. for C26H29NO2: 387.2198 (correct
HRMS).
40.0 [+, N(CH3)2], 47.2 (+, C-6a), 55.1 (+, C-3a), 78.2, 88.4 (Cquat
,
C-3b,7a), 138.3 (Cquat, C-2), 170.2 (Cquat, C-1), 207.8 (Cquat, C-3).
syn-7ae: δ = 7.4, 12.2 (+, CH3), 24.0, 28.8, 36.0, 40.5 (–, C-4,5,6,7),
39.8 [+, N(CH3)2], 54.1, 54.5 (+, C-3a,6a), 79.5, 89.4 (Cquat, C-
3b,7a), 134.3 (Cquat, C-2), 173.1 (Cquat, C-1), 207.7 (Cquat, C-3)
ppm. MS (70 eV): m/z (%) = 249 (42) [M+], 177 (14), 152 (100),
138 (16). C15H23NO2 (249.4): calcd. C 72.25, H 9.30; found
C 71.97, H 8.94.
(3aS,3bR,7aS,8aR)/(3aR,3bS,7aR,8aS)-8a-Dimethyamino-3b-hy-
droxy-1,2-dimethyl-3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta-
[a]inden-3-one (anti-7be), and (3aS,3bS,7aR,8aR)/(3aR,3bR,
7aS,8aS)-8a-Dimethyamino-3b-hydroxy-1,2-dimethyl-
3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta[a]inden-3-one (syn-
7be): According to GP5, concd. hydrochloric acid (5 mL) was
added to a solution of 6be (728 mg, 2.17 mmol) in dioxane
(100 mL), and the mixture was stirred for 2 d. After aqueous work-
up, the residue was subjected to chromatography on silica gel
(60 g). Elution with Et2O/EtOAc/MeOH (from 1:0:0 to 1:0:1) gave
368 mg (64%) of anti-7be [Rf = 0.37 (Et2O/EtOAc, 1:1)] as colorless
crystals (m.p. 102 °C) and 104 mg (18%) of syn-7be [Rf = 0.16
(Et2O/EtOAc, 1:1)] as colorless crystals (m.p. 77–80 °C). Besides
these compounds, two uncharacterized fractions were also isolated:
fraction I [25 mg; Rf = 0.87 (Et2O/EtOAc, 1:1)] and fraction II
[36 mg; Rf = 0.73 and 0.61 (Et2O/EtOAc, 1:1)].
(3aS,3bR,7aS,8aR)/(3aR,3bS,7aR,8aS)-8a-Dimethylamino-3b-hy-
droxy-1,2-diphenyl-3b,4, 5,6,7,7a,8,8a-octahydro-3aH-cyclopenta-
[a]inden-3-one (anti-7ba), (3aS,3bS,7aR,8aR)/(3aR,3bR,7aS,8aS)-
8a-Dimethylamino-3b-hydroxy-1,2-diphenyl-3b,4,5,6,7,7a,8,8a-oc-
tahydro-3aH-cyclopenta[a]inden-3-one (syn-7ba) and (3aS,3bS,7aS,
8aR)/(3aR,3bR,7aR,8aS)-8a-Dimethylamino-3b-hydroxy-1,2-
diphenyl-3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta[a]inden-3-one
(8ba): According to GP5, to a solution of 6ba (924 mg, 2.01 mmol)
in dioxane (200 mL) was added concd. hydrochloric acid (10 mL),
and the mixture was stirred for 2 d. After aqueous work-up, the
residue was subjected to chromatography on silica gel (60 g). Elu-
tion with CH2Cl2/Et2O (from 5:1 to 1:1) gave 73 mg (9%) of 8ba
[Rf = 0.81 (CH2Cl2/Et2O, 3:1)] as a pale-yellow oil, 487 mg (63%)
of anti-7ba [Rf = 0.62 (CH2Cl2/Et2O, 3:1)] as colorless crystals (m.p.
204–205 °C) and 130 mg (17 %) of syn-7ba [Rf = 0.35 (CH2Cl2/
Et2O, 3:1)] as colorless crystals (m.p. 181–183 °C).
anti-7be: IR (KBr): ν = 2932 cm–1 (C–H), 1700 (C=O), 1653, 1172,
˜
1030. 1H NMR (250 MHz, CDCl3): δ = 1.44–1.80 (m, 10 H,
4,5,6,7,8-H), 1.71 (s, 3 H, CH3), 1.99 (s, 3 H, CH3), 2.05–2.17 (m,
1 H, 7a-H), 2.24 [s, 6 H, N(CH3)2], 2.31 (s, 1 H, 3a-H), 2.80 (s, 1 H,
OH) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 7.4,
13.1 (+, CH3), 20.2, 21.1, 22.6, 31.6, 36.0 (–, C-4,5,6,7,8), 39.8 [+,
N(CH3)2], 40.1 (+, C-7a), 57.7 (+, C-3a), 75.3, 75.7 (Cquat, C-
3b,8a), 139.1 (Cquat, C-2), 171.8 (Cquat, C-1), 207.5 (Cquat, C-3)
ppm. MS (70 eV): m/z (%) = 263 (100) [M+], 220 (7), 201 (7), 165
(8), 153 (100), 138 (13), 122 (9). C16H25NO2 (263.4): calcd. C 72.97,
H 9.57; found C 73.27, H 9.35.
anti-7ba: IR (KBr): ν = 3407 cm–1 (O–H), 2932 (C–H), 1695
˜
(C=O), 1166, 1092, 1021, 758, 695. 1H NMR (250 MHz, CDCl3,
plus HH-, CH-COSY and NOESY): δ = 1.18–2.02 (m, 9 H,
4,5,6,7,8-H), 1.97–2.06 (m, 1 H, 7a-H), 2.20 [ЈЈtЈЈ (dd), 2J = 12.6,
3J = 12.6 Hz, 1 H, 8-H], 2.41 [s, 6 H, N(CH3)2], 2.61 (s, 1 H, OH),
2.71 (s, 1 H, 3a-H), 7.15–7.34 (m, 8 H, Ph-H), 7.54–7.58 (m, 2 H, syn-7be: IR (KBr): ν = 2940 cm–1 (C–H), 1696 (C=O), 1653, 1437,
˜
Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 20.7, 1320, 1167. H NMR (250 MHz, CDCl3): δ = 1.11–1.88 (m, 10 H,
1
21.6, 23.2, 31.9, 37.5 (–, C-4,5,6,7,8), 40.3 (+, C-7a), 40.5 [+,
N(CH3)2], 57.3 (+, C-3a), 76.9, 77.4 (Cquat, C-3b,8a), 128.0, N(CH3)2], 2.39–2.48 (m, 1 H, 7a-H), 2.82 (s, 1 H, 3a-H), 2.95–3.10
128.1×2, 129.2, 129.5, 129.8, (+, Ph-C), 131.3, 134.4, 143.0 (Cquat
(br. s, 1 H, OH) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT):
C-2, Ph-C), 171.5 (Cquat, C-1), 206.9 (Cquat, C-3) ppm. MS (70 eV): δ = 7.5, 13.4 (+, CH3), 20.1, 21.2, 23.8, 30.9, 34.2 (–, C-4,5,6,7,8),
m/z (%) = 387 (100) [M+], 370 (9) [M+/OH], 344 (15), 290 (12), 277 39.9 [+, N(CH3)2], 46.8 (+, C-7a), 57.5 (+, C-3a), 75.9, 77.4 (Cquat
4,5,6,7,8-H), 1.65 (s, 3 H, CH3), 1.92 (s, 3 H, CH3), 2.13 [s, 6 H,
,
,
Eur. J. Org. Chem. 2005, 1625–1636
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1633

Y.-T. Wu, D. Vidovic, J. Magull, A. de Meijere,
FULL PAPER
C-3b,8a), 135.8 (Cquat, C-2), 172.0 (Cquat, C-1), 207.9 (Cquat, C-3) 4,5,6,7,8), 40.0 [+, N(CH3)2], 50.2 (+, C-7a), 56.2 (+, C-3a), 77.9,
ppm. MS (70 eV): m/z (%) = 263 (29) [M+], 153 (100), 152 (89),
138 (14). C16H25NO2 (263.4): calcd. C 72.97, H 9.57; found
C 73.38, H 9.19.
78.9 (Cquat, C-3b,8a), 123.9 (Cquat, q, 1JC,F = 272.2 Hz, CF3), 125.5
3
3
(+, q, JC,F = 4.0 Hz, C-4Ј), 130.4 (Cquat, C-1Ј), 127.1 (+, q, JC,F
2
= 3.8 Hz, C-2Ј), 128.4, 129.0 (+, C-5Ј,6Ј), 130.9 (Cquat, q, JC,F
=
32.5 Hz, C-3Ј), 133.7 (+, C-2), 174.0 (Cquat, C-1), 206.5 (Cquat, C-
3). The Unknown Diastereomer: δ = 21.1, 24.4, 25.1, 33.7, 34.2 (–,
C-4,5,6,7,8), 40.5 [+, N(CH3)2], 44.0 (+, C-7a), 58.2 (+, C-3a), 76.9,
80.0 (Cquat, C-3b,8a), 123.9 (Cquat, q, 1JC,F = 272.2 Hz, CF3), 125.5
(3aS,3bR,7aS,8aR)/(3aR,3bS,7aR,8aS)-8a-Dimethylamino-3b-hy-
droxy-1-(3Ј-trifluoromethylphenyl)-3b,4,5,6,7,7a,8,8a-octahydro-
3aH-cyclopenta[a]inden-3-one (anti-7bg), (3aS,3bS,7aR,8aR)/
(3aR,3bR,7aS,8aS)-8a-Dimethylamino-3b-hydroxy-1-(3Ј-trifluoro-
methylphenyl)-3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta[a]inden-
3-one (syn-7bg) and (3aS,3bS,7aS,8aR)/(3aR,3bR,7aR,8aS)-8a-Di-
methylamino-3b-hydroxy-1-(3Ј-trifluoromethylphenyl)-
3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta[a]inden-3-one (8bg):
According to GP5, concd. hydrochloric acid (5 mL) was added to
a solution of 6bg (506 mg, 1.12 mmol) in dioxane (100 mL), and
the mixture was stirred for 2 d. After aqueous work-up, the residue
was subjected to chromatography on silica gel (60 g). Elution with
3
3
(+, q, JC,F = 4.0 Hz, C-4Ј), 127.2 (+, q, JC,F = 3.8 Hz, C-2Ј),
2
129.0, 129.2 (+, C-5Ј,6Ј), 131.0 (Cquat, q, JC,F = 32.5 Hz, C-3Ј),
131.9 (+, C-2), 132.2 (Cquat, C-1Ј), 174.3 (Cquat, C-1), 206.0 (Cquat
,
C-3) ppm. MS (70 eV): m/z (%) = 379 (50) [M+], 362 (100) [M+ –
OH], 282 (86), 269 (60), 268 (46), 164 (26), 138 (21).
(3aS,3bR,7aS,8aR)/(3aR,3bS,7aR,8aS)-8a-Dimethylamino-3b-hy-
droxy-1-trimethylsilyl-3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta-
[a]inden-3-one (anti-7bb), (3aS,3bS,7aR,8aR)/(3aR,3bR,7aS,8aS)-
pentane/Et2O (from 3:1 to 1:2) gave 68 mg of a mixture of 8bg [Rf 8a-Dimethylamino-3b-hydroxy-1-trimethylsilyl-3b,4,5,6,7,7a,8,8a-oc-
= 0.26 (pentane/Et2O, 1:1) and an unidentified diastereomer (ratio
79:21), corresponding to 16% yield of 8bg, 287 mg of a mixture of
anti-7bg [Rf = 0.14 (pentane/Et2O, 1:1)] and an unidentified dia-
stereomer (ratio 88:12), corresponding to 67% yield of anti-7bg and
74 mg (17%) of anti-/syn-7bg [Rf = 0.12 (pentane/Et2O, 1:1), ratio
= 3:1] as colorless oils. The combined yields of anti-7bg were 72%.
Repeated chromatography on silica gel (40 g) and collection of the
first 60% fraction of this product afforded pure anti-7bg as color-
less crystals (m.p. 134–135 °C).
tahydro-3aH-cyclopenta[a]inden-3-one (syn-7bb) and (3aS,3bS,
7aS,8aR)/(3aR,3bR,7aR,8aS)-8a-Dimethylamino-3b-hydroxy-1-tri-
methylsilyl-3b,4,5,6,7,7a,8,8a-octahydro-3aH-cyclopenta[a]inden-3-
one (8bb): According to GP4, to a solution of complex 4b (2.37 g,
5.01 mmol) in pyridine (100 mL) was added 737 mg (7.50 mmol) of
trimethylsilylethyne (5b), and the mixture was kept at 80 °C for 4 d.
After exposure to air, filtration and evaporation of the solvent, the
residue was directly dissolved in dioxane (150 mL), treated with
concd. hydrochloric acid (5 mL), and stirred for another 2 d ac-
cording to GP5. Finally, chromatography on silica gel (60 g) eluting
with pentane/Et2O (from 3:1 to 1:2) gave 36 mg (2%) of 8bb [Rf =
0.49 (pentane/Et2O, 1:1)] as a colorless oil, 441 mg (29%) of anti-
7bb [Rf = 0.25 (pentane/Et2O, 1:1)] as colorless crystals (m.p. 94 °C)
and 154 mg (10%) of syn-7bb [Rf = 0.15 (pentane/Et2O, 1:1), in-
cluding an unknown diastereomer (9%)] as a colorless oil.
anti-7bg: IR (KBr): ν = 2932 cm–1 (C–H), 1681 (C=O), 1429, 1338,
˜
1
1318, 1077. H NMR (250 MHz, CDCl3): δ = 1.28–1.90 (m, 10 H,
4,5,6,7,8-H), 2.24–2.38 (m, 1 H, 7a-H), 2.30 [s, 6 H, N(CH3)2], 2.64
(s, 1 H, OH), 2.83 (s, 1 H, 3a-H), 6.62 (s, 1 H, 2-H), 7.53 [ЈЈtЈЈ (dd),
3J = 7.8 Hz, 1 H, Ar-H], 7.67 (d, 3J = 7.8 Hz, 1 H, Ar-H), 8.25
(d, 3J = 7.8 Hz, 1 H, Ar-H), 8.36 (s, 1 H, Ar-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = 20.6, 21.5, 22.9, 31.9, 36.7 anti-7bb: IR (KBr): ν = 3419 cm–1 (O–H), 2931 (C–H), 1694
˜
(–, C-4,5,6,7,8), 40.3 [+, N(CH3)2], 57.0×2 (+, C-3a,7a), 76.2, 78.5
(C=O), 1289, 1238, 1171, 1024, 995, 904, 835. 1H NMR (250 MHz,
1
(Cquat, C-3b, 8a), 123.8 (q, JC,F = 272.5 Hz, CF3), 125.9 (+, q, CDCl3): δ = 0.22 [s, 9 H, Si(CH3)3], 1.20–1.70 (m, 10 H, 4,5,6,7,8-
3
3JC,F = 3.9 Hz, C-4Ј), 127.2 (+, q, JC,F = 3.7 Hz, C-2Ј), 129.2,
H), 2.08 [s, 6 H, N(CH3)2], 2.08–2.18 (m, 1 H, 7a-H), 2.24 (s, 1 H,
2
131.4 (+, C-5Ј,6Ј), 131.1 (Cquat, q, JC,F = 32.5 Hz, C-3Ј), 131.4 OH), 3.03 (s, 1 H, 3a-H), 6.30 (s, 1 H, 2-H) ppm. 13C NMR
(Cquat, C-1Ј), 133.7 (+, C-2), 174.8 (Cquat, C-1), 207.2 (Cquat, C-3)
ppm. MS (70 eV): m/z (%) = 379 (21) [M+], 362 (8) [M+ – OH],
336 (11), 283 (11), 164 (100), 138 (25), 125 (19). C21H24F3NO2
(379.4): calcd. C66.48, H 6.38; found C 66.39, H 6.07.
(62.9 MHz, CDCl3, plus DEPT): δ = –0.5 [+, Si(CH3)3], 20.4, 21.3,
22.8, 32.9, 36.0 (–, C-4,5,6,7,8), 39.8 (+, C-7a), 40.4 [+, N(CH3)2],
56.9 (+, C-3a), 76.4, 80.4 (Cquat, C-3b,8a), 143.4 (+, C-2), 188.3
(Cquat, C-1), 209.5 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 307
(73) [M+], 290 (16) [M+ – OH], 264 (100), 251 (10), 234 (38), 216
(14), 164 (12), 138 (24), 125 (10), 73 (27) [Si(CH3)3+]. C17H29NO2Si
(307.5): calcd. C 66.40, H 9.51; found C 66.71, H 9.25.
syn-7bg: 1H NMR (250 MHz, CDCl3): δ = 1.28–2.10 (m, 11 H,
4,5,6,7,8-H, OH), 2.25 [s, 6 H, N(CH3)2], 2.48–2.54 (m, 1 H, 7a-
H), 3.10 (s, 1 H, 3a-H), 6.41 (s, 1 H, 2-H), 7.53 [ЈЈtЈЈ (dd), 3J =
7.8 Hz, 1 H, Ar-H], 7.67 (d, 3J = 7.8 Hz, 1 H, Ar-H), 8.25 (d, 3J
syn-7bb and an Unknown Diastereomer: IR (film): ν = 2937 cm–1
˜
= 7.8 Hz, 1 H, Ar-H), 8.36 (s, 1 H, Ar-H) ppm. 13C NMR (C–H), 1700 (C=O), 1248, 909, 841. 1H NMR (250 MHz, CDCl3):
(62.9 MHz, CDCl3, plus DEPT): δ = 19.8, 21.1, 23.5, 31.2, 35.7 δ = 0.18, 0.22 [s, 9 H, Si(CH3)3], 1.15–1.82 (m, 10 H, 4,5,6,7,8-H),
(–, C-4,5,6,7,8), 39.9 [+, N(CH3)2], 46.8 (+, C-7a), 59.4 (+, C-3a), 2.08 [s, 6 H, N(CH3)2], 2.15 (s, 1 H, OH), 2.35–2.43 (m, 1 H, 7a-
77.2, 78.5 (Cquat, C-3b,8a), 123.8 (Cquat, q, 1JC,F = 272.5 Hz, CF3),
H), 2.24 (s, 1 H, OH), 2.54, 2.77 (s, 1 H, 3a-H), 6.05, 6.25 (s, 1 H,
2-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus DEPT): syn-7bb: δ
= –0.8 [+, Si(CH3)3], 19.9, 21.1, 23.5, 31.1, 35.7 (–, C-4,5,6,7,8),
3
3
125.9 (+, q, JC,F = 3.9 Hz, C-4Ј), 127.2 (+, q, JC,F = 3.7 Hz, C-
2
2Ј), 127.9, 129.2 (+, C-5Ј,6Ј), 131.1 (Cquat, q, JC,F = 32.5 Hz, C-
3Ј), 131.4 (Cquat, C-1Ј), 133.1 (Cquat, C-2), 174.1 (Cquat, C-1), 206.9
40.1 [+, N(CH3)2], 47.4 (+, C-7a), 57.7 (+, C-3a), 77.2, 80.2 (Cquat,
(Cquat, C-3) ppm. MS (70 eV): m/z (%) = 379 (100) [M+], 362 (28) C-3b,8a), 139.6 (+, C-2), 187.8 (Cquat, C-1), 209.8 (Cquat, C-3). The
[M+ – OH], 336 (56), 323 (18), 282 (49), 269 (24), 268 (18), 164
(45), 138 (21), 125 (10).
unknown diastereomer: δ = –0.3 [+, Si(CH3)3], 21.0, 24.4, 25.1,
33.9, 34.4 (–, C-4,5,6,7,8), 40.7 [+, N(CH3)2], 43.1 (+, C-7a), 57.5
(+, C-3a), 77.8, 82.3 (Cquat, C-3b,8a), 141.9 (+, C-2), 187.8 (Cquat
,
8bg and an Unknown Diastereomer: IR (film): ν = 2935 cm–1 (C–
˜
C-1), 209.4 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 307 (67) [M+],
290 (25) [M+ – OH], 264 (100), 251 (10), 234 (31), 216 (11), 197
(34), 138 (14), 99 (15), 73 (28) [Si(CH3)3+].
H), 1695 (C=O), 1334, 1168, 1127, 1077, 1019. 1H NMR
(250 MHz, CDCl3): δ = 1.11–1.97 (m, 10 H, 4,5,6,7,8-H), 2.13–2.17
(m, 1 H, 7a-H), 2.20, 2.38 [s, 6 H, N(CH3)2], 2.30 (s, 1 H, OH),
2.81, 2.87 (s, 1 H, 3a-H), 6.40, 6.56 (s, 1 H, 2-H), 7.47–7.69 (m, 8bb: IR (film): ν = 2938 cm–1 (C–H), 1695 (C=O), 1246, 1016, 841.
˜
2 H, Ar-H), 8.20–8.40 (m, 2 H, Ar-H) ppm. 13C NMR (62.9 MHz, 1H NMR (250 MHz, CDCl3): δ = 0.22 [s, 9 H, Si(CH3)3], 1.15–1.96
CDCl3, plus DEPT): 8bg: δ = 20.8, 24.7, 25.3, 36.3, 37.9 (–, C- (m, 11 H, 4,5,6,7,8-H, OH), 2.11 [s, 6 H, N(CH3)2], 2.05–2.12 (m,
1634
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1625–1636

Triquinanes and Homologues via α,β-Unsaturated Fischer Carbene Complexes
FULL PAPER
1 H, 7a-H), 2.51 (s, 1 H, 3a-H), 6.08 (s, 1 H, 2-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = –0.7 [+, Si(CH3)3], 20.9, 24.8,
25.5, 36.8, 38.0 (–, C-4,5,6,7,8), 40.4 [+, N(CH3)2], 50.6 (+, C-7a),
54.7 (+, C-3a), 78.0, 81.7 (Cquat, C-3b,8a), 140.0 (+, C-2), 187.4
25.4 (–, C-4,5,6,7), 39.7 [+, N(CH3)2], 45.5 (–, C-8), 55.0 (+, C-3a),
77.2 (Cquat, C-8a), 127.7, 127.9, 128.1, 129.2, 129.8, 130.1 (+, Ph-
C), 131.2, 132.1, 133.8, 135.0, 138.5 (Cquat, C-2,7a,3b, Ph-C), 169.3
(Cquat, C-1), 203.9 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 369
(Cquat, C-1), 209.0 (Cquat, C-3) ppm. MS (70 eV): m/z (%) = 307 (100) [M+], 341 (14) [M+ – CO], 163 (22), 162 (25), 135 (9).
(24) [M+], 290 (100) [M+ – OH], 216 (16), 197 (33), 164 (21), 101
(20), 87 (11), 73 (28) [Si(CH3)3+], 55 (12), 43 (15). HRMS (EI)
calcd. for C17H29NO2Si: 307.1968 (correct HRMS).
C26H27NO (369.5): calcd. C 84.52, H 7.36; found C 84.35, H 7.05.
9a-Dimethylamino-1,2-diphenyl-3a,4,5,6,7,8,9,9a-octahydrocyclo-
penta[a]azulen-3-one (15ca) and 9a-Dimethylamino-1,2-diphenyl-
3a,5,6,7,8,8a,9,9a-octahydrocyclopenta[a]azulen-3-one (16ca): A
solution of anti-7ca (150 mg, 0.37 mmol) in benzene (80 mL) was
treated with a catalytic amount (15 mg) of pTsOH, and the mixture
was heated under reflux for 18 h. Chromatography on silica gel
(40 g) eluting with pentane/Et2O (from 3:1 to 1:1) gave 78 mg
(54%) of 15ca [Rf = 0.33 (pentane/Et2O, 3:1)] as a pale-yellow solid
(m.p. 173–174 °C), and 59 mg (41%) of 16ca [Rf = 0.16 (pentane/
Et2O, 3:1)] as a colorless solid (m.p. 171 °C).
General Procedure for the Dehydration of Hydroxy Ketones anti-7a–
c (GP6): A solution of the respective anti-7 in benzene (150 mL)
was treated with a catalytic amount (15 mg) of pTsOH, and the
mixture was heated under reflux using a Dean–Stark apparatus.
After cooling to ambient temperature, a satd. solution of potassium
carbonate (50 mL) was added to the mixture, and the aqueous
phase was extracted with Et2O (3×50 mL). The combined organic
extracts were dried with MgSO4. The solvent was removed under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel [or aluminum oxide (activity grade II)].
15ca: IR (KBr): ν = 2913 cm–1 (C–H), 1689 (C=O), 1444, 1341,
˜
1170, 775, 728, 705. 1H NMR (250 MHz, CDCl3): δ = 1.39–1.63
(6 H), 1.98–2.11 (2 H) and 2.10–2.43 (2 H) [m, total 10 H, 4,5,6,7,8-
H], 2.15 [s, 6 H, N(CH3)2], 2.68 (br. s, 2 H, 9-H), 3.47 (br. s, 1 H,
3a-H), 7.08–7.23 (m, 8 H, Ph-H), 7.48–7.54 (m, 2 H, Ph-H) ppm.
13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 27.1, 27.4, 28.2,
29.7, 30.8 (–, C-4,5,6,7,8), 39.8 [+, N(CH3)2], 48.1 (–, C-9), 57.1 (+,
C-3a), 76.9 (Cquat, C-9a), 127.7, 128.0, 128.2, 129.3, 129.9, 130.1
(+, Ph-C), 132.3, 133.9, 134.6, 138.5, 138.7 (Cquat, C-2,3b,8b, Ph-
C), 169.2 (Cquat, C-1), 204.6 (Cquat, C-3) ppm. MS (70 eV): m/z (%)
= 383 (100) [M+], 355 (7) [M+ – CO], 338 (10), 177 (32). C27H29NO
(383.5): calcd. C 84.55, H 7.62; found C 84.32, H 7.32.
7a-Dimethyamino-1,2-diphenyl-3a,4,5,6,7,7a-hexahydrocyclopenta-
[a]pentalen-3-one (15aa) and 7a-Dimethyamino-1,2-diphenyl-
3a,5,6,6a,7,7a-hexahydrocyclopenta[a]pentalen-3-one (16aa): Ac-
cording to GP6, a solution of anti-7aa (200 mg, 0.54 mmol) in ben-
zene (200 mL) was treated with a catalytic amount (20 mg) of
pTsOH, and the mixture was heated under reflux for 2 h. After
work-up, the obtained residue was the starting material anti-7aa.
Upon prolonged (17 h) heating of this mixture, a pale-yellow oil
was obtained, which was subjected to chromatography on alumi-
num oxide (II, 30 g). Elution with pentane/Et2O, (3:1) gave 175 mg
(92%) of 15aa/16aa [Rf = 0.35, ratio = 1.1:1] as a pale-yellow solid.
When the mixture of 102 mg (0.29 mmol) of these regioisomers was
heated under reflux again with a catalytic amount (20 mg) of
pTsOH in benzene (100 mL) for 36 h without using a Dean–Stark
apparatus, 94 mg (92%) of the mixture of 15aa/16aa (ratio 2.1:1)
was isolated. 1H NMR (250 MHz, CDCl3): δ = 1.19–1.56 (1 H) and
2.04–2.80 (7 H) [m, 8 H, 4,5,6,7-H of 15aa and, 5,6,6a,7-H of 16aa],
2.31, 2.39 [s, 6 H, N(CH3)2], 3.30–3.33, 3.58–3.62 (br. m, 1 H, 3a-
H), 5.76 (br. s, 1 H, 4-H of 16aa), 7.11–7.35 (m, 8 H, Ph-H), 7.63–
7.70 (m, 2 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, plus
DEPT): 15aa: δ = 26.5, 28.1, 29.5 (–, C-4,5,6), 39.8 (–, C-7), 40.0
[+, N(CH3)2], 49.7 (+, C-3a), 85.2 (Cquat, C-7a), 127.8, 127.99,
128.20, 129.35, 129.9, 130.2 (+, Ph-C), 132.2, 133.9, 138.8, 141.0,
145.2 (Cquat, C-2,3b,6a, Ph-C), 169.2 (Cquat, C-1), 203.5 (Cquat, C-
3). 16aa: δ = 32.3, 36.3, 43.6 (–, C-5,6,7), 40.2 [+, N(CH3)2], 44.7
(+, C-6a), 53.4 (+, C-3a), 85.2 (Cquat, C-7a), 120.8 (Cquat, C-3b),
127.8, 127.95, 128.16, 129.4, 129.9×2, 130.1 (+, C-4, Ph-C), 131.9,
134.2, 146.6 (Cquat, C-2, Ph-C), 170.1 (Cquat, C-1), 203.0 (Cquat, C-
3) ppm. MS (70 eV): m/z (%) = 355 (100) [M+], 327 (14), 310 (14),
250 (18), 149 (28), 162 (25). HRMS (EI) calcd. for C25H25NO:
355.1936 (correct HRMS).
16ca: IR (KBr): ν = 2916 cm–1 (C–H), 1703 (C=O), 1444, 1337,
˜
1268, 1153, 1033, 766, 697. 1H NMR (250 MHz, CDCl3): δ = 1.37–
1.50 (3 H) and 1.75–2.47 (8 H) [m, total 11 H, 5,6,7,8,9,8a-H], 2.39
[s, 6 H, N(CH3)2], 3.50 (br. s, 1 H, 3a-H), 5.99 (m, 1 H, 4-H), 7.10–
7.35 (m, 8 H, Ph-H), 7.54–7.61 (m, 2 H, Ph-H) ppm. 13C NMR
(62.9 MHz, CDCl3, plus DEPT): δ = 27.4, 28.5, 28.6, 33.0, 39.6 (–
, C-5,6,7,8,9), 40.5 [+, N(CH3)2], 41.0 (+, C-8a), 55.1 (+, C-3a),
78.0 (Cquat, C-9a), 127.6, 127.9, 128.1, 128.2, 129.0, 129.4, 129.8
(+, C-4, Ph-C), 131.7, 134.7, 141.0, 142.9 (Cquat, C-2,3b, Ph-C),
168.0 (Cquat, C-1), 205.0 (Cquat, C-3) ppm. MS (70 eV): m/z (%) =
383 (100) [M+], 355 (28) [M+ – CO], 340 (32), 177 (71), 148 (24),
123 (11), 91 (10), 84 (18). HRMS (EI) calcd. for C27H29NO:
383.2249 (correct HRMS).
Acknowledgments
This work was supported by the State of Niedersachsen and the
Fonds der Chemischen Industrie. Generous gifts of chemicals by
BASF, Bayer, Degussa-Hüls AG and Chemetall GmbH are grate-
fully acknowledged. The authors are indebted to Dr. Burkhard
Knieriem, Göttingen, for his careful proofreading of the final ma-
nuscript.
8a-Dimethyamino-1, 2-diphenyl-4, 5,6, 7,7a, 8, 8a-octa-
hydrocyclopenta[a]inden-3-one (15ba): A solution of anti-7ba
(221 mg, 0.57 mmol) in benzene (150 mL) was treated with a cata-
lytic amount (20 mg) of pTsOH, and the mixture was heated under
reflux for 2 h. Chromatography on aluminum oxide (II, 30 g) elut-
ing with pentane/Et2O (3:1) gave 171 mg (81%) of 15ba [Rf = 0.67
(pentane/Et2O, 3:1)] as a pale-yellow solid (m.p. 155–156 °C). IR
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724–728, and references therein.
(KBr): ν = 2722 cm–1 (C–H), 1695 (C=O), 1458, 1333, 11165, 1032.
˜
1H NMR (250 MHz, CDCl3, plus HH-, CH-COSY, NOESY and
HMBC): δ = 1.63–1.70 (4 H), 1.84–2.42 (4 H) [m, total 8 H, 4,5,6,7-
H], 2.27 [s, 6 H, N(CH3)2], 2.72 (br. s, 2 H, 8-H), 3.57 (br. s, 1 H,
3a-H), 7.19–7.33 (m, 8 H, Ph-H), 7.63–7.69 (m, 2 H, Ph-H) ppm.
13C NMR (62.9 MHz, CDCl3, plus DEPT): δ = 22.5, 22.6, 23.7,
[3] H. Schirmer, F. J. Funke, S. Müller, M. Noltemeyer, B. Flynn,
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1635

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[7] syn-7aa: C25H27NO2, unit cell dimensions: a = 11.345(2), b =
10.413(2), c = 16.729(3) Å3, α = 90, β = 94.56(3), γ = 90°, V [11] The distances of hydrogen bonds (H···O) usually fall in the
= 1970.0(7) Å3, monoclinic, P21/n, 2496 reflections. anti-7ba:
C26H29NO2, unit cell dimensions: a = 13.228(3), b =
9.0213(18), c = 17.290(4) Å3, α = 90, β = 97.31(3), γ = 90°, V
= 2046.4(7) Å3, monoclinic, P21/c, 2664 reflections. Crystallo-
graphic data (excluding structure factors) for the structures re-
ported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
nos. CCDC-249190 (for syn-7aa) and CCDC-249189 (for anti-
7ba) contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.a-
c.uk/data_request/cif.
range between 1.8 to and 2.0 Å for all systems, see: J. P. M.
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Transition Metal Catalysts in Organic Synthesis, Springer,
Berlin, 1999.
Received: December 02, 2004
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 1625–1636