Intramolecular pauson-khand reactions of methylenecyclopropane and bicyclopropylidene derivatives as an approach to spiro(cyclopropanebicyclo[n.3. 0]alkenones)

Article abstract of DOI:10.1002/chem.200400997

Intramolecular Pauson-Khand reactions of methylenecyclopropane and bicyclopropylidene were performed to develop spiro(cyclopropanebicyclo[n.3.0] alkenones. Pauson-Khand reactions of the methylenecyclopropane derivatives with a substituent on the ring as w

Full text of DOI:10.1002/chem.200400997

FULL PAPER
Intramolecular Pauson–Khand Reactions of Methylenecyclopropane and
Bicyclopropylidene Derivatives as an Approach to
Spiro(cyclopropanebicyclo[n.3.0]alkenones)**
Armin de Meijere,*[a] Heike Becker,[a] Andreas Stolle,[a] Sergei I. Kozhushkov,[a]
M. Teresa Bes,[b, c] Jacques Salaꢀn,[d] and Mathias Noltemeyer[b]
Abstract: The trimethylsilyl-protected
enynes 9a–c and 14a,b with alkynyl
substituents on the three-membered
ring or on the double bond of a meth-
ylenecyclopropane or a bicyclopropyl-
idene moiety were prepared in two
steps from the alcohols 6a–c and
12a,b, respectively, by conversion to
the iodides and their coupling with lith-
ium (trimethylsilyl)acetylide (8) in 38–
73% overall yields. The bicyclopropyl-
idene derivative 9d was synthesized in
49% yield directly from bicyclopropyl-
idene (3) by lithiation followed by cou-
pling with (5-iodopent-1-ynyl)trime-
thylsilane (11). Enynes 9b–d were pro-
tiodesilylated by treatment with K2CO3
in methanol to give the corresponding
unprotected enynes 10b–d in 53, 74
and 94% yield, respectively. Enynes
17a–c with a carbonyl group adjacent
to the acetylenic moiety were synthe-
sized from oxo derivatives 15a–c by
Wittig olefination followed by coupling
with 8 in 47, 18 and 12% overall yield,
respectively. Pauson–Khand reactions
of the methylenecyclopropane deriva-
tives with a substituent on the ring
(9a,b and 10a) as well as on the
double bond (14a,b and their in situ
prepared protiodesilylated analogues)
proceeded smoothly by stirring of the
corresponding enyne with [Co2(CO)8]
in dichloromethane at ambient temper-
ature followed by treatment of the
formed complexes with trimethylamine
N-oxide under an oxygen atmosphere
at À788C to give tricyclic or spirocyclo-
propanated bicyclic enones 18a,b, 19a,
20a,b, 21a,b in good yields. Alkynylbi-
cyclopropylidene derivatives 9c,d and
10c,d formed the corresponding cobalt
complexes at À78 to À208C. Treatment
of the latter with N-methylmorpholine
N-oxide under an argon atmosphere at
À208C gave the spirocyclopropanated
tricyclic enones 18c, 19c and 18d in
31–45% yields. The structure of 19c
was proved by X-ray crystal structure
analysis. The cyclization of enynones
17a–c in MeCN at 808C gave the spiro-
cyclopropanated bicyclic diketones
22a–c in 38–65% yields. Intramolecu-
lar PKRs of the enynes 25a,d with a
chiral auxiliary adjacent to the triple
bond gave the corresponding products
26a,d in 70 and 79% yield, respective-
ly, as 5:1 and 8:1 mixtures of diaster-
eomers, respectively. Addition of lithi-
um dimethylcuprate or higher order
cuprates to the double bond of the
former furnished bridgehead-substitut-
ed bicyclo[3.3.0]octanones 27a–c in 57–
86% yields. Protiodesilylation of 27a
followed by acetal cleavage gave the
enantiomerically pure spirocyclopropa-
nated bicyclo[3.3.0]octanedione (1R,5R)-
29a with [a]2D0 =À148 (c=1.0 in
CHCl3) in 55% overall yield.
Keywords: alkynes · bicyclopropyli-
dene
·
cobalt
·
cyclization
·
cyclopropanes · spiro compounds
[c] Dr. M. T. Bes
[a] Prof. Dr. A. de Meijere, Dr. H. Becker, Dr. A. Stolle,
Dr. S. I. Kozhushkov
Current address:
Departamento de Bioquꢂmica y Biologꢂa, Molecular y Celular
Facultad de Ciencias, Universidad de Zaragoza
Pedro Cerbuna 12, 50009 Zaragoza (Spain)
Institut fꢀr Organische und Biomolekulare Chemie
der Georg-August-Universitꢁt Gçttingen
Tammannstrasse 2, 37077 Gçttingen (Germany)
Fax : (+49)551-399-475
[d] Prof. Dr. J. Salaꢀn
E-mail: armin.demeijere@chemie.uni-goettingen.de
Laboratoire des Carbocycles (Associꢃ au CNRS)
Institut de Chimie Molꢃculaire d’Orsay, Bꢄt. 420
Universitꢃ de Paris-Sud, 91405 Orsay (France)
[b] Dr. M. T. Bes, Dr. M. Noltemeyer
Institut fꢀr Anorganische Chemie
der Georg-August-Universitꢁt Gçttingen
Tammannstrasse 4, 37077 Gçttingen (Germany)
[**] Part 108 in the series “Cyclopropyl Building Blocks in Organic Syn-
thesis”. For Part 107 see: M. Limbach, S. Dalai, A. Janssen, M. Es-
Sayed, J. Magull, A. de Meijere, Eur. J. Org. Chem. 2004, in press.
Part 106: F. Brackmann, D. S. Yufit, J. A. K. Howard, M. Es-Sayed,
A. de Meijere, Eur. J. Org. Chem. 2005, in press. See also ref. [1].
Chem. Eur. J. 2005, 11, 2471 – 2482
DOI: 10.1002/chem.200400997
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Introduction
ynyl)trimethylsilane (11)[19] (Scheme 1). Protiodesilylation of
enynes 9b–d by treatment with potassium carbonate in
MeOH gave the corresponding unprotected enynes 10b–d
in 53, 74 and 94% yield, respectively.
Among the known methods for the construction of five-
membered carbocycles, the Pauson–Khand reaction (PKR),
that is the cobalt-mediated cocyclization of an alkyne and
an alkene with carbonyl insertion yielding a cyclopentenone,
has attracted particular interest of synthetically[2] as well as
theoretically[3] oriented organic chemists. Among numerous
reported PKRs, those of substrates containing a three-mem-
bered ring are of special interest, as multifunctional cyclo-
propane derivatives have established their potential as
useful building blocks in organic synthesis.[4–6] The release of
strain involved in the formation of the intermediate bi- or
spirocyclic metallacycle has proved to make such reactive al-
kenes as cyclopropene (1),[7] methylenecyclopropane (2) and
bicyclopropylidene (3)[8] particularly useful in PKRs.
Scheme 1. Preparation of alkynyl-substituted methylenecyclopropane and
bicyclopropylidene derivatives 9, 10 with the tether on the cyclopropane
ring. a) 1,1-dichloroethane, nBuLi, Et2O, À358C, 1 h; b) tBuOK, DMSO,
208C, 12 h; c) pTsOH, MeOH, 208C, 16 h; d) Ph3P, Im-H, I2, Et2O/
MeCN 3:2, 08C, 1 h; e) THF/DMPU, 08C, 1 h; f) K2CO3, MeOH, 208C,
3–6 h; g) nBuLi, THF, 08C, 1 h; h) THF, À78 to 08C, 1 h.
From the preparative point of view, PKRs of such alkenes
offer a convenient synthetic approach to cyclopentenones
containing fused (PKR of 1),[7] spiro-linked (PKR of 2)[1]
and simultaneously fused and spiro-attached (PKR of 3) cy-
clopropane moieties. Surprisingly, after the first examples of
intermolecular[9] and intramolecular[1] PKRs of 2, only a few
more cases for reactions of 2[7b,10] and none for 3 and their
derivatives have been published during the last decade. This
contribution summarizes our results in this area, most of
which were obtained after our preliminary communica-
tions.[1] As our results on enantioselective intramolecular
PKRs of methylenecyclopropane derivatives[1b] have recent-
ly been reproduced and further improved by Krafft et al.
and published as a full paper,[10e] this article focuses mainly
on the new intramolecular PKRs of methylenecyclopropane
and bicyclopropylidene derivatives tethered with alkynyl
groups on the ring and on the double bond in the light of
our preliminary reports.
Applying the same sequence of operations as for 9a–c,
the known 4-(cyclopropylidene)butan-1-ol (12a)[20] and 5-
(cyclopropylidene)pentan-1-ol (12b)[21] were converted into
trimethylsilyl-protected enynes 14a,b with a tether on the
double bond in 73 and 38% overall yield, respectively
(Scheme 2). Their analogues 17a,[1b,22] 17b[23] and 17c con-
taining a carbonyl group adjacent to the acetylenic moiety,
were synthesized from the known methyl 4-oxobutanoate
(15a),[24] ethyl 4-oxopentanoate (15b) and ethyl 4-oxohexa-
noate (15c)[25] by Wittig olefination according to a protocol
of Balme et al.[20] followed by coupling with lithium (tri-
methylsilyl)acetylide (8) under boron trifluoride etherate
catalysis in 47, 18 and 12% overall yield, respectively
(Scheme 2).
Results and Discussion
Preparation of the starting materials: The trimethylsilyl-pro-
tected enynes 9a–c were prepared in two steps from the
known 2-(2-methylenecyclopropyl)ethanol (6a),[11a] 3-(2-
methylenecyclopropyl)propan-1-ol (6b)[12] and 2-(bicyclo-
propyliden-2-yl)ethanol (6c),[11b] in 72, 58 and 68% overall
yield, respectively, by conversion to the iodides applying a
protocol of Corey et al.[13] followed by coupling with lithium
(trimethylsilyl)acetylide (8) in the presence of DMPU[14]
(Scheme 1). The starting material 6b, however, was synthe-
sized from 5-(tetrahydropyran-2-yloxy)pent-1-ene (4)[15]
adopting a protocol of Binger et al.[16] On the other hand,
the bicyclopropylidene derivative 9d was prepared directly
from bicyclopropylidene (3)[17] by lithiation with n-butyllithi-
um in THF[18] followed by coupling with (5-iodopent-1-
Scheme 2. Preparation of alkynyl-substituted methylenecyclopropane de-
rivatives 14, 17 with the tether on the double bond. a) Ph3P, Im-H, I2,
Et2O/MeCN, 08C, 1–2 h; b) THF, DMPU, 08C, 1 h; c) Br(CH2)3P+
Ph3BrÀ,[26] NaH, DME, 708C, 11–13 h; d) BF3·Et2O, THF, À100 to
À788C, 1.5 h.
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Intramolecular Pauson–Khand Reactions
FULL PAPER
Pauson–Khand cyclizations of enynes 9, 10, 14 and 17: The
formation of cobalt complexes from the methylenecyclopro-
pane derivatives with the alkynyl substituent tethered to the
ring (9a,b and 10a,b) as well as to the double bond (14a,b
and their in situ prepared protiodesilylated analogues) pro-
ceeded smoothly upon stirring the corresponding enyne with
1.1 equivalents of [Co2(CO)8] in dichloromethane at ambient
temperature. Treatment of these complexes with trimethyl-
amine N-oxide (TMANO)[27] under an oxygen atmosphere
at À788C gave the tricyclic 4-trimethylsilyl-1,1a,2,3-tetrahy-
same conditions as mentioned above led to the formation of
side products, and this caused low yields in the PKRs (at
best 18% for 9c). However, stirring of the respective enyne
with 1.1 equiv of [Co2(CO)8] in dichloromethane at À78 to
À208C followed by treatment with N-methylmorpholine N-
oxide[28] (NMO, 8 equiv) under an argon atmosphere at
À208C gave 7’-trimethylsilylspiro(cyclopropane-1,9’-tricyclo-
[4.3.0.01,3]non-6’-en-8’-one) (18c), its desilylated analogue
19c and 8’-trimethylsilylspiro(cyclopropane-1,10’-tricyclo-
[5.3.0.01,3]dec-7’-en-9’-one) (18d) in 31, 45 and 37% yield,
respectively. The attempted bicyclization of 10d was unsuc-
cessful. These cobalt-mediated bicyclizations of bicyclopro-
pylidene derivatives 9c,d and 10c leading to the interesting
spirocyclopropanated tricyclic products 18c,d and 19c are
the most striking examples for intramolecular Pauson–
Khand reactions involving a tetrasubstituted double bond.
These successful bicyclizations once again demonstrate the
unique reactivity of the strained double bond in bicyclopro-
pylidene and its derivatives (Scheme 3). The structure of
compound 19c was rigorously proved by X-ray crystal struc-
ture analysis (Figure 1).
drocyclopropa[c]pentalen-5-one
(18a),
5-trimethylsilyl-
1a,2,3,4-tetrahydro-1H-cyclopropa[d]inden-6-one (18b) and
1,1a,2,3-tetrahydrocyclopropa[c]pentalen-5-one (19a) as
well as the bicyclic spirocyclopropanated 3’-trimethylsilyl-
4’,5’,6’,6’a-tetrahydro-1’H-spiro(cyclopropane-1,1’-pentalen-
2’-one) (20a), 1’,4’,5’,6’,7’,7’a-hexahydro-3’-trimethylsilyl-
spiro(cyclopropane-1,1’-inden-2’-one) (20b), 4’,5’,6’,6’a-tetra-
hydro-1’H-spiro(cyclopropane-1,1’-pentalen-2-one)
(21a)
and 1’,4’,5’,6’,7’,7’a-hexahydrospiro(cyclopropane-1,1’-inden-
2-one) (21b) in 51, 18, 19, 53, 69, 40 and 32% yield, respec-
tively (Scheme 3).
Figure 1. Molecular structure of spiro(cyclopropane-1,9’-tricyclo[4.3.0.01,3]-
non-6’-en-8’-one) [1’,1’a,2’,3’-tetrahydrospiro(cyclopropane-1,6’-cyclopropa-
[c]pentalen-5’-one)] (19c) in the crystal.[29]
At last, the bicyclizations of enynones 17a–c were per-
formed adopting a protocol of Hoye et al.[30] (Scheme 4).
While the yield of the spirocyclopropanated bicyclic
parent diketone 22a was only moderate (38%) and not very
well reproducible, as compound 22a is prone to undergo
protiodesilylation accompanied with double-bond migration
upon column chromatography on deactivated silica gel, the
methyl- and ethyl-substituted spirocyclopropanated bicyclic
Scheme 3. PKRs of the enynes 9, 10 and 14. a) [Co2(CO)8], CH2Cl2,
208C, 1–2 h; b) [Co2(CO)8], CH2Cl2, À78 to À208C, 2 h; c) TMANO, O2,
À78 to 208C, 16 h; d) NMO, À20 to 208C, 16 h; e) K2CO3, MeOH, 208C,
12 h.
Comparison of these results for enynes 9a,b and 10a,b
with the alkynyl group tethered to the ring demonstrate that
PKRs are more suitable for the preparation of tricy-
clo[4.3.0.01,3]non-6-en-8-ones 18a, 19a than for their homol-
ogous tricyclo[5.3.0.01,3]dec-7-en-9-ones 18b and 19b, and
that the bicyclizations of the trimethylsilyl-protected alkynyl
derivatives proceed more efficiently than those with termi-
nal triple bonds. Contrary to this, methylenecyclopropane
derivatives 14a,b with the alkynyl group tethered to the
double bond do not differ as drastically in their bicyclization
efficiency with respect to a protected and unprotected termi-
nal triple bond, so that all of the spirocyclopropanated bicy-
clo[3.3.0]oct- (20a, 21a) and bicyclo[4.3.0]nonenones (20b,
21b) were obtained in comparable and relatively good
yields.
Scheme 4. PKRs of the enynes 17. a) [Co2(CO)8], MeCN, 808C, 16 h,
then (for 17b,c) TMANO, CH2Cl2, 208C, 1 h; b) silica gel deactivated
with Et3N.
An attempted preparation of the cobalt complexes of the
bicyclopropylidene derivatives 9c,d and 10c,d under the
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A. de Meijere et al.
diketones 22b and 22c were obtained in 63 and 65% yield,
respectively. However, desilylations of 22b and 22c surpris-
ingly could not be brought about.
analysis in the case of 26d, the absolute configuration of
which was assigned as (7’aS) on the basis of the known
(S,S)-configuration of the hydrobenzoin 24, used in the syn-
thesis of the precursor 25d (Figure 2).
In order to demonstrate the full potential of this approach
to spiro(cyclopropane-1,4’-bicyclo[3.3.0]oct-1’-en-3’,8’-diones),
the possibility of asymmetrically inducing the cyclization
with a chiral auxiliary adjacent to the triple bond in the 1,6-
and 1,7-enyne was also tested. As Magnus et al. have dem-
onstrated,[31] high diastereoselectivities can be obtained in
intramolecular PKRs. On the basis of their mechanistic ra-
tionalization it was conceived that a cyclopropylidenalkyne
of type 25 with a C2-symmetric acetal moiety next to the
triple bond might lead to an asymmetric induction in the
cyclization step. The enynes 25a and 25d were obtained by
transacetalization of enynes 17a and 17d[32] with commer-
cially available (S,S)-(À)-hydrobenzoin (24) and trimethyl
orthoformate in 92 and 96% yield, respectively (Scheme 5).
Although heavily substituted, the trimethylsilyl protected al-
kynes 25a and 25d underwent trialkylamine N-oxide-pro-
moted PKR quite well (70 and 79% yield, respectively,
Scheme 5).[33] The diastereoselection in the cyclization of
25a was 5:1, according to gas chromatographic and
1H NMR-spectroscopic analysis, and increased to 8:1 for the
homologue 25d.[34]
Figure 2. Molecular structures of (7’aS,4’’S,5’’S)-1’,4’,5’,6’,7’,7’a-hexahydro-
3’-trimethylsilyldispiro(cyclopropane-1,1’-inden-2’-one-4’,2’’-1,3-dioxo-
lane) (26d, top) and (3’S,3’aR,6’aS,4’’S,5’’S)-hexahydro-3a-n-butyl-3-tri-
methylsilyldispiro(cyclopropane-1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane)
(27b, bottom) in the crystal.[29]
The diastereomers of 26a,d could be separated by column
chromatography or (in the case of 26d) simply by recrystal-
lization from hexane. According to the predictions of
Magnus et al., the main diastereomer should possess (6’aS)
configuration, and this was proven by X-ray crystal structure
Further transformations were performed with the major
diastereomer of 26a, which was also assumed to have (6’aS)
configuration. First, it was attempted to cleave off the chiral
auxiliarity in the acetal moiety. Upon treatment of 26a with
p-toluenesulfonic acid, however, not only acetal cleavage,
but also protiodesilylation and double bond migration occur-
red to yield, as in the previous case (cf. Scheme 4), the achi-
ral bicyclo[3.3.0]octendione 23a, albeit in better yield (71%,
Scheme 5). Therefore, lithium dimethylcuprate was first
added to the enone moiety in 26a to give 27a as a mixture
of (3’S,3’aR,6’aS)- and (3’R,3’aR,6’aS)-diastereomers in a
ratio of 7:1 (Scheme 5; only the major diastereomer is
shown). Surprisingly, lithium di-n-butylcuprate did not add
to 26a under the same conditions, but the higher order cu-
prates,[35] derived from n-butyl- and sec-butyllithium and
cuprous cyanide according to an established procedure (see
Experimental Section), did add under activation with boron
trifluoride etherate to furnish the corresponding adducts
27b and 27c in 57 and 74% yield, respectively, as a single
diastereomer in the former and a 1.25:1 mixture of diastereo-
mers in the latter case. X-ray crystal structure analysis of
27b disclosed its absolute configuration to be
(3’S,3’aR,6’aS), as assigned on the basis of the known (S,S)-
configuration of the acetal moiety in 27b (Figure 2).
Surprisingly, acetal cleavage in 27a was quite slow, within
2 h at ambient temperature only protiodesolylation occurred
to give 28a in virtually quantitative yield. Only upon pro-
longed heating under reflux the latter eventually gave the
dione (3’aR,6’aR)-29a with [a]2D0 =À148 (c=1.0 in
CHCl3).[35] The CD curve with a negative peak at 287 nm
(ellipticity of 5508) is consistent with the absolute configura-
tion being (3’aR,6’aR) (cf.[36]).
Scheme 5. Preparation and PKRs of the enynes 25a,d as well as subse-
quent transformations of (6’aS,4’’S,5’’S)-4’,5’,6’,6’a-tetrahydro-3’-trimethyl-
silyldispiro(cyclopropane-1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane) 26a.
a) HC(OMe)3, pTsOH, benzene, 508C, 16–17 h; b) [Co2(CO)8], CH2Cl2,
208C, 1 h; then NMO (5 equiv), 208C, 20 h; c) [Co2(CO)8], CH2Cl2, 208C,
3 h; then TMANO, O2, À78 to 208C, 16 h; d) pTsOH, acetone, 568C,
16 h; e) Me2CuLi, Et2O, 0 8C, 2 h; f) R2Cu(CN)Li2, Et2O, BF3·Et2O,
À788C, 0.5 h; g) pTsOH, acetone, 208C, 2 h; h) pTsOH, acetone, 568C,
27 h.
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Intramolecular Pauson–Khand Reactions
FULL PAPER
1034 cmÀ1; MS (70 eV): m/z (%): 232 (1) [M +], 197 (1) [M +ÀCl], 148
Conclusion
(1), 85 (100) [C5H9O+].
3-(2-Methylenecyclopropyl)propan-1-ol (6b): To a solution of the chlo-
ride 5 (20.0 g, 86.0 mmol) in anhydrous DMSO (20 mL) was added drop-
wise under vigorous stirring a solution of tBuOK (19.0 g, 169 mmol) in
DMSO (80 mL) at 208C, the resulting mixture was stirred at ambient
temperature for an additional 12 h and poured into ice-cold water
(100 mL). The inorganic phase was extracted with Et2O (3ꢆ100 mL), the
combined organic extracts were washed with water (3ꢆ50 mL), brine
(50 mL), dried, concentrated under reduced pressure and distilled in
vacuo to give 2-[3-(2-methylenecyclopropyl)propyloxy]tetrahydropyran
(14.4 g, 85%) as a colorless oil. B.p. 858C (1 Torr); 1H NMR (250 MHz,
CDCl3, 258C): d=5.38 (m, 1H; =CH2), 5.33–5.31 (m, 1H; =CH2), 4.57 (t,
J=3.4 Hz, 1H), 3.88–3.71 (m, 2H), 3.53–3.36 (m, 2H), 1.84–1.16 (m,
12H), 0.70 (m, 1H); 13C NMR (62.9 MHz, CDCl3, 258C): d=136.6 (C),
102.4 (CH2), 98.6 (CH), 67.0 (CH2), 62.1 (CH2), 30.6 (CH2), 29.6 (CH2),
29.4 (CH2), 25.4 (CH2), 19.5 (CH2), 15.2 (CH), 9.2 (CH2); IR (film): n˜ =
2932, 2869, 1122, 1077, 1034 cmÀ1; MS (70 eV): m/z (%): 195 (1) [M +
+H], 125 (1), 85 (100) [C5H9O+], 79 (15); elemental analysis calcd (%)
for C12H20O2 (196.3): C 73.42, H 10.27; found C 73.36, H 10.33.
Methylenecyclopropane and even bicyclopropylidene moiet-
ies, the latter with a tetrasubstituted double bond, in 1,6-
and 1,7-enynes do favor intramolecular Pauson–Khand reac-
tions to furnish spirocyclopropanated or/and cyclopropane-
annelated bicyclo[3.3.0]octanone or bicyclo[4.3.0]nonanone
derivatives in good yields. The angularly cyclopropane-anne-
lated skeletons can be regarded as mimics of the corre-
sponding bridgehead-methylated compounds. With a chiral
acetal moiety adjacent to the triple bond in the starting ma-
terial, spirocyclopropanated bicyclo[3.3.0]octanediones can
be obtained in enantiomerically pure form.
Experimental Section
This material (14.1 g, 71.8 mmol) was taken up with MeOH (200 mL), p-
TsOH·H2O (1.0 g, 7.2 mmol) was added, and the resulting solution was
stirred at ambient temperature for 16 h. The solvent was evaporated at
ambient pressure through a 20 cm Vigreux column, the residue was taken
up with Et2O (200 mL), washed with water and brine (50 mL each), dried
and concentrated at ambient pressure. The residue was distilled at ambi-
ent pressure to give 6b (6.55 g, 81%) as a colorless liquid, the 1H and
13C NMR data of which were identical to the reported ones.[12]
General aspects: 1H and 13C NMR spectra were recorded on a Bruker
AM 250 instrument (250 MHz for 1H and 62.9 MHz for 13C NMR) in
CDCl3, if not otherwise specified, multiplicities were determined by
DEPT (distortionless enhancement by polarization transfer) measure-
ments. Chemical shifts are referred to dTMS =0.00 according to the chemi-
cal shifts of residual CHCl3 signals. IR spectra were recorded with a
Bruker IFS 66 (FT-IR) spectrophotometer as KBr pellets or oils between
KBr plates. Mass spectra (EI, 70 eV) were measured with Finnigan MAT
95 spectrometer. High resolution spectra were obtained with a VG-70–
250S instrument, pre-selected ion peak matching at R @ 10000 to be
within Æ2 ppm of the exact masses. Melting points were determined on a
Bꢀchi 510 capillary melting point apparatus, values are uncorrected. TLC
analyses were performed on precoated aluminum sheets (Macherey–
Nagel, 0.25 mm Sil G/UV254). Column chromatography was performed
using Merck silica gel, grade 60, 230–400 mesh. Starting materials: bicy-
clopropylidene (3),[17] 5-(tetrahydropyran-2-yloxy)pent-1-ene (4),[15] 2-(2-
methylenecyclopropyl)ethanol (6a),[11a] 2-(2-iodoethyl)bicyclopropylidene
(7c),[11b] (5-iodopent-1-ynyl)trimethylsilane (11),[19] 4-(cyclopropylidene)-
butan-1-ol (12a),[20] 5-(cyclopropylidene)pentan-1-ol (12b),[21] methyl 4-
oxobutyroate (15a),[24] ethyl 4-oxohexanoate (15c),[25] 6-cyclopropyli-
dene-1-(trimethylsilyl)hex-1-yn-3-one (17a),[22] 3-bromopropyltriphenyl-
phosphonium bromide,[26] and 7-cyclopropylidene-1-trimethylsilylhept-1-
yn-3-one (17d)[32] were prepared according to previously published pro-
cedures. All operations in anhydrous solvents were performed under an
argon atmosphere, if not otherwise specified, and in flame-dried glass-
ware. Dimethoxyethane, diethyl ether and THF were dried by distillation
from sodium/benzophenone, pyridine, DMSO, DMPU and triethylamine
from calcium hydride, MeCN, CH2Cl2 and petroleum ether from P2O5.
All other chemicals were used as commercially available. Organic ex-
tracts were dried over MgSO4, if not otherwise specified.
Preparation of iodides 7a,b and 13a,b
General procedure GP 1: To a vigorously stirred solution of the respec-
tive alcohol (26.7 mmol), Ph3P (12.3 g, 46.9 mmol) and imidazol (3.40 g,
49.9 mmol) in a mixture of anhydrous Et2O (90 mL) and anhydrous
MeCN (60 mL) was added iodine (13.2 g, 52.0 mmol) in small portions at
08C. After stirring at this temperature for an additional 1 h, the mixture
was diluted with Et2O (100 mL), filtered, washed with aq. 20% Na2S2O3
solution (80 mL) and brine (3ꢆ50 mL), dried and concentrated under re-
duced pressure. The residue was pre-absorbed on silica gel (1 g) and puri-
fied by column chromatography.
2-(2-Iodoethyl)methylenecyclopropane (7a): Column chromatography
(35 g of silica gel, column 20ꢆ2.5 cm, pentane) of the reaction mixture
obtained from the alcohol 6a (3.93 g, 40.05 mmol), Im-H (5.10 g,
74.85 mmol), Ph3P (18.45 g, 70.35 mmol), and I2 (19.8 g, 78.0 mmol) ac-
cording to GP 1 gave the iodide 7a (6.83 g, 81%) as a colorless oil. Rf =
0.76 (pentane), the 1H and 13C NMR data of which were identical to the
reported ones.[11b]
2-(3-Iodopropyl)methylenecyclopropane (7b): Column chromatography
(30 g of silica gel, column 20ꢆ2 cm, pentane) of the reaction mixture ob-
tained from the alcohol 6b (3.00 g, 26.7 mmol), Im-H (3.40 g, 49.9 mmol),
Ph3P (12.3 g, 46.9 mmol), and I2 (13.2 g, 52.0 mmol) according to GP 1
gave the iodide 7b (4.31 g, 73%) as a colorless oil. Rf =0.78 (pentane);
1H NMR (250 MHz, CDCl3, 258C): d=5.40–5.39 (m, 1H; =CH2), 5.36–
5.35 (m, 1H; =CH2), 3.23 (t, J=7.0 Hz, 2H; CH2I), 1.97 (quin, J=7.0 Hz,
2H; CH2), 1.54–1.36 (m, 3H), 1.27–1.19 (m, 1H; CH2 Cpr), 0.80–0.73 (m,
1H; CH2 Cpr); 13C NMR (62.9 MHz, CDCl3, 258C): d=136.0 (C), 103.0
(CH2), 33.6 (CH2), 33.3 (CH2), 14.4 (CH), 9.3 (CH2), 6.5 (CH2); IR
(film): n˜ =3066, 2972, 2929, 2849, 1446, 1223, 1173, 888 cmÀ1; MS (70 eV):
m/z (%): 222 (1) [M +], 194 (24), 155 (15) [M +ÀC5H7], 127 (4) [I+], 95
(92) [M +ÀI], 79 (16), 67 (100) [C5H7+], 55 (43); elemental analysis calcd
(%) for C7H11I (222.1): C 37.86, H 4.99; found C 37.70, H 4.79.
2-[3-(2-Chloro-2-methylcyclopropyl)propyloxy]tetrahydropyran (5): To a
vigorously stirred solution of 5-(tetrahydropyran-2-yloxy)pent-1-ene
(4)[15] (36.0 g, 211 mmol) and 1,1-dichloroethane (41.0 g, 414 mmol) in an-
hydrous diethyl ether (100 mL) was added nBuLi (389 mmol, 165 mL of
a 2.36m solution in hexane) at À358C over a period of 1 h. After stirring
for an additional 1 h, the reaction mixture was poured into ice-cold water
(100 mL), and the inorganic phase was extracted with Et2O (3ꢆ50 mL).
The combined organic extracts were washed with water (3ꢆ50 mL),
dried, concentrated under reduced pressure and distilled in vacuo to give
5 (20.2 g, 41%) as a colorless oil. B.p. 458C (0.1 Torr), mixture of four di-
astereomers. 1H NMR (250 MHz, CDCl3, 258C): d=4.61–4.52 (m, 1H),
3.90–3.74 (m, 2H), 3.62–3.38 (m, 2H), 2.0–0.3 (m, 16H); 13C NMR
(62.9 MHz, CDCl3, 258C): d=98.70, 98.67, 98.61, 98.57 (CH), 67.0, 66.9,
66.79, 66.76 (CH2), 62.19, 62.17, 62.11, 62.07 (CH2), 45.44, 45.41, 42.73,
42.69 (C), 30.6 (CH2), 29.3, 29.2 (CH2), 27.3, 27.24, 27.1 (CH2), 28.7,
27.07 (CH3), 26.1, 25.4, 25.3 (CH2), 25.23, 25.2, 22.5 (CH), 22.98, 22.01,
21.8 (CH2), 19.5, 19.47 (CH2); IR (film): n˜ =2942, 2896, 1442, 1121, 1077,
4-Cyclopropylidenebutyl iodide (13a): Column chromatography (15 g of
silica gel, column 10ꢆ2 cm, pentane) of the reaction mixture obtained
from the alcohol 12a (593 mg, 5.29 mmol), Im-H (667 mg, 9.79 mmol),
Ph3P (2.43 g, 9.26 mmol), and I2 (2.63 g, 10.4 mmol) according to GP 1
gave the iodide 13a (1.11 g, 95%) as a colorless oil. Rf =0.88 (pentane);
1H NMR (250 MHz, CDCl3, 258C): d=5.74–5.68 (m, 1H; =CH), 3.20 (t,
J=7.0 Hz, 2H; CH2I), 2.32–2.24 (m, 2H; CH2), 1.98 (quin, J=7.0 Hz,
2H; CH2), 1.05–1.03 (m, 4H; Cpr-H); 13C NMR (62.9 MHz, CDCl3,
258C): d=122.8 (C), 115.9 (CH), 33.0 (CH2), 32.4 (CH2), 6.67 (CH2), 2.3
Chem. Eur. J. 2005, 11, 2471 – 2482
www.chemeurj.org
ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2475

A. de Meijere et al.
(CH2), 2.1 (CH2); IR (film): n˜ =3049, 2977, 2931, 1429, 1220, 1166 cmÀ1
;
(CH2), 0.1 (3CH3); IR (film): n˜ =3050, 2961, 2855, 2175, 1249, 759 cmÀ1
;
MS (70 eV): m/z (%): 222 (1) [M +], 193 (35), 155 (19) [M +ÀC5H7], 127
(11) [I+], 95 (100) [M +ÀI], 79 (13), 67 (49) [C5H7+]; elemental analysis
calcd (%) for C7H11I (222.1): C 37.86, H 4.99; found C 37.63, H 5.14.
MS (70 eV): m/z (%): 203 (1) [M +ÀH], 189 (4) [M +ÀMe], 173 (2), 161
(11), 145 (5), 129 (7), 97 (4) [Me3SiCꢀC+], 91 (12), 83 (10), 73 (100)
[Me3Si+], 59 (18); elemental analysis calcd (%) for C13H20Si (204.4): C
76.40, H 9.86; found C 76.60, H 9.94.
5-Cyclopropylidenepentyl iodide (13b): Column chromatography (20 g of
silica gel, column 15ꢆ2 cm, pentane) of the reaction mixture obtained
from the alcohol 12b (600 mg, 4.75 mmol), Im-H (600 mg, 8.81 mmol),
Ph3P (2.18 g, 8.31 mmol), and I2 (2.36 g, 9.30 mmol) according to GP 1
gave the iodide 13b (680 mg, 61%) as a colorless oil. Rf =0.71 (pentane);
1H NMR (250 MHz, CDCl3, 258C): d=5.76–5.70 (m, 1H; =CH), 3.20 (t,
J=7.0 Hz, 2H; CH2I), 2.25–2.12 (m, 2H; CH2), 1.90–1.70 (m, 2H; CH2),
1.59–1.49 (m, 2H; CH2), 1.03–1.01 (m, 4H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=121.8 (C), 117.4 (CH), 33.1 (CH2), 30.6 (CH2), 30.1
(CH2), 7.1 (CH2), 2.2 (CH2), 1.9 (CH2); IR (film): n˜ =3048, 2977, 2931,
2852, 1209, 1167, 962, 932 cmÀ1; MS (70 eV): m/z (%): 236 (1) [M +], 207
(3), 155 (7), 109 (60) [M +ÀI], 81 (51), 67 (100) [C5H7+]; elemental analy-
sis calcd (%) for C8H13I (236.1): C 40.69, H 5.55; found C 40.78, H 5.37.
[6-(Cyclopropylidene)hex-1-ynyl]trimethylsilane (14a): Column chroma-
tography (5 g of silica gel, column 15ꢆ1 cm, pentane) of the reaction
mixture obtained from trimethylsilylacetylene (709 mg, 1.0 mL,
7.22 mmol) in THF (7 mL), nBuLi (5.4 mmol, 2.3 mL of a 2.36m solution
in hexane) and iodide 13a (1.10 g, 4.95 mmol) as a solution in a mixture
of DMPU (5 mL) and THF (5 mL) according to GP 2 gave the enyne
14a (733 mg, 77%) as a colorless oil. Rf =0.78 (pentane), which was con-
taminated with some of the protiodesilylated product. 1H NMR
(250 MHz, CDCl3, 258C): d=5.77–5.70 (m, 1H; =CH), 2.32–2.16 (m, 4H;
2CH2), 1.67 (quin, J=7.0 Hz, 2H; CH2), 1.03–1.01 (m, 4H; Cpr-H), 0.14
(s, 9H; 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=122.1 (C), 117.1
(C), 107.4 (C), 84.4 (C), 30.8 (CH2), 28.2 (CH2), 19.3 (CH2), 2.8 (CH2),
1.8 (CH2), 0.1 (3CH3); IR (film): n˜ =3051, 2959, 2860, 2175, 1249, 842,
759 cmÀ1; MS (70 eV): m/z (%): 191 (1) [M +ÀH], 177 (4) [M +ÀMe],
149 (9), 117 (15), 109 (6), 83 (7), 73 (100) [Me3Si+], 59 (19).
Coupling of iodides 7a–c and 13a,b with lithium (trimethylsilyl)acetylide
(8)
General procedure GP 2: To a vigorously stirred solution of trimethylsi-
lylacetylene (496 mg, 0.7 mL, 5.05 mmol) in anhydrous THF (5 mL) was
added dropwise at 08C nBuLi (3.78 mmol, 1.6 mL of a 2.36m solution in
hexane). After stirring at this temperature for an additional 0.5 h, a so-
lution of the respective iodide (3.36 mmol) in anhydrous DMPU (7 mL)
was added dropwise, the resulting mixture was stirred at 08C for an addi-
tional 1 h with TLC monitoring and then poured into ice-cold water
(20 mL). The aqueous phase was extracted with pentane (3ꢆ10 mL), the
combined organic extracts were washed with brine (2ꢆ20 mL), dried and
concentrated under reduced pressure. The residue was purified by
column chromatography.
[7-(Cyclopropylidene)hept-1-ynyl]trimethylsilane (14b): Column chroma-
tography (5 g of silica gel, column 15ꢆ1 cm, pentane) of the reaction
mixture obtained from trimethylsilylacetylene (425 mg, 0.6 mL,
4.33 mmol) in THF (5 mL), nBuLi (2.8 mmol, 1.2 mL of a 2.36m solution
in hexane) and iodide 13b (600 mg, 2.54 mmol) as a solution in a mixture
of DMPU (2 mL) and THF (4 mL) according to GP 2 gave the enyne
14b (325 mg, 62%) as a colorless oil. Rf =0.50 (pentane); 1H NMR
(250 MHz, CDCl3, 258C): d=5.78–5.71 (m, 1H; =CH), 2.26–2.17 (m, 4H;
2CH2), 1.56–1.50 (m, 4H; 2CH2), 1.02–1.01 (m, 4H; Cpr-H), 0.14 (s, 9H;
3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=121.3 (C), 117.9 (C),
107.6 (C), 84.3 (C), 31.2 (CH2), 28.4 (CH2), 28.2 (CH2), 19.7 (CH2), 2.2
(CH2), 1.9 (CH2), 0.2 (3CH3); IR (film): n˜ =3051, 2937, 2858, 2175, 1249,
Trimethyl[4-(2-methylenecyclopropyl)but-1-ynyl]silane (9a): Column
chromatography (5 g of silica gel, column 15ꢆ1 cm, pentane) of the reac-
tion mixture obtained from trimethylsilylacetylene (496 mg, 0.7 mL,
5.05 mmol), nBuLi (3.78 mmol, 1.6 mL of a 2.36m solution in hexane)
and iodide 7a (700 mg, 3.36 mmol) according to GP 2 gave the enyne 9a
(535 mg, 89%) as a colorless oil. Rf =0.41 (pentane), which was contami-
nated with some of the protiodesilylated product. 1H NMR (250 MHz,
CDCl3, 258C): d=5.43 (brs, 1H; =CH2), 5.36 (brs, 1H; =CH2), 2.34 (t,
J=7.0 Hz, 2H; CH2), 1.61–1.51 (m, 2H; CH2), 1.29–1.18 (m, 2H; Cpr-H),
0.88–0.77 (m, 1H; Cpr-H), 0.15 (s, 9H; 3CH3); 13C NMR (62.9 MHz,
CDCl3, 258C): d=135.9 (C), 107.0 (C), 103.0 (CH2), 84.5 (C), 32.3 (CH2),
19.9 (CH2), 15.0 (CH), 9.4 (CH2), À0.1 (3CH3).
843 cmÀ1
;
MS (70 eV): m/z (%): 191 (3) [M +ÀMe], 163 (4) [M +
ÀMeÀC2H4], 131 (7), 117 (9), 91 (22), 73 (100) [Me3Si+], 59 (15); ele-
mental analysis calcd (%) for C13H22Si (206.4): C 75.65, H 10.74; found C
76.49, H 10.48.
[5-(Bicyclopropyliden-2-yl)pent-1-ynyl]trimethylsilane (9d): To a vigo-
rously stirred solution of nBuLi (4.36 mmol, 1.85 mL of a 2.36m solution
in hexane) in anhydrous THF (5 mL) was added dropwise at À108C a so-
lution of bicyclopropylidene (3) (380 mg, 4.74 mmol) in THF (3 mL).
After stirring at 08C for an additional 1 h, the reaction mixture was
cooled to À788C, and a solution of (5-iodopent-1-ynyl)trimethylsilane
(11)[19] (1.00 g, 3.76 mmol) in THF (4 mL) was added dropwise at this
temperature. The resulting mixture was allowed to warm up to 08C over
a period of 1 h and then poured into ice-cold water (10 mL). The aque-
ous phase was extracted with Et2O (3ꢆ10 mL), the combined organic ex-
tracts were washed with water and brine (10 mL each), dried and concen-
trated under reduced pressure. The residue was purified by column chro-
matography (15 g of silica gel, column 10ꢆ2 cm, pentane) to give 9d
Trimethyl[5-(2-methylenecyclopropyl)pent-1-ynyl]silane (9b): Column
chromatography (5 g of silica gel, column 15ꢆ1 cm, pentane) of the reac-
tion mixture obtained from trimethylsilylacetylene (2.55 g, 3.6 mL,
26.0 mmol) in THF (25 mL), nBuLi (19.4 mmol, 8.2 mL of a 2.36m so-
lution in hexane) and iodide 7b (3.84 g, 17.3 mmol) in DMPU (30 mL)
according to GP 2 gave the enyne 9b (2.67 g, 80%) as a colorless oil.
Rf =0.41 (pentane) which was contaminated with some protiodesilylated
1
product 10b. H NMR (250 MHz, CDCl3, 258C): d=5.42–5.39 (m, 1H; =
(402 mg, 49%) as
a
colorless oil. Rf =0.52 (pentane); 1H NMR
CH2), 5.34–5.33 (m, 1H; =CH2), 2.30–2.23 (m, 2H; CH2), 1.71–1.34 (m,
5H; 2CH2 + Cpr-H), 1.26–1.18 (m, 1H; Cpr-H), 0.78–0.70 (m, 1H; Cpr-
H), 0.14 (s, 9H; 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=136.5
(C), 107.3 (C), 102.6 (CH2), 84.4 (C), 32.1 (CH2), 28.5 (CH2), 19.5 (CH2),
15.1 (CH), 9.3 (CH2), 0.1 (3CH3); IR (film): n˜ =2939, 2858, 2175, 1250,
843 cmÀ1; MS (70 eV): m/z (%): 177 (5) [M +ÀMe], 159 (7), 118 (14), 91
(8), 73 (100) [Me3Si+], 59 (18).
(250 MHz, CDCl3, 258C): d=2.33–2.26 (m, 2H; CH2), 1.71–1.30 (m, 6H;
2CH2 + 2Cpr-H), 1.17 (brs, 4H; Cpr-H), 0.88–0.83 (m, 1H; Cpr-H),
0.14 (s, 9H, 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=115.7 (C),
109.8 (C), 107.6 (C), 84.3 (C), 32.3 (CH2), 28.6 (CH2), 19.5 (CH2), 15.5
(CH), 9.6 (CH2), 2.9 (CH2), 2.7 (CH2), 0.2 (3CH3); IR (film): n˜ =3051,
2960, 2859, 2175, 1249, 841 cmÀ1; MS (70 eV): m/z (%): 203 (18) [M +
ÀMe], 175 (22), 128 (38), 73 (100) [Me3Si+], 59 (46); elemental analysis
calcd (%) for C14H22Si (218.4): C 76.99, H 10.15; found C 76.94, H 10.28.
[4-(Bicyclopropyliden-2-yl)but-1-ynyl]trimethylsilane (9c): Column chro-
matography (5 g of silica gel, column 15ꢆ1 cm, pentane) of the reaction
mixture obtained from trimethylsilylacetylene (1.28 g, 1.8 mL, 13.0 mmol)
in THF (24 mL), nBuLi (10.4 mmol, 4.4 mL of a 2.36m solution in
hexane) and iodide 7c (2.50 g, 10.7 mmol) in DMPU (20 mL) according
to GP 2 gave the enyne 9c (1.64 g, 75%) as a colorless oil. Rf =0.63 (pen-
tane); 1H NMR (250 MHz, CDCl3, 258C): d=2.36 (t, J=7.0 Hz, 2H;
CH2), 1.67–1.59 (m, 3H; CH2 + Cpr-H), 1.42–1.35 (m, 1H; Cpr-H), 1.17
(brs, 4H; Cpr-H), 0.94–0.88 (m, 1H; Cpr-H), 0.14 (s, 9H, 3CH3);
13C NMR (62.9 MHz, CDCl3, 258C): d=115.2 (C), 110.2 (C), 107.2 (C),
84.4 (C), 32.6 (CH2), 20.0 (CH2), 15.4 (CH), 9.8 (CH2), 2.9 (CH2), 2.8
Protiodesilylation of compounds 9b–d
General procedure GP 3: A solution of the respective trimethylsilyl-pro-
tected enyne 9b–d (1 mmol) in methanol (8 mL) was vigorously stirred
at ambient temperature with potassium carbonate (691 mg, 5 mmol) for
the indicated time, and the mixture then was poured into ice-cold water
(10 mL). The aqueous phase was extracted with pentane (3ꢆ10 mL), the
combined organic extracts were washed with brine (2ꢆ15 mL), dried and
concentrated under reduced pressure. The residue was purified by
column chromatography (15 g of silica gel, column 10ꢆ2 cm, pentane).
2476
ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 2471 – 2482

Intramolecular Pauson–Khand Reactions
FULL PAPER
1-Methylene-2-(pent-4-ynyl)cyclopropane (10b): Column chromatogra-
phy of the residue obtained from 9b (410 mg, 2.13 mmol) according to
GP 3 after 6 h of stirring gave the enyne 10b (137 mg, 53%) as a color-
less liquid. Rf =0.27 (pentane); 1H NMR (250 MHz, CDCl3, 258C): d=
5.41–5.39 (m, 1H; =CH2), 5.32–5.31 (m, 1H; =CH2), 2.27 (dt, J=2.4,
6.9 Hz, 2H; CH2), 1.95 (t, J=2.4 Hz, 1H; ꢀCH), 1.52–1.12 (m, 6H;
2CH2), 1.82 (t, J=1.4 Hz, 3H; CH3), 1.25 (t, J=7.1 Hz, 3H; CH3), 1.07–
1.03 (m, 2H; Cpr-H), 0.94–0.90 (m, 2H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=173.6 (C), 122.5 (C), 115.7 (C), 60.1 (CH2), 32.4 (CH2),
31.6 (CH2), 20.8 (CH3), 14.1 (CH3), 3.1 (CH2), 0.9 (CH2); IR (film): n˜ =
2978, 2912, 1737, 1446, 1372, 1275, 1177 cmÀ1; MS (70 eV): m/z (%): 168
(3) [M +], 153 (5) [M +ÀMe], 139 (5) [M +ÀEt], 123 (30) [M +ÀOEt],
105 (8), 95 (100) [M +ÀCO2Et], 79 (28); HRMS: m/z (%): calcd for
C10H16O2: 168.1150; found 168.1150.
2CH2
+
2Cpr-H), 0.80–0.71 (m, 1H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=136.5 (C), 102.7 (CH2), 84.4 (CH), 68.3 (C), 32.0
(CH2), 28.3 (CH2), 18.1 (CH2), 15.1 (CH), 9.4 (CH2); IR (film): n˜ =3306,
Ethyl 4-(cyclopropylidene)hexanoate (16c): Column chromatography
(180 g of silica gel, column 20ꢆ5 cm, petroleum ether/Et2O 60:1) of the
residue obtained from the ketoester 15c (2.65 g, 16.8 mmol), NaH (2.0 g,
83.3 mmol) and Br(CH2)3P+Ph3BrÀ (19.3 g, 41.6 mmol) according to
GP 4 after 13 h of stirring gave the ester 16c (550 mg, 18%) as a color-
less oil. Rf =0.26 (petroleum ether/Et2O 60:1); 1H NMR (250 MHz,
CDCl3, 258C): d=4.12 (q, J=7.1 Hz, 2H; OCH2), 2.58–2.44 (m, 4H;
2CH2), 2.18 (q, J=7.5 Hz, 2H, CH2), 1.25 (t, J=7.1 Hz, 3H, CH3), 1.07
(t, J=7.5 Hz, 3H, CH3), 0.99 (brs, 4H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=173.8 (C), 127.8 (C), 114.5 (C), 60.1 (CH2), 32.6 (CH2),
29.9 (CH2), 28.5 (CH2), 14.2 (CH3), 12.4 (CH3), 1.7 (CH2), 1.3 (CH2); IR
(film): n˜ =2976, 2936, 1737, 1372, 1254, 1177, 734 cmÀ1; MS (70 eV): m/z
(%): 182 (46) [M +], 167 (16) [M +ÀMe], 153 (33) [M +ÀEt], 137 (95)
[M +ÀOEt], 109 (80) [M +ÀCO2Et], 93 (100), 79 (64), 67 (29); elemental
analysis calcd (%) for C11H18O2 (182.3): C 72.49, H 9.95; found C 72.55,
H 9.90.
3068, 2974, 2939, 2860, 2118, 1441, 887, 633 cmÀ1
.
2-(But-3-ynyl)bicyclopropylidene (10c): Column chromatography of the
residue obtained from 9c (215 mg, 1.05 mmol) according to GP 3 after
4 h of stirring gave the enyne 10c (103 mg, 74%) as a colorless liquid.
Rf =0.67 (pentane); 1H NMR (250 MHz, CDCl3, 258C): d=2.36 (dt, J=
2.6, 7.0 Hz, 2H; CH2), 1.97 (t, J=2.6 Hz, 1H; ꢀCH), 1.73–1.51 (m, 3H;
CH2 + Cpr-H), 1.42–1.34 (m, 1H; Cpr-H), 1.18 (brs, 4H; Cpr-H), 0.94–
0.83 (m, 1H; Cpr-H); 13C NMR (62.9 MHz, CDCl3, 258C): d=115.1 (C),
110.3 (C), 84.4 (CH), 68.3 (C), 32.4 (CH2), 18.6 (CH2), 15.3 (CH), 9.7
(CH2), 3.0 (CH2), 2.8 (CH2); IR (film): n˜ =3309, 3051, 2982, 2930, 2855,
2118, 631 cmÀ1; MS (70 eV): m/z (%): 131 (17) [M +ÀH], 117 (24) [M +
ÀMe], 115 (36), 103 (17), 91 (100), 79 (19) [C6H7+], 77 (47), 65 (24), 51
(20).
2-(Pent-4-ynyl)bicyclopropylidene (10d): Column chromatography of the
residue obtained from 9d (200 mg, 0.92 mmol) according to GP 3 after
3 h of stirring gave the enyne 10d (126 mg, 94%) as a colorless oil. Rf =
0.48; 1H NMR (250 MHz, CDCl3, 258C): d=2.28–2.21 (m, 2H; CH2),
1.92 (t, J=2.6 Hz, 1H; ꢀCH), 1.72–1.20 (m, 6H; 2CH2 + 2Cpr-H), 1.16
(brs, 4H; Cpr-H), 0.88–0.79 (m, 1H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=115.6 (C), 109.9 (C), 84.5 (CH), 68.2 (C), 32.1 (CH2),
28.4 (CH2), 18.0 (CH2), 15.4 (CH), 9.6 (CH2), 2.9 (CH2), 2.6 (CH2); IR
(film): n˜ =3304, 3051, 2978, 2938, 2859, 2118, 1440, 960, 633 cmÀ1; MS
(70 eV): m/z (%): 146 (2) [M +], 131 (20), 129 (11), 105 (28), 91 (100), 79
(48) [C6H7+], 65 (27), 51 (25); elemental analysis calcd (%) for C11H14
(146.2): C 90.34, H 9.66; found C 90.28, H 9.83.
Coupling of esters 16b,c with trimethylsilyl-protected lithioacetylene (8)
General procedure 5 (GP 5): To a vigorously stirred solution of trime-
thylsilylacetylene (1.42 g, 2.00 mL, 14.4 mmol) in anhydrous THF
(27 mL) was added dropwise nBuLi (12.0 mmol, 5.1 mL of a 2.35m so-
lution in hexane) at À788C. After stirring at this temperature for an addi-
tional 10 min, the solution was cooled to À1008C, and a solution pre-
cooled to À788C of the respective ester 16b,c (3.03 mmol) in THF
(8 mL) was added dropwise followed by BF3·Et2O (2.8 mL). The reaction
mixture was allowed to warm up to À788C, stirred at this temperature
for an additional 1.5 h and poured, while still cold, into ice-cold aq. sat.
NH4Cl solution (20 mL). The aqueous phase was extracted with diethyl
ether (3ꢆ20 mL), the combined organic extracts were washed with aq.
sat. NaHCO3 solution (2ꢆ20 mL), dried and concentrated under reduced
pressure. The residue was purified by column chromatography.
Preparation of the esters 16a–c with a methylenecyclopropane moiety
General procedure GP 4: Sodium hydride (4.70 g, 196 mmol) and thor-
oughly powdered 3-bromopropyltriphenylphosphonium bromide[26]
(45.41 g, 97.8 mmol) were suspended in anhydrous dimethoxyethane
(DME), ethanol (2–3 drops) was added, and the resulting mixture was
vigorously stirred at 708C for 7 h. After this, a solution of the respective
aldo/keto ester 15a–c (38.5 mmol) in DME (40 mL) was added dropwise,
and the resulting mixture was stirred for the indicated time at the same
temperature After cooling, the mixture was poured into ice-cold aq. sat.
NH4Cl solution (120 mL), the aqueous phase was extracted with pentane
(3ꢆ100 mL), the combined organic extracts were dried and concentrated
under reduced pressure. The residue was vigorously stirred with pentane
(100 mL) at ambient temperature for 1 h and filtered. The filtrate was
concentrated under reduced pressure again, and the product was purified
by column chromatography.
6-Cyclopropylidene-1-(trimethylsilyl)hept-1-yn-3-one (17b): Column
chromatography (20 g of silica gel, column 15ꢆ2 cm, petroleum ether/
Et2O 40:1) of the residue obtained from trimethylsilylacetylene (1.42 g,
2.00 mL, 14.4 mmol), nBuLi (12.0 mmol, 5.1 mL of a 2.35m solution in
hexane), ester 16b (509 mg, 3.03 mmol) and BF3·Et2O (2.8 mL) according
to GP 5 gave the ketoenyne 17b (468 mg, 70%) as a colorless oil. Rf =
0.40; 1H NMR (250 MHz, CDCl3, 258C): d=2.79 (t, J=7.6 Hz, 2H;
CH2), 2.51 (t, J=7.6 Hz, 2H; CH2), 1.82 (t, J=1.6 Hz, 3H; CH3), 1.08–
1.05 (m, 2H; Cpr-H), 0.95–0.91 (m, 2H; Cpr-H), 0.24 (s, 9H; 3CH3);
13C NMR (62.9 MHz, CDCl3, 258C): d=187.6 (C), 122.0 (C), 116.1 (C),
101.9 (C), 97.5 (C), 43.2 (CH2), 30.7 (CH2), 20.9 (CH3), 3.2 (CH2), 1.0
(CH2), À0.8 (3CH3); IR (film): n˜ =2973, 2909, 1677, 1252, 1105, 847,
762 cmÀ1; MS (70 eV): m/z (%): 220 (12) [M +], 205 (17) [M +ÀMe], 177
(7), 163 (9), 125 (50) [M +ÀC7H11], 97 (38), [Me3SiCꢀC+], 73 (100)
[Me3Si+]; elemental analysis calcd (%) for C13H20OSi (220.4): C 70.85, H
9.15; found C 70.96, H 9.19.
Methyl 4-(cyclopropylidene)butanoate (16a): Column chromatography
(180 g of silica gel, column 20ꢆ5 cm, petroleum ether/Et2O 50:1) of the
residue obtained from the aldoester 15a[24] (4.47 g, 38.5 mmol), NaH
(4.70 g, 196 mmol) and Br(CH2)3P+Ph3BrÀ (45.41 g, 97.8 mmol) according
to GP 4 after 11 h of stirring gave the ester 16a (3.02 g, 56%) as a color-
less liquid. Rf =0.30 (petroleum ether/Et2O 50:1); 1H NMR (250 MHz,
CDCl3, 258C): d=5.70–5.65 (m, 1H, =CH), 3.56 (s, 3H; CH3), 2.38 (brs,
4H; 2CH2), 0.92 (s, 4H; Cpr-H); 13C NMR (62.9 MHz, CDCl3, 258C):
d=173.5 (C), 122.1 (C), 115.9 (CH), 51.1 (CH3), 33.3 (CH2), 26.9 (CH2),
1.7 (2CH2); IR (film): n˜ =2982, 2953, 2846, 1744, 1255, 959, 936 cmÀ1; MS
(70 eV): m/z (%): 140 (1) [M +], 98 (23), 81 (100) [M +ÀCO2Me], 59 (31)
[MeO2C+], 53 (26) [C4H5+].
Ethyl 4-(cyclopropylidene)pentanoate (16b):[23] Column chromatography
(180 g of silica gel, column 20ꢆ5 cm, petroleum ether/Et2O 60:1) of the
residue obtained from the ketoester 15b (2.41 g, 16.7 mmol), NaH (2.0 g,
83.3 mmol) and Br(CH2)3P+Ph3BrÀ (19.3 g, 41.6 mmol) according to
GP 4 after 13 h of stirring gave the ester 16b (733 mg, 26%) as a color-
less oil. Rf =0.24 (petroleum ether/Et2O 60:1); 1H NMR (250 MHz,
CDCl3, 258C): d=4.12 (q, J=7.1 Hz, 2H; OCH2), 2.56–2.47 (m, 4H;
6-Cyclopropylidene-1-(trimethylsilyl)oct-1-yn-3-one (17c): Column chro-
matography (20 g of silica gel, column 15ꢆ2 cm, petroleum ether/Et2O
120:1) of the residue obtained from trimethylsilylacetylene (1.33 g,
1.87 mL, 13.5 mmol), nBuLi (10.6 mmol, 4.6 mL of a 2.30m solution in
hexane), ester 16c (519 mg, 2.85 mmol) and BF3·Et2O (2.6 mL) according
to GP 5 gave the ketoenyne 17c (450 mg, 67%) as a colorless oil. Rf =
0.31 (petroleum ether/Et2O 120:1); 1H NMR (250 MHz, CDCl3, 258C):
d=2.79 (t, J=7.4 Hz, 2H; CH2), 2.52 (t, J=7.4 Hz, 2H; CH2), 2.18 (q,
J=7.5 Hz, 2H; CH2), 1.07 (t, J=7.5 Hz, 3H; CH3), 1.00 (brs, 4H; Cpr-
H), 0.24 (s, 9H; 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=187.9
(C), 127.4 (C), 114.9 (C), 102.0 (C), 97.6 (C), 43.4 (CH2), 29.0 (CH2), 28.5
(CH2), 12.4 (CH3), 1.9 (CH2), 1.5 (CH2), 0.8 (3CH3); IR (film): n˜ =2965,
1678, 1253, 1105, 847, 762 cmÀ1; MS (70 eV): m/z (%): 234 (12) [M +],
219 (12) [M +ÀMe], 105 (18) [M +ÀEt], 187 (12), 125 (21) [M +ÀC8H13],
Chem. Eur. J. 2005, 11, 2471 – 2482
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ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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A. de Meijere et al.
97 (31), [Me3SiCꢀC+], 73 (100) [Me3Si+]; HRMS: m/z (%): calcd for
orless oil. Rf =0.18 (petroleum ether/Et2O 10:1); 1H NMR (250 MHz,
CDCl3, 258C): d=2.65–2.60 (m, 1H), 2.59 (d, J=18.4 Hz, 1H; CH2), 2.48
(d, J=18.4 Hz, 1H; CH2), 2.21–2.04 (m, 3H), 1.87 (m, 1H; Cpr-H), 1.13
(dd, J=4.3, 7.7 Hz; 1H, Cpr-H), 0.96 (dd, J=4.3, 4.3 Hz, 1H; Cpr-H),
0.19 (s, 9H; 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=213.4 (C),
197.6 (C), 134.7 (C), 42.1 (CH2), 39.3 (C), 29.2 (CH2), 24.7 (CH), 23.5
(CH2), 17.1 (CH2), À1.0 (3CH3); IR (film): n˜ =2959, 1688, 1592, 1407,
1246, 1049, 840 cmÀ1; MS (70 eV): m/z (%): 206 (13) [M +], 191 (100)
[M +ÀMe], 147 (2), 135 (3), 115 (5), 91 (4), 73 (16) [Me3Si+]; HRMS: m/
z (%): calcd for C12H18OSi: 206.1126; found 206.1126.
C14H22OSi: 234.1439; found 234.1439.
Transacetalization of enynes 17a and 17d
General procedure GP 6: A solution of the respective ketoenyne 17a or
17d (1 mmol), (S,S)-(À)-hydrobenzoin (24) (2–2.2 equiv), trimethyl or-
thoformate (2 equiv) and p-toluenesulfonic acid (10 mg) in anhydrous
benzene (10 mL) was stirred at 508C for the indicated time (16–17 h)
with TLC monitoring, then cooled and poured into sat. aq. NaHCO3 so-
lution (20 mL). The aqueous phase was extracted with diethyl ether (3ꢆ
15 mL), the combined organic extracts were dried over a Na2SO4/K2CO3
mixture (2:1) and concentrated under reduced pressure. The residue was
purified by column chromatography.
5-Trimethylsilyl-1a,2,3,4-tetrahydro-1H-cyclopropa[d]inden-6-one (18b):
Column chromatography (5 g of silica gel, column 15ꢆ1 cm, petroleum
ether/Et2O 10:1) of the residue obtained from enyne 9b (200 mg,
1.04 mmol), [Co2(CO)8] (423 mg, 1.24 mmol) and TMANO (470 mg,
6.26 mmol) according to GP 7 gave the enone 18b (41 mg, 18%) as a col-
orless oil. Rf =0.27 (petroleum ether/Et2O 10:1); 1H NMR (250 MHz,
CDCl3, 258C): d=2.67 (ddd, J=7.1, 7.1, 17.2 Hz, 1H), 2.48 (d, J=
18.8 Hz, 1H; CH2), 2.32 (d, J=18.6 Hz, 1H; CH2), 2.41–2.29 (m, 1H),
1.95–1.50 (m, 5H), 1.27 (dd, J=5.0, 5.0 Hz, 1H; Cpr-H), 1.12 (dd, J=5.0,
8.4 Hz, 1H, Cpr-H), 0.20 (s, 9H; 3CH3); 13C NMR (62.9 MHz, CDCl3,
258C): d=212.1 (C), 190.7 (C), 137.1 (C), 46.5 (CH2), 30.8 (C), 26.7
(CH2), 23.9 (CH), 22.4 (CH2), 21.4 (CH2), 20.1 (CH2), À0.4 (3CH3); IR
(film): n˜ =2949, 2859, 1683, 1559, 1246, 841 cmÀ1; MS (70 eV): m/z (%):
220 (29) [M +], 205 (76) [M +ÀMe], 177 (4), 131 (12), 73 (20) [Me3Si+],
59 (8); HRMS: m/z (%): calcd for C13H20OSi: 220.1283; found 220.1283.
(4S,5S)-2-(3’-Cyclopropylidenepropyl)-4,5-diphenyl-2-(2’’-trimethylsilyle-
thynyl)-1,3-dioxolane (25a): Column chromatography (100 g of silica gel,
column 20ꢆ4 cm, petroleum ether/Et2O 60:1) of the residue obtained
from ketoenyne 17a (2.09 g, 10.1 mmol), 24 (4.30 g, 20.1 mmol),
HC(OMe)3 (2.11 g, 19.9 mmol) and pTsOH (0.1 g) according to GP 6
(16 h of stirring) gave the acetal 25a (3.74 g, 92%) as a colorless solid.
Rf =0.70 (petroleum ether/Et2O 60:1); m.p. 508C; [a]2D0 =À30.0 (c=1.0 in
CHCl3); 1H NMR (250 MHz, CDCl3, 258C): d=7.29–7.12 (m, 10H; Ar-
H), 5.81–5.75 (m, 1H; 3’-H), 4.99 (d, J=8.5 Hz, 1H; 5*-H), 4.58 (d, J=
8.5 Hz, 1H; 4*-H), 2.54–2.45 (m, 2H; 1’-H), 2.21–2.15 (m, 2H; 2’-H),
0.96–0.95 (m, 4H; Cpr-H), 0.15 (s, 9H; 3CH3); 13C NMR (62.9 MHz,
CDCl3, 258C): d=137.6 (C), 135.7 (C), 128.5 (2 CH), 128.3 (2 CH), 128.2
(CH), 128.1 (CH), 127.1 (2 CH), 126.7 (2 CH), 121.6 (C), 117.1 (CH),
104.2 (C), 103.6 (C), 89.6 (C), 86.5 (CH), 86.2 (CH), 39.4 (CH2), 26.1
(CH2), 2.0 (2CH2), À0.2 (3CH3); IR (KBr): n˜ =3052, 2960, 2903, 1253,
1216, 1194, 1122, 1095, 1060, 1041, 1026, 976, 951, 843, 768, 533 cmÀ1; MS
(70 eV): m/z (%): 321 (9) [M +ÀC6H9], 309 (2), 197 (39), 175 (47), 156
(35), 125 (58), 97 (83) [Me3SiCꢀC+], 81 (20); elemental analysis calcd
(%) for C26H30O2Si (402.6): C 77.57, H 7.51; found C 77.57, H 7.59.
1,1a,2,3-Tetrahydrocyclopropa[c]pentalen-5-one (19a): The trimethylsil-
yl-protected enyne 9a (280 mg, 1.57 mmol) was treated with potassium
carbonate according to GP 3. The crude enyne 10a was taken up with an-
hydrous CH2Cl2 (15 mL), and the solution treated with [Co2(CO)8]
(575 mg, 1.68 mmol) and then with TMANO (644 mg, 8.57 mmol) accord-
ing to GP 7. Column chromatography (5 g of silica gel, column 15ꢆ1 cm,
petroleum ether/Et2O 3:1) of the residue gave the enone 19a (40 mg,
19%) as a colorless oil. Rf =0.13 (petroleum ether/Et2O 3:1); 1H NMR
(250 MHz, CDCl3, 258C): d=5.95 (s, 1H; =CH), 2.67–2.50 (m, 3H),
2.22–2.07 (m, 3H), 1.88 (m, 1H; Cpr-H), 1.16 (dd, J=4.6, 7.7 Hz, 1H;
Cpr-H), 1.01 (dd, J=4.2, 4.6 Hz, 1H; Cpr-H); 13C NMR (62.9 MHz,
CDCl3, 258C): d=209.9 (C), 190.8 (C), 124.1 (CH), 41.3 (CH2), 29.2
(CH2), 28.0 (C), 24.8 (CH), 22.8 (CH2), 16.4 (CH2); IR (film): n˜ =2936,
2869, 1698, 1614, 1501, 1407, 1237, 824, 731 cmÀ1; MS (70 eV): m/z (%):
134 (78) [M +], 119 (15), 106 (31), [M +ÀCO], 91 (100), 78 (33), 65 (12);
elemental analysis calcd (%) for C9H10O (134.2): C 80.56, H 7.51; found
C 80.55, H 7.57.
(4S,5S)-2-(4’-Cyclopropylidene-n-butyl)-4,5-diphenyl-2-(2’’-trimethylsily-
lethynyl)-1,3-dioxolane (25d): Column chromatography (25 g of silica
gel, column 20ꢆ2 cm, petroleum ether/Et2O 80:1) of the residue obtained
from ketoenyne 17d (380 mg, 1.72 mmol), 24 (810 mg, 3.78 mmol),
HC(OMe)3 (365 mg, 3.44 mmol) and pTsOH (15 mg) according to GP 6
(17 h stirring) gave the acetal 25d (688 mg, 96%) as a colorless oil. Rf =
0.70 (petroleum ether/Et2O 80:1); [a]2D0 =À28.1 (c=1.0 in CHCl3);
1H NMR (250 MHz, CDCl3, 258C): d=7.40–7.23 (m, 10H; Ar-H), 5.86–
5.79 (m, 1H; 4’-H), 5.09 (d, J=8.5 Hz, 1H; 5*-H), 4.68 (d, J=8.5 Hz,
1H; 4*-H), 2.36–2.28 (m, 2H; 3’-H), 2.17–2.10 (m, 2H; 1’-H), 1.94–1.81
(m, 2H; 2’-H), 1.06–1.04 (m, 4H; Cpr-H), 0.25 (s, 9H; 3CH3); 13C NMR
(62.9 MHz, CDCl3, 258C): d=137.6 (C), 135.7 (C), 128.4 (2 CH), 128.3 (2
CH), 128.2 (CH), 128.1 (CH), 127.1 (2CH), 126.7 (2CH), 121.6 (C),
117.8 (CH), 104.4 (C), 103.8 (C), 89.4 (C), 86.5 (CH), 86.2 (CH), 39.5
(CH2), 31.6 (CH2), 23.2 (CH2), 2.2 (CH2), 2.0 (CH2), À0.2 (3CH3); IR
(film): n˜ =3034, 2958, 1251, 1024, 844, 762, 699 cmÀ1; MS (CI): m/z (%):
850 (4) [2M ++NH4] 434 (82) [M ++NH4], 417 (100) [M ++H]; elemental
analysis calcd (%) for C27H32O2Si (416.6): C 77.84, H 7.74; found C 77.64,
H 7.64.
3’-Trimethylsilyl-4’,5’,6’,6’a-tetrahydro-1’H-spiro(cyclopropane-1,1’-penta-
len-2’-one) (20a): Column chromatography (20 g of silica gel, column
15ꢆ2 cm, petroleum ether/Et2O 10:1) of the residue obtained from
enyne 14a (179 mg, 0.93 mmol), [Co2(CO)8] (440 mg, 1.29 mmol) and
TMANO (480 mg, 6.39 mmol) according to GP 7, gave the enone 20a
(109 mg, 53%) as a colorless oil. Rf =0.47 (petroleum ether/Et2O 10:1);
1H NMR (250 MHz, CDCl3, 258C): d=2.88 (dd, J=7.3, 12.6 Hz, 1H),
2.69–2.51 (m, 2H), 2.13–1.90 (m, 2H), 1.85–1.75 (m, 1H), 1.29–1.22 (m,
1H; Cpr-H), 1.20–1.06 (m, 1H), 0.97–0.79 (m, 3H; Cpr-H), 0.17 (s, 9H;
3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=213.1 (C), 196.9 (C),
135.0 (C), 54.7 (CH), 33.2 (C), 28.4 (CH2), 27.8 (CH2), 25.7 (CH2), 14.1
(CH2), 12.8 (CH2), À1.2 (3CH3); IR (film): n˜ =2957, 1679, 1603, 1247,
1109, 841 cmÀ1; MS (70 eV): m/z (%): 220 (25) [M +], 205 (100) [M +
ÀMe], 177 (7), 131 (14), 91 (7), 73 (12) [Me3Si+]; elemental analysis
calcd (%) for C13H20OSi (220.4): C 70.85, H 9.15; found C 71.02, H 9.23.
TMANO-induced PKRs of enynes 9a,b, 10a,b, 14a,b and 25d
General procedure GP 7: To a vigorously stirred solution of the respec-
tive enyne (0.25 mmol) in anhydrous dichloromethane (10 mL) was
added in the dark at ambient temperature [Co2(CO)8] (94 mg,
0.27 mmol). The reaction mixture was stirred at the same temperature
for an additional 1–3 h with TLC monitoring, cooled to À788C, trime-
thylamine N-oxide (TMANO) (113 mg, 1.5 mmol, 6 equiv) was added,
the reaction flask was connected to an oxygen cylinder, and the reaction
mixture was allowed to warm up with continued stirring within 16 h. The
reaction mixture was filtered through a 1 cm pad of silica gel, the solid
residue was washed with Et2O (15 mL), and the combined filtrates were
concentrated under reduced pressure. The residue was purified by
column chromatography.
1’,4’,5’,6’,7’,7’a-Hexahydro-3’-trimethylsilylspiro(cyclopropane-1,1’-inden-
2’-one) (20b): Column chromatography (20 g of silica gel, column 15ꢆ
2 cm, petroleum ether/Et2O 10:1) of the residue obtained from enyne
14b (127 mg, 0.62 mmol), [Co2(CO)8] (275 mg, 0.80 mmol) and TMANO
(280 mg, 3.73 mmol) according to GP 7 gave the enone 20b (100 mg,
69%) as a colorless oil. Rf =0.44 (petroleum ether/Et2O 10:1); 1H NMR
(250 MHz, CDCl3, 258C): d=3.10–3.03 (m, 1H), 2.47 (dd, J=5.4,
12.6 Hz, 1H), 2.24 (ddd, J=5.4, 12.9, 12.9 Hz, 1H), 2.07–1.97 (m, 1H),
1.90–1.81 (m, 2H), 1.54–0.80 (m, 7H), 0.23 (s, 9H; 3CH3); 13C NMR
(62.9 MHz, CDCl3, 258C): d=212.2 (C), 189.9 (C), 135.7 (C), 49.4 (CH),
33.0 (C), 32.9 (CH2), 32.0 (CH2), 27.7 (CH2), 25.0 (CH2), 15.4 (CH2), 12.6
4-Trimethylsilyl-1,1a,2,3-tetrahydrocyclopropa[c]pentalen-5-one
(18a):
Column chromatography (5 g of silica gel, column 15ꢆ1 cm, petroleum
ether/Et2O 10:1) of the residue obtained from enyne 9a (91 mg,
0.51 mmol), [Co2(CO)8] (230 mg, 0.67 mmol) and TMANO (270 mg,
3.59 mmol) according to GP 7 gave the enone 18a (54 mg, 51%) as a col-
2478
ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 2471 – 2482

Intramolecular Pauson–Khand Reactions
FULL PAPER
(CH2), À0.2 (3CH3); IR (film): n˜ =2932, 2856, 1685, 1588, 1247,
843 cmÀ1; MS (70 eV): m/z (%): 234 (28) [M +], 219 (100) [M +ÀMe], 95
(2), 73 (11) [Me3Si+]; elemental analysis calcd (%) for C14H22OSi (234.4):
C 71.73, H 9.46; found C 71.86, H 9.50.
was added, the reaction mixture was allowed to warm up to ambient tem-
perature over a period of 16 h and then worked up according to GP 7.
7’-Trimethylsilylspiro(cyclopropane-1,9’-tricyclo[4.3.0.01,3]non-6’-ene-8’-
one) (18c): Column chromatography (20 g of silica gel, column 15ꢆ2 cm,
petroleum ether/Et2O 10:1) of the residue obtained from enyne 9c
(115 mg, 0.56 mmol), [Co2(CO)8] (220 mg, 0.64 mmol) and NMO
(527 mg, 4.50 mmol)) according to GP 8, gave the enone 18c (40 mg,
31%) as a colorless solid. Rf =0.29 (petroleum ether/Et2O 10:1); m.p. 36–
378C; 1H NMR (250 MHz, CDCl3, 258C): d=2.72–2.63 (m, 1H), 2.34–
2.07 (m, 3H), 1.66 (m, 1H; Cpr-H), 1.25 (ddd, J=3.1, 6.3, 10.1 Hz, 1H;
Cpr-H), 1.05 (ddd, J=3.1, 6.3, 10.1 Hz, 1H; Cpr-H), 0.95 (dd, J=4.6,
4.6 Hz, 1H; Cpr-H), 0.79 (dd, J=4.6, 7.9 Hz, 1H; Cpr-H), 0.70–0.54 (m,
2H; Cpr-H), 0.21 (s, 9H, 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=
212.5 (C), 195.3 (C), 134.1 (C), 45.5 (C), 31.8 (C), 29.7 (CH2), 24.1 (CH2),
23.7 (CH), 14.8 (CH2), 14.4 (CH2), 13.6 (CH2), À0.8 (3CH3); IR (KBr):
n˜ =3057, 2990, 2917, 2895, 1679, 1588, 1247, 1163, 1080, 836 cmÀ1; MS
(70 eV): m/z (%): 232 (28) [M +], 217 (100) [M +ÀMe], 201 (9), 73 (23)
[Me3Si+]; HRMS: m/z (%): calcd for C14H20OSi: 232.1283; found
232.1283.
4’,5’,6’,6’a-Tetrahydro-1’H-spiro(cyclopropane-1,1’-pentalen-2-one) (21a):
The trimethylsilyl-protected enyne 14a (323 mg, 1.68 mmol) was treated
with potassium carbonate according to GP 3. The crude product was
taken up with anhydrous CH2Cl2 (20 mL), and the mixture treated with
[Co2(CO)8] (672 mg, 1.97 mmol) and then with TMANO (760 mg,
10.1 mmol) according to GP 7. Column chromatography (5 g of silica gel,
column 15ꢆ1 cm, petroleum ether/Et2O 5:1) of the residue gave the
enone 21a (100 mg, 40%) as a colorless oil. Rf =0.22 (petroleum ether/
Et2O 5:1); 1H NMR (250 MHz, CDCl3, 258C): d=5.95 (d, J=1.6 Hz, 1H;
=CH), 2.89 (dd, J=7.1, 12.1 Hz, 1H), 2.73–2.46 (m, 2H), 2.12–1.91 (m,
2H), 1.88–1.77 (m, 1H), 1.31–1.24 (m, 1H; Cpr-H), 1.17–1.03 (m, 1H),
0.99–0.82 (m, 3H; Cpr-H); 13C NMR (62.9 MHz, CDCl3, 258C): d=210.0
(C), 189.5 (C), 124.6 (CH), 52.8 (CH), 33.2 (C), 28.6 (CH2), 26.6 (CH2),
25.5 (CH2), 14.3 (CH2), 13.3 (CH2); IR (film): n˜ =2997, 2963, 2940, 1679,
1621, 1270, 1120, 866, 841 cmÀ1; MS (70 eV): m/z (%): 148 (80) [M +],
133 (14), 120 (58) [M +ÀCO], 105 (68), 91 (100), 79 (29), 62 (15), 51 (14);
elemental analysis calcd (%) for C10H12O (148.2): C 81.04, H 8.16; found
C 80.87, H 8.03.
1’,1’a,2’,3’-Tetrahydrospiro(cyclopropane-1,6’-cyclopropa[c]pentalen-5’-
one) (19c): Column chromatography (20 g of silica gel, column 15ꢆ2 cm,
petroleum ether/Et2O 5:1) of the residue obtained from enyne 10c
(130 mg, 0.98 mmol), [Co2(CO)8] (372 mg, 1.09 mmol) and NMO
(918 mg, 7.84 mmol) according to GP 8, gave the enone 19c (71 mg,
45%) as a colorless solid. Rf =0.20 (petroleum ether/Et2O 5:1); m.p.
618C; 1H NMR (250 MHz, CDCl3, 258C): d=6.08 (s, 1H; =CH), 2.66–
2.55 (m, 1H), 2.35–2.03 (m, 3H), 1.66 (m, 1H; Cpr-H), 1.32–1.25 (m, 1H;
Cpr-H), 1.15–1.04 (m, 1H; Cpr-H), 0.98 (dd, J=4.9, 4.9 Hz, 1H; Cpr-H),
0.82 (dd, J=4.9, 8.0 Hz, 1H; Cpr-H), 0.74–0.61 (m, 2H; Cpr-H);
13C NMR (62.9 MHz, CDCl3, 258C): d=209.3 (C), 188.2 (C), 123.3 (CH),
44.1 (C), 31.7 (C), 29.6 (CH2), 23.8 (CH), 23.4 (CH2), 14.2 (CH2), 14.0
(CH2), 13.8 (CH2); IR (KBr): n˜ =3038, 2992, 2934, 2867, 1670, 1608,
1124, 829 cmÀ1; MS (70 eV): m/z (%): 160 (100) [M +], 145 (17), 132 (52)
[M +ÀCO], 117 (83), 104 (26), 91 (66), 77 (19), 65 (19), 51 (21); HRMS:
m/z (%): calcd for C11H12O: 160.0888; found 160.0888; elemental analysis
calcd (%) for C11H12O (160.2): C 82.46, H 7.55; found C 82.53, H 7.55.
8’-Trimethylsilylspiro(cyclopropane-1,10’-tricyclo[5.3.0.01,3]dec-7’-ene-9’-
one) (18d): Column chromatography (5 g of silica gel, column 15ꢆ1 cm,
petroleum ether/Et2O 10:1) of the residue obtained from enyne 9d
(86 mg, 0.39 mmol), [Co2(CO)8] (150 mg, 0.44 mmol) and NMO (310 mg,
2.65 mmol), according to GP 8 gave the enone 18d (36 mg, 37%) as a
colorless oil. Rf =0.18 (petroleum ether/Et2O 10:1); 1H NMR (250 MHz,
CDCl3, 258C): d=2.83–2.71 (m, 1H), 2.51–2.39 (m, 1H), 1.88–1.52 (m,
4H), 1.49–1.33 (m, 1H), 1.20 (dd, J=5.4, 5.4 Hz, 1H; Cpr-H), 1.13 (ddd,
J=3.2, 6.6, 9.9 Hz, 1H; Cpr-H), 1.00 (ddd, J=3.1, 6.6, 9.9 Hz, 1H; Cpr-
H), 0.79 (dd, J=5.4, 8.7 Hz, 1H; Cpr-H), 0.61 (ddd, J=3.1, 6.6, 9.6 Hz,
1H; Cpr-H), 0.50 (ddd, J=3.2, 6.6, 9.6 Hz, 1H; Cpr-H), 0.23 (s, 9H;
3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=211.5 (C), 188.9 (C),
135.8 (C), 35.7 (C), 33.9 (C), 26.9 (CH2), 22.2 (CH2), 21.7 (CH2), 21.5
(CH), 17.0 (CH2), 14.0 (CH2), 13.3 (CH2), À0.3 (3CH3); IR (film): n˜ =
3079, 2998, 2951, 2858, 1673, 1562, 1406, 1325, 1247, 1032 cmÀ1; MS
(70 eV): m/z (%): 246 (58) [M +], 231 (100) [M +ÀMe], 215 (13), 203 (9),
141 (7), 73 (35) [Me3Si+]; HRMS: m/z (%): calcd for C15H22OSi:
246.1439; found 246.1439.
1’,4’,5’,6’,7’,7’a-Hexahydrospiro(cyclopropane-1,1’-inden-2-one)
(21b):
The trimethylsilyl-protected enyne 14b (140 mg, 0.68 mmol) was treated
with potassium carbonate according to GP 3. The crude product was
taken up with anhydrous CH2Cl2 (15 mL), and the mixture treated with
[Co2(CO)8] (282 mg, 0.82 mmol) and then with TMANO (310 mg,
4.13 mmol) according to GP 7. Column chromatography (5 g of silica gel,
column 15ꢆ1 cm, petroleum ether/Et2O 5:1) of the residue gave the
enone 20b (35 mg, 32%) as a colorless oil. Rf =0.17 (petroleum ether/
Et2O 5:1); 1H NMR (250 MHz, CDCl3, 258C): d=5.95 (t, J=1.6 Hz, 1H;
=CH), 2.89–2.82 (m, 1H), 2.50 (dd, J=5.3, 12.4 Hz, 1H), 2.35–2.21 (m,
1H), 2.07–1.95 (m, 1H), 1.92–1.75 (m, 2H), 1.51–0.81 (m, 7H); 13C NMR
(62.9 MHz, CDCl3, 258C): d=208.6 (C), 182.5 (C), 126.2 (CH), 47.5
(CH), 33.3 (C), 32.3 (CH2), 31.3 (CH2), 27.2 (CH2), 24.9 (CH2), 15.4
(CH2), 12.7 (CH2); IR (film): n˜ =2932, 2857, 1697, 1618, 1348, 1126,
850 cmÀ1; MS (70 eV): m/z (%): 162 (67) [M +], 147 (17) [M +ÀMe], 134
(38) [M +ÀCO], 119 (39), 105 (38), 91 (100), 77 (27); HRMS: m/z (%):
calcd for C11H14O: 162.1044; found 162.1044.
(7’aS,4’’S,5’’S)-1’,4’,5’,6’,7’,7’a-Hexahydro-3’-trimethylsilyldispiro(cyclopro-
pane-1,1’-inden-2’-one-4’,2’’-1,3-dioxolane) (26d): Column chromatogra-
phy (20 g of silica gel, column 15ꢆ2 cm, petroleum ether/Et2O 15:1) of
the residue obtained from enyne 25d (200 mg, 0.48 mmol), [Co2(CO)8]
(196 mg, 0.56 mmol) and TMANO (216 mg, 2.88 mmol) according to
GP 7 gave the enone 26d (168 mg, 79%) as a colorless solid. M.p. 145–
1558C; Rf =0.38 (petroleum ether/Et2O 15:1), which essentially was a 8:1
mixture of two diastereomers. Recrystallization from hexane gave pure
(7’aS,4’’S,5’’S)-26d; m.p. 1628C; [a]2D0 =À91 (c=1.0 in CHCl3); 1H NMR
(250 MHz, CDCl3, 258C): d=7.39–7.19 (m, 10H; Ar-H), 4.90 (d, J=
8.4 Hz, 1H; 5’’*-H), 4.75 (d, J=8.4 Hz, 1H; 4’’*-H), 3.05 (dd, J=5.2,
12.2 Hz, 1H; 7’a-H), 2.42–2.38 (m, 1H; 5’-H), 1.94–1.82 (m, 4H; 7’-H, 6’-
H, 5’-H), 1.29–0.91 (m, 5H; Cpr-H
+ 7’-H), 0.23 (s, 9H; 3 CH3);
13C NMR (62.9 MHz, CDCl3, 258C): d=212.1 (C), 184.8 (C), 136.7 (C),
135.9 (C), 134.6 (C), 128.6 (2CH), 128.5 (2 CH), 128.4 (CH), 128.3 (CH),
127.1 (2CH), 126.1 (2CH), 109.8 (C), 86.5 (CH), 84.3 (CH), 48.6 (CH),
38.6 (CH2), 33.7 (CH2), 33.5 (C), 22.3 (CH2), 16.5 (CH2), 13.4 (CH2), 1.0
(3CH3); IR (KBr): n˜ =2941, 1687, 1277, 1105, 1022, 845, 766 cmÀ1; MS
(CI): m/z (%): 906 (8) [2M ++NH4] 462 (1) [M ++NH4], 445 (100) [M +
+H]; elemental analysis calcd (%) for C28H32O3Si (444.6): C 75.63, H
7.25; found C 75.85, H 7.38. The structure of this compound was also
verified by X-ray crystal structure analysis.
(6’aS,4’’S,5’’S)-4’,5’,6’,6’a-Tetrahydro-3’-trimethylsilyldispiro(cyclopropane-
1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane) (26a): To a vigorously stirred
solution of the enyne 25a (67 mg, 0.17 mmol) in anhydrous dichloro-
methane (5 mL) was added [Co2(CO)8] (70 mg, 0.20 mmol), and the reac-
tion mixture was stirred at ambient temperature for an additional 1 h.
NMO (100 mg, 0.85 mmol) was added, the reaction mixture stirred at am-
bient temperature for an additional 20 h then worked up according to
GP 7. Column chromatography (8 g of silica gel, column 20ꢆ1 cm, petro-
leum ether/Et2O 10:1) of the residue gave the enone 26a (50 mg, 70%)
as a colorless oil, which essentially was a 5:1 mixture of two diastereo-
mers. Repeated column chromatography gave pure (6’aS,4’’S,5’’S)-26a as
NMO-induced PKRs of enynes 9c,d, 10c,d and 25a
General procedure GP 8: To a vigorously stirred solution of the respec-
tive enyne (0.56 mmol) in anhydrous dichloromethane (25 mL) was
added at À788C [Co2(CO)8] (220 mg, 0.64 mmol), the reaction mixture
was allowed to warm up to À208C and stirred at this temperature for an
additional 2 h. N-Methylmorpholine N-oxide (NMO, 527 mg, 4.50 mmol)
a
colorless solid. Rf =0.32 (petroleum ether/Et2O 10:1); m.p. 938C;
[a]2D0 =À218.1 (c=1.0 in CHCl3); 1H NMR (250 MHz, C6D6, 258C): d=
7.27–7.10 (m, 10H; Ar-H), 5.21 (d, J=8.5 Hz, 1H; 5’’*-H), 4.92 (d, J=
Chem. Eur. J. 2005, 11, 2471 – 2482
www.chemeurj.org
ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2479

A. de Meijere et al.
8.5 Hz, 1H; 4’’*-H), 3.08 (dd, J=8.9, 10.6 Hz, 1H; 6’-H), 2.42–2.32 (m,
1H; 5’-H), 2.22–2.10 (m, 1H; 7’-H), 1.54–1.41 (m, 2H; 6’-H), 1.24–1.10
(m, 2H; Cpr-H), 0.79–0.71 (m, 1H; Cpr-H), 0.66–0.55 (m, 1H; Cpr-H),
0.60 (s, 9H; 3CH3); 13C NMR (62.9 MHz, C6D6, 258C): d=211.5 (C),
187.2 (C), 138.2 (C), 137.8 (C), 136.4 (C), 128.9 (2 CH), 128.5 (2CH),
128.4 (CH), 127.5 (CH), 127.3 (2CH), 126.7 (2CH), 113.3 (C), 86.3 (CH),
84.9 (CH), 50.1 (CH), 39.9 (CH2), 34.1 (C), 24.7 (CH2), 15.1 (CH2), 14.4
silica gel, column 15ꢆ1 cm, petroleum ether/Et2O 5:1) of the residue
gave 22b (117 mg, 63%) as a yellow solid. Rf =0.46 (petroleum ether/
Et2O 5:1); m.p. 37–388C; 1H NMR (250 MHz, CDCl3, 258C): d=2.72–
2.40 (m, 2H), 1.82–1.70 (m, 2H), 1.40–1.33 (m, 1H; Cpr-H), 1.10 (s, 3H;
CH3), 1.10–0.83 (m, 3H; Cpr-H), 0.20 (s, 9H; 3CH3); 13C NMR
(62.9 MHz, CDCl3, 258C): d=212.1 (C), 203.9 (C), 185.4 (C), 143.7 (C),
50.9 (C), 41.9 (C), 37.6 (CH2), 31.0 (CH2), 24.0 (CH3), 17.1 (CH2), 13.7
(CH2), À1.3 (3CH3); IR (KBr): n˜ =2959, 1722, 1692, 1249, 1081,
849 cmÀ1; MS (70 eV): m/z (%): 248 (3) [M +], 233 (100) [M +ÀMe], 215
(2), 205 (7), 191 (11), 177 (83), 75 (13), 73 (6) [Me3Si+]; elemental analy-
sis calcd (%) for C14H20O2Si (248.4): C 67.70, H 8.12; found C 67.83, H
8.12.
(CH2), 0.5 (3CH3); IR (KBr): n˜ =2937, 1695, 1121, 845, 699, 668 cmÀ1
;
MS (70 eV): m/z (%): 430 (10) [M +], 324 (48), 296 (30), 268 (16), 219
(54), 206 (47), 180 (100), 165 (22), 105 (20), 91 (14), 73 (45); elemental
analysis calcd (%) for C27H30O3Si (430.6): C 75.31, H 7.02; found C 75.40,
H 7.06.
Minor diastereomer [(6’aR,4’’S,5’’S)-26a]: colorless solid; Rf =0.27 (petro-
leum ether/Et2O 10:1); m.p. 122–1258C; [a]2D0 =+118.5 (c=1.0 in
CHCl3); H NMR (250 MHz, C6D6, 258C): d=7.45–7.11 (m, 10H; Ar-H),
3’a-Ethyl-2’,3’,3’a,4’-tetrahydro-6’-trimethylsilylspiro(cyclopropane-1,4’-
pentalene-1’,5’-dione) (22c): The residue obtained from enynone 17c
(200 mg, 0.85 mmol) and [Co2(CO)8] (365 mg, 1.07 mmol) according to
GP 9 was taken up with CH2Cl2 (5 mL), the mixture stirred with
TMANO (200 mg, 2.66 mmol) for an additional 1 h, filtered again and
concentrated under reduced pressure. Column chromatography (5 g of
silica gel, column 15ꢆ1 cm, petroleum ether/Et2O 5:1) of the residue
gave 22c (146 mg, 65%) as a yellow solid. Rf =0.46 (petroleum ether/
Et2O 5:1); m.p. 71–728C; 1H NMR (250 MHz, CDCl3, 258C): d=2.74–
2.44 (m, 2H), 1.85–1.78 (m, 2H), 1.67 (dq, J=7.2, 14.4 Hz, 1H; CH2),
1.52 (ddd, J=3.7, 7.1, 10.0 Hz, 1H; Cpr-H), 1.39 (dq, J=7.2, 14.4 Hz,
1H; CH2), 1.08 (ddd, J=3.3, 7.1, 9.6 Hz, 1H; Cpr-H), 0.97 (ddd, J=3.3,
7.1, 10.0 Hz, 1H; Cpr-H), 0.85 (ddd, J=3.7, 7.1, 9.6 Hz, 1H; Cpr-H), 0.64
(t, J=7.2 Hz, 3H; CH3), 0.26 (s, 9H; 3CH3); 13C NMR (62.9 MHz,
CDCl3, 258C): d=212.2 (C), 204.1 (C), 183.1 (C), 145.8 (C), 54.9 (C),
39.5 (C), 37.8 (CH2), 30.7 (CH2), 27.8 (CH2), 17.9 (CH2), 13.7 (CH2), 8.3
(CH3), À1.2 (3CH3); IR (KBr): n˜ =2960, 1724, 1682, 1258, 1086,
850 cmÀ1; MS (70 eV): m/z (%): 262 (6) [M +], 247 (100) [M +ÀMe], 233
(5) [M +ÀEt], 219 (6), 205 (21), 145 (2), 115 (3), 75 (11), 73 (8) [Me3Si+];
elemental analysis calcd (%) for C15H22O2Si (262.4): C 68.65, H 8.45;
found C 68.70, H 8.53.
1
5.27 (d, J=8.8 Hz, 1H; 5’’*-H), 5.06 (d, J=8.8 Hz, 1H; 4’’*-H), 2.87 (dd,
J=7.3, 12.2 Hz, 1H; 5’-H), 2.27–2.21 (m, 2H; 7’-H), 1.55–1.45 (m, 1H;
Cpr-H), 1.45–1.36 (m, 1H; 6’-H), 1.14–1.12 (m, 1H; Cpr-H), 1.08–1.01
(m, 1H; 6’-H), 0.77–0.64 (m, 2H; Cpr-H), 0.63 (s, 9H, 3 CH3); 13C NMR
(62.9 MHz, C6D6, 258C): d=212.6 (C), 187.8 (C), 140.0 (C), 137.8 (C),
134.7 (C), 128.6 (2 CH), 128.4 (2 CH), 128.3 (CH), 127.0 (CH), 126.7 (2
CH), 126.1 (2 CH), 111.3 (C), 84.7 (CH), 83.3 (CH), 52.6 (CH), 41.2
(CH2), 33.4 (C), 25.5 (CH2), 15.1 (CH2), 14.4 (CH2), À0.1 (3CH3); ele-
mental analysis calcd (%) for C27H30O3Si (430.6): C 75.31, H 7.02; found
C 75.44, H 6.93.
Thermally induced PKRs of enynones 16a–c
General procedure GP 9: A thick-walled Pyrex bottle equipped with an
argon inlet was charged with a solution of the respective enynone
(0.45 mmol) in anhydrous MeCN (6 mL), then [Co2(CO)8] (170 mg,
0.50 mmol) was added at ambient temperature, the bottle was hermeti-
cally closed with a screw cap, and the reaction mixture was stirred at
808C for 16 h. After cooling, the reaction mixture was worked up accord-
ing to GP 7.
(3’S,3’aR,6’aS,4’’S,5’’S)-Hexahydro-3a-methyl-3-trimethylsilyldispiro(cy-
clopropane-1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane) (27a): To a stirred
suspension of cuprous iodide (200 mg, 1.05 mmol) in anhydrous Et2O
(5 mL) was added methyl lithium (1.9 mmol, 1.2 mL of a 1.6m solution in
Et2O) at 08C. After stirring at this temperature for an additional 5 min, a
solution of 26a (145 mg, 0.34 mmol) in Et2O (4 mL) was added dropwise,
the reaction mixture was stirred at this temperature for an additional 2 h
and then poured into ice-cold sat. aq. NH4Cl solution (25 mL). The aque-
ous phase was extracted with diethyl ether (3ꢆ20 mL), the combined or-
ganic extracts were dried over Na2SO4 and concentrated under reduced
pressure. Column chromatography (4 g of silica gel, column 10ꢆ1 cm, pe-
troleum ether/Et2O 15:1, Rf =0.39) of the residue gave 27a (130 mg,
86%) as a colorless foam, which essentially was a 7:1 mixture of presum-
ably (3’aR,3’S,6’aS,4’’S,5’’S)-27a and (3’aR,3’R, 6’aS,4’’S,5’’S)-27a.
Major diastereomer: 1H NMR (250 MHz, CDCl3, 258C): d=7.39–7.12
(m, 10H; Ar-H), 4.77–4.66 (m, 2H; 4’’-H, 5’’-H), 2.54 (s, 1H; 3’-H), 2.37–
1.97 (m, 4H; 6’a-H, 6’-H, 5’-H), 1.67–1.52 (m, 1H; 6’-H), 1.56 (s, 3H;
CH3), 1.27–0.78 (m, 4H; Cpr-H), 0.22 (s, 9H; 3CH3); 13C NMR
(62.9 MHz, CDCl3, 258C): d=218.6 (C), 137.4 (C), 136.2 (C), 128.7 (2
CH), 128.5 (2CH), 128.3 (CH), 128.0 (CH), 126.7 (2CH), 126.3 (2 CH),
120.3 (C), 85.7 (CH), 85.0 (CH), 53.6 (C), 52.2 (CH), 50.1 (CH), 35.9 (C),
34.9 (CH2), 25.3 (CH2), 21.3 (CH3), 20.7 (CH2), 11.7 (CH2), 0.2 (3CH3);
IR (KBr): n˜ =3033, 2967, 1705, 1456, 1309, 1290, 1249, 1211, 1182, 1159,
1132, 1107, 1046, 840, 762, 698 cmÀ1; MS (70 eV): m/z (%): 446 (3) [M +],
373 (1) [M +ÀSiMe3], 312 (13), 251 (14), 235 (27), 193 (14), 179 (100),
165 (24), 91 (27), 73 (57); elemental analysis calcd (%) for C28H34O3Si
(446.7): C 75.29, H 7.67; found C 75.44, H 7.68.
2’,3’,3’a,4’-Tetrahydro-6’-trimethylsilylspiro(cyclopropane-1,4’-pentalene-
1’,5’-dione) (22a): a) Column chromatography (5 g of silica gel deactivat-
ed with Et3N, column 15ꢆ1 cm, petroleum ether/Et2O 2:1) of the residue
obtained from enynone 17a (92 mg, 0.45 mmol) and [Co2(CO)8] (170 mg,
0.50 mmol) according to GP 9 gave the enedione 22a (40 mg, 38%) and
2’,3’,4’,6’-tetrahydrospiro(cyclopropane-1,4’-pentalene-1’,5’-dione) (23a)
(30 mg, 41%). 22a: a yellow oil; 1H NMR (250 MHz, CDCl3, 258C): d=
4.63 (dd, J=7.3, 11.1 Hz, 1H), 2.61–2.54 (m, 2H), 2.21–2.10 (m, 1H),
1.59–1.42 (m, 2H; 3’-H + Cpr-H), 1.14–1.00 (m, 3H; Cpr-H), 0.26 (s,
9H; 3CH3); 13C NMR (62.9 MHz, CDCl3, 258C): d=212.1 (C), 203.3 (C),
180.1 (C), 146.1 (C), 51.4 (CH), 40.2 (CH2), 35.3 (CH2), 25.3 (C), 16.2
(CH2), 15.0 (CH2), À1.2 (3CH3); Rf =0.46; IR (film): n˜ =2961, 1729,
1685, 1248, 1105, 855 cmÀ1; MS (70 eV): m/z (%): 234 (3) [M +], 219
(100) [M +ÀMe], 191 (5) [M +ÀMeÀCO], 177 (36), 73 (10) [Me3Si+];
23a: a colorless solid; Rf =0.07 (petroleum ether/Et2O 2:1); m.p. 151–
1548C; 1H NMR (250 MHz, CDCl3, 258C): d=3.14 (t, J=3.0 Hz, 2H),
2.69–2.66 (m, 2H), 2.51–2.48 (m, 2H), 1.66–1.47 (m, 4H; Cpr-H);
13C NMR (62.9 MHz, CDCl3, 258C): d=214.3 (C), 201.7 (C), 183.7 (C),
141.3 (C), 37.8 (CH2), 37.5 (C), 37.2 (CH2), 23.2 (CH2), 18.9 (2CH2); IR
(KBr): n˜ =2926, 1735, 1682, 1602, 1415, 1211, 1095, 1018, 890 cmÀ1; MS
(70 eV): m/z (%): 162 (100) [M +], 133 (15), 120 (23) [M +ÀCOCH2], 105
(21), 91 (74), 78 (26); elemental analysis calcd (%) for C10H10O2 (162.2):
C 74.06, H 6.22; found C 73.88, H 6.10. Repeated column chromatogra-
phy of 22a gave an additional 12 mg (16%) of 23a (total yield 57%).
b) A solution of the enone 26a (50 mg, 0.12 mmol) and p-toluenesulfonic
acid (100 mg) in anhydrous acetone (10 mL) was stirred under reflux for
16 h and then worked up according to GP 6. Column chromatography
(4 g of silica gel, column 10ꢆ1 cm, petroleum ether/Et2O 5:1) of the resi-
due gave 14 mg (71%) of 23a.
Addition of higher order cuprates to 26a
General procedure GP 10: A solution of the respective alkyllithium
(2.23 mmol) was added dropwise to a stirred suspension of cuprous cya-
nide (100 mg, 1.12 mmol) in anhydrous diethyl ether (4 mL) at À788C.
The reaction mixture was allowed to warm to À408C and stirred at this
temperature for ca. 20 min until a clear solution had formed. After this,
the reaction mixture was recooled to À788C, and a solution of the enone
26a (0.25 mmol) in Et2O (3 mL), followed by boron trifluoride etherate
3’a-Methyl-2’,3’,3’a,4’-tetrahydro-6’-trimethylsilylspiro(cyclopropane-1,4’-
pentalene-1’,5’-dione) (22b): The residue obtained from enynone 17b
(165 mg, 0.75 mmol) and [Co2(CO)8] (310 mg, 0.91 mmol) according to
GP 9 was taken up with CH2Cl2 (5 mL), the mixture stirred with
TMANO (200 mg, 2.66 mmol) for an additional 1 h, filtered again and
concentrated under reduced pressure. Column chromatography (5 g of
2480
ꢅ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 2471 – 2482

Intramolecular Pauson–Khand Reactions
FULL PAPER
(0.2 mL), was added dropwise. After stirring at this temperature for an
additional 30 min with TLC monitoring, the reaction was quenched by
adding a 1:1 mixture of sat. aq. NH4Cl solution and 25% aq. ammonia
(5 mL), and the reaction mixture was allowed to warm up to ambient
temperature The aqueous phase was extracted with diethyl ether (2ꢆ
5 mL), the combined organic extracts were dried and concentrated under
reduced pressure. The product was purified by column chromatography.
(22), 105 (31), 91 (62), 77 (36); elemental analysis calcd (%) for C25H26O3
(374.5): C 80.18, H 6.99; found C 80.05, H 6.98.
(3’aR,6’aR)-Hexahydro-3a-methylspiro(cyclopropane-1,1’-pentalene-2’,4’-
dione) (29a): This compound was prepared under conditions of the previ-
ous experiment from 28a (70 mg, 0.19 mmol) and p-toluenesulfonic acid
(20 mg) in anhydrous acetone (80 mL), but the reaction mixture was stir-
red under reflux for 27 h. Column chromatography (5 g of silica gel,
column 15ꢆ1 cm, petroleum ether/Et2O 2:1) gave 29a (19 mg, 57%) as a
colorless solid. Rf =0.13 (petroleum ether/Et2O 2:1); m.p. 62–638C;
[a]2D0 =À148 (c=1.0 in CHCl3); 1H NMR (250 MHz, CDCl3, 258C): d=
2.40 (d, J=18.6 Hz, 1H; 3’-H), 1.90 (d, J=18.6 Hz, 1H; 3’-H), 1.95–1.71
(m, 2H; 5’-H), 1.57 (t, J=6.6 Hz, 1H; 6’a-H), 1.38–1.22 (m, 1H; 6’-H),
1.19–1.10 (m, 1H; 6’-H), 1.02–0.75 (m, 2H; Cpr-H), 0.88 (s, 3H; CH3),
0.39–0.28 (m, 2H; Cpr-H); 13C NMR (62.9 MHz, CDCl3, 258C): d=218.5
(C), 213.7 (C), 51.0 (C), 50.2 (CH), 46.1 (CH2), 36.0 (C), 32.8 (CH2), 22.9
(CH2), 22.5 (CH3), 18.2 (CH2), 14.0 (CH2); IR (KBr): n˜ =2963, 1728,
1410, 1372, 1323, 1126, 1097, 1043 cmÀ1; MS (70 eV): m/z (%): 178 (100)
[M +], 150 (22) [M +ÀCO], 135 (28) [M +ÀCOÀCH3], 122 (41) [M +
À2CO], 108 (13), 93 (27), 79 (50); HRMS: m/z (%): calcd for C11H14O2:
178.0993; found 178.0993.
(3’S,3’aR,6’aS,4’’S,5’’S)-Hexahydro-3a-n-butyl-3-trimethylsilyldispiro(cy-
clopropane-1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane) (27b): Column
chromatography (20 g of silica gel, column 15ꢆ2 cm, petroleum ether/
Et2O 20:1) of the residue obtained from enone 26a (160 mg, 0.37 mmol),
CuCN (100 mg, 1.12 mmol), nBuLi (2.24 mmol, 0.95 mL of a 2.36m so-
lution in hexane) and BF3·Et2O (0.2 mL) according to GP 10 furnished a
single diastereomer of 27b (104 mg, 57%) as a colorless solid. Rf =0.48
(petroleum ether/Et2O 20:1); m.p. 1318C; [a]2D0 =À163.2 (c=1.0 in
CHCl3); 1H NMR (250 MHz, CDCl3, 258C): d=7.40–7.17 (m, 10H; Ar-
H), 4.77 (d, J=8.6 Hz, 1H; 5’’*-H), 4.72 (d, J=8.6 Hz, 1H; 4’’*-H), 2.72
(s, 1H; 3’-H), 2.44–2.18 (m, 3H; 5’-H, 6’a-H), 2.07–1.84 (m, 2H; 6’-H),
1.82–1.11 (m, 8H; 2Cpr-H + 3CH2), 0.99 (t, J=7.0 Hz, 3H; CH3), 0.94–
0.86 (m, 2H; Cpr-H), 0.22 (s, 9H; 3 CH3); 13C NMR (62.9 MHz, CDCl3,
258C): d=219.9 (C), 137.7 (C), 136.1 (C), 128.5 (2CH), 128.3 (2CH),
128.2 (CH), 128.0 (CH), 127.0 (2CH), 126.3 (2CH), 120.6 (C), 85.2 (CH),
85.0 (CH), 57.6 (C), 50.4 (CH), 48.9 (CH), 36.4 (C), 36.1 (CH2), 34.1
(CH2), 28.7 (CH2), 26.7 (CH2), 24.0 (CH2), 21.4 (CH2), 14.1 (CH3), 13.8
(CH2), 0.8 (3CH3); IR (KBr): n˜ =2953, 2928, 1702, 1245, 1147, 1023, 840,
759, 698 cmÀ1; MS (70 eV): m/z (%): 488 (1) [M +], 415 (1) [M +ÀSiMe3],
382 (12), 251 (9), 180 (100), 91 (6), 73 (16). The structure of this com-
pound was verified by X-ray crystal structure analysis.
Acknowledgements
This work was supported by State of Niedersachsen and the Fonds der
Chemischen Industrie. The authors are grateful to the companies BASF
AG, Bayer AG, Chemetall GmbH, Degussa AG and Chisso Petrochemi-
cal for generous gifts of chemicals. We are particularly grateful to Dr. P.
Lubini, Alta Scuola Pedagogica, Locarno, Switzerland, for the X-ray crys-
tal structure analysis of compound 27b, and to Dr. B. Knieriem, Gçttin-
gen, for his careful reading of the final manuscript.
(3’S,3’aR,6’aS,4’’S,5’’S)-Hexahydro-3a-sec-butyl-3-trimethylsilyldispiro(cy-
clopropane-1,1’-pentalene-2’-one-4’,2’’-1,3-dioxolane)
(27c):
Column
chromatography (20 g of silica gel, column 15ꢆ2 cm, petroleum ether/
Et2O 20:1) of the residue obtained from enone 26a (120 mg, 0.28 mmol),
CuCN (100 mg, 1.12 mmol), sBuLi (2.24 mmol, 1.6 mL of a 1.4m solution
in hexane) and BF3·Et2O (0.1 mL) according to GP 10 furnished a 1.25:1
mixture of diastereomers of 27c (101 mg, 74%) as a colorless solid. Rf =
0.44 (petroleum ether/Et2O 20:1); m.p. 136–1428C; 1H NMR (250 MHz,
CDCl3, 258C): d=7.38–7.24 (m, 10H; Ar-H), 4.93, 4.92 (d, J=8.7 Hz,
1H; 5’’*-H), 4.70, 4.69 (d, J=8.7 Hz, 1H; 4’’*-H), 3.38, 3.28 (s, 1H; 3’-H),
2.45–2.34, 2.12–2.05, 1.90–1.82, 1.70–1.24, (several m; 8H), 1.21–1.14 (m,
3H; CH3), 1.01–0.83 (m, 7H; 4Cpr-H + CH3), 0.23, 0.22 (s, 9H; 3 CH3);
13C NMR (62.9 MHz, CDCl3, 258C): d=220.0 (C), 138.1, 138.0 (C), 136.3,
136.1 (C), 128.5 (2CH), 128.2 (2 CH), 128.1 (CH), 126.6 (CH), 126.5 (2
CH), 126.4 (2CH), 118.8 (C), 85.3 (CH), 83.3, 83.2 (CH), 62.8, 62.5 (C),
47.8, 47.7 (CH), 47.1 (CH), 39.7, 39.1 (CH2), 38.9 (CH), 34.7, 34.5 (C),
27.3, 27.1 (CH2), 26.3 (CH2), 20.8, 20.7 (CH2), 16.9, 16.1 (CH3), 15.7
(CH2), 13.0, 12.6 (CH3), 1.3, 1.1 (3CH3); IR (KBr): n˜ =2969, 2877, 1701,
1245, 1149, 1019, 837, 760 cmÀ1; MS (70 eV): m/z (%): 488 (1) [M +], 473
(1) [M +ÀCH3], 421 (1), 415 (1) [M +ÀSiMe3], 382 (8), 326 (3), 291 (2),
180 (100), 91 (5), 73 (13); elemental analysis calcd (%) for C31H40O3Si
(488.7): C 76.18, H 8.25; found C 76.14, H 8.09.
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a
Modern Interdisciplinary Field (Eds.: A. de Meijere, H. tom Dieck),
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(3’aR,6’aR,4’’S,5’’S)-Hexahydro-3a-methyldispiro(cyclopropane-1,1’-pen-
talene-2’-one-4’,2’’-1,3-dioxolane) (28a): A solution of the compound 27a
(93 mg, 0.21 mmol) and p-toluenesulfonic acid (10 mg) in anhydrous ace-
tone (10 mL) was stirred at ambient temperature for 2 h and then
worked up according to GP 6. Column chromatography (5 g of silica gel,
column 15ꢆ1 cm, petroleum ether/Et2O 10:1) of the residue gave 28a
(76 mg, 97%) as a colorless oil. Rf =0.16 (petroleum ether/Et2O 10:1);
1H NMR (250 MHz, CDCl3, 258C): d=7.36–7.15 (m, 10H; Ar-H), 4.77–
4.70 (m, 2H; 4’’*-H, 5’’*-H), 2.82 (d, J=19.0 Hz, 1H; 3’-H), 2.33 (d, J=
19.0 Hz, 1H; 3’-H), 2.24–1.98 (m, 4H; 5’-H, 6’-H, 6’a-H), 1.71–1.56 (m,
1H; 6’-H), 1.48 (s, 3H; CH3), 1.30–1.23 (m, 2H; Cpr-H), 1.02–0.86 (m,
2H; Cpr-H); 13C NMR (62.9 MHz, CDCl3, 258C): d=218.6 (C), 137.1
(C), 135.9 (C), 128.5 (2CH), 128.4 (2CH), 128.2 (CH), 128.0 (CH), 126.9
(2CH), 126.3 (2CH), 119.7 (C), 86.1 (CH), 85.2 (CH), 51.2 (CH), 49.9
(C), 48.4 (CH2), 35.7 (C), 34.9 (CH2), 25.9 (CH2), 22.1 (CH3), 21.7 (CH2),
13.3 (CH2); IR (film): n˜ =2955, 1726, 1456, 1183, 1104, 1027, 763 cmÀ1
MS (70 eV): m/z (%): 374 (2) [M +], 268 (39), 251 (25), 180 (100), 165
;
Chem. Eur. J. 2005, 11, 2471 – 2482
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2481

A. de Meijere et al.
[6] For the application of intermolecular PKRs in the synthesis of illu-
dine-like compounds see: K. M. Brummond, J. Lu, J. Am. Chem.
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[7] a) H. Nꢀske, S. Brꢁse, A. de Meijere, Synlett 2000, 1467–1469; b) B.
Witulski, M. Gçssmann, Synlett 2000, 1793–1797; c) I. Marchueta,
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3, 3193–3196, and ref. [3] cited therein.
[8] The preparation and chemical transformations of methylenecyclo-
propane itself[8a–d] and its close relative bicyclopropylidene[8e–h] have
been reviewed extensively: a) P. Binger, H. M. Bꢀch, Top. Curr.
Chem. 1987, 135, 77–151; b) P. Binger, T. Schmidt, in: Methods of
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Chem. Rev. 1998, 98, 589–635; d) A. Brandi, S. Cicchi, F. M. Cor-
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S. I. Kozhushkov, A. F. Khlebnikov, Zh. Org. Khim. 1996, 32, 1607–
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1990, 31, 5289–5292.
[29] Crystals of compounds 19c, 26d and 27b were obtained by slow
evaporation of their solutions in petroleum ether. The X-ray single
crystal data were collected at 153(2) K on a Bruker STOE AED2
diffractometer (MoKa, graphite monochromator, w scan). The struc-
ture was solved by direct methods and refined by full-matrix least
squares on F2 for all data with the Bruker SHELXTL program
suite. Non-hydrogen atoms were refined with anisotropic displace-
ment parameters, H atoms were refined isotropically.
Crystal data for 19c: C11H12O (160.21), crystal size 0.90ꢆ0.80ꢆ
0.50 mm3, T=153(2) K, monoclinic, Z=4, space group P21/n,
F(000)=344, a=8.3120(10), b=11.764(2), c=8.7500(10) ꢈ, a=g=
90, b=96.090(10)8, V=850.8(2) ꢈ3, 1=1.251 gcmÀ3, m=0.078 mmÀ1
,
intensities measured: 1602 (2qmax =45.828), independent: 1469
(Rint =0.0547), 109 parameters refined, R1 =0.0623, wR2 =0.1531 for
1468 reflections with I
> 2s(Io), R1 (all data)=0.0833, wR2 (all
data)=0.1774, GOF=1.062, maximum and minimum residual elec-
tron density 0.616 and À0.278 eꢈÀ3
.
Crystal data for 26d: C28H32O3Si (444.63), crystal size 0.60ꢆ0.50ꢆ
0.50 mm3, T=193(2) K, orthorhombic, Z=4, space group P212121,
F(000)=952, a=9.881(5), b=10.558(4), c=24.100(14) ꢈ, a=g=b=
908, V=2514(2) ꢈ3, 1=1.175 gcmÀ3
, , intensities
m=0.119 mmÀ1
[9] W. A. Smit, S. L. Kireev, O. M. Nefedov, V. A. Tarasov, Tetrahedron
Lett. 1989, 30, 4021–4024.
measured: 3793 (2qmax =44.988), independent: 3281 (Rint =0.0387),
292 parameters refined, R1 =0.0400, wR2 =0.1027 for 3279 reflec-
tions with I > 2s(Io), R1 (all data)=0.0413, wR2 (all data)=0.1045,
GOF=1.041, maximum and minimum residual electron density
[10] Intermolecular PKRs: a) H. Corlay, I. W. James, E. Fouquet, J.
Schmidt, W. B. Motherwell, Synlett 1996, 990–992; b) B. Witulski, T.
Stengel, Angew. Chem. 1998, 110, 495–498; Angew. Chem. Int. Ed.
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2, 545–555; d) H. Corlay, E. Fouquet, E. Magnier, W. B. Mother-
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lecular PKRs of 2 see also: g) A. Goti, F. M. Cordero, A. Brandi,
Top. Curr. Chem. 1996, 178, 1–97.
0.143 and À0.219 eꢈÀ3
.
Crystal data for 27b: C31H40O3Si (488.72), crystal size 0.50ꢆ0.20ꢆ
0.20 mm3, T=193(2) K, monoclinic, Z=2, space group P21, F(000)=
528, a=9.630(2), b=8.680(2), c=16.530(3) ꢈ, a=g=90, b=
93.30(3)8, V=1379.4(5) ꢈ3, 1=1.177 gcmÀ3, m=0.144 mmÀ1, intensi-
ties measured: 2315 (2qmax =46.028), independent: 2258 (Rint
=
0.1940), 320 parameters refined, R1 =0.0717, wR2 =0.1609 for 2258
reflections with I > 2s(Io), R1 (all data)=0.1051, wR2 (all data)=
0.1609, GOF=1.132, maximum and minimum residual electron den-
sity 0.638 and À0.260 eꢈÀ3. The X-ray crystal structure analysis of
the latter compound does establish its stereochemistry, but the un-
satisfactory high R values do permit neither to discuss any structural
peculiarities in 27b nor to save the results of this measurements in
the Cambridge Crystallographic Data Centre.
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S. I. Kozhushkov, T. Spaeth, N. S. Zefirov, J. Org. Chem. 1993, 58,
502–505; b) A. de Meijere, S. I. Kozhushkov, T. Spꢁth, Org. Synth.
2000, 78, 142–151.
[18] a) A. de Meijere, S. I. Kozhushkov, N. S. Zefirov, Synthesis 1993,
681–683; Cf. also b) S. Lçhr, C. Jacobi, A. Johann, G. Gottschalk,
A. de Meijere, Eur. J. Org. Chem. 2000, 2979–2989.
CCDC-252041 (19c) and -252040 (26d) contain 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.ac.uk/data_request/cif
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4851–4854; c) P. Magnus, L. M. Principe, J. Org. Chem. 1989, 54,
5148–5153; for a kind of short review see also local refs. [3–6] in
ref. [1b] and refs. [2–18] in ref. [10e].
[32] H. Becker, Dissertation, Universitꢁt Gçttingen, 1996. The prepara-
tion of compound 17d is also mentioned in ref. [10e].
[33] The corresponding desilylated compounds gave only low yields of
bicyclic products in the PKRs with almost no diastereoselectivity, in-
dependent of whatever protocol was used.
[19] J. E. Baldwin, R. M. Adlington, R. Singh, Tetrahedron 1992, 48,
3385–3412.
[20] G. Fournet, G. Balme, J. J. Barieux, Tetrahedron 1988, 44, 5821–5832.
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[22] A. Stolle, Dissertation, Universitꢁt Hamburg, 1992.
[34] These values are somewhat lower than those obtained by repetition
of our results, but with 2,5-dimethoxy-2,5-dimethylhexane-3,4-diol as
an auxiliary, for which diastereoselection in the range of 1:10 to 1:20
has recently been reported; see ref. [10e].
[23] This compound is known, however, has been reported without ex-
perimental details and spectroscopic characterization: I. Nakamura,
A. I. Siriwardana, S. Saito, Y. Yamamoto, J. Org. Chem. 2002, 67,
3445–3449.
[24] B. T. Lotz, M. J. Miller, J. Org. Chem. 1993, 58, 618–625.
[25] P. A. Wehrli, V. Chu, J. Org. Chem. 1973, 38, 3436.
[35] Review: B. H. Lipshutz, Synlett 1990, 119–128.
[36] The independently obtained dione (3’aR,6’aR)-29a had [a]=À143
(solvent and concentration were not reported).
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[26] K. Utimoto, M. Tamura, K. Sisido, Tetrahedron 1973, 29, 1169–1171.
[27] N. Jeong, Y. K. Chung, B. Y. Lee, S. H. Lee, S.-E. Yoo, Synlett 1991,
204–206.
Received: September 30, 2004
Published online: February 1, 2005
2482
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Chem. Eur. J. 2005, 11, 2471 – 2482