Construction of bi- and tricyclic skeletons by Domino-Heck-Diels-Alder reactions

Article abstract of DOI:10.1002/1522-2675(200210)85:10<3161::AID-HLCA3161>3.0.CO;2-2

Palladium-catalyzed intramolecular reactions of 2-bromo 1,6-dienes followed by intermolecular [4 + 2] cycloaddition with suitable dienophiles in one-pot operations gave hexahydroindenes 8 and 9 in yields of 40-78%, an hexahydro-s-indacene derivative 13 co

Full text of DOI:10.1002/1522-2675(200210)85:10<3161::AID-HLCA3161>3.0.CO;2-2

Helvetica Chimica Acta Vol. 85 (2002)
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Construction of Bi- and Tricyclic Skeletons by Domino-Heck Diels Alder
Reactions
by Stefanie Kˆrbe and Armin de Meijere*
Institut f¸r Organische Chemie, Georg-August-Universit‰t Gˆttingen, Tammannstrasse 2, D-37077 Gˆttingen
(fax: ‡49-551-399475; e-mail: Armin.deMeijere@chemie.uni-goettingen.de)
and
Thomas Labahn
Institut f¸r Anorganische Chemie, Georg-August-Universit‰t Gˆttingen, Tammannstrasse 4,
D-37077 Gˆttingen
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday
Palladium-catalyzed intramolecular reactions of 2-bromo 1,6-dienes followed by intermolecular [4 ‡ 2]
cycloaddition with suitable dienophiles in one-pot operations gave hexahydroindenes 8 and 9 in yields of 40
78%, an hexahydro-s-indacene derivative 13 could be obtained in up to 25% yield with cyclopent-2-en-1-one
(10) as a dienophile in the presence of different Lewis acids, and a spirocyclopentane-hexahydroindenone 18
could be isolated in 72% yield. When in-situ-formed iminium salts were used as heterodienophiles, hexahydro-
1H-[2]pyrindinols 31 could be obtained in a one-pot two-step operation in 29 46% yield.
Introduction. Domino reactions have emerged as a particularly versatile method
for the construction of bi- and tricyclic systems, as they achieve the stereocontrolled
formation of more than two new bonds in a single operational step [1]. Among the
many new transition-metal-catalyzed reactions, the Pd-catalyzed Heck cross-coupling
reaction has become one of the most important methods for CÀC bond-formation [2].
Hexahydroindenes are easily prepared in a one-pot procedure starting from 2-bromo
1,6-dienes, which, by an intramolecular Heck reaction, first afford a 1,2-dimethylidenyl-
cyclopentane1) that, in the presence of a dienophile, immediately undergoes an
intermolecular Diels Alder reaction. The reaction has been thoroughly studied for 2-
bromo 1,6-dienes containing a dialkyl malonate unit at the 4-position, simply because
the starting materials can easily be prepared by twofold alkylation of dialkyl malonates
[4]. Geminal disubstitution in the open-chain precursor does play a role in the
intramolecular Heck reaction because of the Thorpe-Ingold effect [5], but it is not
essential for the success of the intramolecular coupling [4a]. With regard to the
synthesis of natural products, the geminal ester groups would have to be replaced by
geminal dimethyl groups. Therefore, in this paper, we report a study of the synthesis
and Pd-catalyzed cyclization of 2-bromo 1,6-dienes with geminal dimethyl groups with
respect to various Pd catalysts, solvents, bases, and ligands.
1
)
Dimethylidenylcycloalkanes can also be formed by cyclization of acetylenic vinyllithiums generated from
the corresponding acetylenic vinyl bromides by Li/Br exchange [3].

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Helvetica Chimica Acta Vol. 85 (2002)
Results and Discussion. Formation of Carbocyclic Systems. The synthesis of 2-
bromo 1,6-dienes with geminal dimethyl groups is not as straightforward as that with
geminal diester groups, which are disubstituted dialkyl malonates [4a]. However, the
imine 1, prepared from isobutyraldehyde and cyclohexylamine, can be deprotonated
with lithium diisopropylamide (LDA) [6], and alkylation of the azaenolate with 2,3-
dibromopropene (2) followed by acid-catalyzed hydrolysis furnishes the bromo
aldehyde 3 in 42% isolated yield. Because of its instability, 3 has to be immediately
converted further, e.g., by reaction with vinylmagnesium bromide (4) to give 2-bromo-
4,4-dimethylhepta-1,6-dien-5-ol (5) in 54% yield (Scheme 1).
Scheme 1. Preparation of 2-Bromo-4,4-dimethylhepta-1,6-dien-5-ol (5)
2-Bromo 1,6-dienes of type 5 have been shown to cyclize in the presence of
Pd(OAc)2, Ph3P, and K2CO3 or Ag2CO3 to afford 1,2-bis(exomethylene)cyclopentanes
of type 6, which can subsequently undergo Diels Alder reactions to give hexahy-
droindene derivatives 8 and 9. As previous studies have revealed that the yields without
isolation of intermediate 6 are consistently higher than those obtained in two steps, the
reactions of 5 with acrylates and methyl vinyl ketone were carried out as single one-pot
operations (Scheme 2) [4][7].
Scheme 2. Cyclization of 5 and Diels Alder Reaction
a) or b)
Br
HO
HO
5
6
R
R
7
+
40 78%
R
HO
HO
8
9
a) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), Ag2CO3 (1.2 equiv.), MeCN, 808, 18 h. b) Pd(OAc)2 (5 mol-%),
Ph3P (10 mol-%), K2CO3 (2 equiv.), MeCN, 808, 18 h. For details, see Table 1.

Helvetica Chimica Acta Vol. 85 (2002)
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In a typical experiment, a solution of the bromo diene 5 (1 mmol), the dienophile 7
(3 mmol), a base (1.2 2 mmol), Pd(OAc)2 (5 mol%), and Ph3P (10 mol%) was heated
in anhydrous MeCN at 808 for 18 h.
In an effort to elucidate the conditions for this transformation, the 2-bromo 1,6-
diene 5 in the presence of various dienophiles and different bases was subjected to such
conditions. The products, mixtures of regioisomers and diastereoisomers 8 and 9, were
obtained in higher yields when K2CO3 instead of Ag2CO3 was used as a base. The latter
is known to suppress not only double-bond migration but also the Heck reaction
(Table 1, Entries 1, 3, and 5). The best yields resulted with methyl acrylate (Entries 1
and 2), but the regioisomeric excess was low, even when the sterically more-demanding
tert-butyl acrylate was used (Entries 3 and 4). Each regioisomer was a mixture of
diastereoisomers. The diastereoisomeric ratios could not be determined from the
1H-NMR spectra of the mixtures since the peaks were not well-resolved.
Table 1. Heck Diels Alder Reaction of 5 with Different Dienophiles under Various Conditions
Entry
Base
R
Product
Yield [%]
Ratio 8/9a)
1
2
3
4
5
6
Ag2CO3
K2CO3
Ag2CO3
K2CO3
Ag2CO3
K2CO3
CO2Me
CO2Me
CO2(t-Bu)
CO2(t-Bu)
COMe
8a, 9a
8a, 9a
8b, 9b
8b, 9b
8c, 9c
8c, 9c
41
78
40
62
56
70
1.5 : 1
1.5 : 1
1.9 : 1
1.9 : 1
1.9 : 1
1.9 : 1
COMe
a) The ratios of the regioisomers were determined by integration of the relevant peaks in the 1H-NMR spectra
after oxidation of 8 and 9 to the corresponding ketones.
With cyclopent-2-en-1-one (10) as a dienophile, this Heck Diels Alder reaction
should allow easy access to decahydro-s-indacene derivatives [8]. Because of the low
reactivity of 10 under the established conditions described above, only decomposition
could be detected after 14 days of heating. Carrying out the reaction as a one-pot two-
step operation, in which the Diels Alder reaction was performed at 10 kbar [9], gave
the regioisomeric decahydro-s-indacene derivatives 11 and 12 after 4 d in 31% yield as
a mixture of diastereoisomers (Scheme 3).
Diels Alder reactions can be accelerated not only by high pressure (for recent
reviews on high-pressure chemistry, see [9]), but also by addition of Lewis acids such as
LiBF4 [10], BF3 ¥ OEt2, dialkylaluminum chlorides, trialkylaluminum, or alkoxytita-
nium halides. With LiBF4 added to the mixture of 5, 10, and the catalyst cocktail, the
hexahydro-s-indacene derivative 13 was obtained as the only product, which must be
formed from 11 by Lewis acid promoted elimination of H2O. The reaction time of 14 d
was very long, and even the best yield was only 25% (Table 2, Entry1 ). Apparently, the
dimethylidenylcyclopentanol 6 is not stable enough under these conditions for
extended times. Therefore, Et2AlCl was tested as a Lewis acid. After only 18 h, the
product 13 could be isolated in 22% yield, but a large number of unidentified side
products were also formed (Entry2 ). In our search for a Lewis acid that is not as strong
as Et2AlCl but strong enough to catalyze the reaction, AlMe3 and Ti(OiPr)4 were also
tested (Entries 4 and 5). With these, however, no hexahydro-s-indacene derivative was
observed; only the starting material could be recovered. With only 1.5 equiv. of

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 3. Heck Diels Alder Reaction of 5 with Cyclopentenone 10 as a Dienophile
H
O
11
O
HO
a)
10
Br
+
10 kbar
r.t., 4 d
O
H
HO
HO
31%
5
6
12
HO
a) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), K2CO3 (1 equiv.), MeCN, 808, 18 h.
Scheme 4. Reaction of 5 with 10 in the Presence of a Lewis Acid
Lewis acid
10, MeCN
≤ 25%
a)
13
14
O
Br
Et2AlCl, 7a
HO
HO
MeCN, r.t., 1 d
26%
CO2Me
5
6
a) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), K2CO3 (1 equiv.), MeCN, 808, 18 h. For details, see Table 2.
Table 2. Heck Diels Alder Domino Reaction of 5 with Cyclopentenone 10 in the Presence of Different Lewis
Acids
EntryLewis
acid (equiv.), time
LiBF4 (3), 14 d
Et2AlCl (3), 18 h
Et2AlCl (1.5), 18 h
Me3Al (3), 72 h
Ti(OiPr)4 (3), 72 h
Product
Yield [%]
1
2
3
4
5
13
13
13
5
25
22
6a)
b
)
)
b
5
a) Additionally, 17% of diene 6 was recovered. b) Only decomposition was observed.
Et2AlCl, only 6% of 13 and 17% of the dimethylidenylcycloalkane could be isolated
(Entry3 ).
After this partial success with an added Lewis acid, the Diels Alder reaction of the
preformed intermediate 6 with methyl acrylate (7a) was also tested in the presence of
Et2AlCl.

Helvetica Chimica Acta Vol. 85 (2002)
3165
Towards that end, a solution of Et2AlCl (3 equiv.) and 7a (3 equiv.) in MeCN,
which had been stirred for 15 min, was added to the mixture containing 6, and stirring
was continued at ambient temperature for 1 d. The expected tetrahydroindene 14 could
be isolated in 26% yield, along with a considerable amount of decomposition product.
To avoid the formation of diastereoisomeric mixtures, the bromoheptadienol 5 was
oxidized to the ketone 15 according to the Swern protocol [11]. Surprisingly, when the
bromodienone 15 was treated with the Pd catalyst in the presence of 7a, the expected
product 17 was not observed, but the hexahydrospiro(cyclopentaneinden)one 18 was
isolated as a single product in 72% yield (Scheme 5). Even in the presence of a large
excess of 7a (10 equiv.), only 18 was formed. Apparently, the a,b-unsaturated enone
moiety in the 5,5-dimethyl-2,3-dimethylenecyclopentanone 16 first formed is a far
better dienophile than 7a. It is remarkable that the hexahydroindenone 18 was formed
as a single regio- as well as diastereoisomer, the structure of which was established by
X-ray-analysis (Fig.)2).
Scheme 5. Swern Oxidation of the Bromodiene 5 and Palladium-Catalyzed Reaction of 15
a)
b)
Br
Br
75%
HO
O
O
5
16
15
7a
x 2
O
72%
CO2Me
O
O
17
18
a) (COCl)2, DMSO, Et3N, CH2Cl2, r.t., 18 h. b) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), Ag2CO3 (1.25 equiv.),
MeCN, 808, 18 h.
The mono- and dimethyl-substituted bromodienes 25 and 27 could be prepared
from the t-Bu-substituted isobutyraldehyde imine in close analogy to the synthesis of 5
with (E)-1,2-dibromobut-2-ene (22) and 1,2-dibromo-3-methylbut-2-ene (23) instead
of 2,3-dibromopropene in the alkylation of the azoenolate. In view of the illudine
sesquiterpenes with their tetrahydroindene skeleton, the synthesis of such compounds
2
)
Crystallographic data (excluding structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as deposition No. CCDC-185854. Copies of
this data can be obtained, free of charge, on application to the CCDC, 12 Union Rd., Cambridge CB21EZ,
UK (fax: ‡44(1223)336-033; e-mail: deposit@ccdc.cam.ac.uk).

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Helvetica Chimica Acta Vol. 85 (2002)
Figure. Structure of 18 in the crystal2)
with a Me group at C(4) of the hexahydroindene derivative was of interest in this
context [12].
Deprotonation of 21 with LDA, alkylation with 22 or 23, and acidic workup gave
the aldehydes 24 and 26 in moderate yields of 54 and 48%, respectively. Addition of
vinylmagnesium bromide (4) yielded the bromodienes 25 and 27 in 45 and 47% yields,
respectively (Scheme 6).
When the bromodiene 25 was subjected to the usual conditions of the domino
Heck Diels Alder reaction, the exocyclic diene 20 could be isolated in 45% yield, but
only a trace of the hexahydroindenes 19 could be detected. It is a bit surprising that the
Diels Alder reaction of 20 did not occur easily in spite of the s-cis conformation of its
1,3-diene unit.
Under the same conditions, the dimethyl-substituted bromodiene 27 gave no
bicyclic compound at all. Only the isopropenylcyclopentenol 28 was isolated in 74%
yield; 28 probably results from the exocyclic diene 29 first formed by isomerization,
which can occur either by re-addition with reversed regioselectivity of the eliminated
hydridopalladium bromide and subsequent elimination of hydridopalladium bromide
[13], or by a concerted suprafacial 1,5-H-shift. Cyclopentadienes are known to undergo
such 1,5-H-shifts rapidly at room temperature; for this rearrangement to occur in
acyclic or exocyclic dienes, higher temperatures (>2508) are usually required [14],
although the s-cis conformation of 29 should facilitate such a 1,5-H-shift. The
substitution pattern in the resulting diene 28 does not favor a conformation that would
allow a Diels Alder reaction to occur.
Formation of Heterocyclic Systems. Since N-containing heterocyclic systems are of
particular interest because of their potential biological activities, the domino Heck
Diels Alder sequence was also applied to the preparation of azabicycles. This can be
achieved by incorporation of the N-atom in the cyclization precursor, as described in an
earlier publication [15].
Another possibility is to use N-atom-containing dienophiles, such as imines and
nitroso compounds [16]. For such hetero-Diels Alder reactions, either the imines have
to be electron deficient or the dienes particularly electron rich. Activation by added
Lewis acids has also been used in many cases. Larsen and Grieco reported that imines
formed in situ from formaldehyde and an amine hydrochloride react with unactivated
dienes without added Lewis acids [17]. This approach has been adopted for the use with
formaldehyde and amino acid ester hydrochlorides by Waldmann [18].
Since formaldehyde would immediately reduce the Pd(OAc)2 precatalyst to
inactive Pd black, the domino Heck Diels Alder reaction of the 2-bromo 1,6-diene

Helvetica Chimica Acta Vol. 85 (2002)
3167
Scheme 6. Preparation of the Bromodienes 25 and 27
7a
CO2Me
traces
HO
HO
19
20
45%
a)
1) LDA, THF, 0°
R1 R2
2)
, –78°
8R1
R1
Br
7
R2
R2
Br
6
MgBr
5
22, 23
4
4
H
Br
Br
2
3) H3O+
H
N
t-Bu
O
HO 3
1
21
24 (54%)
(48%)
25 (45%)
26
(47%)
27
R1 = Me, R2 = H
24, 25:
26, 27: R1= R2 = Me
R1= R2 = Me
a)
7a
74%
HO
28
HO
29
a) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), K2CO3 (2 equiv.), MeCN, 808, 18 h.
5 with such iminium hydrochlorides had to be carried out by the one-pot two-step
variant [15]. Thus, a mixture of 5, Pd(OAc)2 (5 mol%), Ph3P (10 mol%), and K2CO3
(1 equiv.) in MeCN was first heated at 808 for 18 h. After cooling to room temperature,
formaldehyde, glycine methyl ester hydrochloride (30a), and H2O were added. After
an additional 18 h at ambient temperature, the hexahydro-1H-[2]pyrindene derivative
31a could be isolated in 26% yield as a single regioisomer (Table 3, Entry1 ). This yield
could be improved to 38% by reducing the amount of K2CO3 from 1 equiv. to 0.5 equiv.
(Entry2 ) [15]. In an effort to evaluate the scope and limitations of this transformation,
5 was subjected to various conditions (Entries 3 6). With Ag2CO3 as the base, the yield
was only 11% (Entry3 ). Neither using MeOH instead of water nor heating to 508
increased the yield (Entries 4 and 5). In a reaction with the in-situ-formed iminium salt
from cyclopentylamine (30d), the change from MeCN to THF for the first step led to
incomplete reaction; 45% of the exocyclic diene 6 could be recovered (Entry11 ). In
an attempt to carry out the Diels Alder reaction under a pressure of 10 kbar, only

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Helvetica Chimica Acta Vol. 85 (2002)
decomposition was observed (Entry6 ). The best yields were obtained when only
0.5 equiv. of K2CO3 was used. Under these optimized conditions, different amines were
tested. The use of NH4Cl led only to decomposition (Entry8 ). Benzylamine hydro-
chloride (30b) gave 31b in 46% yield (Entry7 ); cyclopropylamine hydrochloride (30c)
led to 31c in only 36% yield (Entry9 ). Cyclopentylamine hydrochloride (30d) and
cyclohexylamine hydrochloride (30e) also gave low yields of 31 and 29% of 31d and
31e, respectively (Entries 10 and 12). In all cases, the iminium salts formed in situ gave
only a single isolated regioisomer, in contrast to the reactions with most all-C
dienophiles (see above).
Scheme 7. One-Pot Two-Step Domino Heck Diels Alder Reactions of 5 and In-Situ-Formed Iminium Salts
a) Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), K2CO3 (0.5 1 equiv.), MeCN, 808, 18 h. b) Formaldehyde, amine
hydrochloride, RÀNH3Cl (30, 3 equiv.), H2O, r.t., 18 h. For details, see Table 3.
Table 3. Reaction of 5 with Amine Salts 30 as Heterodienophiles
Entry
Amine salt 30
Base (equiv.)
Product
Yield [%]
1
2
3
4
5
6
7
8
9
a: R ˆ CH2CO2Me
a: R ˆ CH2CO2Me
a: R ˆ CH2CO2Me
a: R ˆ CH2CO2Me
a: R ˆ CH2CO2Me
a: R ˆ CH2CO2Me
b: R ˆ Bn
K2CO3 (1)
31a
31a
31a
31a
31a
31a
31b
26
38
K2CO3 (0.5)
Ag2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
K2CO3 (0.5)
11
4a)
4b)
c
)
46
NH4Cl
c: R ˆ cyclopropyl
d: R ˆ cyclopentyl
d: R ˆ cyclopentyl
e: R ˆ cyclohexyl
31c
31d
31d
31e
36
10
11
12
31
10d)
29
a) MeOH instead of H2O was used. b) Cycloaddition at 508. c) 10 kbar, 3 d, decomposition. d) In THF instead of
MeCN, 45% of 6 could also be isolated.
Conclusions. A one-step synthesis of bicyclic and tricyclic compounds starting
from 2-bromohepta-1,6-dienes with geminal dimethyl groups has been accomplished.
Although, with all-C dienophiles, the regioselectivities are not very high, this approach
is noteworthy in view of its simplicity. With in-situ-generated iminium hydrochlorides,
azabicycles are formed in low-to-moderate yields, but with complete regioselectivity.
This work was supported by the Fonds der Chemischen Industrie. We are grateful to BASF AG, Bayer AG,
Chemetall GmbH, and Degussa AG for generous gifts of chemicals. The authors are indebted to Dr. Burkhard
Knieriem for his careful proofreading of the final manuscript.

Helvetica Chimica Acta Vol. 85 (2002)
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Experimental Part
General. 1H-NMR Spectra: Bruker AM-250 spectrometer (250 MHz) at ambient temp. in CDCl3 with
CHCl3 (d ˆ 7.26) or SiMe4 (d ˆ 0.00) as int. standard; chemical shifts d in ppm, coupling constants Jas abs. values
to the nearest 0.1 Hz. 13C-NMR Spectra: Bruker AM-250 (62.9 MHz) at ambient temp. in CDCl3 with d
(CDCl3) ˆ 77.0 as int. standard; multiplicities determined by the DEPT pulse sequence unless otherwise
indicated; signals that could not be unambiguously assigned, are marked with asterisks (* ***) IR Spectra:
Bruker IFS-66 FT-IR spectrometer n in cmÀ1. MS: Varian MAT-CH-7 or MAT-731; electron-impact (EI)
ionization at 70 eVor direct chemical ionization with NH3 as reactant gas. HR-MS: Varian MAT-311, INCOS 50
with Varian 34000 (GC/MS); preselected ion peak-matching at R ꢀ 10000 within Æ 2 ppm. Elemental analyses
were performed by the Mikroanalytisches Labor des Instituts f¸r Organische Chemie der Universit‰t
Gˆttingen, Germany. All solvents were distilled before use. Column chromatography (CC): Merck silica gel 60
(230 400 mesh, 0.063 0.200 mm); TLC plates: Macherey-Nagel Alugram Sil G/UV, detection under UVat 254
or 366 nm. For substances that were not UV active, the plates were developed with anisaldehyde soln. Unless
specified otherwise, NH4Cl, NaHCO3, and NaCl were used as sat. aq. solns. Anh. solvents were prepared
according to standard laboratory techniques [19]. All reactions with organometallic substances were performed
under N2 and exclusion of H2O. In these cases, the glassware used was heated in vacuo to remove all H2O.
Reactions under high pressure were performed in sealed Teflon tubes in a commercial high-pressure apparatus
from Andreas Hofer GmbH (M¸lheim a.d. Ruhr, Germany). All chemicals were used as commercially
available, unless otherwise noted. The substances N-(cyclohexyl)-N-[(1E)-2-methylpropylidene]amine (1) and
N-(tert-butyl)-N-[(1E)-2-methylpropylidene]amine (21) were prepared according to literature procedures [6].
6-Bromo-4,4-dimethylhepta-1,6-dien-3-ol (5). To a soln. of LDA (60.0 mmol) in anh. THF (25 ml) was
added 1 (7.67 g, 50.0 mmol) and 2,3-dibromoprop-1-ene (2) (10.0 g, 50.0 mmol), and the mixture was stirred at
À788 for 2 h. To the resulting mixture was added a mixture of AcOH/H2O/NaOAc (1:4 :1, 50 ml), the aq. layer
was extracted with Et2O (3 Â 50 ml), and the combined org. layers were dried (MgSO4). The solvent was
removed under reduced pressure to yield 4.01 g (42%) of 4-bromo-2,2-dimethylpent-4-enal (3), which was
immediately dissolved in anh. THF (25 ml), and 30 mmol vinylmagnesium bromide (30 ml, 1.0m in THF) was
added at À788. After warming to r.t., H2O (50 ml) was added, and the aq. layer was extracted with Et2O (3 Â
30 ml). The combined org. layers were dried (Na2SO4), and the solvent was removed under reduced pressure.
CC of the crude product (80 g SiO2, 3.5 Â 20 cm, pentane/Et2O, 4 :1) yielded 2.48 g (54%) of 5. Colorless oil. Rf
(pentane/Et2O, 4 :1) 0.34. IR (film): 3429 (OH), 2965, 2932, 2874, 1623 (CˆC), 1471, 1427, 1389, 1368, 1190,
1124, 1090, 1041, 996, 930, 893. 1H-NMR (250 MHz, CDCl3): 0.97 (s, MeÀC(4)); 1.01 (s, MeÀC(4)); 1.61
(s, OH); 2.42 (d, 2JAB ˆ 14.2 Hz, HÀC(5)); 2.69 (d, 2JAB ˆ 14.2 Hz, HÀC(5)); 3.95 (d, 3J ˆ 6.6 Hz, HÀC(3));
5.19 5.31 (m, 2 HÀC(1)); 5.58 5.59 (m, 2 HÀC(7)); 5.94 (ddd, 3J ˆ 6.6, 3J ˆ 10.5, 3J ˆ 17.1 Hz, HÀC(2)).
13C-NMR (62.9 MHz, CDCl3): 22.4 (MeÀC(4)); 23.6 (MeÀC(4)); 38.4 (C(4)); 49.0 (C(5)); 78.9 (C(3)); 117.1
‡
(C(7)*); 120.9 (C(1)*); 129.9 (C(6)); 137.3 (C(2)). EI-MS: 163/161 (98/100, [M À C3H5O] ), 139 (44, [M À
‡
‡
‡
Br] ), 135/133 (26/26), 121 (17, [M À HBrÀ OH] ), 98 (16, [M À C2H2BrÀ Me] ), 81 (16, [M À C2H2BrÀ
‡
‡
‡
Me À OH] ), 67 (15, [M À C3H5O À BrÀ Me] ), 58 (36), 57 (32, [C3H5O] ). MS (DCI, NH3): 255/253 (25/27,
‡
‡
‡
[M ‡ NH4 ‡ NH3] ), 238/236 (98/100, [M ‡ NH4] ), 220/218 (25/25, [(M À H2O) ‡ NH4) ). Anal. calc. for
C9H15BrO (219.1): C 49.33, H 6.90; found: C 50.56, H 7.01.
General Procedure for the One-Pot Heck and Subsequent Diels Alder Reaction (GP 1). To a soln. of
1 mmol of the respective bromo diene and 3 mmol of a dienophile in 10 ml anh. MeCN in a screw-cap Pyrex
bottle were added 5 mol-% of Pd(OAc)2, 10 mol-% of Ph3P, and 1.25 2 mmol of base. N2 was bubbled through
the mixture for 5 min, then the bottle was closed and heated at 808 for the given time. The mixture was filtered
through a bed of Celite and charcoal and washed with Et2O. The crude product was purified by CC (pentane/
Et2O mixtures).
Methyl 2,3,4,5,6,7-Hexahydro-1-hydroxy-2,2-dimethyl-1H-indene-6-carboxylate (8a) and Methyl 2,3,4,5,6,7-
Hexahydro-1-hydroxy-2,2-dimethyl-1H-indene-5-carboxylate (9a). Method A. According to GP 1, 5 (219 mg,
1.00 mmol) and methyl acrylate (7a, 258 mg, 3.00 mmol) in anh. MeCN (10 ml) were treated with Pd(OAc)2
(11 mg, 0.050 mmol, 5 mol-%), Ph3P (26 mg, 0.10 mmol, 10 mol-%), and Ag2CO3 (345 mg, 1.25 mmol) at 808 for
18 h. CC (18 g SiO2; 2.0 Â 15 cm; pentane/Et2O, 3 :1) yielded 93 mg (41%) of a 1.5 :1 mixture of 8a and 9a.
Colorless oil. Rf (pentane/Et2O, 3 :1) 0.13. IR (film): 3425, 2952, 2840, 1735 (CˆO), 1653 (CˆC), 1437, 1363,
1169, 1033, 998. 1H-NMR (250 MHz, CDCl3, mixture): 1.03 (br. s, 2 MeÀC(2)); 1.27 (br. s, OH); 1.63 2.67
(m, 9 H, HÀC(3), HÀC(4), HÀC(5), HÀC(6), HÀC(7)); 3.68 (s, CO2Me); 3.97 (br. s, HÀC(1)). 13C-NMR
(62.9 MHz, CDCl3): 8a: 22.4 and 22.7 (C(4)*); 22.9 (MeÀC(2)); 25.5, 25.8 (C(5)*); 28.4, (C(7)*); 28.7
(MeÀC(2)); 39.8, 39.9 (C(6)); 41.1 (C(2)); 48.8 (C(3)); 51.7 (CO2Me); 86.2, 86.3 (C(1)); 134.9, 135.0 (C(3a)**);

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Helvetica Chimica Acta Vol. 85 (2002)
136.1, 136.6 (C(7a)**); 176.2 (CO2Me); 9a: 22.9 (MeÀC(2)); 25.0, 25.1 (C(4)*); 26.0 (C(6)*); 28.3 (C(7)*); 28.8
(MeÀC(2)); 39.6, 39.7 (C(5)); 41.0 (C(2)); 48.9 (C(3)); 51.7 (CO2Me); 87.0 (C(1)); 133.7 (C(3a)**); 137.6, 137.9
‡
‡
‡
(C(7a)**); 176.3 (CO2Me). EI-MS (mixture): 224 (11, M ), 206 (33, [M À H2O] ), 191 (56, [M À H2O À Me] ),
‡
‡
‡
164 (21, [M À MeCO2H] ), 149 (48, [M À MeCO2H À Me] ), 147 (100, [M À CO2Me À H2O] ), 131 (63), 121
(16), 105 (15), 93 (21), 91 (33), 79 (25), 77 (17), 41 (21). Anal. calc. for C13H20O3 (224.3): C 69.91, H 8.99; found:
C 69.82, H 9.24.
Method B. According to GP 1, a soln. of 5 (110 mg, 0.500 mmol) and 7a (129 mg, 1.50 mmol) was treated
with Pd(OAc)2, (5.6 mg, 0.025 mmol), Ph3P (13 mg, 0.050 mmol), and K2CO3 (138 mg, 1.00 mmol) in anh.
MeCN (10 ml) for 18 h at 808. A mixture of 8a and 9a in the same ratio as described above was isolated in a yield
of 88 mg (78%).
tert-Butyl 2,3,4,5,6,7-Hexahydro-1-hydroxy-2,2-dimethyl-1H-indene-6-carboxylate (8b) and tert-Butyl
2,3,4,5,6,7-Hexahydro-1-Hydroxy-2,2-dimethyl-1H-indene-5-carboxylate (9b). Method A. According to GP 1,
5 (219 mg, 1.00 mmol) and tert-butyl acrylate (7b) (385 mg, 3.00 mmol) in anh. MeCN (10 ml) were treated with
Pd(OAc)2 (11 mg, 0.050 mmol, 5 mol-%), Ph3P (26 mg, 0.10 mmol, 10 mol%), and Ag2CO3 (345 mg, 1.25 mmol)
at 808 for 18 h. CC (18 g SiO2 ; 2.0 Â 15 cm; pentane/Et2O, 3 :1) yielded 107 mg (40%) of a 1.9 :1 mixture of 8b
and 9b. Colorless oil. Rf (pentane/Et2O, 3 :1) 0.13. IR (film, mixture): 3423, 2955, 2840, 1727 (CˆO), 1461, 1392,
1368, 1288, 1255, 1154, 1105, 1031, 997, 897, 850. 1H-NMR (250 MHz, CDCl3, mixture): 1.02 (s, MeÀC(2)); 1.03
(s, MeÀC(2)); 1.44 (s, C(Me)3); 1.68 2.47 (m, 10 H, HÀC(3), HÀC(4), HÀC(5), HÀC(6), HÀC(7), OH);
3.96 (br. s, HÀC(1)). 13C-NMR (62.9 MHz, CDCl3). 8b: 22.4, 22.7 (C(4)*); 22.9 (MeÀC(2)); 25.8 (C(5)*); 28.1
(C(Me)3); 28.4, 28.5 (C(7)*); 28.8 (MeÀC(2)); 40.8, 40.9 (C(6)); 41.0 (C(2)); 48.9 (C(3)); 80.0 (C(Me)3); 86.3,
86.4 (C(1)); 134.8, 134.9 (C(3a)**); 136.4, 136.8 (C(7a)**); 175.2 (CO2C(Me)3); 9b: 22.9 (MeÀC(2)); 25.0, 25.1
(C(4)*); 25.4, 25.5 (C(6)*); 25.9, 26.2 (C(7)*); 28.1 (C(Me)3), 28.7 (MeÀC(2)); 40.6, 40.7 (C(5)); 41.0 (C(2));
48.8 (C(3)); 80.0 (C(Me)3), 87.0, 87.1 (C(1)); 133.9 (C(3a)**); 137.6, 137.8 (C(7a)**); 175.1 (CO2C(Me)3). EI-
‡
‡
‡
MS (mixture): 266 (3, [M] ), 248 (6, [M À H2O] ), 210 (24), 193 (29, [M À OC4H9] ), 192 (100, [M À
‡
‡
‡
‡
C4H9OH] ), 177 (43, [M À C4H9OH À Me] ), 165 (9, [M À CO2C4H9] ), 164 (9, [M À C4H9CO2H] ), 149
‡
‡
‡
(13, [M À C4H9CO2H À Me] ), 147 (71, [M À CO2C4H9 À H2O] ), 131 (9), 91 (9), 57 (29, C4H9 ), 41 (10). Anal.
calc. for C16H26O3 (266.4): C 72.14, H 9.84; found: C 72.06, H 9.57.
Method B. The use of K2CO3 (276 mg, 2.00 mmol) instead of Ag2CO3 yielded 165 mg (62%) 8b and 9b.
6-Acetyl-2,3,4,5,6,7-hexahydro-1-hydroxy-2,2-dimethyl-1H-indene (8c) and 5-Acetyl-2,3,4,5,6,7-hexahydro-
1-hydroxy-2,2-dimethyl-1H-indene (9c). Method A. According to GP 1, to a soln. of 5 (219 mg, 1.00 mmol) and
methyl vinyl ketone (210 mg, 3.00 mmol) in anh. MeCN (10 ml) was added Pd(OAc)2 (11 mg, 0.050 mmol, 5
mol-%), Ph3P (26 mg, 0.10 mmol, 10 mol-%), and Ag2CO3 (345 mg, 1.25 mmol). The mixture was stirred for
18 h at 808. CC (18 g SiO2; 2.0 Â 15 cm; pentane/Et2O, 1 :1) of the crude product yielded 116 mg (56%) of a 1.9 :1
mixture of 8c and 9c. Colorless oil. Rf (pentane/Et2O, 1:1) 0.18. IR (film, mixture): 3433, 2925, 2838, 1706
1
(CˆO), 1649 (CˆC), 1438, 1363, 1167, 1034, 997. H-NMR (250 MHz, CDCl3): 8c: 1.03 (s, 2 MeÀC(2)); 1.41
(br. s, OH); 1.53 2.43 (m, 8 H, HÀC(3), HÀC(4), HÀC(5), HÀC(7)); 2.18 (s, COMe); 2.55 2.62
(m, HÀC(6)); 3.97 (br. s, HÀC(1)); 9c: 1.01 (s, MeÀC(2)); 1.05 (s, MeÀC(2)); 1.41 (br. s, OH); 1.53 2.43
(m, 8 H, HÀC(3), HÀC(4), HÀC(6), HÀC(7)); 2.18 (s, COMe); 2.55 2.62 (m, HÀC(5)); 3.97 (br. s,
HÀC(1)). 13C-NMR (62.9 MHz, CDCl3): 8c: 22.6, 23.0 (C(4)*); 22.9 (MeÀC(2)); 25.3 (C(5)*); 27.5 (C(7)*);
28.1 (COMe); 28.8 (MeÀC(2)); 41.0 (C(2)); 47.9 (C(6)); 48.8, 48.9 (C(3)); 86.1 (C(1)); 134.9, 135.0 (C(3a)**);
136.2, 136.7 (C(7a)**); 211.5 (COMe). 9c: 22.9 (MeÀC(2)); 24.8, 24.9 (C(4)*); 25.0 (C(6)*); 25.1 (C(7)*); 27.9,
28.2 (COMe); 28.8 (MeÀC(2)); 47.6, 47.8 (C(5)); 41.0 (C(2)); 48.7, 48.8 (C(3)); 86.9, 87.0 (C(1)); 133.8
‡
‡
(C(3a)**); 137.8 (C(7a)**); 211.5 (COMe). EI-MS (mixture): 208 (9, M ), 191 (13, [M À OH] ), 190 (13, [M À
‡
‡
‡
‡
H2O] ), 175 (10, [M À H2O À Me] ), 163 (20, [M À OH À CO] ), 147 (100, [M À COMe À H2O] ), 131 (15),
‡
105 (13), 91 (18). HR-MS: 208.1463 (M , C13H20O2; calc. 208.1463).
Method B. When K2CO3 (276 mg, 2.00 mmol) was used as the base, 145 mg (70%) of a mixture of 8c and 9c
was isolated.
1,2,3,3a,5,6,8,8a-Octahydro-6,6-dimethyl-s-indacene-1-one (13). Method A. According to GP 1, 5 (219 mg,
1.00 mmol) in anh. MeCN (10 ml) was treated with Pd(OAc)2 (11 mg, 0.050 mmol, 5 mol-%), Ph3P (26 mg,
0.10 mmol, 10 mol-%), and K2CO3 (138 mg, 1.00 mmol) at 808 for 18 h. After cooling to ambient temp.,
cyclopentenone (10) (410 mg, 4.99 mmol) and LiBF4 (94 mg, 1.0 mmol) were added. After the mixture had been
stirred at ambient temp. for 14 d, the solvent and dienophile were removed under reduced pressure. CC (18 g
SiO2; 2.0 Â 15 cm; pentane/Et2O, 4 :1) gave 51 mg (25%) of 13 as a colorless oil. Rf (pentane/Et2O, 4 :1) 0.46. IR
(film): 3058, 2961, 1737 (CˆO), 1650, 1434, 1406, 1267, 1172, 1034, 919, 737, 703. 1H-NMR (250 MHz, CDCl3):
0.99 (s, MeÀC(6)); 1.04 (s, MeÀC(6)); 1.84 1.91 (m, HÀC(3)); 2.01 2.40 (m, 7 H, HÀC(2), HÀC(3),
HÀC(5), HÀC(8), HÀC(8a)); 2.83 (d, 3J ˆ 12.8 Hz, HÀC(8)); 3.07 (br. s, HÀC(3a)); 5.19 (br. s, HÀC(4));

Helvetica Chimica Acta Vol. 85 (2002)
3171
5.51 (br. s, HÀC(7)). 13C-NMR (62.9 MHz, CDCl3): 21.8 (C(8)); 27.5 (C(3)); 29.0 (MeÀC(6)); 34.8 (C(2)); 43.0
(C(6)); 44.2 (C(5)); 48.0 (C(8a)); 117.0 (C(4)); 133.8 (C(4a)); 141.3 (C(7)); 147.4 (C(7a)); 219.8 (C(1)). EI-MS:
‡
‡
202 (46, [M] ), 187 (52, [M À Me] ), 143 (100); 131 (37), 115 (16), 91 (23), 77 (9), 41 (10).
Method B. Et2AlCl (3.0 ml, 3.0 mmol, 1.0m in hexane) was added instead of LiBF4, and the resulting
mixture was stirred at ambient temp. for 18 h. The Et2AlCl was hydrolyzed with H2O (15 ml) and the aq. layer
was extracted with Et2O (3 Â 20 ml). The org. phases were dried (MgSO4), and the solvent was removed under
reduced pressure. CC (18 g SiO2 ; 2.0 Â 15 cm; pentane/Et2O 4 :1) gave 45 mg (22%) of 13 as a colorless oil. Rf
(pentane/Et2O, 4 :1) 0.46.
Method C. The use of a soln. of Me3Al (1.50 ml, 3.00 mmol, 2m in toluene) instead of Et2AlCl did not give
any cycloaddition product within 72 h.
Method D. When Ti(OiPr)4 (853 mg, 3.00 mmol) was used as a Lewis acid, only decomposition was
observed within 72 h.
Method E. When the reaction was carried out with a smaller amount of Et2AlCl (1.5 ml, 1.5 mmol, 1.0m in
hexane) within 12 h, only 13 mg (6%) of 13 and 24 mg (17%) of 6 (for spectroscopic data, see 31d) could be
isolated.
Methyl 2,4,5,6-Tetrahydro-2,2-dimethyl-1H-indene-5-carboxylate (14). According to GP 1, 5 (219 mg,
1.00 mmol) in anh. MeCN (10 ml) was treated with Pd(OAc)2 (11 mg, 0.050 mmol, 5 mol-%), Ph3P (26 mg,
0.10 mmol, 10 mol-%), and K2CO3 (138 mg, 1.00 mmol) at 808 for 18 h. After cooling to r.t., 7a (258 mg,
3.00 mmol) and Et2AlCl (3.0 ml, 3.0 mmol, 1.0m in hexane) were added, and stirring was continued for 1 d at
ambient temp. H2O was added (5 ml), the aq. layer was extracted with Et2O (2 Â 10 ml), and the combined org.
phases were dried (MgSO4). After evaporation of the solvent in vacuo, the resulting crude product was purified
by CC (18 g SiO2; 2.0 Â 15 cm; pentane/Et2O, 4 :1) to give 53 mg (26%) of 14 as a colorless oil3). Rf (pentane/
Et2O 4 :1) 0.64. IR (film): 3055, 2956, 1734 (CˆO), 1437, 1367, 1267, 1199, 1106, 1027, 919, 737. 1H-NMR
(250 MHz, CDCl3): 1.06 (s, 2 MeÀC(2)); 2.26 2.78 (m, 7 H, HÀC(1), HÀC(4), HÀC(5), HÀC(6)); 3.68
(s, CO2Me); 5.35 5.37 (m, HÀC(3)*); 5.45 (br. s, HÀC(7)*). 13C-NMR (62.9MHz, CDCl3): 27.5 (C(4)*); 27.9
(C(6)*); 29.2 (MeÀC(2)); 39.8 (C(5)); 43.5 (C(2)); 43.7 (C(1)); 51.7 (CO2Me); 113.2 (C(3)*); 136.3 (C(3a)**);
‡
‡
139.9 (C(7)*); 144.8 (C(7a)**); 176.0 (CO2Me). CI-MS: 224 (96, [M ‡ NH4] ), 207 (100, [M ‡ H] ). Anal. calc.
for C13H18O2 (206.3): C 75.69, H 8.80; found: C 75.81, H 8.98.
6-Bromo-4,4-dimethylhepta-1,6-dien-3-one (15). To a soln. of oxalyl chloride (1.39 g, 0.94 ml, 11.0 mmol) in
anh. CH2Cl2 (30 ml), DMSO (1.72 g, 1.57 ml, 22.0 mmol) was added at À608, and stirring was continued for
20 min at ambient temp. A soln. of 5 (2.19 g, 10.0 mmol) in anh. CH2Cl2 (10 ml) was added, and the soln. was
stirred for 1 h at À608. After addition of Et3N (5.06 g, 6.93 ml, 50.0 mmol), the mixture was allowed to warm to
r.t. The mixture was quenched with 30 ml of H2O and the aq. layer was extracted with CH2Cl2 (3 Â 30 ml). The
combined org. layers were neutralized with sat. aq. NH4Cl, washed with sat. aq. NaCl soln. (30 ml), and dried
(MgSO4). The solvent was removed under reduced pressure and the crude product was purified by CC (50 g
SiO2; 2.5 Â 20 cm; pentane/Et2O 20 :1) to give 1.62 g (75%) of 15. Colorless oil. Rf (pentane/Et2O 20 :1) 0.34. IR
(film): 2971, 2933, 1695 (CˆO), 1624 (CˆC), 1610 (CˆC), 1468, 1401, 1368, 1164, 1103, 1054, 1006, 982, 893.
1H-NMR (250 MHz, CDCl3): 1.24 (s, 3 MeÀC(4)); 2.81 (s, 2 HÀC(5)); 5.50 5.54 (m, 2 HÀC(7)); 5.70
3
3
3
(dd, 2J ˆ 2.0, J ˆ 10.3 Hz, HÀC(1)); 6.37 (dd, 2J ˆ 2.0, J ˆ 16.9 Hz, HÀC(1)); 6.84 (dd, 3J ˆ 10.3, J ˆ 16.9 Hz,
HÀC(2)). 13C-NMR (62.9 MHz, CDCl3): 24.1 (MeÀC(4)); 46.5 (C(4)); 49.8 (C(5)); 120.6 (C(1)*); 128.9
‡
‡
(C(7)*); 129.1 (C(6)); 130.8 (C(2)); 202.8 (C(3)). EI-MS: 163/161 (5/5, [M À C3H3O] ), 137 (100, [M À Br] ),
‡
‡
‡
81 (47, [M À C3H3O À HBr] ), 67 (13, [M À C3H3O À BrÀ Me] ), 55 (50, [C3H3O] ), 41 (29). DCI-MS (NH3):
‡
‡
‡
270/268 (11/14, [M ‡ NH4 ‡ 2 NH3] ), 253/251 (100/99, [M ‡ NH4 ‡ NH3] ), 236/234 (44/45, [M ‡ NH4] ).
Anal. calc. for C9H13BrO (217.1): C 49.79, H 6.04; found: C 50.03, H 6.06.
2',3',4',5',6',7'-Hexahydro-2',2',3,3-tetramethyl-5-methylenespiro[cyclopentane-1,5'(1'H)-indene]-1',2-dione
(18). According to GP 1, a soln. of 15 (217 mg, 1.00 mmol) in anh. MeCN (10 ml) was treated with Pd(OAc)2
(11 mg, 0.050 mmol), Ph3P (26 mg, 0.10 mmol), Ag2CO3 (345 mg, 1.25 mmol), and 7a (258 mg, 3.00 mmol) for
18 h at 808. CC (18 g SiO2; 2.0 Â 15 cm; pentane/Et2O, 8 :1) yielded 195 mg (72%) of 18. Colorless crystals; m.p.
108 1108. Rf (pentane/Et2O, 8 :1) 0.23. IR (KBr): 2962, 2929, 2865, 1736 (CˆO), 1697 (CˆO), 1654 (CˆC),
1462, 1437, 1376, 1359, 1268, 1047, 986, 899. 1H-NMR (250 MHz, CDCl3): 0.98 (s, MeÀC(3)); 1.11
(s, 2 MeÀC(2')); 1.21 (s, MeÀC(3)); 1.41 1.52 (m, 1 H); 1.62 1.71 (m, 1 H); 2.00 2.16 (m, 2 H); 2.27 2.82
(m, 6 H, HÀC(4), HÀC(3'), HÀC(4'), HÀC(6'), HÀC(7')); 4.62 (d, 2J ˆ 2.3 Hz, 1 H, CH2ˆC(5)); 5.05 (d, 2J ˆ
2.3 Hz, 1 H, CH2ˆC(5)). 13C-NMR (62.9 MHz, CDCl3): 16.9 (C(7')); 24.2 (MeÀC(3)); 24.8 (MeÀC(3)); 25.2
3
)
A second fraction contained 61 mg (28%) of the starting material.

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Helvetica Chimica Acta Vol. 85 (2002)
(MeÀC(2')); 25.3 (MeÀC(2')); 28.1 (C(4')*); 35.0 (C(6')*); 43.5 (C(2')); 44.2 (C(4)); 46.5 (C(3)); 46.8 (C(3'));
52.9 (C(5')); 108.8 (CH2ˆC(5)); 134.8 (C(3'a)); 150.2 (C(5)); 168.3 (C(7'a)); 211.9 (C(1')); 223.0 (C(2)). EI-
‡
‡
‡
‡
MS: 272 (37, M ), 257 (37, [M À Me] ), 244 (100, [M À C2H4] ), 229 (19, [M À C3H7] ), 201 (14, [M À C3H7 À
‡
‡
CO] ), 173 (11, [M À C3H7 À 2 CO] ), 145 (7), 107 (8), 91 (12), 77 (6), 41 (6). Anal. calc. for C18H24O2 (272.4):
C 79.37, H 8.88; found: C 79.64, H 8.87.
(E)-6-Bromo-4,4-dimethylocta-1,6-dien-3-ol (25). To a soln. of 50.0 mmol of LDA in anh. THF (25 ml), 21
(4.71 g, 37.0 mmol) and (E)-1,2-dibromobut-2-ene (22) (7.91 g, 37.0 mmol) were added and stirred for 2 h at
À788. The resulting mixture was quenched with AcOH/H2O/NaOAc (1:4 :1), and the aq. layer was extracted
with Et2O (3 Â 50 ml) and dried (MgSO4). The solvent was removed under reduced pressure to yield 4.12 g
(54%) of 4-bromo-2,2-dimethylhex-4-enal (24), which was immediately dissolved in anh. THF (25 ml), and
vinylmagnesium bromide (30 ml, 30 mmol, 1.0m in THF) was added at À788. After warming to r.t., H2O (50 ml)
was added, the aq. layer was extracted with Et2O (3 Â 30 ml), the combined org. layers were dried (Na2SO4),
and the solvent was removed under reduced pressure. CC of the crude product (80 g SiO2; 3.5 Â 20 cm; CH2Cl2)
yielded 2.13 g (45%) of 25 as a colorless oil. Rf (CH2Cl2) 0.48. IR (film): 3433, 2965, 2932, 2873, 1653 (CˆC),
1470, 1427, 1389, 1368, 1309, 1259, 1153, 1123, 1040, 996, 931. 1H-NMR (250 MHz, CDCl3): 0.93 (s, MeÀC(4));
0.94 (s, MeÀC(4)); 1.65 (d, 3J ˆ 4.4 Hz, OH); 1.75 (d, 3J ˆ 6.5 Hz, MeÀC(7)); 2.42 (d, 2JAB ˆ 14.4 Hz, HÀC(5));
2.68 (d, 2JAB ˆ 14.4 Hz, HÀC(5)); 3.92 (dd, 3J ˆ 3.8, 3J ˆ 4.4 Hz, HÀC(3)); 5.17 5.29 (m, 2 HÀC(1)); 5.74
(q, 3J ˆ 6.5 Hz, HÀC(7)); 5.93 (ddd, 3J ˆ 3.8, 3J ˆ 7.1, 3J ˆ 10.5 Hz, HÀC(2)). 13C-NMR (62.9 MHz, CDCl3): 17.4
(C(8)); 22.5 (MeÀC(4)); 22.7 (MeÀC(4)); 38.6 (C(4)); 49.2 (C(5)); 78.9 (C(3)); 116.9 (C(1)); 124.5 (C(6));
‡
‡
127.5 (C(7)); 137.4 (C(2)). EI-MS (70 eV): 177/175 (17/17, [M À C3H5O] ), 153 (13, [M À Br] ), 135/133 (7/7),
‡
‡
113 (12, [M À C3H4Br] ), 95 (81), 81 (17, [M À C3H4Br À Me À OH] ), 67 (33), 55 (44, [M À C3H5O À
‡
‡
C3H4Br À H] ), 43 (100), 41 (37). CI-MS: 269/267 (100/94, [M ‡ NH4 ‡ NH3] ), 252/250 (53/57,
‡
[M ‡ NH4] ). Anal. calc. for C10H17BrO (233.1): C 51.52, H 7.35; found: C 52.81, H 7.31.
4-Ethylidene-2,2-dimethyl-5-methylidenecyclopentan-1-ol (20). According to GP 1, a soln. of 25 (233 mg,
1.00 mmol) in anh. MeCN (10 ml) was treated with Pd(OAc)2 (22 mg, 0.10 mmol), Ph3P (52 mg, 0.20 mmol),
K2CO3 (276 mg, 2.00 mmol), and 7a (258 mg, 3.00 mmol) for 18 h at 808. CC (18 g SiO2; 2.0 Â 15 cm; pentane/
Et2O 4 :1 ! 2 :1) yielded 68 mg (45%) of 20 as a colorless oil. Rf (pentane/Et2O, 4 :1) 0.41. IR (film): 3395, 2956,
1
2867, 1695 (CˆC), 1467, 1367, 1116, 1057, 999, 921, 736. H-NMR (250 MHz, CDCl3): 0.80 (s, MeÀC(2)); 1.05
(s, MeÀC(2)); 1.51 (br. s, OH); 1.86 (d, 3J ˆ 7.3 Hz, MeÀCHˆC(4)); 2.15 2.17 (m, 2 HÀC(3)); 4.00 (br. s,
HÀC(1)); 5.31 5.38 (m, CH2ˆC(5)); 5.60 (q, 3J ˆ 7.3 Hz, HÀC(1')). 13C-NMR (62.9 MHz, CDCl3): 15.3
(C(2')); 19.6 (MeÀC(2)); 25.8 (MeÀC(2)); 39.7 (C(2)); 45.4 (C(3)); 83.6 (C(1)); 110.2 (CH2ˆC(5)); 122.2
‡
‡
(C(1')); 135.3 (C(4)*); 150.8 (C(5)*). EI-MS: 152 (83, M ), 137 (100, [M À Me] ), 123 (33), 109 (56), 95 (31),
‡
81 (31), 43 (26). HR-MS: 152.1201 (M , C10H16O; calc. 152.1201).
6-Bromo-4,4,7-trimethylocta-1,6-dien-3-ol (27). To a soln. of 60.0 mmol of LDA in anh. THF (25 ml), 21
(6.36 g, 50.0 mmol) and 1,2-dibromo-3-methylbut-2-ene (23) (11.4 g, 50.0 mmol) were added and stirred for 2 h
at À788. The resulting mixture was quenched with AcOH/H2O/NaOAc (1:4 :1), the aq. layer was extracted with
Et2O (3 Â 50 ml) and dried (MgSO4). The solvent was removed under reduced pressure to yield 5.21 g (48%) of
4-bromo-2,2,5-trimethylhex-4-enal (26), which was immediately dissolved in anh. THF (25 ml), and vinyl-
magnesium bromide (30 ml, 30 mmol, 1.0m in THF) was added at À788. After warming to r.t., H2O (50 ml) was
added, the aq. layer was extracted with Et2O (3 Â 30 ml). The combined org. layers were dried (Na2SO4), and
the solvent was removed under reduced pressure. CC of the crude product (80 g SiO2; 3.5 Â 20 cm; pentane/
Et2O 10 :1) yielded 2.74 g (47%) of 27 as a colorless oil. Rf (pentane/Et2O 10 :1) 0.27. IR (film): 3445 (OH),
2966, 2932, 2873, 1644 (CˆC), 1470, 1425, 1387, 1367, 1218, 1110, 1041, 994, 926, 905, 865, 798. 1H-NMR
(250 MHz, CDCl3): 0.97 (s, MeÀC(4)); 0.98 (s, MeÀC(4)); 1.72 (d, 3J ˆ 4.3 Hz, OH); 1.79 (s, MeÀC(7)*); 1.91
(s, HÀC(8)*); 2.62 (d, 2JAB ˆ 14.9 Hz, HÀC(5)); 2.73 (d, 2JAB ˆ 14.9 Hz, HÀC(5)); 3.94 (dd, 3J ˆ 4.3, 3J ˆ
6.6 Hz, HÀC(3)); 5.18 5.30 (m, 2 HÀC(1)); 5.95 (ddd, 3J ˆ 6.6, 3J ˆ 10.5, 3J ˆ 17.2 Hz, HÀC(2)). 13C-NMR
(62.9 MHz, CDCl3): 21.7 (C(8)*); 22.7 (MeÀC(4)); 23.9 (MeÀC(4)); 25.9 (MeÀC(7)*); 40.1 (C(4)); 44.7
‡
(C(5)); 79.7 (C(3)); 116.9 (C(1)); 117.9 (C(7)*); 133.8 (C(6)*); 137.4 (C(2)). EI-MS: 248/246 (1/1, M ),191/189
‡
‡
‡
‡
(38/39, [M À C3H5O] ), 167 (34, [M À Br] ), 166 (54, [M À HBr] ), 149 (29, [M À HBrÀ OH] ), 110 (63,
‡
‡
‡
[M À C3H5O À Br] ), 109 (100, [M À C3H5O À HBr] ), 95 (27, [M À C3H5O À Br À Me] ), 81 (20, [M À
‡
‡
C4H6BrÀ Me À OH] ), 67 (63), 55 (32, [M À C3H5O À C4H6Br À H] ), 43 (83). Anal. calc. for C11H19BrO
(247.2): C 53.45, H 7.75; found: C 53.69, H 7.65.
3-Isopropenyl-2,5,5-trimethylcyclopent-2-en-1-ol (28). To a soln. of 27 (247 mg, 1.00 mmol) in anh. MeCN
(10 ml) was added, as described in GP 1, Pd(OAc)2 (11 mg, 0.050 mmol), Ph3P (26 mg, 0.10 mmol), K2CO3
(276 mg, 2.00 mmol), and 7a (258 mg, 3.00 mmol). Stirring was continued for 18 h at 808. CC (18 g SiO2; 2.0 Â
15 cm; pentane/Et2O, 5 :1) of the crude product gave 123 g (74%) of 28 as a colorless oil. Rf (pentane/Et2O 5 :1)

Helvetica Chimica Acta Vol. 85 (2002)
3173
0.37. IR (film): 3354, 2951, 2923, 2862, 1652 (CˆC); 1466, 1366, 1126, 1086, 1061, 999, 891, 798. 1H-NMR
(250 MHz, CDCl3): 0.81 (s, MeÀC(5)); 1.07 (s, MeÀC(5)); 1.47 (br. s, OH); 1.73 (s, MeÀC(2)*); 1.94
(s, MeÀC(1')*); 2.09 (d, 2JAB ˆ 16.1 Hz, HÀC(4)); 2.24 (d, 2JAB ˆ 16.1 Hz, HÀC(4)); 3.95 (br. s, HÀC(1)); 5.18
(m, 2 HÀC(2')). 13C-NMR (62.9 MHz, CDCl3): 20.3 (MeÀC(5)); 22.4 (MeÀC(1')*); 23.2 (MeÀC(2)*); 26.3
(MeÀC(5)); 39.0 (C(5)); 43.1 (C(4)); 83.4 (C(1)); 107.7 (C(2')); 128.7 (C(2)**); 131.1 (C(3)**); 151.6 (C(1')).
‡
‡
‡
EI-MS: 166 (79, M ), 151 (100, [M À Me] ), 133 (25, [M À Me À H2O] ), 109 (27), 95 (33), 81 (19), 67 (14), 41
‡
‡
(13, C3H5 ). HR-MS: 166.1357 (M , C11H18O; calc. 166.1357).
General Procedure for the Heck Hetero-Diels Alder Reaction as a Two-Step One-Pot Operation (GP 2).
In a screw-cap Pyrex bottle was placed the bromo diene (1 mmol) dissolved in anh. MeCN (10 ml). To the
resulting soln. were added Pd(OAc)2 (5 mol-%), Ph3P (10 mol-%), and K2CO3 (50 mol-%). N2 was bubbled
through the mixture for 5 min, then the bottle was closed and heated to 808 for the given time. After cooling to
r.t., formaldehyde (1 ml, 37% in H2O), amine hydrochloride (2 mmol), and H2O (8 ml) was added and stirring
was continued for the given time at ambient temp. The mixture was filtered through Celite and washed with H2O.
The combined filtrates were extracted with Et2O (20 ml), and NaOH (2m) was added to the aq. layer until
pH 13. The aq. layer was extracted with Et2O (3 Â 20 ml). The combined org. layers were washed with sat. NaCl
soln. (20 ml), dried (Na2SO4), and the solvent was removed under reduced pressure. The crude product was
purified by CC.
Methyl (2,3,4,5,6,7-Hexahydro-7-hydroxy-6,6-dimethyl-1H-[2]pyrinden-2-yl)acetate (31a). Method A. As
described in GP 2, a soln. of 5 (219 mg, 1.00 mmol) in anh. MeCN (10 ml) was treated with Pd(OAc)2 (11 mg,
0.050 mmol, 5.0 mol-%), Ph3P (26 mg, 0.10 mmol, 10 mol-%), and K2CO3 (69 mg, 0.50 mmol) and stirred for
18 h at 808. After cooling to r.t., a soln. of HCHO (1.0 ml, 12 mmol, 37% in H2O), methyl glycinate
hydrochloride (30a, 251 mg, 2.00 mmol), and H2O (8 ml) were added, and stirring was continued for 18 h at r.t.
After workup, the crude product was purified by CC (18 g SiO2; 2.0 Â 15 cm; CH2Cl2/MeOH 20 :1 ! 10 :1) to
yield 92 mg (38%) of 31a as a colorless oil. Rf (CH2Cl2/MeOH 10 :1) 0.21. IR (film): 3340 (OH), 2955, 1749
(CˆO), 1646, 1437, 1364, 1205, 1122, 1004, 701, 677, 669. 1H-NMR (250 MHz, CDCl3): 1.03 (s, MeÀC(6)); 1.06
(s, MeÀC(6)); 1.95 2.21 (m, 2 HÀC(4), 2 HÀC(5)); 2.71 (mc, 2 HÀC(1)*); 3.14 3.22 (m, 2 HÀC(3)); 3.37
(s, NCH2); 3.73 (s, CO2Me); 4.03 (br. s, HÀC(7)). 13C-NMR (62.9 MHz, CDCl3): 23.0 (MeÀC(6)); 26.5 (C(4)*);
28.9 (MeÀC(6)); 41.4 (C(6)); 48.7 (C(5)*); 49.9 (C(3)**); 50.9 (C(1)**); 51.7 (CO2Me); 58.8 (CH2CO2Me*);
‡
‡
85.7 (C(7)); 133.5 (C(4a)***); 136.7 (C(7a)***); 171.0 (CO2Me). EI-MS: 239 (2, M ), 221 (8, [M À H2O] ), 206
‡
‡
‡
(3, [M À H2O À Me] ), 180 (29, [M À CO2Me] ), 165 (100, [M À CO2Me À Me] ), 150 (6, [M À CO2Me À 2
‡
‡
‡
Me] ), 132 (5, [M À CO2Me À 2 Me À H2O] ), 107 (7), 91 (4), 77 (5), 42 (10). HR-MS: 239.1521 (M ,
C13H21NO3; calc. 239.1521).
Method B. The use of K2CO3 (138 mg, 1.00 mmol) decreased the yield of 31a to 63 mg (26%).
Method C. When Ag2CO3 (138 mg, 0.500 mmol) was added instead of K2CO3, only 27 mg (11%) of 31a
could be isolated.
Method D. The addition of MeOH (8 ml) instead of H2O lowered the yield of 31a to only 10 mg (4%).
Method E. When the hetero-Diels Alder reaction was carried out at 10 kbar, only a decomposition product
and oligomeric material was obtained.
Method F. When the Diels Alder reaction was performed at 508, an unidentified side product was formed,
and the yield of 31a decreased to 9 mg (4%).
2-Benzyl-2,3,4,5,6,7-hexahydro-6,6-dimethyl-1H-[2]pyrinden-7-ol (31b). According to GP 2, to a soln. of 5
(219 mg, 1.00 mmol) in anh. MeCN (10 ml) was added Pd(OAc)2 (11 mg, 0.050 mmol, 5.0 mol-%), Ph3P (26 mg,
0.10 mmol, 10 mol-%), and K2CO3 (69 mg, 0.50 mmol). The resulting mixture was stirred for 18 h at 808. After
cooling to r.t., a soln. of HCHO (1.0 ml, 12 mmol, 37% in H2O), benzylamine hydrochloride (30b, 287 mg,
2 mmol), and H2O (8 ml) was added and stirred for 18 h at r.t. CC (18 g SiO2; 2.0 Â 15 cm; CH2Cl2/MeOH, 20 :1)
yielded 118 mg (46%) of 31b as a colorless oil. Rf (CH2Cl2/MeOH 20 :1) 0.15. IR (film): 3358 (OH), 3062, 3028,
2953, 2900, 2838, 1667, 1602, 1454, 1362, 1265, 1199, 1065, 1028, 1004, 738, 699. 1H-NMR (250 MHz, CDCl3): 1.04
(s, MeÀC(6)); 1.06 (s, MeÀC(6)); 1.95 2.22 (m, 2 HÀC(4), 2 HÀC(5)); 2.60 (m, 2 HÀC(1)); 2.92 3.02
(m, HÀC(3)); 3.12 3.19 (m, HÀC(3)); 3.65 (s, 1 H, PhCH2); 3.66 (s, 1 H, PhCH2); 4.02 (br. s, HÀC(7)); 7.24
7.37 (m, 5 arom. H). 13C-NMR (62.9 MHz, CDCl3): 23.0 (MeÀC(6)); 26.6 (C(4)*); 28.9 (MeÀC(6)); 41.4
(C(6)); 48.7 (C(5)*); 49.7 (C(3)**); 51.4 (C(1)**); 62.7 (CH2Ph); 85.7 (C(7)); 127.2 (arom. C); 128.3 (arom. C);
‡
‡
129.3 (C(4a)); 129.4 (arom. C); 133.8 (arom. C); 136.7 (C(7a)). EI-MS: 257 (7, M ), 240 (9, [M À OH] ), 224
‡
‡
(12, [M À H2O À Me] ), 201 (21), 185 (35), 172 (4), 132 (3), 120 (4), 91 (4, C7H7 ), 65 (6), 41 (3).
2-Cyclopropyl-2,3,4,5,6,7-hexahydro-6,6-dimethyl-1H-[2]pyrindin-7-ol (31c). As described in GP 2, a soln.
of 5 (219 mg, 1.00 mmol) in anh. MeCN (10 ml) was heated with Pd(OAc)2 (11 mg, 0.050 mmol, 5.0 mol-%),
Ph3P (26 mg, 0.10 mmol, 10 mol-%), and K2CO3 (69 mg, 0.50 mmol) to 808 for 18 h. The mixture was cooled to

3174
Helvetica Chimica Acta Vol. 85 (2002)
r.t., and HCHO (1.0 ml, 12 mmol, 37% in H2O), cyclopropylamine hydrochloride (30c, 187 mg, 2.00 mmol) and
H2O (8 ml) were added. Stirring was continued for 18 h at r.t. The crude product was purified by CC (18 g SiO2;
2.0 Â 15 cm; CH2Cl2/MeOH 10 :1) to give 74 mg (36%) of 31c as a colorless oil. Rf (CH2Cl2/MeOH 10 :1) 0.31.
IR (film): 3368 (OH), 3087, 2953, 2908, 2839, 1669, 1459, 1362, 1265, 1219, 1057, 1018, 1002, 869, 826, 737, 702.
1H-NMR (250 MHz, CDCl3): 0.46 0.50 (m, 4 H, cyclopropyl); 1.02 (s, MeÀC(6)); 1.06 (s, MeÀC(6)); 1.69
1.77 (m, 1 H, cyclopropyl); 1.93 2.20 (m, 2 HÀC(4), 2 HÀC(5)); 2.75 (m, 2 HÀC(1)*); 3.06 3.25
(m, 2 HÀC(3)*); 4.03 (br. s, HÀC(7)). 13C-NMR (75.5 MHz, CDCl3): 5.9 (CH2, cyclopropyl); 23.0 (MeÀC(6));
26.7 (C(4)*); 28.9 (MeÀC(6)); 38.2 (CH, cyclopropyl); 41.4 (C(6)); 48.8 (C(5)*); 50.5 (C(3)**); 51.3 (C(1)**);
‡
‡
85.8 (C(7)); 134.1 (C(4a)***); 136.4 (C(2)***). EI-MS: 207 (64, M ), 192 (100, [M À Me] ), 174 (9, [M À
‡
‡
H2O À Me] ), 151 (4, [M À Me À C3H5] ), 135 (10), 121 (6), 107 (5), 91 (6), 84 (26), 70 (14), 56 (15), 41 (22,
‡
C3H5 ).
2-Cyclopentyl-2,3,4,5,6,7-hexahydro-6,6-dimethyl-1H-[2]pyrinden-7-ol (31d). Method A. As described in
GP 2, a soln. of 5 (219 mg, 1.00 mmol) in anh. MeCN (10 ml) was heated with Pd(OAc)2 (11 mg, 0.050 mmol, 5.0
mol-%), Ph3P (26 mg, 0.10 mmol, 10 mol-%), and K2CO3 (69 mg, 0.50 mmol) to 808 for 18 h. The mixture was
cooled to r.t. and HCHO (1.0 ml, 12 mmol, 37% in H2O), cyclopentylamine hydrochloride (30d, 243 mg,
2.00 mmol), and H2O (8 ml) were added. Stirring was continued for 18 h at r.t. The crude product was purified
by CC (18 g SiO2; 2.0 Â 15 cm; CH2Cl2/MeOH 10 :1) to give 72 mg (31%) of 31d as a colorless oil. Rf (CH2Cl2/
MeOH 10 :1) 0.13. IR (film): 3437 (OH), 3053, 2956, 2864, 2806, 1696, 1464, 1381, 1361, 1265, 1053, 894, 868, 736,
703. 1H-NMR (250 MHz, CDCl3): 1.02 (s, MeÀC(6)); 1.06 (s, MeÀC(6)); 1.48 1.76 (m, 6 cyclopentyl H, OH);
1.88 2.07 (m, 1 cyclopentyl H, HÀC(4), HÀC(5)); 2.15 2.27 (m, 1 cyclopentyl H, HÀC(4), HÀC(5)); 2.58
2.82 (m, 1 cyclopentyl H, 2 HÀC(1)); 2.97 3.13 (m, HÀC(3)); 3.22 3.38 (m, HÀC(3)); 4.00 (br. s, HÀC(7)).
13C-NMR (62.9 MHz, CDCl3): 23.0 (MeÀC(6)); 24.0 (cyclopentyl CH2); 26.1 (C(4)*); 28.9 (MeÀC(6)); 30.2
(cyclopentyl CH2); 41.5 (C(6)); 48.5 (C(5)*); 49.1 (C(1)**); 50.2 (C(3)**); 67.1 (cyclopentyl CH); 85.5 (C(7));
‡
‡
133.0 (C(4a)***); 137.0 (C(7a)***). EI-MS: 235 (62, M ), 218 (15, [M À OH] ), 206 (70), 192 (28, [M À
‡
‡
‡
C2H5N] ), 179 (45, [M À C3H6N] ), 163 (100, [M À C4H10N] ), 150 (6), 123 (7), 98 (10), 84 (8), 68 (14), 41 (22,
‡
C3H5 ).
Method B: When the reaction was carried out in anh. THF (10 ml) instead of MeCN, in addition to 23 mg
(10%) of 31d, 62 mg (45%) of 2,2-dimethyl-4,5-dimethylidenecyclopentan-1-ol (6) could be isolated as a
colorless oil4). Rf (pentane/Et2O 4 :1) 0.45. 1H-NMR (250 MHz, CDCl3): 0.82 (s, MeÀC(2)); 1.07 (s, MeÀC(2));
1.49 (d, 3J ˆ 7.9 Hz, OH); 2.22 (mc, 2 HÀC(3)); 4.06 (ddd, 3J ˆ 7.9, 4J ˆ 2.3, 4J ˆ 2.3 Hz, HÀC(1)); 4.90 (mc, 1 H,
CˆCH2); 5.10 (d, 2 J ˆ 2.2 Hz, 1 H, CˆCH2); 5.43 (mc, 1 H, CˆCH2); 5.48 (d, 2J ˆ 2.2 Hz, 1 H, CˆCH2).
13C-NMR (62.9 MHz, CDCl3): 19.6 (MeÀC(2)); 25.7 (MeÀC(2)); 39.8 (C(2)); 44.3 (C(3)); 82.6 (C(1)); 105.4
‡
‡
(CˆCH2); 105.9 (CˆCH2); 144.0 (C(5)*); 151.0 (C(4)*). EI-MS (70 eV): 138 (33, M ), 123 (100, [M À Me] ),
‡
‡
109 (12), 105 (20, [M À Me À H2O] ), 95 (73), 91 (11), 79 (16), 67 (30), 55 (16), 43 (16), 41 (13, C3H5 ).
2-Cyclohexyl-2,3,4,5,6,7-hexahydro-6,6-dimethyl-1H-[2]pyrinden-7-ol (31e). According to GP 2, to a soln.
of 5 (219 mg, 1.00 mmol) in anh. MeCN (10 ml) was added Pd(OAc)2 (11 mg, 0.050 mmol, 5.0 mol-%), Ph3P
(26 mg, 0.10 mmol, 10 mol-%), and K2CO3 (69 mg, 0.50 mmol). The resulting mixture was stirred for 18 h at 808.
After cooling to r.t., a soln. of HCHO (1.0 ml, 12 mmol, 37% in H2O), cyclohexylamine hydrochloride (30e,
271 mg, 2 mmol), and H2O (8 ml) was added and stirring was continued for 18 h at r.t. CC (18 g SiO2; 2.0 Â
15 cm; CH2Cl2/MeOH 10 :1) yielded 73 mg (29%) of 31e as a colorless oil. Rf (CH2Cl2/MeOH, 10 :1) 0.23. IR
(film): 3352 (OH), 2930, 2856, 1668, 1451, 1380, 1264, 1205, 1135, 1069, 1036, 1003, 894, 737, 702. 1H-NMR
(250 MHz, CDCl3): 1.03 (s, MeÀC(6)); 1.06 (s, MeÀC(6)); 1.14 1.36 (m, 6 cyclohexyl H); 1.62 2.21
(m, 4 cyclohexyl H, 2 HÀC(4), 2 HÀC(5), OH); 2.41 2.48 (m, 1 cyclohexyl H); 2.69 (mc, 2 HÀC(1)*);
3.06 3.34 (m, 2 HÀC(3)*); 4.02 (br. s, HÀC(7)). 13C-NMR (75.5 MHz, CDCl3, APT): 23.08 (MeÀC(6)); 25.95
(cyclohexyl CH2*); 26.25 (C(4)*); 27.08 (cyclohexyl CH2*); 28.80 (cyclohexyl CH2*); 28.92 (MeÀC(6)); 41.48
(C(6)); 46.17 (C(5)*); 46.86 (C(1)**); 48.70 (C(3)**); 63.44 (cyclohexyl CH); 85.85 (C(7)); 134.14 (C(4a)***);
‡
‡
‡
137.08 (C(7a)***). EI-MS: 249 (33, M ), 206 (100, [M À C2H5N] ), 193 (18, [M À C3H6N] ), 177 (28, [M À
‡
‡
C4H10N] ), 165 (4), 133 (5), 26 (6), 84 (13), 68 (11), 53 (14), 49 (18), 41 (15, C3H5 ).
REFERENCES
[1] L. F. Tietze, Chem. Rev. 1996, 96, 115; H. Waldmann, −Domino Reactions×, in −Organic Synthesis Highlights
II×, Ed. H. Waldmann, VCH, Weinheim, 1995, p. 193; L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105,
4
)
Compound 6 has been previously reported [20].

Helvetica Chimica Acta Vol. 85 (2002)
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137 170; Angew. Chem., Int. Ed. 1993, 32, 131; D. P. Curran, in −Comprehensive Organic Synthesis×, Eds.
B. M. Trost, I. Fleming, Vol. 4, Pergamon Press, Oxford, 1991, p. 779 831.
[2] S. Br‰se, A. de Meijere, in −Metal-catalyzed Cross-Coupling Reactions×, Ed. F. Diederich, P. J. Stang, Wiley-
VCH, Weinheim, 1997, pp. 99 166; A. de Meijere, F. E. Meyer, Angew. Chem. 1994, 106, 2473; Angew.
Chem., Int. Ed. 1994, 33, 2379; R. F. Heck, in −Comprehensive Organic Synthesis×, Ed. B. M. Trost, I.
Fleming, Vol. 4, Pergamon Press, Oxford, 1991, pp. 833 863; R. F. Heck, in −Palladium Reagents in
Organic Synthesis×, Academic Press, New York, 1985; A. de Meijere, S. Br‰se, in −Transition Metal
Catalyzed Reactions×, IUPAC Monographs −Chemistry for the 21st Century×, Eds. S. Murahashi, S. G.
Davies, Blackwell Science, Oxford, 1999, pp. 99 131; A. de Meijere, S. Br‰se, J. Organomet. Chem. 1999,
576, 88; I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009; S. Br‰se, A. de Meijere, in
− Handbook of Organopalladium Chemistry×, Ed. E.-I. Negishi, Wiley, New York, 2002, in press.
[3] W. F. Bailey, N. M. Wachter-Jurcsak, M. R. Pineau, T. V. Ovaska, R. R. Warren, C. E. Lewis, J. Org. Chem.
1996, 61, 8216.
[4] K. H. Ang, S. Br‰se, A. G. Steinig, F. E. Meyer, A. Llebaria, K. Voigt, A. de Meijere, Tetrahedron 1996, 52,
11503; b) F. E. Meyer, K. H. Ang, A. G. Steinig, A. de Meijere, Synlett 1994, 191.
[5] E. L. Eliel, −Stereochemistry of Organic Compounds×, Wiley & Sons, New York, 1994; D. F. Detar, N. P.
Luthra, J. Am. Chem. Soc. 1980, 102, 4505.
[6] M. R. Tiollais, Bull. Soc. Chim. Fr. 1947, 14, 708.
[7] S. Kˆrbe, A. G. Steinig, A. de Meijere, −10th IUPAC Symposium on Organo-Metallic Chemistry Directed
Towards Organic Synthesis×, Versailles 1999; S. Kˆrbe, A. de Meijere, −4th International Symposium
Transition Metals in Organic Synthesis×, Leeds, 2000.
[8] F. Fringuelli, L. Minuti, L. Radics, A. Taticchi, E. Wenkert, J. Org. Chem. 1988, 53, 4607.
[9] F.-G. Kl‰rner, F. Wurche, J. Prakt. Chem. 2000, 342; A. Dijca, C. D. Hubbard, R. van Eldik, T. Assano,
M. V. Basilevsky, W. J. Le Noble, Chem. Rev. 1998, 98, 2167; G. Jenner, Tetrahedron 1997, 53, 2669.
[10] J. W. Barton, A. Coop, J. W. Lewis, Tetrahedron Lett. 1993, 34, 6777; D. A. Smith, Tetrahedron Lett. 1991,
32, 1549.
[11] A. J. Mancuso, S. L. Huang, D. Swern, J. Org. Chem. 1978, 43, 2480.
[12] T. C. McMorris, M. Anchel, J. Am. Chem. Soc. 1965, 87, 1594; M. J. Kelner, T. C. McMorris, W. T. Beck,
G. M. Zamora, R. Taetle, Cancer Res. 1987, 47, 3186; T. C. McMorris, M. J. Kelner, W. Wang, L. A. Estes,
M. A. Montoya, R. Taetle, J. Org. Chem. 1992, 57, 6876.
[13] B. M. Trost, G. T. Tanoury, J. Am. Chem. Soc. 1988, 110, 1636.
[14] R. B. Woodward, R. Hoffmann, in −The Conservation of Orbital Symmetry×, Verlag Chemie, Weinheim,
1970.
[15] L. Bhat, A. G. Steinig, R. Appelbe, A. de Meijere, Eur. J. Org. Chem. 2001, 1673.
[16] S. Weinreb, R. R. Staib, Tetrahedron 1982, 38, 3087; H. Waldmann, Synthesis 1994, 535; J. F. Kerwin, S.
Danishefsky, Tetrahedron Lett. 1982, 23, 3739; J. Streith, A. Defoin, Synthesis 1994, 1107; F. Reichel, X. M.
Fang, S. L. Yao, M. Ricci, K. A. Jorgensen, Chem. Commun. 1999, 1505.
[17] S. D. Larsen, P. A. Grieco, J. Am. Chem. Soc. 1985, 107, 1768.
[18] K. Waldmann, Liebigs Ann. Chem. 1989, 231.
[19] D. D. Perrin, W. L. F. Armarengo, −Purification of Laboratory Chemicals×, Pergamon Press, Oxford, 1987.
[20] B. M. Trost, J. M. Tour, J. Am. Chem. Soc. 1987, 109, 5268.
Received May29, 2002