The enantioselective total synthesis of (-)-myltaylenol

Article abstract of DOI:10.1002/(SICI)1521-3765(19980807)4:8<1480::AID-CHEM1480>3.0.CO;2-6

The unusual sesquiterpenoid alcohol (-)-myltaylenol (1) is synthesized by an intramolecular [4+2] cycloaddition of a chiral diene accessible from Hajos-Wiechert ketone by a sequence of reactions including stereoselective alkylation of an unsaturated ketone with thiophenylmethyl iodide as alkylation agent. As the link between diene and olefin a sulfonic ester group is used. The link permits control of the stereoselectivity of the [4+2] cycloaddition. After this key step the sulfonic ester group can be removed under oxidative conditions by molecular oxygen as oxidation agent, leading directly to a hydroxyketone that can be converted to (-)-myltaylenol by successive Shapiro reaction, regioselective hydroboration and Wittig reaction.

Full text of DOI:10.1002/(SICI)1521-3765(19980807)4:8<1480::AID-CHEM1480>3.0.CO;2-6

FULL PAPER
The Enantioselective Total Synthesis of ( )-Myltaylenol
Sven Doye, Torsten Hotopp, Rudolf Wartchow, and Ekkehard Winterfeldt*
Abstract: The unusual sesquiterpenoid alcohol ( )-myltaylenol (1) is synthesized by
an intramolecular [4‡2] cycloaddition of a chiral diene accessible from Hajos ±
Wiechert ketone by a sequence of reactions including stereoselective alkylation of
an unsaturated ketone with thiophenylmethyl iodide as alkylation agent. As the link
between diene and olefin a sulfonic ester group is used. The link permits control of
the stereoselectivity of the [4‡2] cycloaddition. After this key step the sulfonic ester
group can be removed under oxidative conditions by molecular oxygen as oxidation
agent, leading directly to a hydroxyketone that can be converted to ( )-myltaylenol
by successive Shapiro reaction, regioselective hydroboration and Wittig reaction.
Keywords: cycloadditions ´ natural
products ´ oxidations ´ terpenoids ´
total synthesis
In 1994 Srikrishna et al. communicated briefly a very short
racemic synthesis of nonnatural myltaylene (2), which lacks
the C15 hydroxyl group of myltaylenol, starting from cyclo-
geraniol. The key step of this synthesis is an impressive Lewis
acid catalyzed cationic rearrangement leading directly to the
target molecule.[4] Nevertheless, to the best of our knowledge
no other synthesis and no enantioselective approach to this
type of molecule has been reported until we published the first
enantioselective synthesis of ( )-myltaylenol (1).[5] Herein we
want to describe this synthesis in detail.
Introduction
In 1985 Matsuo et al. isolated the unusual sesquiterpenoid
alcohol ( )-myltaylenol (1, Figure 1) from the liverwort Mylia
taylorii and determined its structure by NMR techniques and
Results and Discussion
Figure 1. Structures of ( )-myltaylenol (1), myltaylene (2), ( )-cyclo-
myltaylenol (3), and cyclomyltaylene (4).
Our retrosynthetic analysis is outlined in Scheme 1. It reflects
our experience in the formation of bridged structures similar
to 1 by Diels ± Alder reactions of dienophiles with chiral
dienes[6] derived from Hajos ± Wiechert ketone.[7] We have
chosen an intramolecular [4‡2] cycloaddition, building up
two chiral centers in one step, as the key step in our synthesis.
Cyclopentadiene 11 was supposed to be the key intermediate.
In 11 two of the four desired chiral centers are established
already. To synthesize 11 as a single enantiomer, the well-
documented enantiopure tetrahydropyranyl (THP) ether 12
was considered as a perfect starting material.[8] The alcohol
functionality in 11 should provide the possibility of controlling
the stereochemical outcome of the Diels ± Alder reaction by
introducing a temporary tether (X in 7, Yn in combination with
Z in 10) between diene and the 2p system, which should lead
to a highly stereoselective intramolecular a-attack of the
olefin to the diene. After cycloaddition to 6 or 9 the tether
should then be able to be removed totally (Yn in 9) or to be
cleaved while forming a functional group such as a carbonyl
X-ray crystal structure analysis of the corresponding ben-
zoate.[1] It was the first example of a new class of sesquiter-
penes possessing the myltaylane framework. Other examples
are ( )-cyclomyltaylenol (3), isolated from Mylia taylorii, and
cyclomyltaylene (4), isolated from Bazzania tridens.[2, 3] All
three compounds are characterized by at least four consec-
utive chiral centers (*), three of which are quartenary carbon
atoms.
[*] Prof. Dr. Dr. h.c. E. Winterfeldt, Dr. S. Doye, Dr. T. Hotopp
Institut für Organische Chemie der Universität Hannover
Schneiderberg 1B, D-30167 Hannover (Germany)
Fax: (‡49)511-762-30-11
E-mail: winterfeldt@mbox.oci.uni-hannover.de
Dr. R. Wartchow
Institut für Anorganische Chemie der Universität Hannover
Callinstr. 9, D-30167 Hannover (Germany)
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1480±1488
bifunctional alkylation agent. In order to avoid O-alkylation
we chose the quite soft thiophenylmethyl halides (PhSCH2X)
as alkylation agents, which should be superior to the
corrosponding ethers (Scheme 2). Owing to the sterically
Scheme 2. Diastereoselective alkylation of unsaturated ketones 12 and 13.
Reagents and conditions: a) KOtBu (1.3 equiv), THF, 08C, 45 min, then
PhSCH2X (1.4 equiv), 788C, 30 min.
demanding methyl group on the b-side of the molecule the
functionalized sidechain was introduced on the a-side with
high selectivity. First alkylation experiments were run with the
trimethylsilyl (TMS) ether 13 and potassium tert-butoxide as a
base in tetrahydrofuran (THF) with thiophenylmethyl chloride
as the alkylation reagent at 788C. The diastereoselectivity
de was 85%. In order to improve the selectivity we
synthezised the corresponding bromide and iodide and used
them as alkylation agents.[12] We found that the selectivity
could be increased (Scheme 2, Table 1) by changing the halide
Table 1. Diastereoselective alkylation of unsaturated ketones 12 and 13.
Scheme 1. Retrosynthetic analysis of ( )-myltaylenol (1).
R
X
Yield
de
TMS
TMS
TMS
THP
Cl
Br
I
71%
61%
82%
83%
85%
94%
95%
96%
group at the same position (X in 6). To complete the synthesis
it would be necessary to perform a 1,2-carbonyl shift and a
following olefination reaction (5 to 1) or convert Z into an
exocyclic double bond (8 to 1).
I
One possible tether X is the SO2 unit, introduced by Metz
et al., which can be removed under oxidative conditions
leading to a carbonyl group.[9] Possibilities for Yn in combi-
from chloride through bromide (de ˆ 94%) to iodide (de ˆ
95%). A slight improvement in selectivity (de ˆ 96%) and an
easier chromatographic separation of the resulting diaster-
eomers were achieved with the THP ether 12 instead of the
TMS ether 13. The resulting thioethers 14 and 15 were
isolated with yields between 61% and 83%. The cis config-
uration of the methyl groups was determined by NOE
experiments. Using this procedure we were able to establish
the first two chiral centers of the natural product.
nation with Z are Me2Si,[10] C O,[11] or a direct bond between
ˆ
oxygen and the double-bond carbon, while Z could be an ester
group.
The first step in our synthesis was a diastereoselective
alkylation of an unsaturated ketone like 12 or 13 with a
Abstract in German: Das Sesquiterpen ( )-Myltaylenol 1
wird unter Nutzung einer intramolekularen [4‡2]-Cycloaddi-
tion eines chiralen Diens, welches ausgehend von enantio-
merenreinem Hajos ± Wiechert-Keton leicht zugänglich ist,
synthetisiert. Als Verbindungsglied zwischen Dien- und Ole-
fin-Teil des Moleküls wird eine Sulfonsäureester-Einheit ver-
wendet. Diese Brücke bietet neben einer perfekten Kontrolle
der Stereoselektivität der [4‡2]-Cycloaddition die Möglichkeit,
hinterher oxidativ spaltbar zu sein. Mit molekularem Sauer-
stoff als Oxidationsmittel entsteht dabei direkt ein Hydro-
xyketon, welches durch schrittweise Shapiro-Reaktion, regio-
selektive Hydroborierung und Wittig-Reaktion in 1 überführt
werden kann.
To generate the cyclohexane unit of ( )-myltaylenol 1 it
was then necessary to remove the keto group of 14. A direct
Wolff ± Kishner reduction of the thioether 14 gave cyclo-
pentenol 17 in 80% yield. In order to increase the yield by
eliminating possible side reactions caused by the acetal unit,
we removed the THP protecting group under acidic con-
ditions before conducting the Wolff ± Kishner reduction.
Using this strategy we were able to isolate cyclopentenol 17
in 87% yield over two steps. To generate the necessary diene
unit, the tosylate 18 was formed under standard conditions in
almost quantitative yield and treated with potassium tert-
butoxide in THF at 658C; this resulted in the formation of
diene 19 in 72% yield (Scheme 3).
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FULL PAPER
After alcohol 11 had been obtained as a single enantiomer
in multigram quantities, different olefin units were introduced
into the molecule. Our first strategy was to use the Metz
protocol, which consists of the formation of a vinylsulfonic
ester 23 followed by an intramolecular Diels ± Alder reaction
and an oxidative ring cleavage of the resulting sultone 24.[9]
Alcohol 11 was reacted with ethenesulfonyl chloride[13] in
methylene chloride at 158C to yield 81% of the desired
ester 23, which underwent the intramolecular Diels ± Alder
reaction smoothly. Because of the control by the already
established chiral centers, only a-attack of the dienophile unit
was observed. This resulted in the formation of only one
diastereomer, the sultone 24 with quantitative yield. The
predicted a-configuration of 24 and 25 was secured by X-ray
crystal structure analysis of sultone 25 (see Figure 2).[14] To
Scheme 3. Synthesis of cyclopentadiene 19. Reagents and conditions:
a) HCl, EtOH, 258C, 16 h; b) N2H4 (7.0 equiv), KOH (6.8 equiv), diglycol,
2008C, 4 h; c) TsCl (1.5 equiv), DMAP (2.0 equiv), CH2Cl2, 258C, 16 h;
d) KOtBu (2.0 equiv), THF, 658C, 3.5 h.
The last problem in the synthesis of key intermediate 11 was
the exchange of the thioether unit against an oxygen func-
tionality. This was done by the Pummerer strategy. First the
thioether 19 was oxidized with sodium metaperiodate in a
mixture of water and methanol at room temperature in almost
quantitative yield. A nearly 1:1 mixture of diastereomeric
sulfoxides 20 was obtained. It was not necessary to separate
these diastereomers for the following synthesis. The Pum-
merer rearrangement was carried out in acetic anhydride at
1008C over a period of 62 hours. The yield was 89%. Again
two diastereomers 21 in a nearly 1:1 ratio were obtained but
not separated. Hydrolysis of 21 in KOH/MeOH led to the
very volatile and diastereomerically pure aldehyde 22, which
was reduced immediately with sodium borohydride at 08C to
give the alcohol 11, which was easily isolated. The yield for
this one-pot conversion was 99% (Scheme 4).
Scheme 5. Synthesis of sultone 25. Reagents and conditions:
ˆ
a) ClSO2CH CH2 (1.25 equiv), EtN(iPr)2 (1.2 equiv), CH2Cl2, 158C,
1.5 h; b) toluene, 1118C, 20 h; c) 1 atm H2, Pd/C, 258C, 16 h.
avoid side reactions caused by the double bond in 24,
hydrogenation under one atmosphere H2 was performed
using palladium on carbon as a catalyst in THF at room
temperature (Scheme 5).
In order to achieve an oxidative cleavage of the sultone
bridge, a number of procedures were tried. The goal was to
Scheme 4. Synthesis of alcohol 11. Reagents and conditions: a) NaIO4
(1.3 equiv), MeOH/H2O 6:1, 08C ± 258C, 16 h; b) Ac2O, 1008C, 62 h;
c) KOH (2.0 equiv), MeOH, 258C, 2 h; d) NaBH4 (1.6 equiv), MeOH, 08C,
30 min.
Figure 2. PLATON drawing of sultone 25.
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( )-Myltaylenol
1480±1488
introducea hydroxyl group at the sulfur-bearing carbon atom
by oxidizing the sultone anion, which is easily prepared by
deprotonation of 25 with sBuLi. The carbon ± sulfur bond of
the resulting product should cleave to form the desired
keto function in 5. Unfortunately, the oxidation employing
2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane, which had
been used by Metz at al., failed.[9] Other reagents normally
used for the oxidation of anions, like MoOPH[15] or
N-sulfonyloxaziridines[16] were not useful either; only the
starting material 25 was isolated. The reason for these failures
is probably the fact that the oxidation should take place at a
sterically very hindered center. For this reason we tried to use
less sterically demanding oxidizing agents like molecular
oxygen, which is usually used in combination with a reducing
agent to reduce the primarily formed hydroperoxides.[17]
However, the oxidation of the sultone anion generated from
25 and sBuLi with molecular oxygen at 788C produced the
desired hydroxyketone 5 (Scheme 6) without the need for any
additional reducing agent. Since it was possible to detect
sulfate ions in the aqueous workup one may consider the
sultone unit a reducing agent in an intra- or intermolecular
redox process. The yield and the reproducibility of this
reaction depended strongly on the solvent and the amount of
base. A detailed investigation showed that the best solvent is a
7:1 mixture of THFand hexamethyl phosphoramide (HMPA).
No other additives (for example N,N,N',N'-tetramethyl 1,2-
ethylenediamine (TMEDA), 1,3-dimethyl imidazolidin-2-one
(DMPU), or 1,2-dimethoxyethane (DME)) influenced the
yield, which was about 20% with or without these additives
compared to 30 to 60% with THF/HMPA. Although the
starting sultone 25 could be recovered, a further improvement
was necessary because the reaction, which was first run with
3.0 equiv of sBuLi, was not very reproducible. The yield
varied from 30 to 60%. Use of a much higher amount of base
(10.0 equiv) made the reaction less sensitive and increased the
yield. Now it was possible to isolate the hydroxyketone 5
absolutely reproducibly in 73% yield (Scheme 6, Table 2). A
unconsumed oxygen) as oxidizing agent instead of molecular
oxygen resulted in product formation too. Unfortunately in
this case the yields were low (26%).
Since the outcome of the oxidative cleavage of the sultone
bridge in 25 remained uncertain for quite a long period of
time, we started a parallel investigation using enol ether 26,
silyl ether 27 and esters 28 and 29 as alternative intermediates
for the intramolecular [4‡2] cycloaddition just to keep
additional options. All compounds were prepared in one or
two steps from cyclopentadiene 11 (Scheme 7; yields were not
optimized).
Scheme 7. Alternative starting materials for intramolecular Diels ± Alder
reactions. Reagents and conditions: a) HCCCOOCH3 (1.2 equiv), NEt3
ˆ
(2.0 equiv), THF, 258C, 3.5 h; b) ClSi(CH3)2 ± CH CHCOOCH3
(2.0 equiv), NEt3 (3.0 equiv), CH2Cl2, 258C, 20 h; c) CH3CCCOOH
(1.2 equiv), DCCI (1.2 equiv), DMAP (1.2 equiv), CH2Cl2, 258C, 5 h;
d) LDA (2.2 equiv), THF/HMPA 12:1, 788C, 1 h, then NH4Cl.
Unfortunately enol ether 26 and the esters 28 and 29 did not
undergo intramolecular cycloaddition at all, either under
thermal (1808C) or under Lewis acid catalyzed conditions
(ZnCl2 ´ Et2O, BF3 ´ Et2O). Silyl ether 27 underwent cyclo-
addition at 1808C over a period of 90 hours to give a 2:1
mixture of diastereomers 30 and 31. However, owing to the
harsh reaction conditions the yield was only 20%. The relative
stereochemistry of 30 and 31 could not be determined reliably
by NOE experiments. Nevertheless, in analogy to the cyclo-
addition of 23 we believe that 30 and 31 are both products
resulting from a-attack of the dienophile, which differ only in
the configurations at C4 and C5. Regarding the low yield of
the cycloaddition, which precludes 30 and 31 as useful
synthetic intermediates, no further effort was made to
determine the stereochemistry at these carbon atoms
(Scheme 8).
Scheme 6. Oxidative cleavage of sultone 25. Reagents and conditions:
a) sBuLi (equiv see Table 2), O2, THF/HMPA 7:1, 788C, 3 h.
Table 2. Influence of different amounts of sBuLi.
Amount of sBuLi
Yield 5
Recovered 25
1.0 equiv
5.2 equiv
7.8 equiv
10.4 equiv
0%
43%
49%
73%
92%
36%
24%
12%
possible explanation for this behavior could be the formation
of sec-butyl hydroperoxide in the reaction mixture, which can
act as oxidizing agent. Experiments using sec-butyl hydro-
peroxide (formed in situ from sBuLi and oxygen at 788C
followed by bubbling nitrogen through the solution to remove
Obviously it was necessary to have four atoms in the bridge
between ene and diene unit to form a six-membered ring in
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E. Winterfeldt et al.
FULL PAPER
Scheme 8. Intramolecular Diels ± Alder reaction of 27. Reagents and
conditions: a) o-dichlorobenzene, 1808C, 90 h.
the transition state of the cycloaddition. Furthermore these
four atoms had to be sp3 centers leading to a comparatively
unstrained transition state.[18] The difference in reactivity
between silyl ether 27 and sulfonic ester 23 can be explained
by the strong acceptor property of the SO2 unit, which
activates the olefin in 23 for Diels ± Alder reactions. With
these results available we decided to concentrate on the
oxidative cleavage of the sultone bridge in 25; this finally led
to good results after the detailed investigation described
above.
The following 1,2-carbonyl shift was approached by trans-
formation of the hydroxyketone 5 into the olefin 33 by a
Shapiro reaction with tosylhydrazone 32. The synthesis of this
hydrazone proceeded in 98% yield and produced only one
isomer, probably the sterically less crowded 32. No effort was
made to determine the geometry of this product. The
following Shapiro reaction was run at 758C in THF with
5.0 equiv of nBuLi as a base. The yield was 90%. When the
reaction was performed at lower temperatures ( 788C to
258C) no product was observed.
Scheme 9. Shapiro reaction. Reagents and conditions: a) TsN2H3
(1.0 equiv), TsOH (0.18 equiv), molecular sieves 3 Š, EtOH, 788C, 2 h;
b) nBuLi (5.0 equiv), THF, 758C, 50 min; c) iPr3SiOTf (1.1 equiv), NEt3
(1.8 equiv), CH2Cl2, 788C; d) isobutene, amberlite 15, cyclohexane, 258C.
Because of its usually high regioselectivity we chose
hydroboration to functionalize olefin 33.[19] Since it was hoped
that a very bulky protecting group on the primary alcohol
would change it into a large and inert moiety, which should
result in high selectivity for the subsequent borane attack, the
hydroxyl group was silylated using triisopropyl (TIPS) triflate
in the presence of triethylamine giving the silyl-ether-pro-
tected olefin 34 in 99% yield. As another bulky protecting
group the tert-butyl group was introduced by means of
isobutene in the presence of amberlite giving the tert-butyl
ether protected olefin 35 in 99% yield (Scheme 9).
Interestingly the following hydroboration showed a sur-
prisingly low regioselectivity. Even with the bulky TIPS or
tert-butyl ether groups shielding one side of the double bond,
the highest observed selectivity was 1.5:1 in favor of the
desired product. The TIPS ether 34 showed a slightly higher
selectivity than the tert-butyl ether 35. In general diborane ´
THF delivered the best results, whereas 9-BBN and thex-
ylborane led to no or incomplete conversion with lower
selectivity (Scheme 10, Table 3). The desired alcohol 36, a
mixture of two diastereomers which were only separated for
spectroscopic characterization, was isolated after chromatog-
raphy in 53% yield.
Scheme 10. Hydroboration of olefins 34 and 35. Reagents and conditions:
a) see Table 3.
Table 3. Hydroboration of olefins 34 and 35.
R
Conditions
Yield
Ratio 36:38
or 37:39
tBu
tBu
1) BH3 ´ THF, THF, 08C, 27 h
2) EtOH, H2O2, NaOH, 508C, 3 h
1) thexylborane, THF, 258C, 28 h
2) EtOH, H2O2, NaOH, 788C, 0.5 h
9-BBN, Toluene, 1118C, 48 h
1) BH3 ´ THF, THF, 08C, 27 h
2) EtOH, H2O2, NaOH, 508C, 3 h
1) thexylborane, THF, 258C, 48 h
2) EtOH, H2O2, NaOH, 788C, 0.5 h
9-BBN, THF, 25 ± 508C, 7 h
70%
82%
1.3:1.0
1.2:1.0
tBu
TIPS
no reaction
89%
±
1.5:1.0
TIPS
TIPS
traces
±
±
no reaction
desilylation with tetrabutylammonium fluoride (TBAF), gave
access to the target compound 1 in an overall yield of 6.5%
(Scheme 11).
The comparison of all spectra of 1 with authentic spectra
kindly provided by Dr. Matsuo proved 1 to be identical to the
natural product. The [a]2D0 ˆ 59.08 of synthetic 1 was exactly
the same as reported by Matsuo et al.[1] NMR shift experi-
Having the right functionality at the right position we were
able to oxidize alcohol 36 under Swern conditions to the
corresponding ketone 40 in 93% yield. The subsequent Wittig
reaction proceeded in 87% yield and established the last
missing carbon atom of ( )-myltaylenol. The final step, the
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( )-Myltaylenol
1480±1488
and then cooled to 788C. A solution of freshly prepared thiophenyl-
methyl iodide (17.94 g, 71.3 mmol) in THF (30 mL) was added dropwise.
The resulting solution was stirred at 788C until the starting material was
consumed (30 ± 45 min) and quenched with saturated aqueous NaHCO3.
The mixture was extracted with MTBE. The organic layer was washed with
saturated aqueous NH4Cl, saturated aqueous NaHCO3, and brine, and dried
over MgSO4. After concentration under reduced pressure, purification by
flash chromatography (PE/EtOAc, 10:1) afforded 14 (16.00 g, 81%) as a
colorless oil (mixture of two diastereomers). 1H NMR (400 MHz, CDCl3):
d ˆ 7.39 ± 7.33 (m, 4H; Ar), 7.30 ± 7.23 (m, 4H; Ar), 7.19 ± 7.12 (m, 2H; Ar),
ˆ
5.50 ± 5.46 (m, 2H; HC C), 4.70 ± 4.65 (m, 2H; HCO2), 4.08 (dd, J ˆ 9.0,
7.3 Hz, 1H; HC ± O), 4.00 (dd, J ˆ 9.0, 7.5 Hz; HC ± O), 3.95 ± 3.85 (m, 2H;
H2C ± O), 3.56 ± 3.47 (m, 2H; H2C ± O), 3.37 ± 3.27 (m, 4H; CH2 ± SPh),
2.65 ± 2.52 (m, 4H), 2.49 ± 2.36 (m, 3H), 2.26 (ddd, J ˆ 15.6, 9.0, 1.6 Hz, 1H),
2.04 ± 1.79 (m, 6H), 1.78 ± 1.67 (m, 2H), 1.67 ± 1.48 (m, 8H), 1.33 (s, 3H;
CH3), 1.32 (s, 3H; CH3), 1.18 (s, 6H; CH3); 13C NMR (100.6 MHz, DEPT,
CDCl3): 213.4 (Cquart), 213.2 (Cquart), 151.1 (Cquart), 150.3 (Cquart), 137.6
(Cquart), 137.6 (Cquart), 130.0 (CH), 128.8 (CH), 126.2 (CH), 126.2 (CH), 122.4
(CH), 121.6 (CH), 99.9 (CH), 97.1 (CH), 86.8 (CH), 84.0 (CH), 62.7 (CH2),
62.3 (CH2), 52.7 (Cquart), 52.7 (Cquart), 46.4 (Cquart), 46.0 (Cquart), 43.1 (CH2),
36.7 (CH2), 35.9 (CH2), 35.7 (CH2), 34.7 (CH2), 33.2 (CH2), 32.6 (CH2), 31.0
(CH2), 28.1 (CH3), 27.9 (CH3), 25.5 (CH2), 25.5 (CH2), 19.8 (CH2), 19.6
(CH2), 17.7 (CH3), 17.6 (CH3); IR (CHCl3): nÄ ˆ 3000, 2940, 2852, 1708, 1480,
1452, 1372, 1340, 1260, 1132, 1076, 1028, 976, 868 cm 1; MS (908C): m/z
Scheme 11. Synthesis of ( )-myltaylenol (1). Reagents and conditions:
a) (COCl)2 (1.5 equiv), DMSO (3.0 equiv), CH2Cl2, 608C, 30 min, then
NEt3 (5.6 equiv), 258C, 10 min; b) Ph3PCH3Br (7.0 equiv), KOtBu
(5.0 equiv), benzene, 258C, 44 h; c) TBAF (2.0 equiv), THF, 258C, 18 h.
ments showed an enantiomeric purity of 94%, which was the
same as in the starting material 12. However, the melting
point of 69 ± 70.58C could not be reproduced. The melting
point of synthetic 1 was 648C.
‡
(%) ˆ 387 (28) [M ], 302 (33), 284 (20), 277 (23), 194 (30), 175 (33), 161
(16), 147 (21), 133(29), 123 (100), 105 (30), 85 (99); UV/Vis (CH3CN):
lmax ˆ 256, 209 nm; HRMS: calcd for C23H30O3S 386.1916; found 386.1917.
Thiophenylmethyl iodide: Thiophenylmethyl chloride (15.9 g, 100 mmol)
was dissolved in acetone (140 mL). Dry NaI (18.7 g, 125 mmol) was added
at 258C. The mixture was stirred in the dark at 258C for 2 h, diluted with
ether, washed with saturated aqueous Na2S2O3 and brine. A small amount
of Cu powder was added to the organic layer while it was dried over
MgSO4. Evaporation of the solvent at temperatures below 308C afforded
thiophenylmethyl iodide (25.0 g, 100 mmol) as an extremely noxious
orange liquid. The product was used immediately in the alkylation reaction
described above. 1H NMR (80 MHz, CDCl3): d ˆ 7.55 ± 7.25 (m, 5H; Ar),
4.58 (s, 2H; I ± CH2 ± SPh).
Conclusion
In this article an enantioselective route to ( )-myltaylenol 1 is
described. An intramolecular Diels ± Alder reaction building
up the three consecutive quartenary carbon atoms of the
product is used as the key step of the synthesis. This is
followed by a novel oxidative ring cleavage employing
molecular oxygen and giving rise to a hydroxyketone directly.
The overall yield of the synthesis is 6.5%. The synthetic
compound turned out to be identical with the natural product.
Hydroxyketone 16: A mixture of THP ether 14 (15.30 g, 39.6 mmol) and
HCl (16.0 mL, 37% in water) in EtOH (100 mL) was stirred for 2 h at 258C.
The solution was diluted with MTBE, washed with water (2 Â ) and brine,
and dried over MgSO4. Concentration and purification by flash chroma-
tography (PE/EtOAc, 2:1) afforded hydroxyketone 16 (11.97 g, 100%) as a
colorless solid. M.p. 448C; [a]D20
ˆ
20.38 (c ˆ 1.0 in CHCl3); 1H NMR
(400 MHz, CDCl3): d ˆ 7.40 ± 7.33 (m, 2H; Ar), 7.30 ± 7.23 (m, 2H; Ar),
ˆ
7.20 ± 7.12 (m, 1H; Ar), 5.47 (dd, J ˆ 3.4, 1.7 Hz, 1H; HC C), 4.08 (dd, J ˆ
Experimental Section
9.1, 7.5 Hz, 1H; HC ± OH), 3.35 (d, J ˆ 12.3 Hz, 1H; CH2 ± SPh), 3.31 (d,
J ˆ 12.3 Hz, 1H; CH2 ± SPh), 2.63 ± 2.51 (m, 2H), 2.42 (dt, J ˆ 16.9, 5.2 Hz,
1H), 2.31 (ddd, J ˆ 15.3, 9.1, 1.7 Hz, 1H), 1.96 ± 1.80 (m, 2H), 1.32 (s, 3H;
CH3), 1.16 (s, 3H; CH3); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 213.0
(Cquart), 150.8 (Cquart), 137.5 (Cquart), 130.0 (CH), 128.8 (CH), 126.3 (CH),
121.9 (CH), 81.3 (CH), 52.7 (Cquart), 46.2 (Cquart), 43.1 (CH2), 37.8 (CH2), 35.8
(CH2), 32.3 (CH2), 27.9 (CH3), 16.9 (CH3); IR (CHCl3): nÄ ˆ 3612, 3060,
2976, 2932, 2868, 1708, 1584, 1480, 1452, 1260, 1124, 1076, 1024 cm 1; MS
General techniques: Melting points: Gallenkamp apparatus, uncorrected.
MS spectra and high resolution mass spectra: Finnigan MAT312 and VG
Autospek (EI) with an ionization potential of 70 eV. IR spectra: Perkin ±
Elmer 580 and FT 1710. 1H NMR spectra: Bruker AM400, chemical shifts
relative to Me4Si or CHCl3 (in CDCl3), chemical shift signals (d) are quoted
as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), br (broad).
13C NMR spectra including DEPT: Bruker AM400, chemical shifts relative
to CDCl3. UV spectra: Beckman 3600 spectrophotometer. Optical
‡
(1008C): m/z (%) ˆ 302 (33) [M ], 274 (4), 246 (4), 193 (37), 175 (28), 151
(28), 149 (28), 133 (38), 123 (100), 105 (43), 91 (39); UV/Vis (CH3CN):
lmax ˆ 253, 206 nm; HRMS: calcd for C18H22O2S 302.1341; found 302.1342;
C18H22O2S (302.4): calcd C 71.49, H 7.33; found C 71.10, H 7.45.
rotations were recorded with
a Perkin ± Elmer 241 polarimeter. All
reactions were performed under an inert atmosphere of nitrogen or argon
in oven- or flame-dried glassware. Dry solvents: THF, benzene, and toluene
were distilled from sodium/benzophenone, methylene chloride was dis-
tilled from calcium hydride. All commercially available reagents were used
without further purification unless otherwise noted. All reactions were
monitored by thin-layer chromatography (TLC) carried out on Merck 60F254
(silica) sheets visualized with UV light or Ce(iv)/molybdatophosphoric
acid. Preparative flash chromatography was performed on Baker silica gel
(particle size 30 ± 60 mm) under positive air pressure. Yields refer to
chromatographically and spectroscopically (1H NMR) homogeneous
materials, unless otherwise noted. PE: light petroleum, b.p. 40 ± 608C.
MTBE: methyl tert-butyl ether.
Alcohol 17:
A solution of 16 (11.63 g, 38.4 mmol), KOH (14.60 g,
260 mmol) and N2H4 (16.0 mL, 85% in water, 270 mmol) in diglycol
(220 mL) was heated to 1008C for 1 h and then to 2008C for 4 h. During this
time water was removed by distillation. After cooling down to 258C the
mixture was diluted with MTBE and washed with saturated aqueous
NH4Cl, saturated aqueous NaHCO3 and brine, and dried over MgSO4.
After concentration under reduced pressure, purification by flash chroma-
tography (PE/EtOAc, 5:1) afforded 17 (9.64 g, 87%) as a colorless solid.
M.p. 778C; [a]2D0
ˆ
28.38 (c ˆ 1.0 in CHCl3); 1H NMR (400 MHz, CDCl3):
d ˆ 7.37 ± 7.32 (m, 2H; Ar), 7.28 ± 7.23 (m, 2H; Ar), 7.17 ± 7.12 (m, 1H; Ar),
ˆ
5.36 (dd, J ˆ 3.3, 1.5 Hz, 1H; HC C), 3.90 (dd, J ˆ 9.4, 7.5 Hz, 1H; HC ±
THP ether 14: A solution of KOtBu (7.50 g, 66.9 mmol) in THF (60 mL)
was added slowly to a solution of 12[6] (13.51 g, 51.1 mmol) in THF
(100 mL) at 08C. The resulting brown solution was stirred for 45 min at 08C
OH), 3.21 (d, J ˆ 12.0 Hz, 1H; CH2 ± SPh), 3.06 (d, J ˆ 12.0 Hz, 1H; CH2 ±
SPh), 2.46 (ddd, J ˆ 15.0, 7.5, 3.5 Hz, 1H), 2.13 (ddd, J ˆ 15.0, 9.5, 1.7 Hz,
1H), 1.84 ± 1.54 (m, 5H), 1.43 (dt, J ˆ 13.5, 4.0 Hz, 1H), 1.23 (s, 3H; CH3),
Chem. Eur. J. 1998, 4, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0408-1485 $ 17.50+.25/0
1485

E. Winterfeldt et al.
FULL PAPER
1.07 (s, 3H; CH3); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 153.7 (Cquart),
138.6 (Cquart), 129.1 (CH), 128.8 (CH), 125.6 (CH), 118.0 (CH), 83.7 (CH),
47.6 (CH2), 46.8 (Cquart), 38.7 (CH2), 38.4 (Cquart), 36.8 (CH2), 36.7 (CH2),
26.7 (CH3), 18.7 (CH2), 17.3 (CH3); IR (CHCl3): nÄ ˆ 3612, 3060, 3000, 2932,
2868, 2848, 1580, 1480, 1464, 1376, 1080, 1024 cm 1; MS (708C): m/z (%) ˆ
2932, 2868, 1596, 1444, 1376, 1088, 1032 cm 1; MS (258C): m/z (%) ˆ 286
‡
(9) [M ], 270 (40), 234 (1), 220 (2), 200 (2), 175 (4), 161 (93), 147 (79), 131
(46), 119 (69), 105 (100), 91 (61); UV/Vis (CH3CN): lmax ˆ 253, 208 nm;
HRMS: calcd for C18H22OS 286.1391; found 286.1392.
Acetoxy sulfides 21: A solution of 20 (9.08 g, 31.7 mmol) in acetic
anhydride (200 mL) was heated to 1008C for 62 h. Then the acetic
anhydride was removed under reduced pressure. Water was added to the
residue. The mixture was allowed to stand for 2 h. Then it was extracted
with MTBE (3 Â ). The combined organic layers were washed with water,
saturated aqueous NaHCO3, and brine, and dried over MgSO4. Concen-
tration and purification by flash chromatography (PE/EtOAc, 10:1)
afforded 21 (9.24 g, 89%) as a colorless oil (mixture of two diastereomers).
1H NMR (400 MHz, CDCl3): d ˆ 7.63 ± 7.58 (m, 2H; Ar), 7.56 ± 7.52 (m, 2H;
Ar), 7.34 ± 7.26 (m, 6H; Ar), 6.39 (brs, 1H; HC(SPh)OAc), 6.35 (brs, 1H;
‡
288 (48) [M ], 179 (11), 165 (100), 146 (39), 135 (24), 121 (82), 107 (44), 93
(48); UV/Vis (CH3CN): lmax ˆ 255, 206 nm; HRMS: calcd for C18H24OS
288.1548; found 288.1550; C18H24OS (288.5): calcd C 74.95, H 8.39; found C
74.84, H 8.36.
Tosylate 18: A solution of 17 (11.29 g, 39.1 mmol), 4-N,N-dimethylamino-
pyridine (DMAP, 9.56 g, 78.3 mmol), and p-toluenesulfonylchloride
(11.19 g, 58.7 mmol) in CH2Cl2 (230 mL) was stirred at 258C for 16 h.
The mixture was washed with citric acid (2n), saturated aqueous NaHCO3,
and brine, and dried over MgSO4. After concentration under reduced
pressure, purification by flash chromatography (PE/MTBE, 2:1) afforded
ˆ
HC(SPh)OAc), 6.27 ± 6.18 (m, 6H; HC C), 2.04 (s, 3H; CH3), 2.01 (s, 3H;
18 (17.21 g, 99%) as a colorless oil. [a]D20
ˆ
23.68 (c ˆ 1.0 in CHCl3); 1H
CH3), 1.99 ± 1.76 (m, 5H), 1.68 ± 1.58 (m, 3H), 1.39 (s, 3H; CH3), 1.34 (s, 3H;
CH3), 1.19 (s, 6H; CH3), 1.10 ± 0.78 (m, 4H); 13C NMR (100.6 MHz, DEPT,
CDCl3): d ˆ 170.0 (Cquart), 170.0 (Cquart), 155.9 (Cquart), 155.0 (Cquart), 147.1
(CH), 147.1 (CH), 133.9 (Cquart), 133.8 (Cquart), 133.7 (CH), 132.8 (CH), 129.0
(CH), 129.0 (CH), 128.0 (CH), 127.9 (CH), 126.8 (CH), 123.5 (CH), 122.2
(CH), 90.8 (CH), 89.6 (CH), 54.3 (Cquart), 54.1 (Cquart), 45.4 (Cquart), 44.9
(Cquart), 38.0 (CH2), 37.2 (CH2), 36.8 (CH2), 36.1 (CH2), 27.0 (CH3), 21.3
(CH3), 21.0 (CH3), 20.3 (CH3), 19.9 (CH3), 19.0 (CH2), 19.0 (CH2); IR
(CHCl3): nÄ ˆ 3064, 3000, 2976, 2936, 2868, 2340, 1740, 1584, 1464, 1440,
NMR (400 MHz, CDCl3): d ˆ 7.80 (d, J ˆ 8.2 Hz, 2H; Ar), 7.36 ± 7.29 (m,
4H; Ar), 7.29 ± 7.21 (m, 2H; Ar), 7.18 ± 7.12 (m, 1H; Ar), 5.29 (t, J ˆ 2.5 Hz,
ˆ
1H; HC C), 4.47 (t, J ˆ 8.5 Hz, 1H; HC ± O), 3.17 (d, J ˆ 12.1 Hz, 1H;
CH2 ± SPh), 2.98 (d, J ˆ 12.1 Hz, 1H; CH2 ± SPh), 2.44 (s, 3H; CH3), 2.33
(dd, J ˆ 8.5, 2.5 Hz, 2H), 1.70 ± 1.45 (m, 4H), 1.45 ± 1.33 (m, 1H), 1.20 (s,
3H; CH3), 1.12 (s, 3H; CH3), 0.95 (m, 1H); 13C NMR (100.6 MHz, DEPT,
CDCl3): d ˆ 152.5 (Cquart), 144.5 (Cquart), 138.3 (Cquart), 134.1 (Cquart), 129.7
(CH), 129.2 (CH), 128.8 (CH), 127.9 (CH), 125.7 (CH), 117.6 (CH), 90.1
(CH), 47.5 (CH2) 46.9 (Cquart), 38.5 (Cquart), 38.1 (CH2), 36.3 (CH2), 34.0
(CH2), 26.7 (CH3), 21.6 (CH3), 18.3 (CH2), 18.1 (CH3); IR (CHCl3): nÄ ˆ
2976, 2936, 2856, 1596, 1580, 1480, 1452, 1400, 1364, 1188, 1176, 972,
‡
1372, 1236, 1016 cm 1; MS (258C): m/z (%) ˆ 328 (17) [M ], 303 (2), 268
(34), 253 (4), 219 (10), 190 (28), 181 (34), 177 (28), 159 (39), 147 (100), 131
(30), 120 (36), 105 (37), 91 (36); UV/Vis (CH3CN): lmax ˆ 254, 215 nm;
HRMS: calcd for C20H24O2S 328.1497; found 328.1502.
‡
872 cm 1; MS (1008C): m/z (%) ˆ 442 (26) [M ], 332 (1), 317 (18), 287 (3),
270 (41), 255 (2), 240 (2), 200 (3), 172 (7), 161 (41), 147 (100), 135 (24), 123
(45), 119 (46), 105 (46), 91 (52); UV/Vis (CH3CN): lmax ˆ 256, 224, 210 nm;
HRMS: calcd for C25H30O3S2 442.1636; found 442.1635.
Alcohol 11: A solution of 21 (8.79 g, 26.8 mmol) and KOH (3.00 g,
53.5 mmol) in MeOH (200 mL) was stirred at 258C for 3 h. After cooling to
08C NaBH4 (1.62 g, 42.8 mmol) was added and the mixture was stirred at
08C for 30 min. After acetone (70 mL) was added, the mixture was allowed
to reach 258C. The solution was diluted with MTBE, extracted with water
and brine, and dried over MgSO4. Concentration and purification by flash
chromatography (PE/EtOAc, 5:1) afforded 11 (4.77 g, 99%) as a colorless
solid. M.p. 368C; [a]2D0 ˆ ‡72.88 (c ˆ 1.0 in CHCl3); 1H NMR (400 MHz,
Cyclopentadiene 19: A solution of 18 (16.52 g, 37.3 mmol) and KOtBu
(8.38 g, 74.6 mmol) in THF (300 mL) was heated to 658C for 3.5 h. The cold
mixture was diluted with MTBE, washed with water and brine, and dried
over MgSO4. Concentration and purification by flash chromatography (PE/
EtOAc, 5:1) afforded 19 (8.29 g, 82%) as a colorless oil. [a]2D0 ˆ ‡83.98 (c ˆ
1.0 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 7.41 ± 7.36 (m, 2H; Ar),
ˆ
CDCl3): d ˆ 6.23 (d, J ˆ 1.8 Hz, 1H; HC C), 6.23 (d, J ˆ 1.5 Hz, 1H;
ˆ
ˆ
ˆ
7.30 ± 7.23 (m, 2H; Ar), 7.18 ± 7.12 (m, 1H; Ar), 6.25 ± 6.21 (m, 2H; HC C),
HC C), 5.94 (brt, J ˆ 1.5 Hz, 1H; HC C), 3.68 (d, J ˆ 10.7 Hz, 1H;
CH2OH), 3.62 (d, J ˆ 10.7 Hz, 1H; CH2OH), 2.00 ± 1.92 (m, 1H), 1.86 (tq,
J ˆ 13.8, 3.5 Hz, 1H), 1.67 ± 1.59 (m, 2H), 1.58 ± 1.51 (m, 1H), 1.18 (s, 3H;
CH3), 1.17 (s, 3H; CH3), 1.14 (dt, J ˆ 13.0, 4.2 Hz, 1H), 0.91 (dt, J ˆ 13.3,
3.7 Hz, 1H); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 158.8 (Cquart), 147.1
(CH), 126.8 (CH), 120.3 (CH), 72.2 (CH2), 53.9 (Cquart), 40.5 (Cquart), 36.5
(CH2), 36.3 (CH2), 20.3 (CH3), 20.2 (CH3), 18.8 (CH2); IR (CHCl3): nÄ ˆ
3628, 3000, 2932, 2868, 1464, 1396, 1372, 1236, 1032, 1012 cm 1; MS (258C):
ˆ
6.05 (t, J ˆ 1.6 Hz, 1H; HC C), 3.33 (d, J ˆ 12.0 Hz, 1H; CH2 ± SPh), 3.20
(d, J ˆ 12 Hz, 1H; CH2 ± SPh), 2.00 ± 1.93 (m, 1H), 1.91 ± 1.77 (m, 2H),
1.65 ± 1.57 (m, 1H), 1.31 (s, 3H; CH3), 1.18 (s, 3H; CH3), 1.08 (dt, J ˆ 13.2,
4.0 Hz, 1H), 0.89 (dt, J ˆ 13.3, 3.6 Hz, 1H); 13C NMR (100.6 MHz, DEPT,
CDCl3): d ˆ 159.8 (Cquart), 147.1 (CH), 138.6 (Cquart), 129.0 (CH), 128.8
(CH), 126.7 (CH), 125.6 (CH), 121.5 (CH), 53.9 (Cquart), 48.3 (CH2), 40.1
(CH2), 39.9 (Cquart), 36.6 (CH2), 21.8 (CH3), 20.1 (CH3), 19.4 (CH2); IR
(CHCl3): nÄ ˆ 3060, 3000, 2960, 2932, 2868, 1580, 1480, 1436, 1376, 1088,
‡
m/z (%) ˆ 178 (32) [M ], 163 (9), 147 (100), 145 (28), 131 (30), 119 (51), 105
‡
1024 cm 1; MS (258C): m/z (%) ˆ 270 (33) [M ], 241 (1), 224 (1), 205 (1),
(46), 91 (44), 83 (17), 76 (34); UV/Vis (CH3CN): lmax ˆ 254 nm; HRMS:
calcd for C12H18O 178.1358; found 178.1358; C12H18O (178.1): calcd C 80.85,
H 10.18; found C 80.85, H 10.09.
191 (2), 178 (5), 161 (22), 147 (100), 131 (29), 119 (41), 105 (39), 91 (36), 77
(31); UV/Vis (CH3CN): lmax ˆ 256, 208 nm; HRMS: calcd for C18H22S
270.1442; found 270.1440.
Vinylsulfonic ester 23: A solution of iPr2NEt (3.87 g, 30.0 mmol) in CH2Cl2
(25 mL) was added to a solution of 11 (4.48 g, 25.1 mmol) and ethenesul-
fonyl chloride (3.98 g, 31.4 mmol) in CH2Cl2 (100 mL) at 158C over a
period of 30 min. The solution was stirred at 158C for 1 h. The reaction
was stopped by quenching with citric acid (2n, 100 mL). The mixture was
extracted with MTBE (3 Â ) and the combined organic layers were washed
with water, saturated aqueous NaHCO3, and brine, and dried over MgSO4.
Concentration and purification by flash chromatography (PE/EtOAc, 5:1)
afforded 23 (5.47 g, 81%) as a colorless solid. M.p. 468C; [a]2D0 ˆ ‡63.68
(c ˆ 1.0 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 6.58 (dd, J ˆ 16.6,
Sulfoxides 20: A solution of NaIO4 (9.06 g, 42.4 mmol) in water (75 mL)
was added to a solution of 19 (8.81 g, 32.6 mmol) in MeOH (450 mL) at
08C. The mixture was stirred at 08C for 30 min and at 258C for 16 h. The
reaction was quenched by dilution with water, followed by extraction (3 Â )
with MTBE. The combined organic layers were washed with water and
brine, and dried over MgSO4. Concentration and purification by flash
chromatography (PE/EtOAc, 2:1) afforded 20 (9.33 g, 100%) as a colorless
oil (mixture of two diastereomers). 1H NMR (400 MHz, CDCl3): d ˆ 7.72 ±
ˆ
7.65 (m, 4H; Ar), 7.58 ± 7.47 (m, 6H; Ar), 6.26 ± 6.22 (m, 2H; HC C), 6.21 ±
ˆ
ˆ
ˆ ˆ
9.9 Hz, 1H; HC C), 6.45 (d, J ˆ 16.6 Hz, 1H; HC C), 6.23 (dd, J ˆ 5.2,
6.17 (m, 2H; HC C), 5.88 (t, J ˆ 1.5 Hz, 1H; HC C), 5.85 (t, J ˆ 1.5 Hz,
ˆ
ˆ ˆ
1.5 Hz, 1H; HC C), 6.21 (dd, J ˆ 5.2, 2.0 Hz, 1H; HC C), 6.16 (d, J ˆ
1H; HC C), 3.28 (d, J ˆ 13.5 Hz, 1H; CH2 ± SOPh), 3.12 (d, J ˆ 13.5 Hz,
ˆ
ˆ
1H; CH2 ± SOPh), 3.04 (d, J ˆ 13.5 Hz, 1H; CH2 ± SOPh), 2.97 (d, J ˆ
13.5 Hz, 1H; CH2 ± SOPh), 2.19 ± 2.06 (m, 2H), 2.05 ± 1.81 (m, 4H), 1.77 ±
1.62 (m, 2H), 1.57 (s, 3H; CH3), 1.51 (s, 3H; CH3), 1.23 (s, 3H; CH3), 1.22 (s,
3H; CH3), 1.35 ± 1.10 (m, 2H), 1.00 ± 0.80 (m, 2H); 13C NMR (100.6 MHz,
DEPT, CDCl3): d ˆ 159.1 (Cquart), 159.0 (Cquart), 147.6 (CH), 147.4 (CH),
145.9 (Cquart), 145.9 (Cquart), 130.7 (CH), 129.3 (CH), 129.3 (CH), 126.5
(CH), 126.4 (CH), 124.0 (CH), 123.9 (CH), 121.8 (CH), 121.4 (CH), 74.2
(CH2), 74.0 (CH2), 53.9 (Cquart), 53.9 (Cquart), 40.7 (CH2), 40.3 (CH2), 39.4
(Cquart), 39.3 (Cquart), 36.6 (CH2), 36.3 (CH2), 22.7 (CH3), 22.2 (CH3), 20.3
(CH3), 20.1 (CH3), 19.2 (CH2), 19.1 (CH2); IR (CHCl3): nÄ ˆ 3064, 3000,
9.9 Hz, 1H; HC C), 5.90 (brt, J ˆ 1.5 Hz, 1H; HC C), 4.21 (d, J ˆ 9.0 Hz,
1H; CH2 ± O), 4.05 (d, J ˆ 9.0 Hz, 1H; CH2 ± O), 2.10 ± 1.94 (m, 1H), 1.91 ±
1.77 (m, 1H), 1.74 ± 1.59 (m, 2H), 1.25 (s, 3H; CH3), 1.17 (s, 3H; CH3), 1.01
(dt, J ˆ 13.5, 4.5 Hz, 1H), 0.89 (dt, J ˆ 13.0, 3.5 Hz, 1H); 13C NMR
(100.6 MHz, DEPT, CDCl3): d ˆ 156.2 (Cquart), 147.2 (CH), 132.4 (CH),
130.2 (CH2), 126.8 (CH), 120.9 (CH), 78.8 (CH2), 53.8 (Cquart), 39.0 (Cquart),
36.9 (CH2), 36.3 (CH2), 20.0 (CH3), 19.8 (CH3), 18.7 (CH2); IR (CHCl3):
nÄ ˆ 3064, 3000, 2936, 2868, 2848, 1720, 1464, 1364, 1172, 964, 848 cm 1; MS
‡
(258C): m/z (%) ˆ 268 (28) [M ], 220 (1), 207 (2), 191 (2), 177 (3), 160 (28),
147 (100), 131 (32), 119 (37), 105 (38), 91 (11); UV/Vis (CH3CN): lmax
ˆ
1486
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0408-1486 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 8

( )-Myltaylenol
1480±1488
254, 204 nm; HRMS: calcd for C14H20O3S 268.1133; found 268.1128;
C14H20O3S (268.4): calcd C 62.66, H 7.51; found C 62.55, H 7.50.
(d, J ˆ 12.0 Hz, 1H; CH2 ± OH), 3.49 (d, J ˆ 12.0 Hz, 1H; CH2 ± OH), 2.47
(s, 3H; CH3), 2.39 ± 2.30 (m, 1H), 1.95 ± 1.76 (m, 4H), 1.69 ± 1.55 (m, 1H),
1.45 ± 1.24 (m, 4H), 1.20 ± 1.13 (m, 1H), 1.12 ± 0.87 (m, 2H), 1.08 (s, 3H;
CH3), 0.98 (s, 3H; CH3); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 172.8
(Cquart), 144.3 (Cquart), 135.3 (Cquart), 129.8 (CH), 127.9 (CH), 71.0 (CH2), 59.6
(Cquart), 50.3 (Cquart), 43.6 (CH), 38.9 (Cquart), 33.5 (CH2), 30.3 (CH2), 30.1
(CH2), 27.7 (CH2), 25.4 (CH2), 21.6 (CH3), 21.2 (CH3), 21.1 (CH3), 18.3
(CH2); IR (CHCl3): nÄ ˆ 3292, 3216, 2948, 2868, 1656, 1596, 1388, 1340, 1164,
Sultone 24: A solution of 23 (4.85 g, 18.1 mmol) in toluene (1000 mL) was
heated under reflux to 1118C for 22 h. Evaporation of the solvent afforded
crude 24 (4.85 g, 100%) as a purple solid which was pure enough for the
next reaction. For elemental analysis the crude product was washed with
cold MTBE. Sultone 24 (4.80 g, 99%) was isolated as a colorless solid. M.p.
2298C; [a]2D0 ˆ ‡76.38 (c ˆ 1.0 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ
‡
1092, 1072 cm 1; MS (1808C): m/z (%) ˆ 390 (1) [M ], 361 (10), 331 (4), 235
ˆ
ˆ
6.35 (dd, J ˆ 5.9, 3.3 Hz, 1H; HC C), 6.10 (d, J ˆ 5.9 Hz, 1H; HC C), 4.38
(d, J ˆ 12.0 Hz, 1H; CH2 ± O), 4.07 (dd, J ˆ 9.4, 5.7 Hz, 1H; HC ± SO2), 3.85
(d, J ˆ 12.0 Hz, 1H; CH2 ± O), 2.57 (t, J ˆ 3.5 Hz, 1H), 2.30 (ddd, J ˆ 12.6,
9.5, 3.5 Hz, 1H), 2.17 (dt, J ˆ 14.0, 5.7 Hz, 1H), 1.86 ± 1.67 (m, 2H), 1.46 ±
(17), 220 (32), 205 (76), 190 (8), 175 (47), 161 (15), 147 (25), 133 (26), 119
(29), 105 (48), 91 (100); HRMS: calcd for C21H30N2O3S 390.1977; found
390.1994; C21H30N2O3S (390.5): calcd C 64.58, H 7.74; found C 64.50, H 7.72.
1.36 (m, 2H), 1.33 ± 1.24 (m, 2H), 1.09 (s, 3H; CH3), 0.99 (s, 3H; CH3); 13
C
Olefin 33: nBuLi (15.6 mL, 1.6m in hexane, 25 mmol) was added to a
solution of 32 (2.00 g, 5.12 mmol) in THF (150 mL) at 258C. The solution
was immediately heated up to 758C and stirred continually at this
temperature for 50 min. After cooling of the solution to 308C, saturated
aqueous NH4Cl (20 mL) was added. The mixture was diluted with MTBE,
washed with saturated aqueous NH4Cl and brine, and dried over MgSO4.
Concentration and purification by flash chromatography (PE/EtOAc, 5:1)
afforded 33 (950 mg, 90%) as a colorless solid. M.p. 728C; [a]2D0 ˆ ‡2.68
(c ˆ 1.0 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 5.97 (d, J ˆ 5.9 Hz,
NMR (100.6 MHz, DEPT, CDCl3): d ˆ 137.7 (CH), 130.2 (CH), 79.3 (CH2),
61.7 (Cquart), 58.7 (Cquart), 57.2 (CH), 52.4 (CH), 34.0 (Cquart), 28.2 (CH2), 28.1
(CH2), 26.0 (CH2), 19.2 (CH3), 18.0 (CH3), 17.3 (CH2); IR (CHCl3): nÄ ˆ
3000, 2972, 2944, 2880, 1456, 1356, 1312, 1264, 1176, 968, 912, 824 cm 1; MS
‡
(908C): m/z (%) ˆ 268 (1) [M ], 203 (11), 185 (4), 173 (8), 157 (13), 147
(76), 131 (70), 118 (49), 105 (100), 91 (60); HRMS: calcd for C14H20O3S
268.1133; found 268.1132; C14H20O3S (268.37): calcd C 62.66, H 7.51; found
C 62.61, H 7.47.
ˆ
ˆ
1H; HC CH), 5.87 (1H, dd, J ˆ 5.9, 3.1 Hz, HC CH), 3.67 (d, J ˆ 10.8 Hz,
1H; CH2 ± OH), 3.44 (d, J ˆ 10.8 Hz, 1H; CH2 ± OH), 2.23 (brt, J ˆ 3.0 Hz,
1H), 1.91 ± 1.75 (m, 3H), 1.54 (tq, J ˆ 13.5, 4.0 Hz, 1H), 1.46 ± 1.39 (m, 1H),
1.34 ± 1.28 (m, 1H), 1.22 (dt, J ˆ 13.3, 4.2 Hz, 1H), 1.04 (s, 3H; CH3), 1.20 ±
0.89 (m, 3H), 0.95 (s, 3H; CH3); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ
136.0 (CH), 133.8 (CH), 72.4 (CH), 57.9 (Cquart), 56.9 (Cquart), 52.7 (CH), 37.8
(Cquart), 33.1 (CH2), 29.5 (CH2), 25.4 (CH2), 24.0 (CH2), 21.1 (CH3), 18.4
(CH2), 17.0 (CH3); IR (CHCl3): nÄ ˆ 3628, 3064, 2956, 2868, 1448, 1368, 1206,
Sultone 25: Pd/C (1.50 g, 0.15 g Pd) was added to a solution of 24 (3.85 g,
14.2 mmol) in THF (210 mL). The mixture was stirred under 1 atm of H2 at
258C for 48 h. Filtration, concentration, and purification by flash chroma-
tography (PE/Et2O, 7:3) afforded 25 (3.80 g, 99%) as a colorless solid.
Crystals acceptable for X-ray crystal structure analysis were obtained by
slow evaporation of the solvent (PE/Et2O, 7:3). M.p. 2388C; [a]2D0 ˆ ‡31.98
(c ˆ 1.0 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 4.24 (d, J ˆ 11.8 Hz,
1H; CH2 ± O), 4.01 (ddd, J ˆ 10.0, 7.4, 2.5 Hz, 1H; HC ± SO2), 3.74 (d, J ˆ
11.8 Hz, 1H; CH2 ± O), 2.65 (dddd, J ˆ 13.5, 9.5, 4.0, 1.0 Hz, 1H), 2.19 ± 2.07
(m, 2H), 1.89 ± 1.48 (m, 7H), 1.36 ± 1.28 (m, 2H), 1.22 (ddd, J ˆ 14.8, 5.0,
2.3 Hz, 1H), 1.12 (s, 3H; CH3), 0.97 (s, 3H; CH3); 13C NMR (100.6 MHz,
DEPT, CDCl3): d ˆ 78.9 (CH2), 57.5 (CH), 52.9 (Cquart), 49.0 (Cquart), 45.3
(CH), 36.0 (Cquart), 28.9 (CH2), 28.6 (CH2), 27.6 (CH2), 26.3 (CH2), 19.4
(CH2), 18.9 (CH3), 17.9 (CH2), 17.1 (CH3); IR (CHCl3): nÄ ˆ 2944, 2884, 1464,
1172, 1060, 1024, 924 cm 1; MS (258C): m/z (%) ˆ 206 (3) [M ], 188 (1), 175
‡
(13), 159 (3), 147 (100), 131 (9), 119 (19), 105 (27), 91 (25); HRMS: calcd for
C14H22O 206.1671; found 206.1662; C14H22O (206.3): calcd C 81.50, H 10.75;
found C 81.55, H 10.54.
TIPS ether 34: iPr3OTf (919 mg, 3.00 mmol) was added to a solution of 33
(582 mg, 2.82 mmol) and NEt3 (508 mg, 5.02 mmol) in CH2Cl2 (10 mL) at
788C. The mixture was stirred at 788C for 3 h. The reaction was
quenched by dilution with MTBE and washing with citric acid (2n),
saturated aqueous NaHCO3 and brine. After drying the organic layer over
MgSO4, concentration and purification by flash chromatography (PE)
‡
1388, 1356, 1316, 1176, 964 cm 1; MS (1108C): m/z (%) ˆ 270 (4) [M ], 255
(17), 241 (3), 223 (2), 205 (17), 189 (15), 176 (25), 161 (100), 147 (68), 133
(71), 119 (55), 105 (93), 91 (99); HRMS: calcd for C14H22O3S 270.1290;
found 270.1292; C14H22O3S (270.4): calcd C 62.19, H 8.20; found C 62.16, H
8.18.
afforded 34 (1.01 g, 99%) as a colorless oil. [a]D20
ˆ
5.88 (c ˆ 1.0 in CHCl3);
1
ˆ
H NMR (400 MHz, CDCl3): d ˆ 6.00 (d, J ˆ 5.9 Hz, 1H; HC CH), 5.83
Hydroxyketone 5: sBuLi (32 mL, 1.3m in hexane, 44.8 mmol) was added
dropwise to a solution of 25 (1.08 g, 4.0 mmol) in THF (56.0 mL) and
HMPA (8.0 mL) at 788C. The mixture was stirred at 788C for 30 min.
Then dry oxygen was bubbled through the solution at 788C for 3 h. The
cooling bath was removed and after reaching 258C the mixture was diluted
with MTBE, washed with saturated aqueous NH4Cl (2 Â ), saturated
aqueous NaHCO3 (2 Â ), and dried over MgSO4. Concentration and
purification by fast flash chromatography (PE/EtOAc, 2:1) afforded 5
ˆ
(dd, J ˆ 5.9, 3.1 Hz, 1H; HC CH), 3.67 (d, J ˆ 9.4 Hz, 1H; CH2 ± O), 3.46
(d, J ˆ 9.4 Hz, 1H; CH2 ± O), 2.19 (brt, J ˆ 3.0 Hz, 1H), 1.87 ± 1.71 (m, 3H),
1.53 (tq, J ˆ 13.6, 3.8 Hz, 1H), 1.44 ± 1.35 (m, 1H), 1.34 ± 1.15 (m, 2H),
1.15 ± 1.04 (m, 24H), 1.01 (s, 3H; CH3), 0.93 (s, 3H; CH3); 13C NMR
(100.6 MHz, DEPT, CDCl3): d ˆ 136.7 (CH), 133.3 (CH), 72.4 (CH2), 58.1
(Cquart), 56.8 (Cquart), 52.9 (CH), 38.3 (Cquart), 33.4 (CH2), 29.7 (CH2), 25.4
(CH2), 24.0 (CH2), 21.2 (CH3), 18.6 (CH2), 18.2 (CH3), 18.1 (CH3), 17.5
(CH3), 12.0 (CH); IR (CHCl3): nÄ ˆ 3060, 2944, 2864, 1460, 1380, 1112, 1088,
(649 mg, 73%) as a colorless solid. M.p. 1728C; [a]D20
ˆ
18.28 (c ˆ 1.0 in
‡
1012, 996 cm 1; MS (258C): m/z (%) ˆ 363 (2) [M ], 334 (4), 319 (76), 291
1
CHCl3); H NMR (400 MHz, CDCl3): d ˆ 3.71 (d, J ˆ 11.6 Hz, 1H; CH2 ±
OH), 3.57 (d, J ˆ 11.6 Hz, 1H; CH2 ± OH), 2.50 ± 2.42 (m, 1H), 2.06 ± 1.88
(m, 3H), 1.83 (d, J ˆ 18.5 Hz, 1H), 1.73 ± 1.53 (m, 3H), 1.52 ± 1.40 (m, 1H),
1.46 ± 1.33 (m, 2H), 1.30 ± 1.21 (m, 2H), 1.14 (s, 3H; CH3), 0.93 (s, 3H;
CH3); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 223.1 (Cquart), 70.4 (CH2),
64.2 (Cquart), 49.2 (Cquart), 43.3 (CH2), 42.6 (CH), 38.4 (Cquart), 31.3 (CH2),
30.7 (CH2), 27.5 (CH2), 22.7 (CH2), 21.4 (CH3), 19.8 (CH3), 18.3 (CH2); IR
(CHCl3): nÄ ˆ 3628, 3396, 2996, 2944, 2872, 1720, 1452, 1384, 1236, 1068,
(9), 277 (12), 249 (4), 237 (5), 223 (7), 209 (5), 187 (16), 171 (15), 159 (10),
145 (26), 131 (100), 117 (10), 103 (43), 91 (21); HRMS: calcd for C23H42OSi
362.3005; found 362.2994.
Alcohols 36: BH3 ´ THF (1.0 mL, 1.0m in THF, 1.0 mmol) was added
dropwise to a solution of 34 (60 mg, 0.17 mmol) in THF (4.0 mL) at 08C.
The resulting solution was stirred at 08C for 27 h. After complete
conversion, EtOH (3.0 mL) was added and the cooling bath was removed.
At 258C, aqueous NaOH (3.0 mL, 3m) was added and the mixture was
stirred for 15 min at the same temperature. Then the flask was cooled again
to 08C and H2O2 (8.0 mL, 35% in H2O) was added slowly. Now the mixture
was stirred at 08C for 10 min, at 258C for 1.5 h and at 60 ± 708C for 1 h.
After cooling, the mixture was diluted with MTBE and washed with water
(3 Â ), saturated aqueous NaS2O3, saturated aqueous NaHCO3, and brine,
and dried over MgSO4. Concentration and purification by flash chroma-
tography (PE/EtOAc, 5:1) afforded 36 (34 mg, 53%) as a colorless oil
(mixture of two diastereomers, which could be separated for spectroscopic
characterization by flash chromatography (PE/EtOAc, 10:1)). Major
diastereomer: 1H NMR (400 MHz, CDCl3): d ˆ 3.78 (dd, J ˆ 8.2, 3.0 Hz,
1H; CH ± OH), 3.47 (d, J ˆ 9.5 Hz, 1H; CH2 ± O), 3.22 (d, J ˆ 9.5 Hz, 1H;
CH2 ± O), 2.28 (ddd, J ˆ 13.0, 13.0, 4.2 Hz, 1H), 2.08 ± 1.93 (m, 1H), 1.84 ±
0.85 (m, 14H), 1.06 (s, 21H), 1.00 (s, 3H); IR (CHCl3): nÄ ˆ 3612, 2944, 2864,
‡
1024 cm 1; MS (258C): m/z (%) ˆ 222 (2) [M ], 192 (100), 177 (15), 163
(86), 147 (56), 133 (9), 121 (11), 107 (28), 93 (26), 79 (23); HRMS: calcd for
C14H22O2 222.1620; found 222.1624; C14H22O2 (222.3): calcd C 75.63, H 9.97;
found C 75.57 H 9.92.
Tosylhydrazone 32: A mixture of 5 (1.27 g, 5.71 mmol), TsNHNH2 (1.08 g,
5.80 mmol), p-toluenesulfonic acid, molecular sieves (3 Š, 2.0 g) and EtOH
(50 mL) was heated under reflux at 788C for 3 h. The mixture was filtered
after dilution with MTBE. The resulting solution was washed with water,
saturated aqueous NaHCO3 (3 Â ), and brine, and dried over MgSO4. After
evaporation of the solvent, the crude product was usually used in the next
step without further purification. For elemental analysis purification by
flash chromatography (PE/EtOAc, 2:1) afforded 32 (2.18 g, 98%) as a
colorless solid. M.p. 1418C; [a]D20
(400 MHz, CDCl3): d ˆ 7.93 ± 7.89 (m, 2H; Ar), 7.40 ± 7.36 (m, 2H; Ar), 3.63
ˆ
3.88 (c ˆ 1.0 in CHCl3); 1H NMR
Chem. Eur. J. 1998, 4, No. 8
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0408-1487 $ 17.50+.25/0
1487

E. Winterfeldt et al.
FULL PAPER
1464, 1380, 1244, 1188, 1112, 1092, 1068, 1024, 880 cm 1; MS (508C): m/z
(m, 7H), 1.06 (s, 3H; CH3), 1.02 (s, 3H; CH3); 13C NMR (100.6 MHz,
DEPT, CDCl3): d ˆ 154.1 (Cquart), 101.7 (CH2), 72.3 (CH2), 56.8 (CH), 51.1
(Cquart), 47.4 (Cquart), 39.5 (CH2), 38.6 (Cquart), 30.8 (CH2), 29.9 (CH2), 29.2
(CH2), 27.9 (CH2), 19.2 (CH3), 18.2 (CH2), 17.4 (CH3); IR (CHCl3): nÄ ˆ
3628, 3068, 2956, 2932, 2872, 1772, 1660, 1468, 1380, 1340, 1296, 1236, 1164,
‡
(%) ˆ 380 (3) [M ], 337 (27), 319 (8), 292 (2), 263 (1), 189 (46), 175 (11), 161
(16), 149 (100), 131 (48), 119 (92), 109 (26), 95 (39); HRMS: calcd for
C23H44O2Si 380.3111; found 380.3109. Minor diastereomer: 1H NMR
(400 MHz, CDCl3): d ˆ 4.47 ± 4.34 (m, 1H; CH ± OH), 3.42 (d, J ˆ 9.0 Hz,
1H; CH2 ± O), 3.20 (d, J ˆ 9.0 Hz, 1H; CH2 ± O), 2.46 (ddd, J ˆ 13.8, 10.4,
3.8 Hz, 1H), 2.01 ± 0.85 (m, 12H), 1.05 (s, 24H), 1.01 (s, 3H); IR (CHCl3):
nÄ ˆ 3612, 2944, 2864, 1464, 1380, 1240, 1096, 1072, 1016, 880 cm 1; MS
‡
1060, 1028, 992, 876 cm 1; MS (258C): m/z (%) ˆ 220 (15) [M ], 205 (4), 189
(56), 174 (10), 165 (66), 152 (27), 147 (27), 133 (40), 119 (57), 107 (68), 93
(94), 86 (15); HRMS: calcd for C15H24O 220.1827; found 220.1826; C15H24O
(220.4): calcd C 81.76, H 10.98; found C 81.60, H 10.86.
‡
‡
(1108C): m/z (%) ˆ 379 (1) [M
1], 337 (100) [M
iPr], 318 (3), 293 (2),
239 (8), 225 (3), 199 (3), 189 (30), 175 (11), 161 (13), 148 (74), 131 (86), 119
(92), 109 (53), 95 (71), 81 (48); HRMS: calcd for C20H37O2Si (M
337.2563; found 337.2561.
‡
iPr)
Acknowledgments: The work described was supported by the Fonds der
Â
Chemischen Industrie, and S.D. is grateful for a Kekule scholarship from
this institution. The kind help provided by Dr. Matsuo is highly
appreciated.
Ketone 40: DMSO (181 mg, 2.32 mmol) was added to a solution of (COCl)2
(147 mg, 1.16 mmol) in CH2Cl2 (5.0 mL) at 608C. The mixture was stirred
at the same temperature for 20 min. Then a solution of 36 (294 mg,
Received: February 6, 1998 [F990]
0.77 mmol) in CH2Cl2 (2.0 mL) was added at
608C. Stirring was
continued at 608C for 30 min before Et3N (0.6 mL, 4.3 mmol) was added
at the same temperature. After 15 min at 608C the cooling bath was
removed. At 258C water (3.0 mL) was added and 10 min later MTBE. The
layers were separated and the organic layer was washed twice with citric
acid (2n), with saturated aqueous NaHCO3, and with brine, and dried over
MgSO4. Concentration and purification by flash chromatography (PE/
EtOAc, 10:1) afforded 40 (272 mg, 93%) as a colorless solid. M.p. 438C;
[a]2D0 ˆ ‡8.68 (c ˆ 0.67 in CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 3.43 (d,
J ˆ 9.4 Hz, 1H; CH2 ± O), 3.32 (d, J ˆ 9.4 Hz, 1H; CH2 ± O), 2.49 (dd, J ˆ
18.4, 3.2 Hz, 1H), 2.10 ± 1.93 (m, 3H), 1.83 (d, J ˆ 18.4 Hz, 1H), 1.80 ± 1.53
(m, 3H), 1.52 ± 1.19 (m, 5H), 1.11 (s, 3H; CH3), 1.09 (s, 3H; CH3), 1.07 ± 1.03
(m, 21H); 13C NMR (100.6 MHz, DEPT, CDCl3): d ˆ 217.2 (Cquart), 72.6
(CH2), 61.5 (CH), 51.3 (Cquart), 47.1 (Cquart), 45,7 (CH2), 39.1 (Cquart), 30.8
(CH2), 30.4 (CH2), 28.4 (CH2), 22.9 (CH2), 18.8 (CH3), 18.3 (CH3), 18.1
(CH3), 18.1 (CH3), 18.1 (CH2), 11.9 (CH); IR (CHCl3): nÄ ˆ 2944, 2892, 2864,
1736, 1464, 1380, 1196, 1000, 1044, 880, 816 cm 1; MS (708C): m/z (%) ˆ
[1] D. Takaoka, A. Matsuo, J. Kuramoto, M. Nakayama, S. Hayashi, J.
Chem. Soc. Chem. Commun. 1985, 482 ± 483.
[2] D. Takaoka, H. Tani, A. Matsuo, J. Chem. Res. 1988, 130 ± 131.
[3] C.-L. Wu, S.-J. Chang, Phytochemistry 1992, 31, 2150 ± 2152.
[4] A. Srikrishna, C. V. Yelamaggad, K. Krishnan, M. Nethaji, J. Chem.
Soc. Chem. Commun. 1994, 2259 ± 2260.
[5] S. Doye, T. Hotopp, E. Winterfeldt, J. Chem. Soc. Chem. Commun.
1997, 1491 ± 1492.
[6] E. Winterfeldt, Chem. Rev. 1993, 93, 827 ± 843.
[7] a) U. Eder, G. Sauer, R. Wiechert, Angew. Chem. 1971, 83, 492 ± 493;
Angew. Chem. Int. Ed. Engl. 1971, 10, 496 ± 497; b) L.-F. Tietze, Th.
Eicher, Reaktionen und Synthesen im organisch-chemischen Prakti-
kum, Georg Thieme, Stuttgart, New York, 1981, p. 401 ± 402.
[8] D. J. Crispin, A. E. Vanstone, J. S. Whitehurst, J. Chem. Soc. (C) 1970,
10 ± 18.
[9] P. Metz, M. Fleischer, R. Fröhlich, Tetrahedron 1995, 51, 711 ± 732.
[10] a) G. Stork, T. Y. Chan, G. A. Breault, J. Am. Chem. Soc. 1992, 114,
7578 ± 7579; b) M. Bols, T. Skrydstrup, Chem. Rev. 1995, 95, 1253 ±
1277.
[11] For several examples see: D. Craig in Houben ± Weyl, Methods of
Organic Chemistry, Vol. E 21c (Eds.: G. Helmchen, R. W. Hoffmann,
J. Mulzer, E. Schaumann), Georg Thieme, Stuttgart, 1995, pp. 2872 ±
2904.
[12] a) H. Böhme, H. Fischer, R. Frank, Liebigs Ann. Chem. 1949, 563,
54 ± 72; b) H. Bredereck, E. Bäder, G. Höschele, Chem. Ber. 1954, 87,
784 ± 788.
[13] C. S. Rondestvedt, Jr., J. Am. Chem. Soc. 1954, 76, 1926 ± 1929.
[14] Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
no. CCDC-101094. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK
(Fax: (‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
[15] E. Vedejs, D. A. Engler, J. E. Telschow, J. Org. Chem. 1978, 43, 188 ±
196.
[16] a) F. A. Davis, L. C. Vishwakarma, J. M. Billmers, J. Finn, J. Org.
Chem. 1984, 49, 3241 ± 3243; b) F. A. Davis, O. D. Stringer, J. Org.
Chem. 1982, 47, 1774 ± 1775.
[17] a) W. Hartwig, L. Born, J. Org. Chem. 1987, 52, 4352 ± 4358; b) H. H.
Wasserman, B. H. Lipshutz, Tetrahedron Lett. 1975, 1731 ± 1734.
[18] R. K. Boeckman, Jr., D. M. Demko, J. Org. Chem. 1982, 47, 1789 ±
1792.
‡
378 (5) [M ], 335 (100), 306 (2), 291 (2), 279 (2), 265 (2), 227 (3), 213 (13),
201 (3), 187 (47), 173 (5), 159 (8), 145 (28), 131 (26), 119 (11), 103 (27);
HRMS: calcd for C23H42O2Si 378.2954; found 378.2957; C23H42O2Si (378.7):
calcd C 72.95, H 11.18; found C 72.96, H 11.04.
Olefin 41: A solution of 40 (221 mg, 0.58 mmol), Ph3PCH3Br (1.45 g,
4.06 mmol) and KOtBu (328 mg, 2.92 mmol) in benzene (10 mL) was
stirred at 258C for 44 h. After dilution with MTBE the mixture was washed
with citric acid (2n), saturated aqueous NaHCO3, and brine, and dried over
MgSO4. Concentration and purification by flash chromatography (PE)
afforded 41 (191 mg, 87%) as a colorless oil. [a]D20
ˆ
25.48 (c ˆ 1.1 in
CHCl3); 1H NMR (400 MHz, CDCl3): d ˆ 4.72 (dd, J ˆ 3.7, 2.3 Hz, 1H;
ˆ
ˆ
H2C C), 4.53 (dd, J ˆ 3.7, 1.8 Hz, 1H; H2C C), 3.46 (d, J ˆ 9.3 Hz, 1H;
CH2 ± O), 3.23 (d, J ˆ 9.3 Hz, 1H; CH2 ± O), 2.58 ± 2.50 (m, 1H), 2.05 (d,
J ˆ 4.2 Hz, 1H), 1.98 ± 1.77 (m, 3H), 1.72 ± 1.58 (m, 1H), 1.55 ± 1.45 (m, 1H),
1.45 ± 1.16 (m, 6H), 1.07 (s, 21H), 1.06 (s, 3H; CH3), 1.02 (s, 3H; CH3); 13
C
NMR (100.6 MHz, DEPT, CDCl3): d ˆ 154.8 (Cquart), 101.3 (CH2), 72.4
(CH2), 57.0 (CH), 51.3 (Cquart), 47.4 (Cquart), 39.6 (CH2), 39.1 (Cquart.), 31.0
(CH2), 30.0 (CH2), 29.3 (CH2), 28.0 (CH2), 19.3 (CH3), 18.4 (CH2), 18.1
(CH3), 18.1 (CH3), 17.9 (CH3), 11.9 (CH); IR (CHCl3): nÄ ˆ 2994, 2864, 1660,
1616, 1608, 1464, 1380, 1096, 1012, 996, 880 cm 1; MS (708C): m/z (%) ˆ
‡
376 (10) [M ], 347 (10), 332 (100), 304 (10), 289 (9), 240 (10), 201 (16), 189
(11), 175 (9), 161 (13), 145 (21), 131 (82), 119 (22), 103 (53), 91 (23); HRMS:
calcd for C24H44OSi 376.3161; found 376.3163.
(
)-Myltaylenol (1): A solution of 41 (120 mg, 0.32 mmol) and TBAF
(201 mg, 0.64 mmol) in THF (6.0 mL) was stirred at 258C for 18 h. MTBE
was added and the mixture was washed with water, saturated aqueous
NaHCO3, and brine, and dried over MgSO4. Concentration and purifica-
tion by flash chromatography (PE/EtOAc, 5:1) afforded 1 (69 mg, 98%) as
a colorless solid. M.p. 648C; [a]D20
ˆ
59.08 (c ˆ 1.0 in CHCl3); 1H NMR
ˆ
(400 MHz, CDCl3): d ˆ 4.75 ± 4.72 (m, 1H; H2C C), 4.56 ± 4.53 (m, 1H;
[19] Another strategy using the corresponding epoxide followed by a
regioselective ring opening met with only limited success. These
experiments led to interesting fragmentations, which will be reported
in a separate publication.
ˆ
H2C C), 3.45 (d, J ˆ 10.7 Hz, 1H; CH2 ± OH), 3.23 (d, J ˆ 10.7 Hz, 1H;
CH2 ± OH), 2.59 ± 2.51 (m, 1H), 2.08 (d, J ˆ 4.2 Hz, 1H), 2.02 ± 1.92 (m,
1H), 1.90 ± 1.78 (m, 2H), 1.74 ± 1.59 (m, 1H), 1.56 ± 1.48 (m, 1H), 1.44 ± 1.18
1488
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0408-1488 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 8