Synthesis of (E,E)-Germacrane Sesquiterpene Alcohols via Enolate-Assisted 1,4-Fragmentation

Article abstract of DOI:10.1021/jo970901z

An efficient method has been developed for the synthesis of (E,E)-germacrane sesquiterpene alcohols. The key step in these syntheses involves the enolate-assisted 1,4-fragmentation of properly functionalized perhydro-1-naphthalenecarboxaldehydes with 1 equiv of sodium tert-amylate as base, to give the corresponding (E,E)-germacrane aldehydes. These aldehydes are not very stable, and in situ reduction of the aldehyde function with Red-Al is required to obtain high yields of the desired germacrane alcohols. This procedure has led to the successful synthesis of 15-hydroxygermacrene B (4) and 15-hydroxyhedycaryol (35) from the mesylates 6 and 33, respectively. When KHMDS is used instead of sodium tert-amylate in the fragmentation reaction of 6, isomerization of the initially formed C(4)-C(5) E double bond cannot be avoided and results, after in situ reduction with Red-Al, in the formation of the (E,Z)-germacrane alcohol 24. The 15-hydroxy-(E,E)-germacranes are excellent starting materials for the selective synthesis of the corresponding 4,5-epoxides, which in turn can perfectly well be used in studies on the biomimetic formation of guaiane sesquiterpenes.

Full text of DOI:10.1021/jo970901z

7336
J . Org. Chem. 1997, 62, 7336-7345
Syn th esis of (E,E)-Ger m a cr a n e Sesqu iter p en e Alcoh ols via
En ola te-Assisted 1,4-F r a gm en ta tion
Adriaan J . Minnaard, J oannes B. P. A. Wijnberg,* and Aede de Groot*
Laboratory of Organic Chemistry, Agricultural University, Dreijenplein 8,
6703 HB Wageningen, The Netherlands
Received May 20, 1997X
An efficient method has been developed for the synthesis of (E,E)-germacrane sesquiterpene alcohols.
The key step in these syntheses involves the enolate-assisted 1,4-fragmentation of properly
functionalized perhydro-1-naphthalenecarboxaldehydes with 1 equiv of sodium tert-amylate as base,
to give the corresponding (E,E)-germacrane aldehydes. These aldehydes are not very stable, and
in situ reduction of the aldehyde function with Red-Al is required to obtain high yields of the desired
germacrane alcohols. This procedure has led to the successful synthesis of 15-hydroxygermacrene
B (4) and 15-hydroxyhedycaryol (35) from the mesylates 6 and 33, respectively. When KHMDS is
used instead of sodium tert-amylate in the fragmentation reaction of 6, isomerization of the initially
formed C(4)-C(5) E double bond cannot be avoided and results, after in situ reduction with Red-
Al, in the formation of the (E,Z)-germacrane alcohol 24. The 15-hydroxy-(E,E)-germacranes are
excellent starting materials for the selective synthesis of the corresponding 4,5-epoxides, which in
turn can perfectly well be used in studies on the biomimetic formation of guaiane sesquiterpenes.
Sch em e 1
In tr od u ction
Because of their unique structural and conformational
features, their general occurrence in nature,1 and their
central role in the biosynthesis of other sesquiterpenes,2
germacranes have received much attention in modern
organic chemistry.3 The main synthetic approaches
toward the cyclodeca-1(10),4-diene ring system of ger-
macranes can be classified as intramolecular C-C bond
formation, ring expansion reactions, and cleavage of the
central bond in decalin systems. In the latter approach,
three closely related Grob-type fragmentation reactions
can be distinguished. First, the Wharton fragmentation4
in which 5-cyclodecenone systems are formed upon treat-
ment of perhydronaphthalene-1,3-diol monosulfonate
esters with strong bases (Scheme 1, eq 1). This method
has been used several times in sesquiterpene synthesis5
but suffers from the fact that only one double bond is
formed regio- and stereospecifically. Its application in
germacrane synthesis is therefore limited.
spectively. The usually moderate regio- and stereose-
lectivity of the BH3 addition to tetrasubstituted double
bonds10 and the fact that several functional groups are
not compatible with the use of BH311 limit the application
of the boronate fragmentation reaction in germacrane
synthesis.
The boronate fragmentation reaction introduced by
Marshall circumvents this problem because both double
bonds are formed regio- and stereospecifically (Scheme
1, eq 2).6 The method has been applied in the synthesis
of hedycaryol7 and its C(5)-C(6) and C(9)-C(10) double
bond isomers allohedycaryol8 and neohedycaryol,9 re-
The third reaction, developed by Mander et al.,12
involves an enolate-assisted 1,4-fragmentation via R-depro-
tonation of an ester function.13 The synthesis of the
heliangolide sericenine is the only known example of this
approach in germacrane synthesis (Scheme 1, eq 3).14
Under the basic conditions, isomerization of the C(4)-
X Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) Connolly, J . D.; Hill, R. A. Dictionary of Terpenoids; Chapman
& Hall: London, 1991; Vol. 1, Mono- and Sesquiterpenoids.
(2) Banthorpe, D. V. In Natural Products: Their Chemistry and
Biological Significance; Longman Scientific & Technical: Harlow, 1994;
Chapter 5.
(3) Nicolaou, K. C.; Sorensen, E. J . Classics in Total Synthesis;
VCH: Weinheim, 1996; Chapter 13 and 21.
(4) For a review of the Wharton fragmentation, see: Caine, D. Org.
Prep. Proced. Int. 1988, 20, 1.
(5) (a) Gonza´lez, A. G.; Galindo, A.; Mansilla, H.; Gutie´rrez, A.;
Palenzuela, J . A. J . Org. Chem. 1985, 50, 5856. (b) Cauwberghs, S.;
De Clercq, P. J . Tetrahedron Lett. 1988, 29, 6501.
(6) Marshall, J . A.; Bundy, G. L. J . Am. Chem. Soc. 1966, 88, 4291.
(7) (a) Wharton, P. S.; Sundin, C. E.; J ohnson, D. W.; Kluender, H.
C. J . Org. Chem. 1972, 37, 34. (b) Minnaard, A. J .; Wijnberg, J . B. P.
A.; de Groot, A. Tetrahedron 1994, 50, 4755.
(10) Marshall J . A. Synthesis 1971, 229.
(11) For an example, see ref 9.
(12) Brown, J . M.; Cresp, T. M.; Mander, L. N. J . Org. Chem. 1977,
42, 3984.
(13) The fragmentation reaction induced by R-deprotonation of a
ketone in a bicyclo[5.4.0]undecane derivative has been used to construct
an 11-membered ring system: (a) Clark, D. A.; Fuchs, P. L. J . Am.
Chem. Soc. 1979, 101, 3567. Wender et al. reported the ester enolate-
assisted fragmentation of a cis-fused decalin system resulting in the
formation of a cyclodecadiene with a double bond stereochemistry that
cannot be explained by the stereochemical rules valid for this reaction.
(b) Wender, P. A.; Manly, C. J . J . Am. Chem. Soc. 1990, 112, 8579.
(14) Honan, M. C.; Balasuryia, A.; Cresp, T. M. J . Org. Chem. 1985,
50, 4326.
(8) Zhabinskii, V. A.; Minnaard, A. J .; Wijnberg, J . B. P. A.; de Groot,
A. J . Org. Chem. 1996, 61, 4022.
(9) Minnaard, A. J .; Stork, G. A.; Wijnberg, J . B. P. A.; de Groot, A.
J . Org. Chem. 1997, 62, 2344.
S0022-3263(97)00901-8 CCC: $14.00 © 1997 American Chemical Society

(E,E)-Germacrane Sesquiterpene Alcohols
J . Org. Chem., Vol. 62, No. 21, 1997 7337
Sch em e 2
Sch em e 3
C(5) double bond in the initially formed (E,E)-germacrane
led to the (E,Z)-germacrane ring system present in
sericenine. We realized that, if the isomerization of the
C(4)-C(5) double bond could be prevented, the enolate-
assisted 1,4-fragmentation would offer an efficient method
for the synthesis of (E,E)-germacranes in which the Me
group at C(4) is oxidized.15 To establish whether this is
indeed the case, we decided to synthesize the aldehydes
3 and 6 (Scheme 2). In contrast to the fragmentation
reaction leading to sericenine (Scheme 1, eq 3), it was
expected that the fragmentation of 3 would lead to
selective formation of the (E,E)-germacrane derivative 216
without isomerization (E f Z) of the C(4)-C(5) double
bond because the carbon atom at the 7-position in 2
possesses sp3 hybridization which makes H-6 less acidic.
Reduction of the aldehyde function in 2 and subsequent
elimination of water would then complete the synthesis
of 15-hydroxygermacrene C (1). In a similar way,
fragmentation of 6 followed by reduction of the resulting
aldehyde 5 would lead to 15-hydroxygermacrene B (4).
We realized that sp2 hybridization at C(7) in 5 could lead
to isomerization of the C(4)-C(5) double bond, but it was
hoped that the use of only 1 equiv of strong base would
suppress this isomerization. The presence of a hydroxyl
group at C(15) in 1 and 4 allows the regioselective
epoxidation of the C(4)-C(5) double bond. This is an
important aspect because easy access to germacrane 4,5-
epoxides will facilitate investigations on the biomimetic
formation of guaiane sesquiterpenes. In addition, asym-
metric Sharpless epoxidation creates the possibility to
develop a synthetic route toward enantiomerically en-
riched guaianes in which chirality is introduced at a very
late stage of the reaction sequence.17
Because the introduction of the isopropyl side chain
at C(7) via an organometal addition is not compatible
with the presence of an aldehyde group, the presence of
a masked aldehyde function at C(4) is required and for
that purpose 8 was converted into the methyl enol ether
10 in 89% yield with (methoxymethyl)triphenylphos-
phonium chloride21 and (dimethylsulfinyl)sodium in dry
DMSO. In contrast to 8, application of these reaction
conditions on mesylate 9 completely failed due to a
competitive γ-elimination of the mesylate group via
abstraction of H-5.22 Only the use of KHMDS in THF in
this reaction gave a moderate yield (48%) of the desired
product 11. The hydrolysis of the dimethyl acetal func-
tion in 10 and 11 with PPTS in aqueous acetone18
proceeded smoothly and afforded 12 and 13, respectively,
in almost quantitative yield.
At this stage of the reaction sequence, the isopropyl
group at C(7) was introduced. Because addition of
iPrMgCl to the keto group of 12 failed, probably as a
result of enolization and reduction, iPrMgCl was trans-
metalated with CeCl3.23 With this cerium analogue, 12
gave an easily separable 5:1 mixture of 14 and 15,
respectively, in excellent yield (Scheme 4). In order to
obtain reproducible high yields in this reaction, ultrasonic
treatment of the CeCl3 suspension turned out to be
essential.24 After removal of the TBDMS protecting
group in 14 with TBAF in hot DMSO,25 treatment of the
resulting alcohol 16 with MsCl in pyridine afforded the
mesylate 17.26 In contrast to 12, the organocerium
reaction mentioned above applied on 13 proceeded se-
lectively and gave 17 as the sole product in 93% yield.
Hydrolysis of the masked aldehyde function in 17 with
Resu lts a n d Discu ssion
(20) The TBDMS ether 8 has been used a number of times in
synthesis, see: (a) Wijnberg, J . B. P. A.; J enniskens, L. H. D.;
Brunekreef, G. A.; de Groot, A. J . Org. Chem. 1990, 55, 941. (b)
J enniskens, L. H. D.; Wijnberg, J . B. P. A.; de Groot, A. J . Org. Chem.
1991, 56, 6585. (c) Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.;
Danishefsky, S. J . J . Org. Chem. 1992, 57, 3274. (d) Masters, J . J .;
Link, J . T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J . Angew.
Chem. 1995, 107, 2017.
(21) For an overview of the use of this reagent, see: Anderson, C.
L.; Soderquist, J . A.; Kabalka, G. W. Tetrahedron Lett. 1992, 33, 6915.
(22) Heathcock, C. H.; Ratcliffe, R. J . Am. Chem. Soc. 1971, 93, 1746.
(23) (a) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.;
Kamiya, Y. J . Am. Chem. Soc. 1989, 111, 4392. (b) Denmark, S. E.;
Edwards, J . P.; Nicaise, O. J . Org. Chem. 1993, 58, 569.
(24) Greeves, N.; Lyford, L. Tetrahedron Lett. 1992, 33, 4759.
(25) Orruj, R. V. A.; Wijnberg, J . B. P. A.; Bouwman, C. T.; de Groot,
A. J . Org. Chem. 1994, 59, 374.
For the synthesis of the aldehyde 3, two slightly
different reaction pathways were followed starting from
the easily accessible racemic acetate 718 (Scheme 3). By
modest adaptions of existing procedures,19 7 was con-
verted into the known TBDMS ether 820 and also into
the mesylate 9, both in a six-step reaction sequence
without the need of interim purification. In this way, 8
and 9 were obtained in 31% and 55% overall yield,
respectively, from acetate 7.
(15) This kind of (E,E)-germacranes, especially those with a carbinol
group at C(4), are regularly found in nature; see ref 1.
(16) The numbering system as given in structure 2 will be followed
throughout the text of this paper.
(17) See following paper.
(18) Wijnberg, J . B. P. A.; Vader, J .; de Groot, A. J . Org. Chem. 1983,
48, 4380 and references cited therein.
(26) The stereochemistry at C(7) in 17 could be ascertained with
NMR experiments. With the use of the shift reagent Eu(fod)3 in 1H
NMR measurements, the close proximity of H-5 and the hydroxyl group
at C(7) was demonstrated. NOE-difference studies showed a clear
NOE between H-1 and H-5. A NOE between H-5 and the isopropyl
group at C(7) was not observed.
(19) Kim, M.; Kawada, K.; Watt, D. S. Synth. Commun. 1989, 19,
2017.

7338 J . Org. Chem., Vol. 62, No. 21, 1997
Minnaard et al.
Sch em e 4
Sch em e 6
rangement is a characteristic feature of (E,E)-cyclodeca-
1(10),4-diene systems33 and makes the isolation of (E,E)-
germacranes from natural sources and reaction mixtures
rather complicated.34
Because the Cope rearrangement can only take place
via the chairlike transition state, the fast and selective
formation of 21 may be an indication that intermediate
20 easily adopts such a chair-like conformation. Since
the nature of the C(7) side chain has a profound impact
on the conformational behavior of these compounds,32 it
is obvious that the rate of the Cope rearrangement (20
f 21) strongly depends on the stereochemistry and
structural features of the C(7) substituents. Another
structural characteristic of 20 that might favor the Cope
rearrangement is the aldehyde function at C(15). This
has been concluded from the observation that natural
germacrane aldehydes undergo Cope rearrangement at
a much lower temperature than their corresponding
alcohols or C(15) unfunctionalized derivatives.35
Confronted with the easy Cope rearrangement of 20
to 21, we stopped trying to synthesize 15-hydroxyger-
macrene C (1) and focused our attention on the synthesis
of 15-hydroxygermacrene B (4). We opted for an isopro-
pylidene group at C(7) because an additional sp2 center
in the 10-membered ring will partly relieve the strain,36
thereby diminishing the tendency toward Cope rear-
rangement. Introduction of the isopropylidene side chain
was easily achieved by treatment of 12 with isopropyl-
triphenylphosphonium iodide and (dimethylsulfinyl)so-
dium in DMSO to give 22 in high yield (Scheme 7).
Further conversion of 22 into the crystalline aldehyde 6
was accomplished with standard procedures.
Sch em e 5
35% aqueous HClO4 in ether27 completed the synthesis
of 3 in which the aldehyde group most likely possesses
the axial orientation.28 The route 7 w 13 w 3 was
slightly shorter (10 steps) than the one via 12 (12 steps),
but both routes gave about the same overall yield of 3
(ca 20%).
With aldehyde 3 in hand, the enolate-assisted 1,4-
fragmentation reaction could now be investigated. Upon
treatment of 3 with KHMDS in THF,14 a fast reaction
took place resulting in a product which partly decom-
posed during flash chromatography. Instead of the
expected 10-membered ring system 2, the isolated prod-
uct (20% yield) turned out to be the linear compound 18
(Scheme 5). The stereochemistry of the enal function in
Initially, the fragmentation reaction of 6 was studied
in THF with ca. 1 equiv of KHMDS (Scheme 8). These
reaction conditions led to the formation of a complex
18 follows from its H NMR spectrum.29 Its formation
can easily be explained by a vinologous retro-aldol
reaction of the initially formed fragmentation product 2
under the basic reaction conditions used.30
In order to avoid the undesired retro-aldol reaction, the
hydroxyl group in 3 was protected as its TMS ether 19.31
When 19 was treated with KHMDS in THF, again a fast
reaction took place to give the rather unstable elemane-
like compound 21 as the sole product that could be
isolated (Scheme 6). It is obvious that the formation of
21 proceeds via a Cope rearrangement of the initially
formed intermediate 20.32 This [3,3]-sigmatropic rear-
1
(31) The stereochemistry at C(4) in aldehyde 19 could be established
unambiguously by reduction with NaBH4 to the corresponding alco-
hol: 1H NMR δ 0.10 (s, 9 H), 0.78 (s, 3 H), 0.88 (d, J ) 6.8 Hz, 6 H),
1.40-1.97 (m, 14 H), 2.98 (s, 3 H), 3.56 (br d, J ) 6.8 Hz, 2 H), 4.31
(dd, J ) 7.1, 9.2 Hz, 1 H); 13C NMR δ 2.67 (3 q), 13.53 (q), 17.45 (q),
17.58 (q), 24.69 (t), 25.93 (t), 28.43 (t), 33.56 (t), 35.30 (t), 38.42 (q),
38.61 (d), 38.61 (s), 39.91 (d), 41.70 (d), 60.87 (t), 78.68 (s), 91.44 (d);
MS m/ z (relative intensity) 363 (M+ - 43, 100), 181 (11), 131 (11),
119 (11), 73 (11), 69 (22); HRMS calcd for C16H31O5SSi (M+ - 43)
363.1662, found 363.1655. NOE-difference experiments showed a
strong NOE between the angular Me group and the carbinol group at
C(4), thereby establishing the axial orientation of the C(4) substituent.
(32) Cleavage of the C(2)-C(3) bond via a 1,4-fragmentation reaction
would result in the same product, but it has been shown that this
process is very unlikely: Marshall, J . A.; Babler, J . H. J . Org. Chem.
1969, 34, 4186.
(33) Takeda, K. Tetrahedron 1974, 30, 1525.
(34) Reichardt, P. B.; Anderson, B. J .; Clausen, T. P.; Hoskins, L.
C. Can. J . Chem. 1989, 67, 1174.
(35) (a) Bohlmann, F.; Zdero, C. Phytochemistry 1979, 18, 95. (b)
Appendino, G.; O¨ zen, H. C. Gazz. Chim. Ital. 1993, 123, 93.
(36) (a) Allen, F. H.; Rogers, D. J . Chem. Soc., Chem. Commun. 1967,
588. (b) Allen, F. H.; Rogers, D. J . Chem. Soc. B 1971, 257.
(27) Levine, S. G. J . Am. Chem. Soc. 1958, 80, 6150.
(28) (a) Nagata, W.; Sugasawa, T.; Narisada, M.; Wakabayashi, T.;
Hayase, Y. J . Am. Chem. Soc. 1967, 89, 1483. 1H NMR studies on a
system similar to 3 revealed that an axially oriented aldehyde gives
rise to a singlet whereas an equatorially oriented aldehyde appears
as a doublet (J ) 3.9 Hz): (b) Garc´ıa, B.; Skaltsa, H.; Navarro, F. I.;
Pedro, J . R.; Lazari, D. Phytochemistry 1996, 41, 1113.
(29) Herz, W.; Kalyanaraman, P. S. J . Org. Chem. 1975, 40, 3486.
(30) For a related example of this reaction, see: Walborsky, H. M.;
Reddy, S. M. J . Org. Chem. 1988, 53, 4851.

(E,E)-Germacrane Sesquiterpene Alcohols
J . Org. Chem., Vol. 62, No. 21, 1997 7339
Sch em e 7
The fragmentation reactions of 6 with KHMDS as base
also showed that, regardless of the amount of KHMDS
employed in these reactions, the E f Z isomerization of
the C(4)-C(5) conjugated double bond could not be
avoided. A possible explanation could be that hexameth-
yldisilazane formed during these reactions would act as
a basic catalyst for the isomerization and, therefore, we
decided to use sodium tert-amylate (NaO-t-amyl) instead
of KHMDS. NaO-t-amyl in benzene or toluene is the
most effective base-solvent combination in the fragmen-
tation reactions of 1,4-diol monosulfonate esters,43 and
in contrast to hexamethyldisilazane, tert-amyl alcohol
should not interfere with the reaction. When 6 was
treated with 1 equiv of NaO-t-amyl in toluene44 under
oxygen-free conditions, a fast reaction took place result-
ing in the formation of the unstable (E,E)-germacrane
aldehyde 5 and trace amounts of 23 (Scheme 8). The
Cope rearrangement was not observed in this reaction.45
The same reaction combined with in situ reduction with
Red-Al afforded 15-hydroxygermacrene B (4) together
with a small amount of 24. Purification was easily
achieved with aqueous AgNO3 extraction46 and gave 4
in 72% yield. The byproduct 24 was not extracted with
aqueous AgNO3.47 Conversion of the phosphordiamidate
of 4, via a short treatment (5 min) with Li in EtNH2,48
into germacrene B (26)49 confirmed the E geometry of the
C(4)-C(5) double bond in 4.
Sch em e 8
product mixture from which only the unstable aldehyde
23 with a C(4)-C(5) Z double bond could be isolated in
rather poor yield (27%). From this experiment it was
concluded that, despite the fact that only 1 equiv of
KHMDS was used, isomerization of the initially formed
C(4)-C(5) E double bond immediately followed the
fragmentation of 6. Support for the presence of an
aldehyde group connected to a Z double bond in 23 was
obtained from its 1H NMR spectrum in which a one-
proton signal appears at δ 9.28.29 A much better product
yield was achieved when the fragmentation reaction of
6 was performed with KHMDS under oxygen-free condi-
tions37 and the reaction mixture quenched with Red-Al
at -78 °C. In this way, the (E,Z)-germacrane alcohol 24
was obtained as the sole product in 77% yield. The
presence of the C(4)-C(5) Z double bond in 24 was
demonstrated by its conversion into the known (E,Z)-
germacrane 25.38 Whereas treatment of 24 with SO3‚
pyridine and in situ reduction of the resulting sulfate39
led to complex product mixtures,40 reduction of the
Significant differences between the aldehydes 5 and
23 and between the alcohols 4 and 24 were observed in
the H NMR spectra of these compounds. The H NMR
1
1
spectrum of 5 shows the aldehyde singlet at δ 9.93, while
1
the corresponding signal in the H NMR spectrum of 23
appears at δ 9.28. These observations obey the empirical
NMR rules formulated by Lange et al.42a Distinction
between 4 and 24 can be made by comparing the
multiplicities of the C(15) carbinol protons in their 1H
NMR spectra; an AB system was found for 4, a broad
singlet for 24. Marshall and Flynn observed similar
differences in the 1H NMR spectra of the related be-
tweenanenes.50
Although the results described above clearly show that
both 5 and 23 (or 4 and 24, after reduction with Red-Al)
can be synthesized selectively and in good yield from 6
by changing the base (KHMDS vs NaO-t-amyl), the
reason for this difference in reaction outcome remains
unclear. Our initial idea that hexamethyldisilazane
might act as a basic catalyst for the isomerization of 5 to
23 proved to be incorrect. This was concluded from an
experiment in which 5 was exposed to hexamethyldisi-
lazane in toluene51 at room temperature for 1 h. Al-
though 5 partly decomposed, isomerization to 23 was not
observed.
41
phosphordiamidate of 24 with Li in EtNH2 was more
1
successful and provided 25 in 42% yield.42 The H NMR
data of 25 were identical with those reported in the
literature,38 thereby confirming the Z geometry of the
C(4)-C(5) double bond in 24.
(37) Autoxidation of the trienol form of 23 might be responsible for
the low yield (27%) of 23 in the fragmentation reaction of 6. For
example, see: Wydra, R.; Paryzek, Z. Pol. J . Chem. 1984, 58, 705.
(38) Itoh, A.; Nozaki, H.; Yamamoto, H. Tetrahedron Lett. 1978,
2903.
(43) (a) Reference 20a. (b) Bastiaansen, P. M. F. M.; Wijnberg, J . P.
B. A.; de Groot, A. J . Org. Chem. 1995, 60, 4240.
(39) Corey, E. J .; Achiwa, K. J . Org. Chem. 1969, 34, 3667.
(40) The formation of a complex product mixture was partly caused
by shifting of the C(4)-C(5) double bond. This complication has been
noted before in germacrane synthesis: Matsuo, A.; Nozaki, H.; Kubota,
N.; Uto, S.; Nakayama, M. J . Chem. Soc., Perkin Trans. 1 1984, 203.
(41) (a) Ireland, R. E.; Muchmore, D. C.; Hengartner, U. J . Am.
Chem. Soc. 1972, 94, 5098. (b) Trost, B. M.; Renaut, P. J . Am. Chem.
Soc. 1982, 104, 6668.
(42) Another product similar to 25 but with the E C(1)-C(10) double
bond assumably being reduced was also formed in this reaction. This
assumption was based on the empirical NMR rules developed for the
structure elucidation of germacrane sesquiterpenes: (a) Lange, G. L.;
Lee, M. Magn. Reson. Chem. 1984, 106, 723. The hydrogenation of
the C(1)-C(10) double bond with Li in EtNH2 was rather unexpected,
all the more so because reduction of 8-acetoxygermacrene B with Li
in NH3 only gave germacrene B: (b) Brown, E. D.; Sam, T. W.;
Sutherland, J . K.; Torre, A. J . Chem. Soc., Perkin Trans. 1 1975, 2326.
(44) The use of more than one equiv of NaO-t-amyl also led to E f
Z isomerization of the conjugated C(4)-C(5) double bond.
(45) After completion of this research, we noticed that in a recent
synthesis of a nine-membered 3-ene-1,5-diyne system the same tactic
has been employed. Thus, an exocyclic double bond was introduced
to avoid rapid Cope rearrangement: Iida, K.; Hirama, M. J . Am. Chem.
Soc. 1994, 116, 10310.
(46) Southwell, I. A. Phytochemistry 1970, 9, 2243.
(47) Cyclic (E)-olefins complexate stronger with silver than cyclic
(Z)-olefins: van Beek, T. A.; Subrtova, D. Phytochem. Anal. 1995, 6,
1.
(48) Longer reaction times led to a mixture of 27 and hydrogenated
products with the latter compounds in excess.
(49) Germacrene B, a widespread naturally occurring hydrocarbon,
has been synthesized before from natural germacrone, see ref 42b and
references cited therein.
(50) Marshall, J . A.; Flynn, K. E. J . Am. Chem. Soc. 1984, 106, 723.

7340 J . Org. Chem., Vol. 62, No. 21, 1997
Minnaard et al.
Sch em e 9
Sch em e 10
group was needed to avoid the use of more than 1 equiv
of base in the fragmentation step.
The fragmentation reaction of 33 was performed with
1 equiv of NaO-t-amyl in toluene and afforded, after
reduction and workup, almost pure 34 in high yield
(Scheme 10). No Cope rearrangement products were
found. Removal of the TES protecting group in 34 was
achieved by treatment with TBAF in THF, and the
following purification by aqueous AgNO3 extraction af-
forded pure 15-hydroxyhedycaryol (35) in good yield. J ust
1
as found for hedycaryol,57 the H NMR spectrum of 35
indicates the presence of at least three distinct conform-
ers at room temperature.
As has been demonstrated here, the enolate-assisted
1,4-fragmentation reaction with NaO-t-amyl as base
offers an useful method for the synthesis of (E,E)-
germacranes with sp2 hybridization at C(7). The question
raised, however, whether this method could also be
employed for the synthesis of (E,E)-germacranes with sp3
hybridization at C(7). We had already demonstrated that
the fragmentation product of aldehyde 19 with two
subsituents at C(7) easily underwent Cope rearrange-
ment. On the other hand, an (E,E)-germacrane like
hedycaryol, with only one substituent at C(7), is stable
at room temperature and undergoes Cope rearrangement
only at (slightly) elevated temperatures.7a,52 These two
facts combined led to the assumption that it might be
possible to employ the enolate-assisted 1,4-fragmention
for the synthesis of (E,E)-germacranes with only one C(7)
substituent.53 To test this hypothesis, we decided to
investigate the fragmentation of the aldehyde 33 with a
protected 2-hydroxyisopropyl side chain at C(7).
Con clu d in g Rem a r k s
In the first instance, our study on the use of the
enolate-assisted 1,4-fragmentation in (E,E)-gemacrane
synthesis was frustrated by reactions (vinologous retro-
aldol reaction, Cope rearrangement, isomerization) im-
mediately following the fragmentation step. Neverthe-
less, by the characterization of the isolated products, it
was clear that the fragmentation reaction itself proceeds
rapidly and unambiguously. After the discovery that the
E f Z isomerization of the C(4)-C(5) double bond in the
initially formed (E,E)-germacrane can be suppressed by
the use of 1 equiv of sodium tert-amylate as base, the
desired breakthrough was realized and resulted in the
synthesis of 15-hydroxygermacrene B and germacrene B
itself. The synthesis of 15-hydroxyhedycaryol proved
that this approach was not limited to germacranes with
sp2 hybridization at C(7).
The synthesis of aldehyde 33 with the TBDMS ether
12 as the starting material required the conversion of a
carbonyl function into a 2-hydroxyisopropyl group. For
this purpose, the approach of Marshall et al.54 was
followed, except that the three-step reaction sequence to
convert a ketone into a nitrile was replaced by a one-
step procedure using tosylmethyl isocyanide (TosMIC).55
Finally, as stated in the Introduction, the asymmetric
Sharpless epoxidation of 15-hydroxygermacranes lacking
a chiral carbon atom like 15-hydroxygermacrene B cre-
ates the possibility to synthesize enantiomerically en-
riched guaiane sesquiterpenes.17
Exp er im en ta l Section 58
Treatment of 12 with TosMIC gave 27 as an epimeric
mixture of two nitriles (Scheme 9). Addition of MeLi to
27 afforded, after basic hydrolysis, selectively compound
28 possessing an equatorial acyl group.54 The introduc-
tion of the second Me group was performed with the
cerium analogue of MeLi to avoid enolization of the acyl
group and afforded 29 in excellent yield. Via standard
procedures 29 was converted into the aldehyde 32, i.e.,
29 f 30 f 31 f 32. Treatment of 32 with chlorotrieth-
ylsilane (TESCl) gave the corresponding TES ether 33
in 56% yield.56 The protection of the C(11) hydroxyl
Ma ter ia ls. All reagents were purchased from Aldrich or
J anssen except for N,N,N′,N′-tetramethylphosphorodiamidic
chloride (TMPDCl) which was purchased from Fluka. (Meth-
oxymethyl)triphenylphosphonium chloride and isopropyltri-
phenylphosphonium iodide were dried in a vacuum desiccator
over P2O5 before use. The compounds 7,18 8,20b 25,38 and 2642b
have been characterized before.
(4a r,5r)-(()-5-Acetoxy-4,4a ,5,6,7,8-h exa h yd r o-4a -m eth -
yl-2(3H)-n a p h th a len on e (7). To a stirred solution of crude
(4aR,5R)-(()-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methyl-2(3H)-
naphthalenone (prepared from 2-methylcyclohexane-1,3-dione
(100 g, 0.79 mol) and freshly distilled methyl vinyl ketone
(MVK) (129 mL, 1.58 mol) following known procedures)59 in
500 mL of dry pyridine was added dropwise 252 mL of Ac2O
at 10-15 °C. When the addition was complete, the reaction
mixture was stirred at room temperature (rt) for 3 days.
Standard workup gave an oil which was taken up in 500 mL
of diisopropyl ether and left overnight to crystallize. The
crystals were filtered off to give 60.9 g of pure 7. The mother
(51) The outcome of the fragmentation reaction did not depend on
the solvent used. Fragmentation of 6 with KHMDS in toluene or THF
both afforded 23.
(52) Kodama, M.; Yokoo, S.; Matsuki, Y.; Itoˆ, S. Tetrahedron Lett.
1979, 1687.
(53) The majority of (E,E)-germacranes found in nature possesses
only one substituent at C(7), see ref 1.
(54) Marshall, J . A.; Pike, M. T.; Carroll, R. D. J . Org. Chem. 1966,
31, 2933.
(55) Oldenziel, O. H.; van Leusen, D.; van Leusen, A. M. J . Org.
Chem. 1977, 42, 3114.
(56) This reaction also gave a byproduct with a silyl enol ether
function at C(4).
(57) (a) Wharton, P. S.; Poon, Y. C.; Kluender, H. C. J . Org. Chem.
1973, 38, 735. (b) Minnaard, A. J . unpublished results.
(58) For
a general description of the experimental procedures
employed in this research, see ref 7b.

(E,E)-Germacrane Sesquiterpene Alcohols
J . Org. Chem., Vol. 62, No. 21, 1997 7341
liquor was concentrated and dissolved in a mixture of 150 mL
of diisopropyl ether and 50 mL of petroleum ether (bp 40-60
°C). After standing overnight at 0 °C, a second crop (9.7 g) of
pure 7 was obtained. The remaining mother liquor was
concentrated and afforded, after flash chromatography (4:1
petroleum ether (bp 40-60 °C)/EtOAc) and crystallization from
diisopropyl ether, a third portion (17.0 g) of pure 7. The total
yield of pure 7 amounted to 87.6 g (50% overall from 2-meth-
ylcyclohexane-1,3-dione). The spectroscopic data of 7 were
identical with those reported in the literature.18
spectroscopic data of 8 were identical with those reported in
the literature.20b
(4r,4a r,8a â)-(()-Octa h yd r o-7,7-d im eth oxy-4a -m eth yl-
4-[(m eth ylsu lfon yl)oxy]-1(2H)-n a p h th a len on e (9). The
procedures described above for the synthesis of 8 were
employed with the exception of the silylation step which was
replaced by the following mesylation procedure. To a stirred
solution of 14.9 g of crude octahydro-4-hydroxy-7,7-dimethoxy-
4a-methyl-1(2H)-naphthalenone in 100 mL of pyridine was
added 11 mL (143 mmol) of MsCl at 0 °C. The reaction
mixture was allowed to come to rt, stirred for 4 h, and
concentrated under reduced pressure. The concentrate was
taken up in EtOAc, mixed with saturated aqueous NaHCO3,
and stirred for 10 min. After addition of water and separation
of the two-phase mixture, the aqueous layer was extracted
with EtOAc. The combined organic layers were washed with
brine, dried, and evaporated. Flash chromatography (3:1 to
1:1 petroleum ether (bp 40-60 °C)/EtOAc) gave 16.13 g (55%
overall from 7) of 9 as an oil: 1H NMR δ 0.82 (s, 3 H), 0.90-
2.51 (m, 11 H), 3.02 (s, 3 H), 3.06 (s, 3 H), 3.16 (s, 3 H), 4.81
(dd, J ) 4.5, 11.5 Hz, 1 H); 13C NMR δ 11.29 (q), 26.79 (t),
27.39 (t), 27.90 (t), 33.25 (t), 38.10 (t), 38.79 (q), 41.37 (s), 47.43
(q), 47.74 (q), 51.07 (d), 85.68 (d), 99.56 (s), 208.04 (s); MS m/ z
(relative intensity) 320 (M+, 23), 289 (54), 224 (25), 193 (46),
114 (41), 101 (100), 88 (28), 84 (40); HRMS calcd for C14H24O6S
(M+) 320.1294, found 320.1290.
(4a r,5r,8a â)-(()-Deca h yd r o-2,2-d im eth oxy-8-(1-m eth -
oxym eth ylen e)-4a -m eth yl-5-[[(1,1-d im eth yleth yl)d im eth -
ylsilyl]oxy]n a p h th a len e (10). To 210 mL of 0.40 M (di-
methylsulfinyl)sodium in DMSO was added with stirring 100
mL of THF at rt. The solution was cooled to 0 °C and, after
addition of a slurry of 30.0 g (85 mmol) of (methoxymethyl)-
triphenylphosphonium chloride in 50 mL of DMSO, stirred at
0 °C for 1 h. To the dark red reaction mixture was then added,
via syringe, a solution of 14.81 g (41.6 mmol) of 8 in 40 mL of
THF. Stirring was continued at 0 °C for 0.5 h and at rt for 1
h. The reaction mixture was poured into ice-water and
extracted with ether. The combined organic layers were
washed with brine, dried, and evaporated. Flash chromatog-
raphy (100:1 to 12:1 petroleum ether (bp 40-60 °C)/EtOAc)
gave 14.25 g (89%) of 10 as a clear oil: 1H NMR δ 0.00 (s, 6
H), 0.66 (s, 3 H), 0.84 (s, 9 H), 1.05-1.94 (m, 10 H), 2.76 (ddd,
J ) 2.0, 4.5, 11.0 Hz, 1 H), 3.11 (s, 3 H), 3.19 (s, 3 H), 3.30
(dd, J ) 4.3, 10.9 Hz, 1 H), 3.51 (s, 3 H), 5.47 (br s, 1 H); 13C
NMR δ -4.75 (q), -3.93 (q), 9.57 (q), 18.03 (s), 23.75 (t), 25.85
(3 q), 28.34 (t), 29.67 (t), 31.07 (t), 33.59 (t), 40.44 (s), 41.15
(d), 47.45 (q), 47.49 (q), 59.45 (q), 79.54 (d), 100.57 (s), 117.54
(s), 139.58 (d); MS m/ z (relative intensity) 352 (M+ - 32, 100),
295 (47), 263 (28), 221 (27), 220 (67), 189 (80), 157 (35), 75
(30), 73 (23); HRMS calcd for C21H40O4Si (M+) 384.2696, found
384.2699.
(4r,4a r,8a â)-(()-Octa h yd r o-7,7-d im eth oxy-4a -m eth yl-
4-[[(1,1-d im eth yleth yl)d im eth ylsilyl]oxy]-1(2H)-n a p h th a -
len on e (8). To a stirred solution of 87.6 g (398 mmol) of 7
and 250 g NaI in 600 mL of Ac2O was added dropwise 200 mL
of TMSCl over a period of 30 min at 0 °C. After being stirred
at 0 °C for 1 h, the reaction mixture was filtered and
concentrated under reduced pressure. The concentrate was
carefully mixed with 500 mL of saturated aqueous NaHCO3
and, after addition of 120 g of Na2S2O3, stirred at 0 °C for 1 h.
The aqueous layer was then extracted with three 500-mL
portions of EtOAc. The combined organic layers were washed
with saturated aqueous NaHCO3 and brine, dried, and evapo-
rated to leave 103 g of a brown oil. To a solution of this oil in
850 mL of MeOH was added 250 g of NaHCO3. The mixture
was stirred vigorously, and then 1.3 L of 1 M oxone in water
was added dropwise at 0 °C. After stirring at 0 °C for 2.5 h,
an additional 130 mL of 1 M oxone in water was added
dropwise. The reaction mixture was stirred 0 °C for another
1 h and then filtered. After removal of MeOH under reduced
pressure, the remaining aqueous phase was extracted with
four 500 mL portions of CH2Cl2. The combined organic layers
were washed with brine, dried, and evaporated to leave 71 g
of a yellow solid. To a stirred solution of this solid in a mixture
of 280 mL of CH2Cl2 and 800 mL of ether was added 5 mL of
47% aqueous HBr. After being stirred at rt for 45 min, the
reaction mixture was cooled to 0 °C and mixed with 250 mL
of saturated aqueous NaHCO3. The two-phase mixture was
separated and the aqueous layer was extracted with ether. The
combined organic layers were washed with brine, dried, and
evaporated to leave 67 g of a brown solid. To a stirred solution
of this solid in 1.4 L of CH2Cl2 was added 105 mL of trimethyl
orthoformate and 1.4 g of TsOH. After being stirred at rt for
2.5 h, the reaction mixture was quenched with 15 mL of Et3N,
washed with brine, dried, and evaporated to leave 82 g of a
brown oil. To a stirred solution of this oil in 1 L of dry MeOH
was added dropwise 200 mL of 0.076 M NaOMe in dry MeOH.
The reaction mixture was stirred at rt overnight and concen-
trated under reduced pressure to a volume of ca. 250 mL. After
addition of 2 L of CH2Cl2, the organic layer was washed with
200 mL of water and 400 mL of brine, dried, and evaporated
to leave 55 g of a dark brown oil. This oil was taken up in
400 mL of diisopropyl ether and filtered. Evaporation of the
filtrate afforded 50 g of crude octahydro-4-hydroxy-7,7-
dimethoxy-4a-methyl-1(2H)-naphthalenone as a light brown
oil.60 This oil was dissolved in 270 mL of dry DMF, and then
35.0 g (515 mmol) of imidazole and 37.4 g (248 mmol) of
TBDMSCl were added. The reaction mixture was stirred at
rt overnight and then poured into 600 mL of ice-water. The
aqueous layer was extracted with five 250-mL portions of
petroleum ether (bp 40-60 °C). The combined organic layers
were washed with brine, dried, and evaporated to leave ca.
70 g of crude 8. Flash chromatography (20:1 to 3:1 petroleum
ether (bp 40-60 °C)/EtOAc) and recrystallization from dry
EtOH afforded 44.4 g (31% overall from 7) of pure 8. The
(1r,4a â,8a r)-(()-Deca h yd r o-6,6-d im eth oxy-4-(1-m eth -
oxym et h ylen e)-8a -m et h yl-1-n a p h t h a len ol Met h a n esu l-
fon a te (11). To a stirred suspension of 6.08 g (17.2 mmol) of
(methoxymethyl)triphenylphosphonium chloride in 45 mL of
THF was added dropwise 35.4 mL of KHMDS (15% in toluene)
at -40 °C. When the addition was complete, the reaction
mixture was stirred at 0 °C for 20 min. To the resulting deep
red solution was added, via syringe, a solution of 1.891 g (5.91
mmol) of 9 in 10 mL of THF. After being stirred at 0 °C for
15 min, the reaction mixture was allowed to come to rt and
then stirred for an additional 4 h. The brown reaction mixture
was poured into water and extracted with EtOAc. The
combined organic layers were washed with brine, dried, and
evaporated. Flash chromatography (2:1 petroleum ether (bp
40-60 °C)/EtOAc) afforded 0.977 g (2.81 mmol, 48%) of 11:
1
(59) The reaction sequence employed for the synthesis of crude
(4aR,5R)-(()-4,4a,5,6,7,8-hexahydro-5-hydroxy-4a-methyl-2(3H)-naph-
thalenone from 2-methylcyclohexane-1,3-dione and MVK involved (a)
Michael addition (1 mol % of hydroquinone, water, 50 °C, 2 days), (b)
cyclization (0.15 equiv of pyrrolidine, toluene, 100 °C), and (c) reduction
(NaBH4, EtOH, 0 °C). In all cases, the crude product of each individual
step was used for the next reaction. See: (a) Hajos, Z. G.; Parrish, D.
R. J . Org. Chem. 1974, 39, 1612. (b) Marshall, J . A.; Seitz, D. E.;
Snyder, W. R.; Goldberg, B. Synth. Commun. 1974, 4, 79. (c) Boyce, C.
B. C.; Whitehurst, J . S. J . Chem. Soc. 1960, 2680.
mp 118 °C (from diisopropyl ether); H NMR δ 0.75 (s, 3 H),
1.07-2.08 (m, 10 H), 2.85 (dd, J ) 2.2, 9.0 Hz, 1 H), 2.97 (s, 3
H), 3.09 (s, 3 H), 3.18 (s, 3 H), 3.52 (s, 3 H), 4.42 (dd, J ) 4.9,
11.2 Hz, 1 H), 5.51 (br s, 1 H); 13C NMR δ 10.17 (q), 23.33 (t),
27.70 (t), 28.44 (t), 29.49 (t), 32.91 (t), 38.77 (q), 39.43 (s), 41.31
(d), 47.46 (q), 47.59 (q), 59.57 (q), 89.99 (d), 99.94 (s), 115.08
(s), 140.61 (d); MS m/ z (relative intensity) 316 (M+ - 32, 100),
285 (37), 271 (14), 221 (21), 220 (15), 205 (17), 189 (23), 173
(11), 101 (12), 85 (20), 83 (26), 79 (12); HRMS calcd for
C15H24O5S (M+ - 32) 316.1344, found 316.1340. Anal. Calcd
for C16H28O6S: C, 55.15; H, 8.10. Found: C, 54.96; H, 8.13.
(60) The 1H NMR spectrum of crude octahydro-4-hydroxy-7,7-
dimethoxy-4a-methyl-1(2H)-naphthalenone was identical with that
reported in ref 20a.

7342 J . Org. Chem., Vol. 62, No. 21, 1997
Minnaard et al.
(4a r,5r,8a â)-(()-Oct a h yd r o-8-(1-m et h oxym et h ylen e)-
4a-m eth yl-5-[[(1,1-dim eth yleth yl)dim eth ylsilyl]oxy]-2(3H)-
n a p h th a len on e (12). To a solution of 16.2 g (42.2 mmol) of
10 in 250 mL of acetone and 25 mL of water was added 5 g of
PPTS. After being stirred at rt for 1 h, the reaction mixture
was diluted with EtOAc, washed with saturated aqueous
NaHCO3 and brine, and dried. Evaporation and flash chro-
matography (10:1 petroleum ether (bp 40-60 °C)/EtOAc)
afforded 13.98 g (98%) of 12 as a white solid: mp 101 °C (from
diisopropyl ether); 1H NMR δ 0.01 (s, 3 H), 0.03 (s, 3 H), 0.86
(s, 9 H), 0.88 (s, 3 H), 1.10-1.69 (m, 6 H), 2.03-2.50 (m, 4 H),
2.82 (dd, J ) 3.9, 10.5 Hz, 1 H), 3.31 (dd, J ) 4.7, 10.7 Hz, 1
H), 3.54 (s, 3 H), 5.44 (br, s 1 H); 13C NMR δ -4.87 (q), -3.92
(q), 9.41 (q), 17.99 (s), 23.62 (t), 25.79 (3 q), 30.71 (t), 36.80 (t),
37.64 (t), 39.69 (t), 40.27 (s), 45.26 (d), 59.59 (q), 79.31 (d),
116.41 (s), 140.33 (d), 211.64 (s); MS m/ z (relative intensity)
338 (M+, 21), 282 (24), 281 (100), 206 (48), 189 (21), 171 (30),
75 (33), 73 (16); HRMS calcd for C19H34O3Si (M+) 338.2277,
found 338.2274. Anal. Calcd for C19H34O3Si: C, 67.42; H,
10.13. Found: C, 67.53; H, 10.38.
(4a r,5r,8a â)-(()-Oct a h yd r o-8-(1-m et h oxym et h ylen e)-
4a -m et h yl-5-[(m et h ylsu lfon yl)oxy]-2(3H )-n a p h t h a len -
on e (13). The mesylate 11 (1.396 g, 4.01 mmol) was treated
with PPTS for 1.5 h as described for 10. Workup and flash
chromatography (2:1 petroleum ether (bp 40-60 °C)/EtOAc)
gave 1.123 g (93%) of 13 as a white solid: mp 107 °C (from
diisopropyl ether/acetone); 1H NMR δ 0.98 (s, 3 H), 1.52-1.90
(m, 3 H), 2.02-2.42 (m, 7 H), 2.93 (ddd, J ) 2.3, 2.3, 10.5 Hz,
1 H), 3.00 (s, 3 H), 3.56 (s, 3 H), 4.44 (dd, J ) 4.9, 11.4 Hz, 1
H), 5.51 (br s, 1 H); 13C NMR δ 10.02 (q), 23.23 (t), 28.18 (t),
35.87 (t), 37.03 (t), 39.01 (q), 39.20 (t), 39.24 (s), 45.13 (d), 59.80
(q), 88.84 (d), 114.01 (s), 141.50 (d), 209.80 (s); MS m/ z
(relative intensity) 302 (M+, 94), 207 (40), 206 (100), 191 (24),
174 (23), 159 (17), 135 (20), 132 (17), 131 (18), 119 (23), 105
(18), 79 (17); HRMS calcd for C14H22O5S (M+) 302.1188, found
302.1189. Anal. Calcd for C14H22O5S: C, 55.61; H, 7.33.
Found: C, 55.38; H, 7.34.
(s), 139.82 (d); MS m/ z (relative intensity) 382 (M+, 41), 339
(31), 325 (31), 308 (27), 307 (100), 275 (54), 250 (84), 232 (31),
75 (56), 73 (34), 71 (30), 43 (39); HRMS calcd for C22H42O3Si
(M+) 382.2903, found 382.2900. Anal. Calcd for C22H42O3Si:
C, 69.07; H, 11.07. Found: C, 69.21; H, 11.34.
(1r,4a â,6â)-(()-Deca h yd r o-4-(1-m et h oxym et h ylen e)-
8a -m eth yl-6-(1-m eth yleth yl)-1,6-n a p h th a len ed iol (16). To
a solution of 0.865 g (2.26 mmol) of 14 in 15 mL of dry DMSO
was added at once 5.13 mL of TBAF (1.1 M in THF) at 100
°C. The resulting brown reaction mixture was stirred at 100
°C for 80 min, poured into water, and extracted with EtOAc.
The combined organic layers were washed with brine, dried,
and evaporated. Flash chromatography (2:1 petroleum ether
(bp 40-60 °C)/EtOAc) gave 0.522 g (87%) of 16: mp 99 °C
(from pentane/diisopropyl ether); 1H NMR δ 0.63 (s, 3 H), 0.93
(d, J ) 6.8 Hz, 6 H), 1.10 (br s, OH), 1.32-1.80 (m, 11 H), 2.12
(dd, J ) 5.0, 10.8 Hz, 1 H), 2.82 (ddd, J ) 2.1, 2.1, 13.6 Hz, 1
H), 3.39 (dd, J ) 4.3, 11.0 Hz, 1 H), 3.54 (s, 3 H), 5.48 (br s, 1
H); 13C NMR δ 8.93 (q), 16.80 (2 q), 23.76 (t), 28.84 (t), 30.38
(t), 30.97 (t), 31.66 (t), 38.98 (d), 39.43 (d), 39.76 (s), 59.41 (q),
73.21 (s), 79.18 (d), 117.87 (s), 139.58 (d); MS m/ z (relative
intensity) 268 (M+, 2), 250 (15), 208 (14), 207 (100), 175 (17),
131 (14), 69 (5); HRMS calcd for C16H28O3 (M+) 268.2038, found
268.2036. Anal. Calcd for C16H28O3: C, 71.60; H, 10.52.
Found: C, 71.85; H, 10.73.
(2r,4aâ,5â,8ar)-(()-Decah ydr o-8-(1-m eth oxym eth ylen e)-
4a -m et h yl-2-(1-m et h ylet h yl)-5-[(m et h ylsu lfon yl)oxy]-2-
n a p h th a len ol (17). a . To a stirred solution of 0.194 g (0.72
mmol) of 16 in 3 mL of pyridine was added 0.084 mL (1.09
mmol) of MsCl at rt. The reaction mixture was stirred at rt
for 1.5 h and, after addition of water, extracted with EtOAc.
The combined organic layers were washed with brine, dried,
and evaporated. Flash chromatography (3:1 petroleum ether
(bp 40-60 °C)/EtOAc) gave 0.247 g (99%) of 17: mp 101 °C
(from diisopropyl ether); 1H NMR δ 0.66 (s, 3 H), 0.86 (d, J )
6.8 Hz, 6 H), 1.20-2.01 (m, 11 H), 2.18 (br d, J ) 9.8 Hz, 1 H),
2.81 (dd, J ) 2.1, 9.1 Hz, 1 H), 2.93 (s, 3 H), 3.49 (s, 3 H), 4.41
(dd, J ) 4.8, 11.2 Hz, 1 H), 5.47 (br s, 1 H); 13C NMR δ 9.74
(q), 16.76 (2 q), 23.38 (t), 28.48 (t), 28.64 (t), 30.65 (t), 31.72
(t), 38.57 (q), 38.82 (d), 39.41 (d), 39.63 (s), 59.45 (q), 72.79 (s),
90.49 (d), 115.84 (s), 140.37 (d); MS m/ z (relative intensity)
328 (M+ - 18, 12), 287 (7), 286 (19), 285 (100), 207 (7), 189
(11), 157 (10), 83 (8); HRMS calcd for C17H28O4S (M+ - 18)
328.1708, found 328.1708. Anal. Calcd for C17H30O5S: C,
58.93; H, 8.73. Found: C, 59.14; H, 8.93.
(2r,4a â,5â,8a r)- a n d (2r,4a r,5r,8a â)-(()-Deca h yd r o-8-
(1-m et h oxym et h ylen e)-4a -m et h yl-2-(1-m et h ylet h yl)-5-
[[(1,1-d im eth yleth yl)d im eth ylsilyl]oxy]-2-n a p h th a len ol
(14 a n d 15). Anhydrous CeCl3 (prepared from 3.15 g (8.45
mmol) of CeCl3‚7H2O according to the procedure of Imamoto
et al.)23a and 20 mL of THF were mixed at 0 °C and stirred at
rt overnight under Ar. The flask was then placed in an
ultrasonic bath for 1.5 h. To the resulting fine dispersion was
added, via syringe, 8.3 mL of i-PrMgCl (ca. 1 M in ether) at 0
°C. The mixture was stirred at 0 °C for 2.5 h and then, via
syringe, a solution of 0.940 g (2.78 mmol) of 12 in 10 mL of
THF was added. After being stirred at 0 °C for another 0.5 h,
the reaction mixture was treated with concentrated aqueous
KF and extracted with EtOAc. The combined organic layers
were washed with brine, dried, and evaporated. Flash chro-
matography (20:1 to 12:1 petroleum ether (bp 40-60 °C)/
EtOAc) gave 0.859 g (81%) of 14 and 0.170 g (16%) of 15, both
as white solids. The physical and spectroscopic data of 14 and
15 are shown below.
b. The procedure described above for the organocerium
addition to 12 was employed, except that the reaction mixture
was stirred at 0 °C for 2.5 h. Starting from 1.126 g of mesylate
13 (3.73 mmol), workup and flash chromatography (2:1
petroleum ether (bp 40-60 °C)/EtOAc) afforded 1.197 g (93%)
of pure 17 as the sole product.
(1r,4r,4a r,7â,8a â)-(()-Deca h yd r o-7-h yd r oxy-4a -m eth -
yl-7-(1-m eth yleth yl)-4-[(m eth ylsu lfon yl)oxy]-1-n a p h th a -
len eca r boxa ld eh yd e (3). To a stirred solution of 0.500 g
(1.44 mmol) of 17 in 20 mL of ether was added dropwise 4 mL
of 35% aqueous HClO4 at 0 °C. The solution was allowed to
come to rt and stirred for 1 h. After addition of water, the
reaction mixture was extracted with EtOAc. The combined
organic layers were washed with saturated aqueous NaHCO3
(twice) and brine, dried over Na2SO4, and evaporated. Flash
chromatography (1:1 petroleum ether (bp 40-60 °C)/EtOAc)
gave 0.463 g (97%) of 3 as an oil:61 1H NMR δ 0.68 (s, 3 H),
0.86 (d, J ) 6.8 Hz, 6 H), 1.30-2.32 (m, 14 H), 2.92 (s, 3 H),
4.30 (dd, J ) 6.0, 10.4 Hz, 1 H), 9.82 (br s, 1 H); 13C NMR δ
11.39 (q), 16.63 (q), 16.72 (q), 23.03 (t), 25.49 (t), 29.51 (t), 32.91
(t), 33.60 (t), 38.65 (d), 38.76 (q), 39.07 (s), 40.31 (d), 49.86 (d),
73.29 (s), 89.64 (d), 203.74 (d); MS m/ z (relative intensity) 289
(M+ - 43, 100), 261 (37), 193 (98), 163 (31), 147 (52), 105 (30),
83 (30), 81 (44), 57 (37), 55 (38), 43 (52); HRMS calcd for
C13H21O5S (M+ - 43) 289.11097, found 289.11095.
1
14: mp 77-78 °C (from pentane); H NMR δ 0.03 (s, 6 H),
0.63 (s, 3 H), 0.86 (s, 9 H), 0.93 (d, J ) 6.9 Hz, 3 H), 0.94 (d,
J ) 6.9 Hz, 3 H), 0.97 (s, OH), 1.34-1.70 (m, 10 H), 2.10 (dd,
J ) 4.15, 13.5 Hz, 1 H), 2.79 (ddd, J ) 1.6, 1.6, 13.4 Hz, 1 H),
3.36 (dd, J ) 4.4, 11.4 Hz, 1 H), 3.54 (s, 3 H), 5.48 (s, 1 H); 13
C
NMR δ -4.78 (q), -3.96 (q), 9.11 (q), 16.78 (q), 16.84 (q), 18.02
(s), 23.77 (t), 25.83 (3 q), 28.98 (t), 31.09 (t), 31.27 (t), 32.31
(t), 39.00 (d), 39.65 (d), 40.37 (s), 59.38 (q), 73.30 (s), 79.61 (d),
118.35 (s), 139.33 (d); MS m/ z (relative intensity) 382 (M+,
3), 364 (58), 322 (29), 321 (100), 232 (34), 189 (50), 163 (21),
132 (28), 123 (20), 75 (30), 73 (24); HRMS calcd for C22H42O3Si
(M+) 382.2903, found 382.2900. Anal. Calcd for C22H42O3Si:
C, 69.07; H, 11.07. Found: C, 69.03; H, 11.31.
1
15: mp 131-133 °C (from pentane); H NMR δ 0.02 (s, 6
(E,E)-2-E t h ylid en e-6,10-d im et h yl-9-oxo-5-u n d ecen a l
(18). To a stirred solution of 1.46 mL of KHMDS (0.5 M in
toluene) in 4 mL of dry THF was added dropwise, via syringe,
a solution of 0.097 g (0.29 mmol) of 3 in 2 mL of THF at rt.
H), 0.72 (s, 3 H), 0.85 (s, 9 H), 0.85 (d, J ) 6.8 Hz, 3 H), 0.91
(d, J ) 6.8 Hz, 3 H), 0.95-1.86 (m, 11 H), 2.01 (septet, J ) 6.8
Hz, 1 H), 2.77 (dd, J ) 2.2, 9.8 Hz, 1 H), 3.27 (dd, J ) 4.2,
10.9 Hz, 1 H), 3.53 (s, 3 H), 5.52 (br s, 1 H); 13C NMR δ -4.77
(q), -3.93 (q), 10.33 (q), 15.93 (q), 16.07 (q), 18.00 (s), 23.79
(t), 25.81 (3 q), 28.84 (d), 31.12 (t), 31.97 (t), 33.45 (t), 34.17
(t), 40.43 (s), 41.61 (d), 59.43 (q), 74.11 (s), 79.99 (d), 117.38
(61) Aldehyde 3 was susceptible to air oxidation and had to be stored
under N2 in the refrigerator.

(E,E)-Germacrane Sesquiterpene Alcohols
J . Org. Chem., Vol. 62, No. 21, 1997 7343
The reaction mixture was stirred at rt for 10 min and, after
addition of saturated aqueous NH4Cl, extracted with EtOAc.
The combined organic layers were washed with brine and dried
over Na2SO4. After evaporation at rt, the remaining residue
(0.057 g) was taken up in a 4:1 mixture of petroleum ether
(bp 40-60 °C) and ether and filtered over a short neutral
alumina column to give 0.014 g (20%) of 18: 1H NMR δ 1.07
(d, J ) 6.9 Hz, 6 H), 1.56 (br s, 3 H), 1.97 (d, J ) 7.1 Hz, 3 H),
2.00-2.51 (m, 8 H), 2.56 (septet, J ) 6.9 Hz, 1 H), 5.10 (dd, J
) 5.8, 6.5 Hz, 1 H), 6.56 (dd, J ) 7.1, 14.1 Hz, 1 H), 9.34 (s, 1
H); 13C NMR δ 14.87 (q), 16.02 (q), 18.22 (2 q), 23.61 (t), 26.61
(t), 33.39 (t), 38.92 (t), 40.84 (d), 123.75 (d), 134.85 (s), 144.25
(s), 150.10 (d), 194.97 (d), 214.81 (s); MS m/ z (relative
intensity) 236 (M+, 46), 193 (33), 150 (76), 138 (45), 135 (100),
133 (50), 121 (47), 109 (41), 107 (59), 81 (63), 71 (88), 43 (60);
HRMS calcd for C15H24O2 (M+) 236.1776, found 236.1772.
(1r,4r,4a r,7â,8a â)-(()-Deca h yd r o-4a -m eth yl-7-(1-m eth -
yleth yl)-7-[(tr im eth ylsilyl)oxy]-4-[(m eth ylsu lfon yl)oxy]-
1-n a p h th a len eca r boxa ld eh yd e (19). To a stirred solution
of 0.525 g (1.58 mmol) of 3 in 15 mL of pyridine was added
0.34 mL (1.6 mmol) of hexamethyldisilazane and 0.63 mL (4.8
mmol) of TMSCl at 0 °C. After being stirred at 0 °C for 3 h,
the reaction mixture was poured into ice-water and extracted
with EtOAc. The combined organic layers were washed with
saturated aqueous NaHCO3 and brine, dried, and evaporated.
Flash chromatography (3:2 petroleum ether (bp 40-60 °C)/
EtOAc) gave 0.510 g (80%) of 19 as an oil: 1H NMR δ 0.12 (s,
9 H), 0.74 (s, 3 H), 0.90 (d, J ) 6.8 Hz, 3 H), 0.91 (d, J ) 6.8
Hz, 3 H), 1.42-1.60 (m, 6 H), 1.72 (septet, J ) 6.8 Hz, 1 H),
1.81-2.38 (m, 6 H), 2.97 (s, 3 H), 4.31 (dd, J ) 6.0, 10.6 Hz, 1
H), 9.86 (d, J ) 0.7 Hz, 1 H); 13C NMR δ 2.66 (3 q), 11.75 (q),
17.48 (q), 17.56 (q), 23.12 (t), 25.51 (t), 28.61 (t), 32.52 (t), 33.91
(t), 38.37 (q), 38.79 (d), 39.09 (s), 40.49 (d), 49.94 (d), 78.58 (s),
50), 307 (70), 232 (100), 231 (61), 145 (30), 84 (31), 75 (54), 73
(36); HRMS calcd for C22H40O2Si (M+) 364.2798, found 364.2793.
(1r,4r,4a r,8a â)-(()-Deca h yd r o-4a -m eth yl-7-(1-m eth yl-
et h ylid en e)-4-[(m et h ylsu lfon yl)oxy]-1-n a p h t h a len eca r -
boxa ld eh yd e (6). The TBDMS ether 22 (8.897 g, 24.4 mmol)
was desilylated with TBAF for 45 min as described for 14.
Workup and flash chromatography (10:1 petroleum ether (bp
40-60 °C)/EtOAc) gave 5.429 g (89%) of the corresponding
1
alcohol: mp 131 °C (from diisopropyl ether); H NMR δ 0.76
(s, 3 H), 1.65 (br s, 6 H), 1.00-1.18 (m, 2 H), 1.35-1.98 (m, 7
H), 2.43-2.58 (m, 2 H), 2.82 (ddd, J ) 2.2, 4.6, 11.2 Hz, 1 H),
3.28 (dd, J ) 4.1, 11.0 Hz, 1 H), 3.57 (s, 3 H), 5.58 (br s, 1 H);
13C NMR δ 9.59 (q), 19.97 (q), 20.07 (q), 23.67 (t), 25.06 (t),
26.87 (t), 30.36 (t), 37.42 (t), 40.23 (s), 45.97 (d), 59.50 (q), 79.53
(d), 117.87 (s), 121.20 (s), 130.63 (s), 139.91 (d); MS m/ z
(relative intensity) 250 (M+, 100), 232 (8), 218 (11), 207 (16),
168 (54), 153 (71), 135 (40), 93 (20); HRMS calcd for C16H26O2
(M+) 250.1933, found 250.1929. Anal. Calcd for C16H26O2: C,
76.75; H, 10.47. Found: C, 76.36; H, 10.66. A solution of this
alcohol (7.114 g, 28.5 mmol) in pyridine was treated with MsCl
as described for 16. Workup and flash chromatography (10:1
petroleum ether (bp 40-60 °C)/EtOAc) gave 9.24 g (99%) of
the corresponding mesylate: mp 103 °C (from pentane/
diisopropyl ether); 1H NMR δ 0.81 (s, 3 H), 1.14 (ddd, J ) 4.1,
9.3, 9.3 Hz, 1 H), 1.60 (br s, 6 H), 1.60-2.00 (m, 7 H), 2.40-
2.56 (m, 2 H), 2.83 (ddd, J ) 2.3, 2.3, 9.1 Hz, 1 H), 2.93 (s, 3
H), 3.30 (s, 3 H), 4.30 (dd, J ) 4.9, 11.2 Hz, 1 H), 5.53 (br s, 1
H); 13C NMR δ 10.42 (q), 19.99 (q), 20.07 (q), 23.33 (t), 24.83
(t), 26.65 (t), 28.49 (t), 37.52 (t), 38.67 (q), 39.88 (s), 46.26 (d),
59.54 (q), 90.42 (d), 115.86 (s), 121.81 (s), 129.66 (s), 140.74
(d); MS m/ z (relative intensity) 328 (M+, 41), 285 (22), 246
(16), 232 (33), 217 (14), 189 (20), 135 (43), 73 (100); HRMS
calcd for C17H28O4S (M+) 328.1708, found 328.1705. Anal.
Calcd for C17H28O4S: C, 62.16; H, 8.59. Found: C, 61.86; H,
8.79. A solution of this mesylate (2.38 g, 7.26 mmol) in ether
was treated with 35% HClO4 for 3.5 h as described for 17.
Workup and recrystallization from diisopropyl ether/acetone
89.94 (d), 203.69 (d); MS m/ z (relative intensity) 361 (M+
-
43, 100), 347 (15), 333 (40), 171 (15); HRMS calcd for
C16H29O5SSi (M+ - 43) 361.1505, found 361.1506.
(()-2-[2-Eth en yl-2-m eth yl-5-(1-m eth yleth yl)-5-[(tr im eth -
ylsilyl)oxy]-1-cycloh exyl]-2-p r op en a l (21). The TMS ether
19 (0.157 g, 0.39 mmol) was treated with KHMDS for 15 min
as described for 3. After workup, the remaining residue (0.120
g) was flash chromatographed (10:1 petroleum ether (bp 40-
60 °C)/EtOAc) to give 0.043 g (36%) of 21:62 1H NMR δ 0.13
(s, 9 H), 0.85 (s, 3 H), 0.91 (d, J ) 6.8 Hz, 6 H), 1.03-2.0 (m,
7 H), 3.21 (dd, J ) 3.2, 13.4 Hz, 1 H), 4.71 (dd, J ) 1.4, 17.3
Hz, 1 H), 4.77 (dd, J ) 1.4, 10.9 Hz, 1 H), 5.68 (dd, J ) 10.9,
17.3 Hz, 1 H), 6.01 (br s, 1 H), 6.06 (br s, 1 H), 9.38 (s, 1 H);
13C NMR δ 2.56 (3 q), 14.20 (q), 17.44 (q), 17.54 (q), 28.72 (t),
34.42 (t), 34.68 (t), 36.38 (d), 38.72 (d), 39.46 (s), 78.42 (s),
110.26 (t), 134.88 (t), 149.19 (d), 151.95 (s), 194.22 (d); MS m/ z
(relative intensity) 265 (M+ - 43, 19), 86 (51), 84 (100), 51
(27), 50 (92); HRMS calcd for C15H25O2Si (M+ - 43) 265.1624,
found 265.1623.
(1r,4a â,8a r)-(()-Deca h yd r o-4-(1-m eth oxym eth ylen e)-
8a -m et h yl-6-(1-m et h ylet h ylid en e)-1-[[(1,1-d im et h ylet h -
yl)d im eth ylsilyl]oxy]n a p h th a len e (22). To a stirred solu-
tion of 150 mL of 0.50 M (dimethylsulfinyl)sodium in DMSO
was added a slurry of 32.5 g (75.2 mmol) of isopropyltriphen-
ylphosphonium iodide in 30 mL of DMSO at rt. The reaction
mixture was stirred at rt for 1.5 h.63 To the resulting deep
red solution was added, via syringe, a solution of 9.90 g (29.3
mmol) of 12 in 60 mL of THF. After being stirred at rt
overnight, the reaction mixture was poured into ice-water and
extracted with EtOAc. The combined organic layers were
washed with brine, dried, and evaporated. Repeated flash
chromatography (50:1 petroleum ether (bp 40-60 °C)/tert-butyl
methyl ether) gave 8.897 g (83%) of 22: 1H NMR δ 0.00 (s, 6
H), 0.75 (s, 3 H), 0.85 (s, 9 H), 1.57 (br s, 6 H), 0.93-1.96 (m,
8 H), 2.41-2.58 (m, 2 H), 2.77 (dd, J ) 4.2, 9.7 Hz, 1 H), 3.23
(dd, J ) 5.0, 10.9 Hz, 1 H), 3.55 (s, 3 H), 5.55 (s, 1 H); 13C
NMR δ -4.76 (q), -3.90 (q), 9.86 (q), 18.08 (s), 19.99 (q), 20.09
(q), 23.77 (t), 25.36 (t), 25.91 (3 q), 27.10 (t), 31.15 (t), 38.26
(t), 40.88 (s), 46.29 (d), 59.55 (q), 79.92 (d), 118.50 (s), 120.70
(s), 131.25 (s), 139.64 (d); MS m/ z (relative intensity) 364 (M+,
1
afforded 2.228 g (98%) of 6: mp 126 °C; H NMR δ 0.89 (s, 3
H), 1.14 (ddd, J ) 4.2, 9.4, 9.4 Hz, 1 H), 1.38 (m, 1 H), 1.65 (s,
3 H), 1.68 (s, 3 H), 1.60-1.99 (m, 5 H), 2.24-2.46 (m, 3 H),
2.55-2.76 (m, 2 H), 2.98 (s, 3 H), 4.29 (dd, J ) 6.9, 9.3 Hz, 1
H), 9.96 (d, J ) 1.0 Hz, 1 H); 13C NMR δ 11.83 (q), 20.03 (q),
20.07 (q), 22.92 (t), 24.98 (t), 25.51 (t), 29.22 (t), 38.83 (q), 39.21
(t), 39.51 (s), 46.96 (d), 50.42 (d), 89.61 (d), 122.42 (s), 129.49
(s), 203.40 (d); MS m/ z (relative intensity) 314 (M+, 10), 218
(11), 189 (9), 147 (8), 136 (9), 135 (100), 107 (8); HRMS calcd
for C16H26O4S (M+) 314.1552, found 314.1547. Anal. Calcd
for C16H26O4S: C, 61.11; H, 8.33. Found: C, 61.24; H, 8.61.
(E,E)-7-Met h yl-4-(1-m et h ylet h ylid en e)-1,7-cyclod eca -
d ien eca r boxa ld eh yd e (23). To a stirred solution of 0.053 g
(0.17 mmol) of 6 in 2 mL of THF was added 0.37 mL of
KHMDS (0.5 M in toluene) at -78 °C. The reaction mixture
was stirred at -78 °C for 10 min and, after removal of the
dry-ice bath, for an additional 25 min. After addition of ether,
the reaction mixture was washed with water and brine, dried,
and evaporated. Column chromatography on neutral alumina
(5:1 petroleum ether (bp 40-60 °C)/tert-butyl methyl ether)
afforded 0.010 g (27%) of 23: 1H NMR δ 1.34 (s, 3 H), 1.65 (s,
3 H), 1.73 (s, 3 H), 1.95-2.36 (m, 8 H), 2.98 (m, 2 H), 5.13 (dd,
J ) 7.8, 7.8 Hz, 1 H), 6.49 (dd, J ) 8.5, 8.5 Hz, 1 H), 9.28 (s,
1 H); 13C NMR δ 18.96 (q), 20.48 (q), 21.19 (q), 23.10 (t), 25.99
(t), 33.51 (t), 36.40 (t), 37.20 (t), 123.61 (d), 128.50 (s), 128.99
(s), 135.70 (s), 140.36 (s), 155.09 (d), 195.94 (d); MS m/ z
(relative intensity) 218 (M+, 100), 190 (9), 175 (68), 162 (57),
136 (71), 135 (52), 122 (54), 121 (82), 107 (91), 105 (48), 93
(68), 91 (65), 79 (59), 67 (46); calcd for C15H22O (M+) 218.1671,
found 218.1678.
(E,E)-7-Met h yl-4-(1-m et h ylet h ylid en e)-1,7-cyclod eca -
d ien em eth a n ol (24). To a degassed solution of 0.111 g (0.35
mmol) of 6 in 3 mL of toluene was added with stirring 0.74
mL of KHMDS (0.5 M in toluene) at -40 °C under an Ar
atmosphere. After being stirred at -40 °C for 30 min, the
reaction mixture was gradually warmed to 0 °C over a period
of 20 min. The yellowish reaction mixture was cooled to -78
°C, and then excess Red-Al (65% in toluene) was added
dropwise. After being stirred at -78 °C for 10 min, the
reaction mixture was allowed to come to rt and carefully
(62) The NMR spectra of 21 revealed the presence of a trace amount
of an isomer.
(63) Shorter reaction times led to lower yields.

7344 J . Org. Chem., Vol. 62, No. 21, 1997
Minnaard et al.
quenched with 1 mL of water. The reaction mixture was then
diluted with EtOAc, dried, and evaporated. The remaining
residue (0.091 g) was flash chromatographed (5:1 hexane/tert-
butyl methyl ether) to afford 0.059 g (77%) of 24: 1H NMR
(C6D6) δ 1.51 (d, J ) 1.2 Hz, 3 H), 1.65 (s, 3 H), 1.71 (s, 3 H),
1.95-2.3 (m, 9 H), 2.79 (m, 2 H), 3.93 (s, 2 H), 5.25 (br m, 1
H), 5.65 (dd, J ) 8.2, 8.2 Hz, 1H); 13C NMR (C6D6) δ 18.47 (q),
20.32 (q), 20.96 (q), 25.94 (t), 26.91 (t), 33.53 (t), 34.76 (t), 37.92
(t), 67.40 (t), 123.84 (d), 126.29 (d), 126.67 (s), 131.54 (s), 135.17
(s), 135.73 (s); MS m/ z (relative intensity) 220 (M+, 26), 205
(12), 202 (26), 189 (48), 136 (38), 133 (37), 121 (66), 107 (36),
93 (44), 91 (49), 31 (100); HRMS calcd for C15H24O (M+)
220.1827, found 220.1827.
(E,Z)-1,5-Dim et h yl-8-(1-m et h ylet h ylid en e)-1,5-cyclo-
d eca d ien e (25). To a stirred solution of 0.078 g (0.35 mmol)
of 24 and 0.7 mL of N,N,N′,N′-tetramethylethylenediamine in
3 mL of THF was added dropwise 0.26 mL of BuLi (1.6 M in
hexane) at -78 °C. The reaction mixture was stirred at -78
°C for 15 min, and then 0.075 mL (0.52 mmol) of TMPDCl was
added. After being stirred at -78 °C for 5 min, the reaction
mixture was allowed to come to rt and stirred for an additional
1 h. The reaction mixture was then added, via syringe, to a
solution of 0.09 g (12.9 mmol) of Li in 25 mL of EtNH2 at 0 °C.
Stirring was continued at 0 °C for 25 min, and excess aqueous
NH4Cl was added. The reaction mixture was stirred for
another 40 min and extracted with pentane. The combined
organic layers were washed with brine, dried, and carefully
evaporated. Repeated flash chromatography (pentane) gave
0.017 g (23%) of (Z)-1,7-dimethyl-4-(1-methylethenyl)cyclo-
decene64 and 0.030 g (42%) of 25: 1H NMR δ 1.54 (d, J ) 1.2
Hz, 3 H), 1.66 (s, 3 H), 1.70 (s, 6 H), 2.02-2.25 (m, 8 H), 2.67
(m, 2 H), 5.18 (dd, J ) 7.8, 7.8 Hz, 1 H), 5.31 (ddd, J ) 1.2,
8.2, 8.2 Hz, 1 H); 13C NMR δ 18.44 (q), 20.48 (q), 21.06 (q),
24.41 (q), 25.11 (t), 30.96 (t), 33.39 (t), 34.84 (t), 37.91 (t),
123.69 (d), 125.24 (d), 126.70 (s), 131.49 (s), 131.65 (s), 135.71
(s); MS m/ z (relative intensity) 204 (M+, 55), 189 (35), 161
(35), 147 (20), 136 (21), 133 (35), 121 (100), 107 (50), 105 (47),
93 (54), 41 (35); HRMS calcd for C15H24 (M+) 204.1878, found
204.1876. The 1H NMR spectrum of 25 corresponded with that
reported in the literature.38
(Z,E)-7-Meth yl-4-(1-m eth yleth ylid en e)-1,7-cyclod eca d i-
en eca r boxa ld eh yd e (5). To a degassed solution of 0.122 g
(0.39 mmol) of 6 in 4 mL of toluene was added with stirring
0.25 mL of NaO-t-amyl (1.55 M in benzene)65 at -78 °C under
an Ar atmosphere. The reaction mixture was stirred at -78
°C for 10 min and then allowed to come to 0 °C. After being
stirred at 0 °C for an additional 35 min, the reaction mixture
was poured into water and extracted with tert-butyl methyl
ether. The combined organic layers were washed with brine
and dried. Evaporation afforded 0.082 g (97%) of almost pure
5:66 1H NMR (C6D6) δ 1.23 (s, 3 H), 1.52 (s, 3 H), 1.57 (s, 3 H),
1.9-2.45 (m, 7 H), 2.7-3.0 (m, 2 H), 3.12 (ddd, J ) 1.6, 5.3,
12.3 Hz, 1 H), 4.70 (dd, J ) 4.9, 11.7 Hz, 1 H), 5.58 (dd, J )
5.7, 9.9 Hz, 1 H), 9.93 (s, 1 H); 13C NMR (C6D6)67 δ 16.96 (q)*,
20.09 (q), 20.36 (q), 26.81 (t), 30.08 (t), 31.21 (t), 31.99 (t)*,
40.70 (t)*, 125.72 (d), 130.65 (s), 136.28 (s), 138.07 (s), 150.89
(d), 188.53 (d); MS m/ z (relative intensity) 218 (M+, 66), 203
(28), 189 (25), 175 (44), 136 (100), 135 (75), 123 (55), 122 (51),
121 (63), 107 (83), 105 (52), 96 (57), 93 (53), 91 (61), 79 (54);
HRMS calcd for C15H22O (M+) 218.1671, found 218.1677.
(Z,E)-7-Meth yl-4-(1-m eth yleth ylid en e)-1,7-cyclod eca d i-
en em eth a n ol (15-Hyd r oxyger m a cr en e B) (4). To a de-
gassed solution of 0.285 g (0.91 mmol) of 6 in 5 mL of dry
toluene was added with stirring 0.59 mL of NaO-t-amyl (1.55
M in benzene) at -78 °C under an Ar atmosphere. After being
stirred at -78 °C for 15 min, the reaction mixture was allowed
to come to rt, stirred at that temperature for 15 min, and then
cooled to 0 °C. Stirring was continued at 0 °C for an additional
20 min, after which the reaction mixture was cooled again to
-78 °C. After dropwise addition of 1 mL of Red-Al (65% in
toluene) followed by stirring at -78 °C for 15 min, excess Red-
Al was destroyed by careful addition of saturated aqueous
NH4Cl. The reaction mixture was allowed to come to rt and,
after addition of Na2SO4, stirred for 20 min. The resulting
suspension was diluted with EtOAc and filtered over a short
silica column. After thorough evaporation, the remaining
residue was dissolved in 15 mL of tert-butyl methyl ether and
extracted with five portions of 20% aqueous AgNO3. The
combined aqueous layers were washed with tert-butyl methyl
ether and then cooled to 0 °C. After addition of 15 mL of 25%
aqueous NH3, the aqueous layer was extracted with tert-butyl
methyl ether. The combined organic layers were washed with
brine, dried, and evaporated to afford 0.143 g (72%) of 4: 1H
NMR (C6D6)68 δ 1.37 (br s, 3 H), 1.64 (s, 3 H), 1.67 (s, 3 H),
1.7-2.7 (m, 10 H), 3.00 (m, 1 H), 3.81 (d, AB system, J ) 11.8
Hz, 1 H), 4.13 (d, AB system, J ) 11.8 Hz, 1 H), 4.78 (m, 2 H);
13C NMR (C6D6)67 δ 16.86 (q)*, 20.15 (q), 20.48 (q), 26.39 (t),
32.13 (t), 32.78 (t)*, 34.57 (t), 40.42 (t)*, 59.71 (t), 126.18 (d),
131.39 (d), 132.80 (s)*, 135.13 (s), 136.81 (s)*; MS m/ z (relative
intensity) 220 (M+, 31), 205 (18), 202 (46), 189 (82), 137 (91),
133 (63), 122 (72), 121 (100), 119 (79), 107 (96), 105 (81), 93
(87), 91 (87), 81 (93), 79 (70); HRMS calcd for C15H24O (M+)
220.1827, found 220.1825.
Ger m a cr en e B (26). The germacrane alcohol 4 (0.047 g,
0.21 mmol) was treated with TMPDCl and then with Li in
EtNH2 for 5 min as described for 24. Workup and flash
chromatography (pentane) gave, in order of elution, 0.013 g
of a mixture of hydrogenated products and 0.023 g (53%) of
pure germacrene B (26). The NMR and mass spectral data
for 26 corresponded with those reported in the literature.42b
(2r,4a r,5r,8a â)- a n d (2â,4a r,5r,8a â)-(()-Deca h yd r o-8-
(1-m et h oxym et h ylen e)-4a -m et h yl-5-[[(1,1-d im et h ylet h -
yl)d im eth ylsilyl]oxy]-2-n a p h th a len eca r bon itr ile (27). To
a stirred solution of 1.158 g (3.42 mmol) of 12, 0.870 g (4.46
mmol) of TosMIC, and 0.34 mL (5.82 mmol) of dry EtOH in
20 mL of dry DME was added 0.667 g (8.6 mmol) of KOt-Bu
at 0 °C. After being stirred at 0 °C for 5 min, the reaction
mixture was warmed to 35 °C and stirred at this temperature
overnight. After addition of water, the reaction mixture was
extracted with EtOAc. The combined organic layers were
washed with brine, dried, and evaporated. Flash chromatog-
raphy (20:1 petroleum ether (bp 40-60 °C)/EtOAc) gave 0.883
g (74%) of 27 as a 1:1 mixture of two diastereomers: 1H NMR
(major peaks) δ 0.00, 0.01, 0.02, 0.04 (s, s, s, s, 1:1:1:1 ratio, 6
H), 0.66, 0.69 (s, s, 1:1 ratio, 3 H), 0.84, 0.85 (s, s, 1:1 ratio, 9
H), 3.52, 3.53 (s, s, 1:1 ratio, 3 H), 5.42, 5.47 (s, s, 1:1 ratio, 1
H); 13C NMR δ -4.85 (q), -3.94 (q), 10.01 (q), 17.98 (s), 23.38
(t), 25.19 (t), 25.78 (3 q), 26.75 (t), 28.51 (d), 30.75 (t), 35.72
(t), 40.09 (s), 44.42 (d), 59.56 (q), 79.27 (d), 116.23 (s), 122.66
(s), 140.03 (d); HRMS calcd for C20H35NO2Si (M+) 349.2437,
found 349.2438.
(2r,4a r,5r,8a â)-(()-1-[Deca h yd r o-8-(1-m eth oxym eth yl-
en e)-4a-m eth yl-5-[[(1,1-dim eth yleth yl)dim eth ylsilyl]oxy]-
2-n a p h th a len yl]eth a n on e (28). To a stirred solution of
1.526 g (4.37 mmol) of 27 in 50 mL of ether was added
dropwise 8.2 mL of MeLi (1.6 M in ether) at 0 °C. The reaction
mixture was stirred at 0 °C for 2 h and, after addition of water,
extracted with ether. The combined organic layers were
washed with brine, dried, and evaporated. Flash chromatog-
raphy (30:1 petroleum ether (bp 40-60 °C)/EtOAc) gave 1.311
g (82%) of 28 as an oil: 1H NMR δ 0.02 (s, 6 H), 0.66 (s, 3 H),
0.85 (s, 9 H), 1.09 (ddd, J ) 3.9, 13.2, 13.2 Hz, 1 H); 1.2-1.85
(m, 8 H), 1.96 (ddd, J ) 3.3, 3.3, 12.9 Hz, 1 H), 2.14 (s, 3 H),
2.34 (dddd, J ) 3.3, 3.3, 12.9, 12.9 Hz, 1 H), 2.78 (dd, J ) 4.6,
9.8 Hz, 1 H), 3.26 (dd, J ) 4.6, 9.8 Hz, 1 H), 3.53 (s, 3 H), 5.54
(br s, 1 H); 13C NMR δ -4.84 (q), -3.97 (q), 10.11 (q), 17.96
(64) This compound has been characterized by NMR and MS: 1H
NMR δ 0.81 (d, J ) 6.6 Hz, 3 H), 1.67 (br s, 9 H), 0.9-2.3 (m, 10 H),
2.45 (ddd, J ) 4.0, 4.0, 11.9 Hz, 1 H), 2.89 (m, 2 H), 5.20 (dd, J ) 8.7,
8.7 Hz, 1 H); 13C NMR δ 20.40 (2 q), 21.58 (t), 22.15 (q), 22.70 (q),
26.88 (t), 28.10 (d), 28.61 (t), 29.46 (t), 30.89 (t), 36.77 (t), 124.79 (d),
125.31 (s), 131.65 (s), 134.95 (s); MS m/ z (relative intensity) 206 (M+,
72), 191 (18), 163 (43), 135 (33), 121 (50), 109 (52), 107 (70), 95 (73),
93 (59), 81 (100), 41 (65); HRMS calcd for C15H26 (M+) 206.2035, found
206.2034.
(65) A stock solution of NaO-t-amyl (1.55
M in benzene) was
prepared as described: Conia, M. J .-M. Bull. Soc. Chim. Fr. 1950, 17,
537.
(66) The NMR spectra of 5 revealed the presence of trace amounts
of 23.
(67) Coalescence was observed for the marked signals. One singlet
(68) In the 1H NMR spectrum of 4 the peaks are slightly coales-
cenced.
in the 13C NMR spectrum was obscured.

(E,E)-Germacrane Sesquiterpene Alcohols
J . Org. Chem., Vol. 62, No. 21, 1997 7345
(s), 23.51 (t), 23.90 (t), 24.63 (t), 25.78 (3 q), 28.06 (q), 30.94
(t), 37.57 (t), 40.48 (s), 44.64 (d), 51.61 (d), 59.37 (q), 79.69 (d),
117.15 (s), 139.91 (d), 211.80 (s); MS m/ z (relative intensity)
366 (M+, 35), 310 (20), 309 (100), 234 (73), 185 (35), 159 (23),
135 (16), 119 (19), 75 (46); HRMS calcd for C21H38O3Si (M+)
366.2590, found 366.2584.
at rt. After being stirred at rt for 90 min, the reaction mixture
was diluted with water and extracted with petroleum ether
(bp 40-60 °C). The combined organic layers were washed with
brine, dried, and evaporated. Flash chromatography (7:1
petroleum ether (bp 40-60 °C)/EtOAc) gave 0.137 g (19%) of
(1R,4aâ,6R,8aR)-(() decahydro-4-[1-[(triethylsilyl)oxy]methyl-
ene]-6-[1-[(triethylsilyl)oxy]-1-methylethyl]-1-naphthalenol meth-
anesulfonate: 1H NMR δ 0.58 (q, J ) 7.4 Hz, 6 H),) 0.60 (q, J
) 7.4 Hz, 6 H), 0.65 (s, 3 H), 0.92 (t, J ) 7.4 Hz, 9 H), 0.97 (t,
J ) 7.4 Hz, 9 H), 1.18 (s, 3 H), 1.22 (s, 3 H), 1.1-2.15 (m, 11
H), 2.95 (m, 1 H), 2.99 (s, 3 H), 4.42 (dd, J ) 4.7, 11.2 Hz, 1
H), 5.89 (br s, 1 H); 13C NMR δ 4.43 (t), 5.79 (t), 6.41 (t), 6.55
(t), 6.59 (t), 6.80 (t), 6.88 (3 q), 7.17 (3 q), 10.84 (q), 21.88 (t),
23.23 (t), 23.23 (t), 27.16 (q), 28.43 (q), 28.64 (t), 36.82 (t), 38.81
(q), 39.68 (s), 45.62 (d), 49.62 (d), 74.92 (s), 91.05 (d), 119.49
(s), 132.82 (d); MS m/ z (relative intensity) 560 (M+, 4), 464
(2), 435 (3), 291 (7), 217 (73), 189 (49), 173 (65), 103 (100), 75
(82); HRMS calcd for C28H56O5SSi2 (M+) 560.3387, found
560.3389. Further elution afforded 0.322 g (56%) of 33: mp
105 °C (from diisopropyl ether); 1H NMR δ 0.54 (q, J ) 7.5
Hz, 6 H), 0.77 (s, 3 H), 0.93 (t, J ) 7.5 Hz, 9 H), 1.18 (s, 3 H),
1.19 (s, 3 H), 1.1-1.5 (m, 3 H), 1.63-1.95 (m, 8 H), 2.19 (ddd,
J ) 0.8, 4.8, 4.8 Hz, 1 H), 2.37 (ddd, J ) 1.5, 1.5, 13.5 Hz, 1
H), 2.98 (s, 3 H), 4.31 (dd, J ) 7.4, 9.1 Hz, 1 H), 9.91 (d, J )
1.0 Hz, 1 H); 13C NMR δ 6.80 (3 t), 7.13 (3 q), 12.05 (q), 21.87
(t), 22.88 (t), 25.50 (t), 26.03 (t), 27.57 (q), 28.05 (q), 38.40 (t),
38.82 (q), 39.21 (s), 46.18 (d), 50.72 (d), 50.72 (d), 74.60 (s),
(2r,4ar,5r,8aâ)-(()-Decah ydr o-8-(1-m eth oxym eth ylen e)-
r,r,4a-tr im eth yl-5-[[(1,1-dim eth yleth yl)dim eth ylsilyl]oxy]-
2-n a p h th a len em eth a n ol (29). The same procedure as de-
scribed above for the organocerium addition to 12 was employed,
except that MeLi was used instead of iPrMgCl, and the
reaction mixture stirred at -78 °C for 15 min. Starting from
1.19 g of 28 (3.25 mmol), workup and crystallization from
1
heptane afforded 1.222 g (98%) of 29: mp 121 °C; H NMR δ
0.00 (s, 6 H), 0.63 (s, 3 H), 0.84 (s, 9 H), 1.16 (s, 3 H), 1.18 (s,
3 H), 0.9-1.7 (m, 11 H), 1.91 (ddd, J ) 3.2, 3.2, 13.0 Hz, 1 H),
2.75 (m, 1 H), 3.24 (dd, J ) 4.2, 11.1 Hz, 1 H), 3.52 (s, 3 H),
5.51 (s, 1 H); 13C NMR δ -4.81 (q), -3.96 (q), 10.32 (q), 18.00
(s), 22.44 (t), 23.70 (t), 23.70 (t), 25.83 (3 q), 26.57 (q), 27.60
(q), 31.08 (t), 37.25 (t), 40.52 (s), 45.47 (d), 49.25 (d), 59.36 (q),
72.73 (s), 79.94 (d), 118.14 (s), 139.64 (d); MS m/ z (relative
intensity) 382 (M+, 32), 325 (100), 307 (31), 250 (97), 232 (36),
123 (38), 85 (35), 83 (54), 75 (46); HRMS calcd for C22H42O3Si
(M+) 382.2903, found 382.2904. Anal. Calcd for C22H42O3Si:
C, 69.07; H, 11.07. Found: C, 68.84; H, 11.32.
(2r,4a r,5r,8a â)-(()-Deca h yd r o-5-h yd r oxy-8-(1-m et h -
oxym et h ylen e)-r,r,4a -t r im et h yl-2-n a p h t h a len em et h a -
n ol (30). The TBDMS ether 29 (0.734 g, 1.92 mmol) was
treated with TBAF as described for 14. Workup and flash
chromatography (3:2 petroleum ether (bp 40-60 °C)/EtOAc)
gave 0.432 g (84%) of 30 as white crystals: mp 174 °C (from
89.83 (d), 203.53 (d); MS m/ z (relative intensity) 431 (M+
-
15, 1), 417 (5), 403 (1), 321 (3), 173 (100), 115 (20); HRMS calcd
for C21H39O5SSi (M+ - 15) 431.2288, found 431.2291. Anal.
Calcd for C22H42O5SSi: C, 59.16; H, 9.48. Found: C, 59.06;
H, 9.54.
1
acetone); H NMR δ 0.67 (s, 3 H), 1.19 (s, 3 H), 1.20 (s, 3 H),
(Z,E)-(()-4-[1-[(Tr ieth ylsilyl)oxy]-1-m eth yleth yl]-7-m eth -
yl-1,7-cyclod eca d ien em eth a n ol (34). The mesylate 33
(0.112 g, 0.25 mmol) was treated with NaO-t-amyl and Red-
Al under oxygen-free conditions as described for 6. Workup
afforded 0.086 g (97%) of almost pure 34: 1H NMR (C6D6,
major peaks)69 δ 0.67 (q, J ) 7.9 Hz, 6 H), 1.09 (t, J ) 7.9 Hz,
9 H), 1.13 (s, 6 H); MS m/ z (relative intensity) 305 (M+ - 47,
1), 220 (8), 202 (3), 173 (100), 115 (26), 87 (9), 75 (10); HRMS
calcd for C19H33OSi (M+ - 47) 305.2301, found 305.2293.
(Z,E)-(()-4-H yd r oxym et h yl-r,r,8-t r im et h yl-3,7-cyclo-
d eca d ien em eth a n ol (15-Hyd r oxyh ed yca r yol) (35). To a
stirred solution of 0.027 g (0.077 mmol) of 34 in 1 mL of THF
was added 0.1 mL of TBAF (1 M in THF) at rt. After stirring
at rt for 4 h, another 0.05 mL of TBAF was added, and stirring
was continued at rt overnight. After addition of tert-butyl
methyl ether, the reaction mixture was washed with water
and brine, dried on Na2SO4, and evaporated. The remaining
residue was dissolved in 3 mL of tert-butyl methyl ether and
extracted with four 1-mL portions of 20% aqueous AgNO3. The
combined aqueous layers were washed with tert-butyl methyl
ether and cooled to 0 °C. After addition of 10 mL of 25%
aqueous NH3, the aqueous layer was extracted with tert-butyl
methyl ether. The combined organic layers were washed with
brine, dried on Na2SO4, and evaporated to afford 0.017 g (94%)
of 35: 1H NMR (C6D6, major peaks)69 δ 1.08 (s, 3 H), 1.12 (s,
3 H); MS m/ z (relative intensity) 220 (M+ - 18, 45), 205 (7),
202 (24), 189 (84), 177 (66), 162 (44), 159 (79), 147 (56), 133
(98), 119 (56), 107 (67), 105 (84), 93 (89), 91 (60), 81 (60), 79
(57), 59 (100); HRMS calcd for C15H24O (M+ - 18) 220.1827,
found 220.1823.
1.0-1.82 (m, 12 H), 1.96 (ddd, J ) 2.8, 2.8, 11.1 Hz, 1 H), 2.83
(ddd, J ) 2.5, 2.5, 11.9 Hz, 1 H), 3.32 (dd, J ) 4.2, 15.0 Hz, 1
H), 3.55 (s, 3 H), 5.55 (br s, 1 H); 13C NMR δ 10.10 (q), 22.20
(t), 23.60 (t), 23.60 (t), 26.75 (q), 27.54 (q), 30.42 (t), 36.52 (t),
39.98 (s), 45.25 (d), 49.09 (d), 59.11 (q), 73.02 (s), 79.61 (d),
118.05 (s), 140.00 (d); MS m/ z (relative intensity) 268 (M+,
100), 250 (45), 178 (18), 160 (59), 145 (41), 59 (54); HRMS calcd
for C16H28O3 (M+) 268.2038, found 268.2037. Anal. Calcd for
C16H28O3: C, 71.60; H, 10.52. Found: C, 71.53; H, 10.71.
(2r,4ar,5r,8aâ)-(()-Decah ydr o-8-(1-m eth oxym eth ylen e)-
r,r,4a -tr im eth yl-5-[(m eth ylsu lfon yl)oxy]-2-n a p h th a len e-
m eth a n ol (31). The alcohol 30 (0.571 g, 2.13 mmol) was
treated with MsCl for 2 h as described for 16. Workup and
flash chromatography (3:2 petroleum ether (bp 40-60 °C)/
EtOAc) gave 0.716 g (97%) of 31: 1H NMR δ 0.70 (s, 3 H),
1.13 (s, 3 H), 1.14 (s, 3 H), 1.0-2.1 (m, 12 H), 2.82 (ddd, J )
2.8, 2.8, 11.3 Hz, 1 H), 2.94 (s, 3 H), 3.50 (s, 3 H), 4.35 (dd, J
) 4.9, 11.1 Hz, 1 H), 5.53 (br s, 1 H); 13C NMR δ 10.86 (q),
21.95 (t), 23.32 (t), 23.32 (t), 26.60 (q), 27.66 (q), 28.45 (t), 36.59
(t), 38.77 (q), 39.55 (s), 45.52 (d), 48.76 (d), 59.50 (q), 72.48 (s),
90.54 (d), 115.59 (s), 140.78 (d); MS m/ z (relative intensity)
346 (M+, 3), 293 (15), 250 (6), 229 (27), 203 (58), 161 (41), 86
(63), 84 (100), 49 (82); HRMS calcd for C17H30O5S (M+)
346.1814, found 346.1813.
(1r,4r,4a r,7â,8a â)-(()-Deca h yd r o-7-(1-h yd r oxy-1-m eth -
ylet h yl)-4a -m et h yl-4-[(m et h ylsu lfon yl)oxy]-1-n a p h t h a -
len eca r boxa ld eh yd e (32). The mesylate 31 (0.131 g, 0.38
mmol) was treated with 35% aqueous HClO4 as described for
17. Workup and flash chromatography (2:3 petroleum ether
(bp 40-60 °C)/EtOAc) gave 0.110 g (87%) of 32: 1H NMR δ
0.76 (s, 3 H), 1.18 (s, 3 H), 1.19 (s, 3 H), 1.1-1.45 (m, 4 H),
1.6-1.95 (m, 8 H), 2.21 (dd, J ) 3.4, 4.9 Hz, 1 H), 2.37 (ddd,
J ) 1.7, 1.7, 13.6 Hz, 1 H), 2.98 (s, 3 H), 4.29 (dd, J ) 6.1, 10.4
Hz, 1 H), 9.89 (d, J ) 1.0 Hz, 1 H); 13C NMR δ 12.23 (q), 22.18
(t), 22.87 (t), 25.45 (t), 26.06 (t), 26.66 (q), 27.67 (q), 38.34 (t),
38.83 (q), 39.18 (s), 46.20 (d), 49.83 (d), 50.46 (d), 72.29 (s),
89.66 (d), 203.56 (d); MS m/ z (relative intensity) 332 (M+, 2),
314 (8), 218 (15), 178 (100), 149 (63), 135 (39), 107 (35), 59
(58); HRMS calcd for C15H22O (M+ - 114) 218.1671, found
218.1667.
Ack n ow led gm en t. We thank A. van Veldhuizen for
recording 1H and 13C NMR spectra and H. J ongejan for
mass spectral data and elemental analyses.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
those new compounds lacking combustion data (17 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
(1r,4r,4a r,7â,8a â)-(()-Deca h yd r o-7-[1-[(tr ieth ylsilyl)-
oxy]-1-m eth yleth yl]-4a -m eth yl-4-[(m eth ylsu lfon yl)oxy]-
1-n a p h th a len eca r boxa ld eh yd e (33). To a stirred solution
of 0.430 g (1.29 mmol) of 32 in 3 mL of DMF was added 0.175
g (2.57 mmol) of imidazole and 0.32 mL (1.94 mmol) of TESCl
J O970901Z
(69) In the NMR spectra of this compound strong coalescence was
observed. The 1H NMR spectrum pointed to the presence of at least
three different conformers.