Enantiospecific synthesis of a novel rearranged eunicellane diterpenoid by Sml2-Mediated cyclization

Article abstract of DOI:10.1055/s-0029-1216990

Aiming at the assembly of marine-derived diterpenoids, the synthesis and cyclization of a-geranylated carvones was investigated. 3-Hydroxyalkylation of side-chain hydrogenated carvone with geraniol-derived aldehydes gave access to diterpenoid allyl phosph

Full text of DOI:10.1055/s-0029-1216990

PAPER
3941
Enantiospecific Synthesis of a Novel Rearranged Eunicellane Diterpenoid by
SmI2-Mediated Cyclization
Synthesis of
a
R
l
e
arrang
i
e
d
E
un
s
icellane
Diterpenoidbeth Schöttner, Peter G. Jones, Thomas Lindel*
Technische Universität Braunschweig, Institutes of Organic, Inorganic and Analytical Chemistry, Hagenring 30, 38106 Braunschweig,
Germany
Fax +49(531)3917744; E-mail: Th.Lindel@tu-bs.de
Received 16 June 2009; revised 20 July 2009
In this paper, we report on our experience with the samar-
Abstract: Aiming at the assembly of marine-derived diterpenoids,
ium(II) iodide mediated cyclization of diterpenoid 3-(2,6-
dimethyl-2,6-octadienyl)carvones of type 2 (Figure 1). It
was unclear whether the eunicellane skeleton 3 (C9–C10
the synthesis and cyclization of a-geranylated carvones was inves-
tigated. 3-Hydroxyalkylation of side-chain hydrogenated carvone
with geraniol-derived aldehydes gave access to diterpenoid allyl
phosphates. It was shown that retro-aldol fragmentation of ring-hy- bond) or the hitherto unknown regioisomeric skeleton 4
drogenated 3-hydroxyalkylcarvones is surprisingly facile, because
the preferred conformation resembles a Zimmerman–Traxler type
(C9–C12 bond) could be accessed starting from 2. It was
also unclear if an organosamarium species would prefer-
transition-state. The hitherto unknown rearranged eunicellane skel-
entially react as an a- or g-nucleophile.7 We included cy-
eton can be obtained in one step by treatment of an a,b-unsaturated
clohexenone- and cyclohexanone-type carvones with the
diterpenoid with samarium diiodide generated in situ in THF.
aim of influencing the regiocontrol of the envisaged cy-
clization.
NOESY-based structure analysis revealed the presence of an ansa
bridge across a twist-boat six-membered ring.
Key words: diterpenoids, retro-aldol reaction, samarium diiodide,
isoeunicellane, NOESY-based analysis
To our surprise, hydroxyalkylation of tetrahydrocarvone
(12) with geraniol-derived aldehyde 88 predominantly led
to recovery of the starting materials (Scheme 1, Table 1).9
Therefore, we investigated the reaction of (S)-carvone (9)
and its hydrogenated derivatives 10–12 with benzalde-
hyde (5), methacroleine (6) and the isoprenoid aldehydes
7 and 8 (Scheme 1, Table 1).
Products 15, 17 and 18 had been obtained previously.9–11
Stereochemical assignments are based on NOESY spec-
tra. X-ray analyses were carried out on adducts 15, 16, and
22a (Figure 2), which confirmed in each case both the rel-
ative and absolute configurations. Hydroxyalkylation oc-
curred from the sterically less hindered side,
corresponding to the situation in the natural product 1.
Anti-aldol adducts were always preferred. Only in the case
of hydroxybenzylation were the two (3R)-diastereomers
isolated as minor side products.
Eunicellane-type diterpenoids from marine organisms
share a unique bicyclo[8.4.0]tetradecane framework
which may be oxygen-bridged.1 Examples include the
natural product 1 (Figure 1)2 and the microtubule-stabiliz-
ing secondary metabolite eleutherobin.3 Several total syn-
theses of eunicellanoids have been published.1,4
There are also many strategies for assembling the eunicel-
lanoid core structures.5 However, cyclizations of eunicel-
lanoids lacking an oxygen bridge have rarely been
investigated.6
cross-coupling?
HO
H
[Sm]
O
AcO
AcO
Cyclohexanones 11 and 12 afforded much lower yields
(7–54%) than cyclohexenones 9 and 10 (53–98%).10,12,13
Particularly sluggish were the reactions of 11 and 12 with
H
H
H
OTBS
1
O
O
(i) LDA,
THF, –78 °C
O
aldol addition
12
1
2
+
R
R
3
9
O
R
H
H
(ii)
10
OH
OH
9
1
major
minor
1
5
6
7
R =
3
4
OAc
Figure 1 Will the SmI2-induced cyclization afford the eunicellane
(3) or the rearranged eunicellane (4) skeleton?
8
OAc
SYNTHESIS 2009, No. 23, pp 3941–3956
x
x.
x
x
.
2
0
0
9
Advanced online publication: 03.09.2009
DOI: 10.1055/s-0029-1216990; Art ID: T11909SS
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Hydroxyalkylation of (S)-carvone and hydrogenated
derivatives with aldehydes 5–8 (see Table 1)

3942
E. Schöttner et al.
PAPER
In the cyclohexenone adducts, there appears to be no
O–H···O bond in the plane of the C=O double bond
(Figure 2).15 X-ray analysis of the deacetylated TBS-ether
22a of the major anti-aldol diastereomer 22 is in accor-
dance with our conformational analysis.
Table 1 Isolated Yields and Diastereomeric Excess of Hydroxy-
alkylations of Four Carvones with Aldehydes 5–8 (THF, LDA, –78 °C,
see Scheme 1). Column and Row Heads Combine to Aldol Adducts
13–28
O
O
O
O
Even the hydroxyalkylated cyclohexenones were quite
sensitive towards retro-aldol reaction. Treatment of diter-
penoid 26 under basic conditions (LDA in THF, NaH in
THF, LiOH in THF–H2O) afforded the starting material
8,9-dihydrocarvone (10). Conversion of 26 into the TBS-
ether was possible through treatment with TBSCl-imida-
zole in DMF. Retro-aldol cleavage also occurred upon
treatment of the TBS-ether 29 with TBAF in THF
(Scheme 2).
9
10
11
12
5
6
7
8
13, 60%
14, 75%
15, 40%c
19, 54%c
23, 40%c
27, 15%c
16, 30%c
20, 47%c
24, 31%c
28, 7%b,c
7% dea
33% de
17, 98%
94% de
18, 86%
71% de
For a reliable synthesis of cyclohexenone and cyclohex-
anone allyl phosphates 30 and 32, we chose TBS-ether 29
as a common intermediate, which was accessed by silyla-
tion and deacetylation (LiOH, THF–H2O, 3 d) of cyclo-
hexenone 26 (Scheme 2). For the synthesis of
cyclohexanone 31, reduction of the a,b-double bond of 29
was performed by employing NaBH4/BiCl3 in ethanol.16
Phosphorylation of 29 and 31 by treatment with diethyl
chlorophosphate and pyridine in dichloromethane pro-
ceeded smoothly in 94% (30) and 54% (32) yields, respec-
tively.
21, 74%
84% de
22, 72%
78% de
25, 53%
73% de
26, 87%
72% de
a The two other diastereomers were also isolated in minor amounts.
b Determined by NMR because of facile retro-aldol reaction.
c Only one diastereomer was isolated.
In the presence of SmI2, intermolecular cross-coupling of
diethyl geranylphosphate with saturated tetrahydrocar-
vone (12) led to the carbinol in good yield,17 whereas we
did not isolate cross-coupling products when employing
a,b-unsaturated dihydrocarvone (10).
Attempted intramolecular reaction of saturated diterpe-
noid 32 did not afford any carbinol product upon treat-
ment with SmI2 in THF. We could only isolate products
that resulted from reduction of the allylphosphate moiety
to the symmetrical dimer 33 (39%) and a mixture of mo-
nomeric isomers 34 and 35 (15% overall, Scheme 3). Re-
duction of allylphosphates to olefins in the presence of
SmI2 and either alcohol or water as proton source has been
described.18
A different picture arose when diterpenoid cyclohexenone
30 was used. A new, major product was formed almost ex-
clusively and could be isolated in 46% yield after column
chromatography on silica. The 1H NMR spectrum
(CDCl3, 600 MHz) indicated that, in this case, cyclization
had taken place (Scheme 4).
Figure 2 Preferred conformations of the cyclohexanone (left) and
cyclohexenone type (right) carvone aldol adducts with isopropyl or
isopropenyl side chains
The relative stereochemistry and conformation of the bi-
cyclo[8.2.2]tetradecane diterpenoid 36 were determined
by NOESY analysis. Both trisubstituted (E)-double bonds
were found to maintain their configuration and were ar-
ranged in an antiparallel manner with the methyl groups
pointing to the same side. NOESY correlations indicated
that the olefinic protons (d = 4.68 and 5.12 ppm) were sit-
uated on the side of the carbinol proton (d = 5.31 ppm).
The six-membered ring displays a twist-boat conforma-
tion (Scheme 4). Decisive NOESY correlations were ob-
served between the secondary proton of the isopropyl
the monoterpenoid aldehyde 8, which afforded diterpe-
noids 27 and 28 in yields of only 15% and 7%, respective-
ly.
According to NMR analysis (CDCl3), the labile cyclohex-
anone-type adducts prefer a conformation closely resem-
bling the Zimmerman–Traxler type transition-state
leading to a retro-aldol reaction (Figure 2).14 The confor-
mations of benzaldehyde adducts 15 and 16 in the crystal
agree well with the 1H NMR data.
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3943
O
O
O
LiOH
or NaH
O
OEt
P
OAc
O
or LDA
OEt
H
H
OH
OTBS
10
26
32
1) TBSCl, DMF,
imidazole,
retro aldol
(i) Sm (6.6 equiv),
diiodoethane (6 equiv),
THF, r.t., 3 h
r.t., 16 h
TBAF, THF,
0 °C to r.t.,
15 h
(ii) 32, r.t., 16 h
83%
2) LiOH,
THF–H2O,
r.t., 3 d
O
O
NaBH4/BiCl3, EtOH,
0 °C, 4.5 h
+
O
H
H
OTBS
OTBS
OH
34
35
70%
H
OTBS
15%: mixture of diastereomers (10:1)
+
29
O
O
H
TBSO
ClPO(OEt)2,
pyr, 0 °C to r.t.,
2.5 h
94%
OH
H
O
H
OTBS
OTBS
31
33: 39%
O
O
P
Scheme 3 Treatment of diterpenoid allyl phosphate 32 with SmI2
generated in situ affords olefins 34, 35 and dimer 33
OEt
ClPO(OEt)2,
pyr, CH2Cl2
0 °C, 1 h
O
54%
OEt
H
OTBS
30
O
O
O
O
OEt
P
O
OEt
P
OEt
O
H
OTBS
OEt
H
OTBS
30
32
(i) Sm (6 equiv),
Scheme 2 Synthesis of diterpenoid allyl phosphates 30 and 32 of
the cyclohexenone and cyclohexanone types
diiodoethane (5 equiv),
THF, r.t., 4 h
(ii) 30, r.t., 60 min
group (d = 1.98 ppm) and the proton situated at the methyl
branch on the opposite side of the six-membered ring (d =
2.61 ppm).
H
12
The cyclization of the allylphosphate 30 to ansa diterpe-
noid 36 represents one of the rare cases of twelve-mem-
bered ring assembly by SmI2-mediated cross-coupling.19
In the terpene field, this is the first example. The cycliza-
tion only occurred when SmI2 was prepared in situ, by
adding 1,2-diiodoethane (5 equiv) to a suspension of sa-
marium (6 equiv) in THF, followed by addition of diter-
penoid cyclohexenone 30. Upon adding a commercial
solution of SmI2 in THF (2.5 equiv) to a solution of the
diterpenoid cyclohexenone 30, the only isolable products
resulted from the reduction of the allylphosphate moiety
to the symmetrical dimer, and a mixture of monomeric
isomers comparable to 32.
H
H
36
H
10
H
46%
O
1
H
H
H
TBSO
Scheme 4 SmI2-mediated cyclization to the novel ansa diterpenoid
36, including decisive NOESY correlations
ular reaction was successful. We are currently investigat-
ing this hypothesis.
The bicyclic diterpenoid skeleton of 36 is unprecedented
and we propose the name isoeunicellane. The short syn-
thetic sequence starting from carvone and geraniol now
allows us to study the chemistry of 36 with the aim of in-
troducing further structural variations at the skeleton lev-
el.
Possibly, SmI2 transfers its electron not only to the allyl
phosphate, but also to the a,b-unsaturated ketone, forming
an oxyallyl radical, which then recombines with an allylic
radical formed from the allylic phosphate. It cannot be ex-
cluded that even the bulky OTBS group can chelate
Sm(II/III) and thereby facilitate electron transfer to the
enone.20 This could also explain why only the intramolec-
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3944
E. Schöttner et al.
PAPER
NMR spectra were recorded with a Varian NMR-System 300
(300.1 MHz for 1H; 75.5 MHz for 13C), a Bruker AV II-300
(300.1 MHz for 1H; 75.5 MHz for 13C), a Bruker DRX-400
MS (EI): m/z (%) = 256 (12) [M+], 238 (8), 187 (8), 154 (15), 150
(100), 147 (40), 135 (75), 121 (30).
HRMS (EI): m/z [M+] calcd for C17H20O2: 256.14633; found:
256.14529.
1
(400.1 MHz for H, 100.6 MHz for 13C) and a Bruker AV II-600
(600.1 MHz for 1H; 150.9 MHz for 13C), referenced to solvent sig-
nal or TMS. All measurements were carried out at 300 K. Mass
spectra were obtained with a Finnigan MAT95Q, a Thermo Finni-
gan LTQ FT, a SM 1B Varian MAT, a Thermo Finnigan MAT95 or
a Finnigan MAT 95 XLT spectrometer. IR spectra were recorded
with a Bruker Tensor 27 spectrometer. UV/Vis spectra were mea-
sured with a Varian Cary 100 Bio UV/Vis-spectrometer. Optical ro-
tations were measured on a Dr. Kernchen Propol Automatic
Polarimeter. Chemicals were purchased from commercial suppliers
and used without further purification. Silica gel 60 (40–63 mm,
Merck) was used for column chromatography. Petrol ether (PE),
where used, had a boiling range of 40–80 °C. For all hydroxyalky-
lations: * Complete yield of all diastereomers (ratio of diastereo-
mers determined via NMR spectroscopy); ** yield of the isolated
compound.
UV (MeOH): lmax (log e) = 202 (4.03), 241 (3.79), 324 nm (2.01).
(5S,6S)-6-[(S)-Hydroxy(phenyl)methyl]-2-methyl-5-(prop-1-
en-2-yl)cyclohex-2-enone (13a)
Yield: 140 mg (16%)**; colorless oil; Rf = 0.17 (silica; PE–EtOAc,
7:1); [a]D25 –66.8 (c 0.96, CHCl3).
IR (ATR): 3453 (br), 3064 (w), 3028 (w), 2973 (w), 2921 (w), 1655
(s), 1494 (w), 1451 (m), 1368 (m), 1201 (w), 1121 (w), 1093 (w),
1078 (w), 1044 (s), 981 (w), 893 (m), 835 (w), 766 (m), 747 (m),
699 (s), 619 (w), 569 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.70 (s, 3 H, CH2CCH3), 1.76 (dd,
4J = 3.5 Hz, 5J = 1.9 Hz, 3 H, COCCH3), 2.43–2.48 (m, 2 H,
CHCHCH2CH), 2.71–2.76 (m, 1 H, CHCHCH2CH), 2.93 (dd,
3
3J = 5.1 Hz, J = 8.3 Hz, 1 H, CHCHCH2CH), 3.18–3.21 (m, 1 H,
OH), 4.82–4.85 (m, 2 H, CH2CCH3, CHOH), 4.87–4.88 (m, 1 H,
CH2CCH3), 6.67–6.69 (m, 1 H, CHCHCH2CH), 7.24–7.28 (m, 1 H,
p-Ph-H), 7.33–7.40 (m, 4 H, o-Ph-H, m-Ph-H).
Hydroxyalkylation; General Procedure
n-BuLi was added under argon at 0 °C to a solution of NH(i-Pr)2 in
THF. After stirring for 15 min at 0 °C, the solution was cooled to
–78 °C and stirred for 10 min. The carvone derivative was added
and stirring at –78 °C was continued for ~1 h. The aldehyde was
added and the resulting solution was stirred for 2–7.5 h. AcOH was
added and the solution was slowly warmed to r.t. After dilution with
sat. NH4Cl, the mixture was extracted with Et2O and the organic
phase was dried over MgSO4. The residue obtained after evapora-
tion of the solvent was purified by column chromatography on silica
(PE–EtOAc) to give the following hydroxylalkylated products.
13C NMR (100 MHz, CDCl3):
d = 15.7 (COCCH3), 20.1
(CH2CCH3), 29.5 (CHCHCH2CH), 44.7 (CHCHCH2CH), 56.1
(CHCHCH2CH), 72.9 (CHOH), 113.5 (CH2CCH3), 126.0 (2 × C, o-
Ph-C), 127.3 (p-Ph-C), 128.4 (2 × C, m-Ph-C), 135.4 (COCCH3),
143.2 (Ph-Cq), 143.5 (CHCHCH2CH), 145.0 (CH2CCH3), 201.2
(CO).
MS (EI): m/z (%) = 256 (5) [M+], 238 (4), 187 (9), 150 (24), 135
(18), 108 (32), 105 (85), 82 (100), 77 (93), 54 (42), 51 (30).
HRMS (EI): m/z [M+] calcd for C17H20O2: 256.14633; found:
256.14658.
(5S,6S)-6-[(R)-Hydroxy(phenyl)methyl]-2-methyl-5-(prop-1-
en-2-yl)cyclohex-2-enone (13)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.70 mL, 5.00 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (2.00 mL, 5.00 mmol, 1.50 equiv), carvone (9; 500
mg, 3.33 mmol, 1.00 equiv) for 1.0 h; benzaldehyde (5; 0.51 mL,
5.00 mmol, 1.50 equiv) in THF (6.0 mL) for 3.5 h; AcOH (0.30 mL,
5.00 mmol, 1.50 equiv). The product was purified by column chro-
matography (PE–EtOAc, 7:1) to give four diastereomers 13, 13a,
13b, and 13c (550 mg, 65%) in a ratio of 32:28:2:2*.
UV (MeOH): lmax (log e) = 202 (4.07), 238 (3.82), 326 nm (1.99).
(5S,6R)-6-[(S)-Hydroxy(phenyl)methyl]-2-methyl-5-(prop-1-
en-2-yl)cyclohex-2-enone (13b)
Yield: 20 mg (2%)**; colorless solid; mp 150–153 °C; Rf = 0.33
(silica; PE–EtOAc, 7:1); [a]D25 –21.8 (c 0.77, CHCl3).
IR (ATR): 3472 (m), 3092 (w), 3060 (w), 3033 (w), 2952 (w), 2922
(m), 2852 (w), 1631 (s), 1452 (w), 1409 (m), 1378 (m), 1331 (w),
1256 (w), 1240 (w), 1200 (m), 1117 (w), 1079 (m), 1032 (m), 1005
(s), 953 (w), 893 (m), 777 (m), 758 (m), 700 (s), 651 (m), 618 (m),
564 (s) cm–1.
13
Yield: 40 mg (5%)**; colorless oil; Rf = 0.24 (silica; PE–EtOAc,
7:1); [a]D25 –27.3 (c 2.0, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.51 (s, 3 H, CH2CCH3), 1.84
IR (ATR): 3440 (br), 3066 (w), 3029 (w), 2922 (m), 2854 (w), 1642
(s), 1494 (w), 1451 (m), 1435 (m), 1375 (m), 1239 (w), 1197 (w),
1069 (w), 1043 (m), 1003 (m), 894 (m), 757 (s), 700 (s), 592 (m),
571 (s) cm–1.
4
5
5
(ddd, J = 2.6 Hz, J = 1.4 Hz, J = 1.4 Hz, 3 H, COCCH3), 2.19–
2.22 (m, 1 H, CHCHCH2CH), 2.26–2.32 (m, 1 H, CHCHCH2CH),
2.50–5.59 (m, 1 H, CHCHCH2CH), 2.82 (dd, 3J = 4.9 Hz,
3J = 8.9 Hz, 1 H, CHCHCH2CH), 4.51 (s, 1 H, CH2CCH3), 4.67 (br,
1 H, OH), 4.89 (s, 1 H, CH2CCH3), 5.16 (dd, 3J = 1.1 Hz,
3J = 8.9 Hz, 1 H, CHOH), 6.57–6.59 (m, 1 H, CHCHCH2CH),
7.72–7.35 (m, 5 H, o-Ph-H, m-Ph-H, p-Ph-H).
1H NMR (400 MHz, CDCl3): d = 1.73 (m, 3 H, CH2CCH3), 1.74–
1.75 (m, 3 H, COCCH3), 2.26–2.41 (m, 2 H, CHCHCH2CH), 2.53–
3
3
2.59 (m, 1 H, CHCHCH2CH), 3.02 (dd, J = 4.7 Hz, J = 11.4 Hz,
1 H, CHCHCH2CH), 4.79 (m, 1 H, CH2CCH3), 4.86 (dd,
3J = 4.7 Hz, 3J = 9.5 Hz, 1 H, CHOH), 4.92–4.93 (m, 1 H,
13C NMR (100 MHz, CDCl3):
d = 15.6 (COCCH3), 23.1
(CH2CCH3), 31.2 (CHCHCH2CH), 43.0 (CHCHCH2CH), 56.4
(CHCHCH2CH), 73.3 (CHOH), 114.0 (CH2CCH3), 127.1 (2 × C,
o-Ph-C), 127.9 (p-Ph-C), 128.3 (2 × C, m-Ph-C), 135.8 (COCCH3),
141.1 (Ph-Cq), 143.1 (CHCHCH2CH), 143.3 (CH2CCH3), 203.7
(CO).
3
CH2CCH3), 5.01 (d, J = 9.5 Hz, 1 H, OH), 6.69–6.72 (m, 1 H,
CHCHCH2CH), 7.22–7.30 (m, 5 H, o-Ph-H, m-Ph-H, p-Ph-H).
13C NMR (100 MHz, CDCl3):
d = 15.6 (COCCH3), 19.3
(CH2CCH3), 31.0 (CHCHCH2CH), 44.1 (CHCHCH2CH), 54.0
(CHCHCH2CH), 74.7 (CHOH), 114.1 (CH2CCH3), 127.6 (2 × C,
o-Ph-C), 127.5 (p-Ph-C), 128.0 (2 × C, m-Ph-C), 136.0 (COCCH3),
141.6 (Ph-Cq), 145.0 (CH2CCH3), 145.4 (CHCHCH2CH), 202.5
(CO).
MS (EI): m/z (%) = 256 (18) [M+], 238 (32), 223 (10), 187 (10), 150
(100), 135 (62), 121 (22), 115 (18).
HRMS (EI): m/z calcd for C17H20O2: 256.14633; found: 256.14709.
UV (MeOH): lmax (log e) = 202 (4.03), 239 nm (3.84).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3945
(5S,6R)-6-[(R)-Hydroxy(phenyl)methyl]-2-methyl-5-(prop-1-
en-2-yl)cyclohex-2-enone (13c)
(5R,6S)-6-[(S)-Hydroxy(phenyl)methyl]-5-isopropyl-2-methyl-
cyclohex-2-enone (14a)
Yield: 13 mg (2%)**; colorless oil; Rf = 0.24 (silica; PE–EtOAc,
Yield: 207 mg (24%)**; colorless oil; Rf = 0.36 (silica; PE–EtOAc,
7:1); [a]D25 +27.7 (c 1.3, CHCl3).
5:1); [a]D25 –13.1 (c 0.57, CHCl3).
IR (ATR): 3463 (br), 3086 (w), 3064 (w), 3030 (w), 2922 (m), 2855
(w), 1666 (s), 1494 (w), 1452 (m), 1375 (m), 1192 (w), 1105 (m),
1078 (m), 1041 (m), 1024 (m), 893 (m), 803 (w), 765 (m), 700 (s),
559 (m), 535 (m) cm–1.
IR (ATR): 3423 (br), 3063 (w), 3028 (w), 2957 (m), 2925 (w), 2874
(w), 1647 (s), 1452 (m), 1433 (w), 1367 (m), 1178 (w), 1096 (w),
1080 (w), 1028 (s), 761 (m), 746 (m), 700 (s), 656 (w), 629 (w), 590
(m), 555 (m), 533 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.69–1.71 (m, 3 H, COCCH3),
1.88 (s, 3 H, CH2CCH3), 2.43–2.46 (m, 2 H, CHCHCH2CH), 2.93
(dd, 3J = 6.2 Hz, 3J = 11.8 Hz, 1 H, CHCHCH2CH), 3.00 (d,
3J = 3.9 Hz, 1 H, OH), 3.15 (dd, 3J = 6.4 Hz, 3J = 6.7 Hz, 1 H,
CHCHCH2CH), 4.89 (s, 1 H, CH2CCH3), 5.02 (m, 1 H, CH2CCH3),
5.06 (dd, 3J = 4.4 Hz, 3J = 6.5 Hz, 1 H, CHOH), 6.57–6.61 (m, 1 H,
CHCHCH2CH), 7.21–7.29 (m, 5 H, o-Ph-H, m-Ph-H, p-Ph-H).
1H NMR (400 MHz, CDCl3): d = 0.81 [d, 3J = 6.9 Hz, 3 H,
3
CH(CH3)2], 0.82 [d, J = 6.9 Hz, 3 H, CH(CH3)2], 1.70–1.71 (m,
3 H, COCCH3), 1.73–1.82 [m, 1 H, CH(CH3)2], 1.92–1.98 (m, 1 H,
CCHCHCH2), 2.12–2.20 (m, 1 H, CCHCHCH2), 2.41–2.50 (m,
1 H, CCHCHCH2), 2.79 (dd, 3J = 6.2 Hz, 3J = 6.2 Hz, 1 H,
CCHCHCH2), 4.07 (d, 3J = 6.7 Hz, 1 H, OH), 4.99 (dd, 3J = 6.2 Hz,
3J = 6.7 Hz, 1 H, CHOH), 6.64–6.67 (m, 1 H, CHCH2CHCH),
7.20–7.31 (m, 5 H, o-Ph-H, m-Ph-H, p-Ph-H).
13C NMR (100 MHz, CDCl3):
d = 15.8 (COCCH3), 22.4
(CH2CCH3), 28.6 (CHCHCH2CH), 43.3 (CHCHCH2CH), 56.4
(CHCHCH2CH), 72.3 (CHOH), 112.6 (CH2CCH3), 126.7 (2 × C,
o-Ph-C), 127.8 (p-Ph-C), 128.3 (2 × C, m-Ph-C), 135.9 (COCCH3),
142.0 (Ph-Cq), 143.5 (CHCHCH2CH), 146.9 (CH2CCH3), 200.3
(CO).
13C NMR (100 MHz, CDCl3):
d = 15.7 (COCCH3), 18.5
[CH(CH3)2], 20.5 [CH(CH3)2], 25.3 (CCHCHCH2), 28.8
[CH(CH3)2], 40.6 (CCHCHCH2), 55.5 (CCHCHCH2), 74.5
(CHOH), 126.5 (2 × C, o-Ph-C), 127.5 (p-Ph-C), 128.1 (2 × C,
m-Ph-C), 135.5 (COCCH3), 142.1 (Ph-Cq), 145.2 (CHCH2CHCH),
202.0 (CO).
MS (EI): m/z (%) = 256 (4) [M+], 238 (10), 223 (8), 187 (10), 150
(55), 135 (52), 121 (20), 109 (60), 105 (100), 91 (24), 82 (63), 77
(95), 54 (28).
MS (EI): m/z (%) = 258 (4) [M+], 152 (37), 109 (64), 105 (84), 82
(100), 77 (85), 51 (28).
UV (MeOH): lmax (log e) = 204 (3.95), 238 (3.74), 297 nm (2.65).
HRMS (EI): m/z [M+] calcd for C17H22O2: 258.16199; found:
258.16117.
(5R,6S)-6-[(R)-Hydroxy(phenyl)methyl]-5-isopropyl-2-methyl-
cyclohex-2-enone (14)
UV (MeOH): lmax (log e) = 205 (4.00), 240 (3.86), 330 nm (2.04).
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.69 mL, 4.94 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.97 mL, 4.94 mmol, 1.50 equiv), dihydrocarvone 10
(500 mg, 3.29 mmol, 1.00 equiv) for 1.0 h; benzaldehyde (5; 0.50
mL, 4.94 mmol, 1.50 equiv) in THF (6.0 mL) for 3.5 h; AcOH (0.30
mL, 4.94 mmol, 1.50 equiv). The product was purified by column
chromatography (PE–EtOAc, 6:1) to give two diastereomers 14,
and 14a (643 mg, 2.49 mmol, 75%) in a ratio of 2:1*.
(2S,3S,6S)-2-[(R)-Hydroxy(phenyl)methyl]-6-methyl-3-(prop-
1-en-2-yl)cyclohexanone (15)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.34 mL, 2.44 mmol, 1.50 equiv) in THF (3.0
mL), n-BuLi (0.97 mL, 2.44 mmol, 1.50 equiv), dihydrocarvone 11
(246 mg, 1.62 mmol, 1.00 equiv) for 1.0 h; benzaldehyde (5; 0.25
mL, 2.44 mmol, 1.50 equiv) for 3.0 h; AcOH (0.15 mL, 2.44 mmol,
1.50 equiv). The product was purified by column chromatography
(PE–EtOAc, 10:1).
14
Yield: 167 mg (40%); colorless solid; mp 85–88 °C; Rf = 0.60 (sil-
ica; PE–EtOAc, 5:1); [a]D25 –91.0 (c 0.98, CHCl3).
Yield: 172 mg (20%)**; colorless oil; Rf = 0.27 (silica; PE–EtOAc,
5:1); [a]D25 +19.0 (c 1.37, CHCl3).
IR (ATR): 3463 (br), 3078 (w), 2972 (m), 2930 (m), 2889 (w), 2861
(w), 1687 (s), 1645 (w), 1494 (w), 1450 (m), 1376 (w), 1240 (w),
1194 (w), 1167 (w), 1126 (m), 1096 (w), 1070 (w), 1023 (s), 955
(m), 927 (m), 893 (s), 828 (w), 799 (w), 745 (s), 697 (s), 635 (s), 597
(m), 557 (s) cm–1.
IR (ATR): 3476 (br), 3064 (w), 3030 (w), 2957 (m), 2965 (m), 2925
(m), 2888 (w), 1663 (s), 1455 (m), 1382 (m), 1366 (m), 1316 (w),
1079 (m), 1052 (s), 1025 (m), 828 (m), 767 (m), 746 (m), 700 (s),
624 (m), 560 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.75 [d, 3J = 6.7 Hz, 3 H,
1H NMR (400 MHz, CDCl3): d = 0.92 (d, 3J = 6.4 Hz, 3 H,
COCHCH3), 1.37–1.47 (m, 1 H, CHCHCH2CH2), 1.83 (m, 3 H,
CH2CCH3), 1.85–1.91 (m, 2 H, CHCHCH2CH2), 2.06–2.12 (m,
1 H, CHCHCH2CH2), 2.36–2.46 (m, 1 H, COCHCH3), 2.83–2.93
3
CH(CH3)2], 0.78 [d, J = 6.7 Hz, 3 H, CH(CH3)2], 1.37–1.42 (m,
1 H, CCHCHCH2), 1.65 [dq, 3J = 6.7 Hz, 3J = 13.5 Hz, 1 H,
CH(CH3)2], 1.81 (dt, 4J = 2.7 Hz, 5J = 1.5 Hz, 3 H, COCCH3),
2.20–2.26 (m, 1 H, CCHCHCH2), 2.42–2.51 (m, 1 H,
CCHCHCH2), 2.81 (dd, 3J = 3.4 Hz, 3J = 8.7 Hz, 1 H,
CCHCHCH2), 3.02 (d, 3J = 4.1 Hz, 1 H, OH), 4.80 (dd, 3J = 4.0 Hz,
3J = 8.7 Hz, 1 H, CHOH), 6.64–6.67 (m, 1 H, CHCH2CHCH),
7.28–7.34 (m, 1 H, p-Ph-H), 7.35–7.38 (m, 4 H, o-Ph-H, m-Ph-H).
3
(m, 2 H, CHCHCH2CH2, CHCHCH2CH2), 4.25 (d, J = 11.6 Hz,
3
1 H, OH), 4.69 (d, J = 12.0 Hz, 1 H, CHOH), 4.96–4.97 (m, 1 H,
CH2CCH3), 5.02 (br, 1 H, CH2CCH3), 7.17–7.21 (m, 1 H, p-Ph-H),
7.28–7.34 (m, 4 H, o-Ph-H, m-Ph-H).
13C NMR (100 MHz, CDCl3): d = 13.9 (COCHCH3), 18.9
(CH2CCH3), 31.4 (CHCHCH2CH2), 36.1 (CHCHCH2CH2), 46.6
(COCHCH3), 51.7 (CHCHCH2CH2), 58.6 (CHCHCH2CH2), 71.8
(CHOH), 113.5 (CH2CCH3), 125.5 (2 × C, o-Ph-C), 126.5 (p-Ph-C),
128.0 (2 × C, m-Ph-C), 144.4 (Ph-Cq), 145.4 (CH2CCH3), 216.2
(CO).
MS (EI): m/z (%) = 258 (4) [M+], 219 (3), 189 (3), 176 (83), 152
(38), 137 (60), 106 (80), 105 (62), 95 (43), 77 (100), 67 (58).
HRMS (EI): m/z [M+] calcd for C17H22O2: 258.16199; found:
258.16172.
13C NMR (100 MHz, CDCl3):
d = 15.8 (COCCH3), 20.1
[CH(CH3)2], 20.4 [CH(CH3)2], 25.6 (CCHCHCH2), 29.3
[CH(CH3)2], 41.8 (CCHCHCH2), 56.8 (CCHCHCH2), 73.7
(CHOH), 126.4 (2 × C, o-Ph-C), 127.9 (p-Ph-C), 128.5 (2 × C,
m-Ph-C), 134.9 (COCCH3), 142.2 (Ph-Cq), 143.5 (CHCH2CHCH),
201.9 (CO).
MS (ESI): m/z (%) = 281/282 (100/15) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H22O2Na: 281.15175;
found: 281.15078.
UV (CHCl3): lmax (log e) = 204 (3.99), 239 (3.78), 326 nm (2.14).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3946
E. Schöttner et al.
PAPER
UV (MeOH): lmax (log e) = 202 (4.08), 258 nm (2.44).
13C NMR (75 MHz, CDCl3):
d
=
15.8 (COCCH3), 17.7
(CHOHCCH3), 20.5 (CHCH2CHCCH3), 28.7 (CHCH2CHCH),
44.1 (CHCH2CHCH), 52.5 (CHCH2CHCH), 74.7 (CHOH), 112.5
(CHOHCCH2), 113.3 (CHCH2CHCCH2), 135.1 (COCCH3), 143.4
(CHCH2CHCH), 145.4 (CHCH2CHCCH2), 145.9 (CHOHCCH2),
201.2 (CO).
MS (EI): m/z (%) = 220 (3) [M+], 150 (23), 135 (18), 108 (30), 93
(30), 82 (100), 70 (25), 54 (40).
(2S,3R,6S)-2-[(R)-Hydroxy(phenyl)methyl]-3-isopropyl-6-
methylcyclohexanone (16)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.68 mL, 4.87 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.95 mL, 4.87 mmol, 1.50 equiv), tetrahydrocarvone
(12; 500 mg, 3.25 mmol, 1.00 equiv) for 1.0 h; benzaldehyde (5;
0.49 mL, 4.87 mmol, 1.50 equiv) for 3.0 h; AcOH (0.30 mL, 4.87
mmol, 1.50 equiv). The product was purified by column chroma-
tography (PE–EtOAc, 15:1→10:1→5:1).
HRMS (EI): m/z [M+] calcd for C14H20O2: 220.14633; found:
220.14614.
UV (MeOH): lmax (log e) = 201 (3.77), 239 (3.78), 324 nm (2.03).
Yield: 253 mg (30%); colorless solid; mp 72–74 °C; Rf = 0.33 (sil-
ica; PE–EtOAc, 10:1); [a]D25 –80.0 (c 1.34, CHCl3).
(5R,6S)-6-[(1R)-1-Hydroxy-2-methylallyl]-5-isopropyl-2-meth-
ylcyclohex-2-enone (18)
IR (ATR): 3509 (br), 3061 (w), 3027 (w), 2960 (m), 2931 (m), 2871
(m), 1694 (s), 1494 (w), 1450 (m), 1409 (w), 1371 (m), 1235 (w),
1197 (w), 1175 (w), 1103 (m), 1070 (m), 1021 (s), 951 (m), 924 (w),
824 (w), 749 (m), 698 (s), 633 (m), 599 (m) cm–1.
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (1.11 mL, 7.89 mmol, 1.50 equiv) in THF (7.9
mL), n-BuLi (3.16 mL, 7.89 mmol, 1.50 equiv), dihydrocarvone 10
(800 mg, 5.26 mmol, 1.00 equiv) for 0.50 h; methacrolein (6; 0.87
mL, 10.5 mmol, 2.00 equiv) for 4.0 h; AcOH (0.46 mL, 7.89 mmol,
1.50 equiv). The product was purified by column chromatography
(PE–EtOAc, 5:1) to give two diastereomers 18 and 18a (1.00 g, 4.50
mmol, 86%) in a ratio of 6:1*.
1H NMR (400 MHz, CDCl3): d = 0.87 (d, 3J = 6.4 Hz, 3 H,
COCHCH3), 0.96 [d, 3J = 7.0 Hz, 3 H, CH(CH3)2], 1.04 [d,
3J = 6.9 Hz, 3 H, CH(CH3)2], 1.26–1.36 (m, 1 H, CHCHCH2CH2),
1.48–1.58 (m, 1 H, CHCHCH2CH2), 1.86 (ddd, 2J = 13.4 Hz,
3J = 3.5 Hz, 3J = 6.7 Hz, 1 H, CHCHCH2CH2), 2.06–2.16 (m, 2 H,
CHCHCH2CH2, CHCHCH2CH2), 2.24–2.31 [m, 1 H, CH(CH3)2],
2.40–2.31 (m, 1 H, COCHCH3), 2.81–2.83 (m, 1 H,
CHCHCH2CH2), 4.25 (d, 3J = 11.5 Hz, 1 H, OH), 4.89 (d,
3J = 11.6 Hz, 1 H, CHOH), 7.16–7.20 (m, 1 H, p-Ph-H), 7.28–7.36
(m, 4 H, o-Ph-H, m-Ph-H).
13C NMR (100 MHz, CDCl3): d = 13.9 (COCHCH3), 14.8
[CH(CH3)2], 21.4 [CH(CH3)2], 23.7 (CHCHCH2CH2), 27.3
[CH(CH3)2], 36.3 (CHCHCH2CH2), 46.4 (COCHCH3), 48.1
(CHCHCH2CH2), 59.0 (CHCHCH2CH2), 70.2 (CHOH), 125.3 (2 ×
C, o-Ph-C), 126.4 (p-Ph-C), 128.0 (2 × C, m-Ph-C), 144.4 (Ph-Cq),
217.6 (CO).
18
Yield: 540 mg (46%)**; colorless oil; Rf = 0.20 (silica; PE–EtOAc,
5:1); [a]D25 +12.2 (c 1.3, CHCl3).
IR (ATR): 3485 (br), 2974 (m), 2956 (m), 2922 (m), 2888 (m), 2871
(w), 1663 (s), 1446 (m), 1388 (m), 1365 (m), 1315 (m), 1183 (w),
1100 (w), 1085 (w), 1052 (s), 1022 (m), 960 (w), 905 (s), 854 (w),
829 (w), 779 (w), 701 (w), 592 (m), 560 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.87 [d, 3J = 6.5 Hz, 3 H,
3
CH(CH3)2], 0.90 [d, J = 6.5 Hz, 3 H, CH(CH3)2], 1.60–1.71 [m,
2 H, CH(CH3)2, CCHCHCH2], 1.74 (m, 3 H, CH2CCH3), 1.78–1.79
(m, 3 H, COCCH3), 2.24–2.30 (m, 1 H, CCHCHCH2), 2.43–2.52
(m, 1 H, CCHCHCH2), 2.57 (dd, 3J = 2.6 Hz, 3J = 9.4 Hz, 1 H,
CCHCHCH2), 2.65 (d, 3J = 3.9 Hz, 1 H, OH), 4.26 (dd, 3J = 3.8 Hz,
3J = 9.4 Hz, 1 H, CHOH), 4.96–4.97 (m, 1 H, CH2C), 5.01 (m, 1 H,
CH2C), 6.63–6.66 (m, 1 H, CHCH2CHCH).
MS (EI): m/z (%) = 260 (12) [M+], 242 (9), 155 (13), 154 (100), 126
(8), 125 (17).
HRMS (EI): m/z [M+] calcd for C17H24O2: 260.17764; found:
260.17792.
UV (MeOH): lmax (log e) = 204 (3.91), 252 nm (2.47).
13C NMR (100 MHz, CDCl3):
d = 15.7 (COCCH3), 15.8
(CH2CCH3), 20.6 [CH(CH3)2], 20.6 [CH(CH3)2], 25.3
(CCHCHCH2), 29.3 [CH(CH3)2], 42.1 (CCHCHCH2), 52.8
(CCHCHCH2), 75.7 (CHOH), 114.1 (CH2C), 134.7 (COCCH3),
143.4 (CHCH2CHCH), 145.1 (CH2C), 201.8 (CO).
MS (ESI): m/z (%) = 245/246 (100/13) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C14H22O2Na: 245.1518;
(5S,6S)-6-[(1R)-1-Hydroxy-2-methylallyl]-2-methyl-5-(prop-1-
en-2-yl)cyclohex-2-enone (17)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.70 mL, 5.00 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (2.00 mL, 5.00 mmol, 1.50 equiv), carvone (9; 500
mg, 3.33 mmol, 1.00 equiv) for 1.0 h; methacrolein (6; 0.41 mL,
5.00 mmol, 1.50 equiv) in THF (3.0 mL) for 3.5 h; AcOH (0.30 mL,
5.00 mmol, 1.50 equiv). The product was purified by column chro-
matography (PE–EtOAc, 6:1) to give two diastereomers (726 mg,
99%) in a ratio of 33:1*.
found: 245.1511.
UV (MeOH): lmax (log e) = 201 (3.65), 240 (3.79), 330 nm (1.99).
(5R,6S)-6-[(1S)-1-Hydroxy-2-methylallyl]-5-isopropyl-2-meth-
ylcyclohex-2-enone (18a)
Yield: 550 mg (75%)**; colorless oil; Rf = 0.23 (silica; PE–EtOAc,
5:1); [a]D25 +1.76 (c 1.31, CHCl3).
Yield: 70 mg (6%)**; colorless oil; Rf = 0.27 (silica; PE–EtOAc,
IR (ATR): 3459 (br), 3076 (w), 2973 (w), 2946 (w), 2920 (w), 1654
(s), 1445 (m), 1369 (m), 1207 (m), 1095 (w), 1050 (s), 893 (s), 837
(w), 567 (m) cm–1.
5:1); [a]D25 –9.3 (c 0.54, CHCl3).
IR (ATR): 3432 (br), 3073 (w), 2958 (m), 2924 (m), 1651 (s), 1451
(m), 1436 (m), 1368 (m), 1181 (w), 1099 (w), 1034 (s), 1014 (s),
896 (s), 871 (w), 772 (w), 712 (w), 635 (m), 560 (s) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.73 (s, 3 H, CHCH2CHCCH3),
1.77–1.79 (m, 6 H, CHOHCCH3, COCCH3), 2.35–2.56 (m, 2 H,
CHCHCH2CH), 2.66–2.71 (m, 2 H, CHCHCH2CH, OH), 2.78 (dd,
3J = 6.1 Hz, 3J = 12.3 Hz, 1 H, CHCHCH2CH), 4.20 (dd,
3J = 6.4 Hz, 3J = 6.4 Hz, 1 H, CHOH), 4.79–4.80 (m, 1 H,
CHCH2CHCCH2), 4.86–4.87 (m, 1 H, CHCH2CHCCH2), 4.97–
4.98 (m, 1 H, CHOHCCH2), 5.02 (m, 1 H, CHOHCCH2), 6.66–6.69
(m, 1 H, CHCHCH2CH).
1H NMR (400 MHz, CDCl3): d = 0.87 [d, 3J = 6.8 Hz, 3 H,
3
CH(CH3)2], 0.89 [d, J = 6.8 Hz, 3 H, CH(CH3)2], 1.68–1.77 [m,
7 H, CH(CH3)2, CH2CCH3, COCCH3], 2.00–2.05 (m, 1 H,
CCHCHCH2), 2.19–2.26 (m, 1 H, CCHCHCH2), 2.53–2.62 (m,
1 H, CCHCHCH2), 2.65 (dd, 3J = 5.7 Hz, 3J = 6.4 Hz, 1 H,
CCHCHCH2), 3.08 (d, 3J = 5.8 Hz, 1 H, OH), 4.38 (dd, 3J = 6.2 Hz,
3J = 6.2 Hz, 1 H, CHOH), 4.87–4.89 (m, 2 H, CH2C), 6.66–6.68 (m,
1 H, CHCH2CHCH).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3947
13C NMR (100 MHz, CDCl3):
d
=
15.9 (COCCH3), 18.2
1H NMR (400 MHz, CDCl3): d = 0.86 [dd, 3J = 7.0 Hz, 4J = 1.0 Hz,
3 H, CH(CH3)2], 0.96 (dd, 3J = 6.4 Hz, 4J = 1.2 Hz, 3 H,
(CH2CCH3), 19.3 [CH(CH3)2], 20.7 [CH(CH3)2], 25.4
(CCHCHCH2), 29.1 [CH(CH3)2], 40.6 (CCHCHCH2), 52.6
(CCHCHCH2), 76.3 (CHOH), 113.2 (CH2C), 135.6 (COCCH3),
144.4 (CHCH2CHCH), 145.8 (CH2C), 201.7 (CO).
MS (ESI): m/z (%) = 245/246 (100/14) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C14H22O2Na: 245.1518;
3
4
COCHCH3), 1.00 [dd, J = 6.9 Hz, J = 1.1 Hz, 3 H, CH(CH3)2],
1.30 (ddq, 2J = 13.0 Hz, 3J = 3.8 Hz, 4J = 1.1 Hz, 1 H,
CHCHCH2CH2), 1.50 (ddd, 2J = 16.4 Hz, 3J = 3.3 Hz, 3J = 12.6 Hz,
1 H, CHCHCH2CH2), 1.74 (br, 3 H, CH2CCH3), 1.81–1.87 (m, 1 H,
CHCHCH2CH2), 1.97–2.05 (m, 1 H, CHCHCH2CH2), 2.12–2.18
[m, 2 H, CHCHCH2CH2, CH(CH3)2], 2.40–2.50 (m, 1 H,
3
found: 245.1519.
COCHCH3), 2.63 (d, J = 11.7 Hz, 1 H, CHCHCH2CH2), 3.71 (d,
3
3J = 11.6 Hz, 1 H, OH), 4.13 (d, J = 11.0 Hz, 1 H, CHOH), 4.90–
UV (MeOH): lmax (log e) = 241 (3.83), 330 nm (1.88).
4.92 (m, 1 H, CH2CCH3), 4.98–4.99 (m, 1 H, CH2CCH3).
13C NMR (100 MHz, CDCl3): d = 14.0 (COCHCH3), 14.8
[CH(CH3)2], 20.4 (CH2CCH3), 21.5 [CH(CH3)2], 23.7
(CHCHCH2CH2), 27.2 [CH(CH3)2], 36.4 (CHCHCH2CH2), 46.4
(COCHCH3), 48.0 (CHCHCH2CH2), 55.4 (CHCHCH2CH2), 71.3
(CHOH), 110.0 (CH2CCH3), 146.8 (CH2CCH3), 217.8 (CO).
MS (ESI): m/z (%) = 247/248 (100/13) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C14H24O2Na: 247.1674;
(2S,3S,6S)-2-[(1R)-1-Hydroxy-2-methylallyl]-6-methyl-3-
(prop-1-en-2-yl)cyclohexanone (19)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.69 mL, 4.93 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.97 mL, 4.93 mmol, 1.50 equiv), dihydrocarvone 11
(500 mg, 3.29 mmol, 1.00 equiv) for 1.0 h; methacrolein (6; 0.41
mL, 4.93 mmol, 1.50 equiv) for 4.0 h; AcOH (0.30 mL, 4.93 mmol,
1.50 equiv). The product was purified by column chromatography
(PE–EtOAc, 15:1).
found: 247.1671.
Yield: 395 mg (54%); colorless oil; Rf = 0.42 (silica; PE–EtOAc,
10:1); [a]D25 –67.3 (c 1.48, CHCl3).
UV (MeOH): lmax (log e) = 202 (3.49), 283 nm (1.77).
(4R,2E)-4-Hydroxy-3-methyl-4-[(1S,6S)-3-methyl-2-oxo-6-
(prop-1-en-2-yl)cyclohex-3-enyl]but-2-enyl Acetate (21)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.70 mL, 5.00 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (2.00 mL, 5.00 mmol, 1.50 equiv), carvone (9; 500
mg, 3.33 mmol, 1.00 equiv) for 1.0 h; aldehyde 7 (710 mg, 5.00
mmol, 1.50 equiv) in THF (3.0 mL) for 3.0 h; AcOH (0.30 mL, 5.00
mmol, 1.50 equiv). The product was purified by column chroma-
tography (PE–EtOAc, 3:1) to give two diastereomers 21 and 21a
(720 mg, 74%) in a ratio of 23:2*.
IR (ATR): 3514 (br), 3076 (w), 2971 (m), 2931 (m), 2860 (w), 1696
(s), 1646 (m), 1449 (m), 1409 (m), 1376 (m), 1223 (w), 1167 (w),
1125 (m), 1093 (m), 1030 (m), 1030 (m), 1001 (w), 938 (w), 891 (s),
836 (w), 723 (w), 596 (m), 567 (s), 536 (s) cm–1.
1H NMR (400 MHz, CDCl3): d = 0.98 (d, 3J = 6.4 Hz, 3 H,
COCHCH3), 1.35–1.46 (m, 1 H, CHCHCH2CH2), 1.73 (m, 3 H,
CHOHCCH3), 1.75 (m, 3 H, CH2CHCCH3), 1.83–1.89 (m, 2 H,
2
3
3
CHCHCH2CH2), 2.12 (tdd, J = 13.0 Hz, J = 5.7 Hz, J = 3.4 Hz,
1 H, CHCHCH2CH2), 2.45–2.55 (m, 1 H, COCHCH3), 2.70 (td,
3J = 1.3 Hz, 3J = 12.1 Hz, 1 H, CHCHCH2CH2), 2.77–2.84 (m, 1 H,
CHCHCH2CH2), 3.74 (d, 3J = 11.6 Hz, 1 H, OH), 3.94 (d,
3J = 11.6 Hz, 1 H, CHOH), 4.88–4.91 (m, 2 H, CH2CHCCH2,
CHOHCCH2), 4.94 (br, 1 H, CHOHCCH2), 4.96 (br, 1 H,
CH2CHCCH2).
21
Yield: 620 mg (64%)**; colorless oil; Rf = 0.33 (silica; PE–EtOAc,
3:1); [a]D25 –12.2 (c 1.64, CHCl3).
IR (ATR): 3480 (br), 2923 (w), 1736 (s), 1661 (s), 1439 (m), 1367
(m), 1229 (s), 1090 (w), 1021 (s), 959 (m), 894 (m), 836 (m), 755
(w), 607 (m), 575 (m) cm–1.
13C NMR (100 MHz, CDCl3): d = 13.8 (COCHCH3), 18.6
(CH2CHCCH3), 20.2 (CHOHCCH3), 31.3 (CHCHCH2CH2), 36.0
(CHCHCH2CH2), 46.4 (COCHCH3), 51.4 (CHCHCH2CH2), 54.7
(CHCHCH2CH2), 72.7 (CHOH), 109.8 (CHOHCCH2), 113.3
(CH2CHCCH2), 145.2 (CH2CHCCH2), 146.6 (CHOHCCH2), 216.2
(CO).
MS (EI): m/z (%) = 222 (4) [M+], 152 (37), 137 (28), 109 (43), 82
(42), 81 (43), 68 (50), 67 (100), 55 (38), 43 (28).
HRMS (EI): m/z [M+] calcd for C14H22O2: 222.16199; found:
222.16113.
1H NMR (300 MHz, CDCl3): d = 1.72 (m, 3 H, CH2CCH3), 1.73 (s,
4
3 H, CHOHCCH3), 1.78 (d, J = 1.9 Hz, 3 H, COCCH3), 2.05 (s,
3 H, COCH3), 2.35–2.56 (m, 2 H, CHCH2CHCH), 2.65–2.72 (m,
2 H, CHCH2CHCH, CHCH2CHCH), 2.79 (d, 3J = 6.0 Hz, 1 H,
3
3
OH), 4.17 (dd, J = 5.8 Hz, J = 5.8 Hz, 1 H, CHOH), 4.59–4.73
(m, 2 H, CH2O), 4.77 (s, 1 H, CH2CCH3), 4.86 (s, 1 H, CH2CCH3),
5.63–5.68 (m, 1 H, CHCH2O), 6.68 (ddd, 3J = 4.1 Hz, 3J = 4.2 Hz,
4J = 1.3 Hz, 1 H, CHCH2CHCH).
13C NMR (75 MHz, CDCl3): d = 12.0 (CHOHCCH3), 15.8
UV (MeOH): lmax (log e) = 204 (3.67), 286 (1.79).
(COCCH3),
20.7
(CH2CCH3),
20.9
(COCH3),
28.4
(CHCH2CHCH), 43.8 (CHCH2CHCH), 52.5 (CHCH2CHCH), 60.9
(CH2O), 75.7 (CHOH), 113.2 (CH2CCH3), 121.3 (CHCH2O), 135.1
(COCCH3), 141.9 (CHOHC), 143.6 (CHCH2CHCH), 145.3
(CH2CCH3), 170.9 (COCH3), 201.1 (CO).
MS (EI): m/z (%) = 292 (1) [M+], 232 (4), 150 (23), 135 (18), 121
(10), 108 (23), 93 (22), 82 (100), 71 (23), 54 (37), 42.8 (63).
(2S,3R,6S)-2-[(1R)-1-Hydroxy-2-methylallyl]-3-isopropyl-6-
methylcyclohexanone (20)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.68 mL, 4.87 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.95 mL, 4.87 mmol, 1.50 equiv), tetrahydrocarvone
(12; 500 mg, 3.25 mmol, 1.00 equiv) for 1.0 h; methacrolein (6;
0.40 mL, 4.87 mmol, 1.50 equiv) in THF (6.0 mL) for 2.0 h; AcOH
(0.30 mL, 4.87 mmol, 1.50 equiv). The product was purified by col-
umn chromatography (PE–EtOAc, 15:1).
HRMS (EI): m/z [M+] calcd for C17H24O4: 292.16748; found:
292.16671.
UV (MeOH): lmax (log e) = 202 (3.93), 239 (3.77), 325 nm (1.99).
Yield: 340 mg (47%); colorless oil; Rf = 0.53 (silica; PE–EtOAc,
10:1); [a]D25 –68.9 (c 1.42, CHCl3).
(4S,2E)-4-Hydroxy-3-methyl-4-[(1S,6S)-3-methyl-2-oxo-6-
(prop-1-en-2-yl)cyclohex-3-enyl]but-2-enyl Acetate (21a)
Yield: 35 mg (4%)**; colorless oil; Rf = 0.40 (silica; PE–EtOAc,
3:1); [a]D25 –12.2 (c 0.49, CHCl3).
IR (ATR): 3513 (br), 2961 (m), 2932 (m), 2872 (m), 1697 (s), 1453
(m), 1371 (m), 1234 (w), 1177 (w), 1105 (m), 1081 (w), 1054 (w),
1027 (m), 1004 (w), 937 (w), 891 (m), 838 (w), 725 (w), 600 (m),
560 (s) cm–1.
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3948
E. Schöttner et al.
PAPER
IR (ATR): 3460 (br), 3082 (w), 2972 (w), 2924 (w), 1737 (s), 1661
(s), 1439 (m), 1368 (m), 1230 (s), 1022 (s), 958 (m), 894 (m), 578
(m) cm–1.
(4S,2E)-4-Hydroxy-4-[(1S,6R)-6-isopropyl-3-methyl-2-oxocy-
clohex-3-enyl]-3-methylbut-2-enyl Acetate (22b)
Yield: 94 mg (5%)**; colorless oil; Rf = 0.33 (silica; PE–EtOAc,
5:2); [a]D25 –12.4 (c 0.54, CHCl3).
1H NMR (300 MHz, CDCl3): d = 1.63–1.64 (m, 3 H, CHOHCCH3),
1.72 (dd, 4J = 0.7 Hz, 4J = 1.3 Hz, 3 H, CH2CCH3), 1.77 (dd,
IR (ATR): 3469 (br), 2959 (m), 1738 (s), 1669 (m), 1442 (w), 1366
(m), 1230 (s), 1172 (w), 1138 (m), 1110 (m), 1022 (m), 958 (w), 853
(w), 779 (w), 607 (w), 569 (w) cm–1.
5
4J = 3.6 Hz, J = 1.6 Hz, 3 H, COCCH3), 2.04 (s, 3 H, COCH3),
2.29–2.54 (m, 2 H, CHCH2CHCH), 2.65–2.78 (m, 2 H,
CHCH2CHCH, CHCH2CHCH), 4.14 (d, 3J = 7.7 Hz, 1 H, OH),
4.29 (dd, 3J = 5.6 Hz, 3J = 7.4 Hz, 1 H, CHOH), 4.59 (d,
3J = 6.8 Hz, 2 H, CH2O), 4.74 (m, 1 H, CH2CCH3), 4.83–4.85 (m,
1 H, CH2CCH3), 5.45–5.50 (m, 1 H, CHCH2O), 6.73–6.77 (m, 1 H,
CHCH2CHCH).
1H NMR (400 MHz, CDCl3): d = 0.86 [d, 3J = 6.5 Hz, 3 H,
3
CH(CH3)2], 0.88 [d, J = 6.4 Hz, 3 H, CH(CH3)2], 1.65–1.70 [m,
1 H, CH(CH3)2], 1.69–1.70 (m, 3 H, CHOHCCH3), 1.72–1.74 (m,
3 H, COCCH3), 1.98–2.00 (m, 1 H, CCHCHCH2), 2.04 (s, 3 H,
COCH3), 2.20–2.28 (m, 1 H, CCHCHCH2), 2.53–2.62 (m, 1 H,
CCHCHCH2), 2.65 (dd, 3J = 4.7 Hz, 3J = 7.1 Hz, 1 H,
CCHCHCH2), 2.92 (d, 3J = 4.9 Hz, 1 H, OH), 4.35 (dd, 3J = 4.3 Hz,
3J = 6.8 Hz, 1 H, CHOH), 4.53–4.64 (m, 2 H, CH2O), 5.47–5.51
(m, 1 H, CHCH2O), 6.64–6.65 (m, 1 H, CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = 12.4 (CHOHCCH3), 15.9
(COCCH3), 19.7 [CH(CH3)2], 20.6 [CH(CH3)2], 20.9 (COCH3),
25.4 (CCHCHCH2), 29.3 [CH(CH3)2], 40.5 (CCHCHCH2), 52.7
(CCHCHCH2), 60.7 (CH2O), 77.1 (CHOH), 121.5 (CHCH2O),
135.5 (COCCH3), 141.7 (CHOHC), 144.2 (CHCH2CHCH), 170.9
(COCH3), 201.2 (CO).
13C NMR (75 MHz, CDCl3): d = 13.0 (CHOHCCH3), 15.9
(COCCH3),
20.0
(CH2CCH3),
20.9
(COCH3),
30.0
(CHCH2CHCH), 43.0 (CHCH2CHCH), 51.4 (CHCH2CHCH), 60.8
(CH2O), 77.3 (CHOH), 113.1 (CH2CCH3), 122.8 (CHCH2O), 135.7
(COCCH3), 140.4 (CHOHC), 144.9 (CHCH2CHCH), 145.1
(CH2CCH3), 170.9 (COCH3), 202.0 (CO).
MS (EI): m/z (%) = 292 (2) [M+], 232 (8), 215 (10), 150 (74), 135
(67), 121 (26), 109 (60), 82 (100), 71 (35), 54 (43).
HRMS (EI): m/z [M+] calcd for C17H24O4: 292.16748; found:
292.16661.
MS (ESI): m/z (%) = 317/318 (100/17) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H26O4Na: 317.17288;
UV (MeOH): lmax (log e) = 201 (3.95), 240 (3.80), 323 nm (2.02).
(4R,2E)-4-Hydroxy-4-[(1S,6R)-6-isopropyl-3-methyl-2-oxocy-
clohex-3-enyl]-3-methylbut-2-enyl Acetate (22)
found: 317.17238.
UV (MeOH): lmax (log e) = 202 (3.82), 240 (3.81), 325 nm (2.03).
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (1.58 mL, 11.3 mmol, 1.60 equiv) in THF (10.0
mL), n-BuLi (4.52 mL, 11.3 mmol, 1.60 equiv), dihydrocarvone 10
(1.07 g, 7.04 mmol, 1.00 equiv) for 0.75 h; aldehyde 7 (1.5 g, 10.6
mmol, 1.50 equiv) in THF (10.0 mL) for 3.0 h; AcOH (0.65 mL,
11.3 mmol, 1.60 equiv). The product was purified by column chro-
matography (PE–EtOAc, 5:2) to give two diastereomers 22 and 22b
(1.48 g, 5.05 mmol, 72%) in a ratio of 8:1*.
(4R,2E)-4-Hydroxy-3-methyl-4-[(1S,3S,6S)-3-methyl-2-oxo-6-
(prop-1-en-2-yl)cyclohexyl]but-2-enyl Acetate (23)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.69 mL, 4.93 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.97 mL, 4.93 mmol, 1.50 equiv), dihydrocarvone 11
(500 mg, 3.29 mmol, 1.00 equiv) for 1.0 h; aldehyde 7 (700 mg,
4.93 mmol, 1.50 equiv) in THF (5.0 mL) for 3.0 h; AcOH (0.30 mL,
4.93 mmol, 1.50 equiv). The product was purified by column chro-
matography (PE–EtOAc, 5:1).
22
Yield: 750 mg (36%)**; colorless oil; Rf = 0.25 (silica; PE–EtOAc,
5:1); [a]D25 –11.6 (c 0.35, CHCl3).
Yield: 390 mg (40%); colorless oil; Rf = 0.48 (silica; PE–EtOAc,
5:1); [a]D25 –54.6 (c 1.59, CHCl3).
IR (ATR): 3467 (br), 2959 (m), 2927 (w), 2895 (w), 1738 (s), 1664
(m), 1437 (w), 1367 (m), 1229 (s), 1086 (w), 1020 (s), 959 (m), 851
(w), 831 (w), 607 (w), 568 (w) cm–1.
IR (ATR): 3509 (br), 3075 (w), 2971 (w), 2932 (m), 2862 (w), 1734
(s), 1695 (s), 1646 (w), 1447 (m), 1376 (m), 1229 (s), 1167 (w),
1124 (w), 1087 (w), 1023 (m), 955 (m), 896 (m), 602 (m), 548 (s)
cm–1.
1H NMR (400 MHz, CDCl3): d = 0.98 (d, 3J = 6.4 Hz, 3 H,
COCHCH3), 1.35–1.46 (m, 1 H, CHCHCH2CH2), 1.67 (d,
4J = 0.5 Hz, 3 H, CHCCH3), 1.75 (m, 3 H, CH2CCH3), 1.82–1.88
(m, 2 H, CHCHCH2CH2), 2.04 (s, 3 H, COOCH3), 2.08–2.14 (m,
1 H, CHCHCH2CH2), 2.44–2.54 (m, 1 H, COCHCH3), 2.66 (td,
3J = 1.3 Hz, 3J = 12.0 Hz, 1 H, CHCHCH2CH2), 2.75–2.82 (m, 1 H,
CHCHCH2CH2), 3.85 (d, 3J = 11.3 Hz, 1 H, OH), 3.95 (dd,
3J = 0.6 Hz, 3J = 11.4 Hz, 1 H, CHOH), 4.57–4.68 (m, 2 H, CH2O),
4.90–4.93 (m, 2 H, CH2CCH3), 5.58–5.63 (m, 1 H, CHCCH3).
13C NMR (100 MHz, CDCl3): d = 13.9 (COCHCH3), 14.4
(CHCCH3), 18.9 (CH2CCH3), 21.0 (COOCH3), 31.4
(CHCHCH2CH2), 36.1 (CHCHCH2CH2), 46.6 (COCHCH3), 51.7
(CHCHCH2CH2), 54.7 (CHCHCH2CH2), 61.2 (CH2O), 73.5
(CHOH), 113.5 (CH2CCH3), 118.3 (CHCCH3), 142.1 (CHCCH3),
145.2 (CH2CCH3), 171.0 (COOCH3), 216.4 (CO).
1H NMR (400 MHz, CDCl3): d = 0.86 [d, 3J = 6.7 Hz, 3 H,
3
CH(CH3)2], 0.88 [d, J = 6.7 Hz, 3 H, CH(CH3)2], 1.50–1.54 (m,
1 H, CCHCHCH2), 1.62–1.70 [m, 1 H, CH(CH3)2], 1.71–1.72 (m,
3 H, CHOHCCH3), 1.78–1.80 (m, 3 H, COCCH3), 2.06 (s, 3 H,
COCH3), 2.25–2.31 (m, 1 H, CCHCHCH2), 2.40–2.49 (m, 1 H,
CCHCHCH2), 2.58 (dd, 3J = 2.4 Hz, 3J = 9.6 Hz, 1 H,
CCHCHCH2), 2.62 (d, 3J = 3.2 Hz, 1 H, OH), 4.20 (dd, 3J = 3.1 Hz,
3J = 9.6 Hz, 1 H, CHOH), 4.60–4.70 (m, 2 H, CH2O), 5.62–5.66
(m, 1 H, CHCH2O), 6.64–6.67 (m, 1 H, CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = 10.6 (CHOHCCH3), 15.7
(COCCH3), 20.6 [CH(CH3)2], 20.8 [CH(CH3)2], 20.8 (COCH3),
25.3 (CCHCHCH2), 29.3 [CH(CH3)2], 42.1 (CCHCHCH2), 52.7
(CCHCHCH2), 60.7 (CH2O), 76.7 (CHOH), 123.0 (CHCH2O),
134.7 (COCCH3), 140.6 (CHOHC), 143.7 (CHCH2CHCH), 170.8
(COCH3), 201.6 (CO).
MS (ESI): m/z (%) = 317/318 (100/16) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H26O4Na: 317.17288;
MS (EI): m/z (%) = 294 (20) [M+], 235 (25), 234 (100), 221 (42),
216 (28), 205 (41), 179 (20).
found: 317.17238.
UV (MeOH): lmax (log e) = 202 (3.85), 240 (3.77), 329 nm (2.01).
HRMS (EI): m/z [M+] calcd for C17H26O4: 294.18311; found:
294.18254.
UV (MeOH): lmax (log e) = 204 nm (3.90).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3949
(4R,2E)-4-Hydroxy-4-[(1S,3S,6R)-6-isopropyl-3-methyl-2-oxo-
cyclohexyl]-3-methylbut-2-enyl Acetate (24)
13C NMR (75 MHz, CDCl3): d = 10.6 (CHOHCCH3), 15.8
(COCCH3), 16.2 (OCH2CHCCH3), 20.9 (COCH3), 21.4
(CHCHCCH3), 25.6 (CH2CH2CCH3), 27.2 (CHCH2CHCH), 38.8
(CH2CH2CCH3), 42.8 (CHCH2CHCH), 52.9 (CHCH2CHCH), 61.2
(CH2O), 77.2 (CHOH), 112.3 (CHCHCCH2), 118.7 (OCH2CH),
128.2 (CHOHCCH), 134.6 (COCCH3), 135.6 (CHOHCCH), 141.4
(OCH2CHC), 143.0 (CHCH2CHCH), 145.4 (CHCHCCH2), 171.0
(COCH3), 201.2 (CO).
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.68 mL, 4.88 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (1.95 mL, 4.88 mmol, 1.50 equiv), tetrahydrocarvone
(12; 500 mg, 3.25 mmol, 1.00 equiv) for 1.0 h; aldehyde 7 (692 mg,
4.88 mmol, 1.50 equiv) in THF (4.0 mL) for 2.0 h; AcOH (0.30 mL,
4.88 mmol, 1.50 equiv). The product was purified by column chro-
matography (PE–EtOAc, 7:1).
MS (ESI): m/z (%) = 383/384 (100/24) [M + Na]+.
Yield: 301 mg (31%); colorless oil; Rf = 0.37 (silica; PE–EtOAc,
7:1); [a]D25 –48.9 (c 1.51, CHCl3).
HRMS (ESI): m/z [M + Na]+ calcd for C22H32O4Na: 383.2199;
found: 383.2192.
IR (ATR): 3500 (br), 2961 (m), 2933 (m), 2873 (w), 1737 (s), 1696
(s), 1453 (m), 1369 (m), 1229 (s), 1177 (w), 1102 (m), 1079 (w),
1023 (s), 955 (m), 913 (w), 603 (m), 562 (m) cm–1.
UV (MeOH): lmax (log e) = 203 (4.14), 235 (3.79), 315 nm (2.28).
(8S,2E,6E)-8-Hydroxy-3,7-dimethyl-8-[(1S,6S)-3-methyl-2-
oxo-6-(prop-1-en-2-yl)cyclohex-3-enyl]octa-2,6-dienyl Acetate
(25a)
1H NMR (400 MHz, CDCl3): d = 0.86 [d, 3J = 6.7 Hz, 3 H,
CH(CH3)2], 0.96 (d, 3J = 6.4 Hz, 3 H, COCHCH3), 1.00 [d,
3J = 6.9 Hz, 3 H, CH(CH3)2], 1.30 (ddd, 2J = 25.9 Hz, 3J = 12.9 Hz,
3J = 3.8 Hz, 1 H, CHCHCH2CH2), 1.50 (ddd, 2J = 25.5 Hz,
3J = 3.8 Hz, 3J = 13.1 Hz, 1 H, CHCHCH2CH2), 1.69 (s, 3 H,
CHOHCCH3), 1.80–1.87 (m, 1 H, CHCHCH2CH2), 1.96–2.04 (m,
1 H, CHCHCH2CH2), 2.05 (s, 3 H, OCOCH3), 2.11–2.19 [m, 2 H,
CHCHCH2CH2, CH(CH3)2], 2.40–2.50 (m, 1 H, COCHCH3), 2.59–
Yield: 60 mg (5%)**; colorless oil; Rf = 0.23 (silica; PE–EtOAc,
3:1); [a]D25 –7.7 (c 0.61, CHCl3).
IR (ATR): 3492 (br), 3083 (w), 2922 (w), 1736 (s), 1665 (m), 1440
(m), 1366 (m), 1230 (s), 1021 (s), 955 (m), 893 (m), 607 (w), 574
(m) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.54 (d, 4J = 0.9 Hz, 3 H,
3
2.63 (m, 1 H, CHCHCH2CH2), 3.82 (d, J = 11.4 Hz, 1 H, OH),
4
4.13 (d, 3J = 11.3 Hz, 1 H, CHOH), 4.58–4.69 (m, 2 H, CHCH2O),
5.62–5.66 (m, 1 H, CHCH2O).
CHOHCCH3), 1.69 (d, J = 0.7 Hz, 3 H, OCH2CHCCH3), 1.72 (s,
3 H, CHCHCCH3), 1.76 (dd, 4J = 3.1 Hz, 5J = 1.5 Hz, 3 H,
COCCH3), 2.03–2.19 (m, 4 H, CH2CH2CCH3, CH2CH2CCH3), 2.05
(s, 3 H, COCH3), 2.29–2.39 (m, 1 H, CHCH2CHCH), 2.43–2.54 (m,
1 H, CHCH2CHCH), 2.66–2.77 (m, 2 H, CHCH2CHCH,
CHCH2CHCH), 4.04 (d, 3J = 7.5 Hz, 1 H, OH), 4.19 (d,
13C NMR (100 MHz, CDCl3): d = 14.0 (COCHCH3), 14.4
(CHOHCCH3), 14.9 [CH(CH3)2], 21.0 (OCOCH3), 21.5
[CH(CH3)2], 23.7 (CHCHCH2CH2), 27.3 [CH(CH3)2], 36.4
(CHCHCH2CH2), 46.4 (COCHCH3), 48.2 (CHCHCH2CH2), 55.2
(CHCHCH2CH2), 61.2 (CHCH2O), 72.0 (CHOH), 118.4
(CHCH2O), 142.2 (CHOHCCH3), 171.1 (OCOCH3), 217.8 (CO).
3
3
3J = 5.7 Hz, J = 7.3 Hz, 1 H, CHOH), 4.57 (d, J = 7.0 Hz, 2 H,
CH2O), 4.72 (s, 1 H, CHCHCCH2), 4.82–4.83 (m, 1 H,
CHCHCCH2), 5.22–5.27 (m, 1 H, CHOHCCH), 5.30–5.35 (m, 1 H,
CHCH2O), 6.71–6.74 (m, 1 H, CHCH2CHCH).
MS (ESI): m/z (%) = 319/320 (100/16) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C17H28O4Na: 319.1885;
found: 319.1878.
13C NMR (75 MHz, CDCl3): d = 12.5 (CHOHCCH3), 15.9
(COCCH3), 16.4 (OCH2CHCCH3), 20.1 (CHCHCCH3), 21.0
(COCH3), 25.7 (CH2CH2CCH3), 29.6 (CHCH2CHCH), 38.9
(CH2CH2CCH3), 43.1 (CHCH2CHCH), 51.7 (CHCH2CHCH), 61.3
(CH2O), 78.1 (CHOH), 112.9 (CHCHCCH2), 118.6 (OCH2CH),
128.6 (CHOHCCH), 135.2 (CHOHCCH), 135.7 (COCCH3), 141.7
(OCH2CHC), 144.5 (CHCH2CHCH), 145.3 (CHCHCCH2), 171.1
(COCH3), 200.2 (CO).
UV (MeOH): lmax (log e) = 203 (3.75), 283 nm (2.23).
(8R,2E,6E)-8-Hydroxy-3,7-dimethyl-8-[(1S,6S)-3-methyl-2-
oxo-6-(prop-1-en-2-yl)cyclohex-3-enyl]octa-2,6-dienyl Acetate
(25)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.70 mL, 5.00 mmol, 1.50 equiv) in THF (6.0
mL), n-BuLi (2.00 mL, 5.00 mmol, 1.50 equiv), carvone (9; 500
mg, 3.33 mmol, 1.00 equiv) for 1.0 h; aldehyde 8 (1.025 g, 4.88
mmol, 1.47 equiv) in THF (6.0 mL) for 3.0 h; AcOH (0.30 mL, 5.00
mmol, 1.50 equiv). The product was purified by column chroma-
tography (PE–EtOAc, 4:1) to give two diastereomers 25 and 25a
(621 mg, 1.73 mmol, 53%) in a ratio of 13:2*.
MS (ESI): m/z (%) = 383/384 (100/21) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C22H32O4Na: 383.2199;
found: 383.2191.
UV (MeOH): lmax (log e) = 203 (4.18), 239 nm (3.81).
(8R,2E,6E)-8-Hydroxy-8-[(1S,6R)-6-isopropyl-3-methyl-2-oxo-
cyclohex-3-enyl]-3,7-dimethylocta-2,6-dienyl Acetate (26)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.80 mL, 5.70 mmol, 1.50 equiv) in THF (7.0
mL), n-BuLi (2.28 mL, 5.70 mmol, 1.50 equiv), dihydrocarvone 10
(580 mg, 3.80 mmol, 1.00 equiv) for 0.75 h; aldehyde 8 (1.2 g, 5.70
mmol, 1.50 equiv) in THF (5.0 mL) for 7.5 h; AcOH (0.33 mL, 5.70
mmol, 1.50 equiv). The product was purified by column chroma-
tography (PE–EtOAc, 5:1) to give two diastereomers 26 and 26a
(1.19 g, 3.29 mmol, 87%) in a ratio of 25:4*.
25
Yield: 360 mg (31%)**; colorless oil; Rf = 0.17 (silica; PE–EtOAc,
3:1)]; [a]D25 +11.2 (c 1.15, CHCl3).
IR (ATR): 3490 (br), 3083 (w), 2971 (w), 2922 (w), 1736 (s), 1664
(m), 1439 (m), 1366 (m), 1230 (s), 1021 (s), 955 (m), 893 (m), 607
(w), 574 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 1.65 (s, 3 H, CHOHCCH3), 1.71
(s, 6 H, OCH2CHCCH3, CHCHCCH3), 1.78 (s, 3 H, COCCH3),
2.04 (s, 3 H, COCH3), 2.08–2.26 (m, 4 H, CH2CH2CCH3,
CH2CH2CCH3), 2.32–2.39 (m, 1 H, CHCH2CHCH), 2.47–2.54 (m,
2 H, CHCH2CHCH, CHCH2CHCH), 2.62 (dd, 3J = 3.2 Hz,
26
Yield: 1.03 g (75%)**; colorless oil; Rf = 0.16 (silica; PE–EtOAc,
5:1); [a]D25 –55.8 (c 0.22, CHCl3).
3
3J = 8.6 Hz, 1 H, CHCH2CHCH), 2.72 (d, J = 4.0 Hz, 1 H, OH),
IR (ATR): 3483 (br), 2957 (m), 2925 (m), 2896 (m), 1737 (s), 1671
(s), 1437 (m), 1366 (s), 1229 (s), 1021 (s), 955 (m), 857 (w), 567 (w)
cm–1.
4.14 (d, 3J = 4.0 Hz, 3J = 8.6 Hz, 1 H, CHOH), 4.57 (d, 3J = 7.1 Hz,
2 H, CH2O), 4.68 (s, 1 H, CHCHCCH2), 4.81 (m, 1 H,
CHCHCCH2), 5.31–5.37 (m, 1 H, CHCH2O), 5.43–5.47 (m, 1 H,
CHOHCCH), 6.64–6.66 (m, 1 H, CHCH2CHCH).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3950
E. Schöttner et al.
PAPER
1H NMR (400 MHz, CDCl3): d = 0.86 [d, 3J = 6.9 Hz, 3 H,
2.46 mmol, 1.50 equiv). The product was purified by column chro-
matography (PE–EtOAc, 6:1).
3
CH(CH3)2], 0.88 [d, J = 6.9 Hz, 3 H, CH(CH3)2], 1.46–1.49 (m,
1 H, CHCHCH2), 1.60–1.64 [m, 4 H, CH(CH3)2, CHOHCCH3],
1.71 (d, 4J = 1.1 Hz, 3 H, CH2CH2CCH3), 1.78–1.79 (m, 3 H,
COCCH3), 2.06 (s, 3 H, OCOCH3), 2.09–2.13 (m, 2 H,
CH2CH2CCH3), 2.19–2.23 (m, 2 H, CH2CH2CCH3), 2.25–2.28 (m,
1 H, CHCHCH2), 2.39–2.48 (m, 1 H, CHCHCH2), 2.51 (br, 1 H,
OH), 2.56 (dd, 3J = 10.0 Hz, 3J = 1.7 Hz, 1 H, CHCHCH2), 4.14 (d,
3J = 10.0 Hz, 1 H, CHOH), 4.58 (d, 3J = 7.1 Hz, 2 H, CH2O), 5.32–
5.36 (m, 1 H, CCHCH2O), 5.41–5.45 (m, 1 H, CCHCH2CH2), 6.61–
6.64 (m, 1 H, CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = 10.0 (CHOHCCH3), 15.8
(COCCH3), 16.3 (CH2CH2CCH3), 20.7 [CH(CH3)2], 21.0
(OCOCH3), 21.2 [CH(CH3)2], 25.4 (CHCHCH2), 25.5
(CH2CH2CCH3), 29.5 [CH(CH3)2], 38.9 (CH2CH2CCH3), 42.4
(CHCHCH2), 52.9 (CHCHCH2), 61.3 (CHCH2OCOCH3), 77.7
(CHOHCCH3), 118.7 (CHCH2OCOCH3), 129.0 (CHCH2CH2),
134.7 (COCCH3), 135.5 (CHOHCCH3), 141.5 (CH2CH2CCH3),
143.5 (CHCH2CHCH), 171.1 (OCOCH3), 202.1 (CO).
Yield: 89 mg (15%); colorless oil; Rf = 0.89 (silica; PE–EtOAc,
3:1); [a]D25 –21.8 (c 0.66, CHCl3).
IR (ATR): 3501 (br), 3075 (w), 2970 (w), 2932 (m), 2859 (w), 1736
(s), 1696 (s), 1446 (m), 1368 (m), 1230 (s), 1123 (w), 1022 (s), 951
(m), 895 (m), 603 (m), 549 (m) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.98 (d, 3J = 6.4 Hz, 3 H,
COCHCH3), 1.34–1.48 (m, 1 H, CHCHCH2CH2), 1.58 (d,
4J = 0.8 Hz, 3 H, CHOHCCH3), 1.68–1.69 (m, 3 H,
OCH2CHCCH3, OH), 1.73–1.74 (m, 3 H, CHCHCCH3), 1.80–1.88
(m, 2 H, CHCHCH2CH2), 2.04–2.19 (m, 5 H, CHCHCH2CH2,
CH2CH2CCH3, CH2CH2CCH3), 2.05 (s, 3 H, COOCH3), 2.42–2.55
(m, 1 H, COCHCH3), 2.63 (d, 3J = 12.0 Hz, 1 H, CHCHCH2CH2),
2.73–2.82 (m, 1 H, CHCHCH2CH2), 3.95 (s, 1 H, CHOH), 4.58 (dd,
3J = 7.0 Hz, 5J = 0.3 Hz, 2 H, CH2O), 4.88–4.90 (m, 1 H,
CHCHCCH2), 4.92 (m, 1 H, CHCHCCH2), 5.29–5.38 (m, 2 H,
CHOHCCH, CHCH2O).
13C NMR (75 MHz, CDCl3):
d = 14.0 (COCHCH3), 14.1
MS (EI): m/z (%) = 362 (6) [M+], 259 (10), 241 (23), 235 (20), 211
(CHOHCCH3), 16.5 (OCH2CHCCH3), 18.8 (CHCHCCH3), 21.0
(COOCH3), 26.0 (CH2CH2CCH3), 31.4 (CHCHCH2CH2), 36.1
(CHCHCH2CH2), 39.1 (CH2CH2CCH3), 46.6 (COCHCH3), 51.8
(CHCHCH2CH2), 54.8 (CHCHCH2CH2), 61.4 (CH2O), 74.0
(CHOH), 113.3 (CHCHCCH2), 118.4 (OCH2CH), 123.6
(CHOHCCH), 136.3 (CHOHCCH), 142.0 (OCH2CHC), 145.4
(CHCHCCH2), 171.1 (COOCH3), 216.7 (CO).
(6), 153 (11), 152 (38), 150 (37), 109 (100), 82 (62), 43 (76).
HRMS (EI): m/z [M+] calcd for C22H34O4: 362.2457; found:
362.2461.
UV (MeOH): lmax (log e) = 204 (4.08), 234 (3.82), 327 nm (2.08).
(8S,2E,6E)-8-Hydroxy-8-[(1S,6R)-6-isopropyl-3-methyl-2-oxo-
cyclohex-3-enyl]-3,7-dimethylocta-2,6-dienyl Acetate (26a)
Yield: 160 mg (12%)**; colorless oil; Rf = 0.22 (silica; PE–EtOAc,
5:1); [a]D25 –9.2 (c 0.22, CHCl3).
MS (ESI): m/z (%) = 385/386 (100/17) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C22H34O4Na: 385.23548;
found: 385.23493.
IR (ATR): 3465 (br), 2957 (m), 2925 (m), 1737 (s), 1667 (s), 1438
(m), 1366 (s), 1230 (s), 1022 (s), 954 (m), 857 (w), 733 (w), 607
(w), 567 (w) cm–1.
UV (MeOH): lmax (log e) = 202 nm (4.01).
(5R,6S)-6-[(1R,E)-1-(tert-Butyldimethylsilyloxy)-4-hydroxy-2-
methylbut-2-enyl]-5-isopropyl-2-methylcyclohex-2-enone (22a)
via 22c
1H NMR (400 MHz, CDCl3): d = 0.87 [d, 3J = 6.7 Hz, 3 H,
CH(CH3)2], 0.89 [d, 3J = 6.8 Hz, 3 H, CH(CH3)2], 1.61 (s, 3 H,
CHOHCCH3), 1.64–1.73 [m, 7 H, CH(CH3)2, CH2CH2CCH3,
COCCH3], 1.98–2.05 (m, 6 H, OCOCH3, CHCHCH2,
CH2CH2CCH3), 2.07–2.16 (m, 2 H, CH2CH2CCH3), 2.20–2.27 (m,
1 H, CHCHCH2), 2.53–2.61 (m, 1 H, CHCHCH2), 2.66 (dd,
3J = 7.7 Hz, 3J = 4.6 Hz, 1 H, CHCHCH2), 2.88 (br, 1 H, OH), 4.26
To a solution of 22 (740 mg, 2.52 mmol, 1.00 equiv) in DMF
(3.0 mL), imidazole (377 mg, 5.54 mmol, 2.20 equiv) was added.
After 10 min, TBSCl (491 mg, 3.28 mmol, 1.30 equiv) was added
and the solution was stirred for 16 h at r.t. The reaction was
quenched with H2O (10 mL) and extracted with Et2O (4 × 10 mL).
After drying the organic phase over MgSO4, the solvent was evap-
orated. Purification by column chromatography (silica; PE–EtOAc,
12:1) gave 22c.
3
3
(d, J = 7.6 Hz, 1 H, CHOH), 4.57 (d, J = 7.1 Hz, 2 H, CH2O),
5.22–5.26 (m, 1 H, CCHCH2CH2), 5.30–5.34 (m, 1 H, CCHCH2O),
6.61 (br, 1 H, CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = 11.8 (CHOHCCH3), 15.9
(COCCH3), 16.3 (CH2CH2CCH3), 19.8 [CH(CH3)2], 20.6
[CH(CH3)2], 21.0 (OCOCH3), 25.3 (CHCHCH2), 25.6
(CH2CH2CCH3), 29.1 [CH(CH3)2], 38.9 (CH2CH2CCH3), 40.8
(CHCHCH2), 53.1 (CHCHCH2), 61.3 (CHCH2OCOCH3), 77.7
(CHOHCCH3), 118.6 (CHCH2OCOCH3), 127.3 (CHCH2CH2),
135.5 (COCCH3), 136.3 (CHOHCCH3), 141.6 (CH2CH2CCH3),
143.6 (CHCH2CHCH), 171.1 (OCOCH3), 202.4 (CO).
Yield: 951 mg (93%); colorless oil; Rf = 0.34 (silica; PE–EtOAc,
12:1); [a]D25 –136.8 (c 0.23, CHCl3).
IR (ATR): 2956 (m), 2930 (m), 2892 (w), 2857 (w), 1741 (m), 1678
(m), 1466 (w), 1366 (m), 1229 (s), 1066 (s), 1023 (m), 878 (m), 835
(s), 775 (s), 669 (w), 585 (w) cm–1.
1H NMR (300 MHz, CDCl3): d = –0.09 [s, 3 H, Si(CH3)], –0.07 [s,
3 H, Si(CH3)], 0.82 [s, 9 H, SiC(CH3)3], 0.85 [d, 3J = 6.6 Hz, 3 H,
3
MS (EI): m/z (%) = 362 (2) [M+], 152 (43), 150 (25), 121 (26), 109
CH(CH3)2], 0.85 [d, J = 6.6 Hz, 3 H, CH(CH3)2], 1.38–1.43 (m,
1 H, CHCHCH2), 1.53–1.62 [m, 1 H, CH(CH3)2], 1.67–1.70 [m,
3 H, CH(OSi)CCH3], 1.76 (ddd, 4J = 2.6 Hz, 5J = 1.4 Hz,
5J = 1.4 Hz, 3 H, COCCH3), 2.05 (s, 3 H, OCOCH3), 2.16–2.25 (m,
1 H, CHCHCH2), 2.39–2.51 (m, 1 H, CHCHCH2), 2.65 (dd,
3J = 2.3 Hz, 3J = 9.5 Hz, 1 H, CHCHCH2), 4.32 [d, 3J = 9.5 Hz,
(100), 93 (22), 85 (25), 84 (60), 82 (90), 81 (50), 67 (23), 55 (45).
HRMS (EI): m/z [M+] calcd for C22H34O4: 362.24571; found:
362.24638.
UV (MeOH): lmax (log e) = 203 (4.13), 238 nm (3.87).
3
1 H, CH(OSi)CCH3], 4.63 (d, J = 6.8 Hz, 2 H, CHCH2O), 5.56–
(8R,2E,6E)-8-Hydroxy-3,7-dimethyl-8-[(1S,3S,6S)-3-methyl-2-
oxo-6-(prop-1-en-2-yl)cyclohexyl]octa-2,6-dienyl Acetate (27)
The general procedure was used with the following quantities and
times: NH(i-Pr)2 (0.34 mL, 2.46 mmol, 1.50 equiv) in THF (3.0
mL), n-BuLi (0.98 mL, 2.46 mmol, 1.50 equiv), dihydrocarvone 11
(250 mg, 1.64 mmol, 1.00 equiv) for 1.0 h; aldehyde 8 (517 mg,
2.46 mmol, 1.50 equiv) in THF (3.0 mL) for 3.0 h, AcOH (0.15 mL,
5.61 (m, 1 H, CHCH2O), 6.47–6.50 (m, 1 H, CHCH2CHCH).
13C NMR (75 MHz, CDCl3): d = –5.3 [Si(CH3)], –4.9 [Si(CH3)],
10.7 [CH(OSi)CCH3], 16.1 (COCCH3), 18.1 [SiC(CH3)3], 20.5
[CH(CH3)2], 20.8 (OCOCH3), 21.2 [CH(CH3)2], 25.5 (CHCHCH2),
25.7 [3 × C, SiC(CH3)3], 29.3 [CH(CH3)2], 42.4 (CHCHCH2), 53.8
(CHCHCH2), 60.6 (CHCH2O), 78.6 [CH(OSi)CCH3], 122.0
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3951
(CHCH2O), 134.7 (COCCH3), 141.2 (CHCH2CHCH), 142.2
[CH(OSi)CCH3], 170.9 (OCOCH3), 199.9 (CO).
MS (EI): m/z (%) = 393 (1) [M – Me]+, 351 (38), 291 (100), 257
(75), 117 (96), 83 (59), 75 (92), 73 (80), 43 (33).
HRMS (EI): m/z [M – t-Bu]+ calcd for C19H31O428Si: 351.19916;
1H NMR (400 MHz, CDCl3): d = –0.10 [s, 3 H, Si(CH3)], –0.09 [s,
3 H, Si(CH3)], 0.82 [s, 9 H, SiC(CH3)3], 0.84 [d, 3J = 6.6 Hz, 3 H,
CH(CH3)2], 0.85 [d, J = 6.6 Hz, 3 H, CH(CH3)2], 1.37–1.41 (m,
3
1 H, CHCHCH2), 1.51–1.60 [m, 4 H, CH(CH3)2, CH(OSi)CCH3],
4
5
1.71 (s, 3 H, CH2CH2CCH3), 1.76 (ddd, J = 2.6 Hz, J = 1.3 Hz,
5J = 1.3 Hz, 3 H, COCCH3), 2.06 (s, 3 H, OCOCH3), 2.07–2.23 (m,
5 H, CHCHCH2, CH2CH2CCH3, CH2CH2CCH3), 2.40–2.49 (m,
1 H, CHCHCH2), 2.64 (dd, 3J = 2.0 Hz, 3J = 9.8 Hz, 1 H,
found: 351.19894.
UV (MeOH): lmax (log e) = 202 (3.88), 237 (3.70), 323 nm (2.07).
3
CHCHCH2), 4.25 [d, J = 9.8 Hz, 1 H, CH(OSi)CCH3], 4.59 (d,
3J = 7.0 Hz, 2 H, CHCH2O), 5.33–5.38 (m, 2 H, CHCH2CH2,
CHCH2O), 6.44–6.47 (m, 1 H, CHCH2CHCH).
Synthesis of 22a
Ester 22c (500 mg, 1.23 mmol, 1.00 equiv) was dissolved in THF/
H2O (1:1, 6.0 mL) and LiOH (147 mg, 6.13 mmol, 5.00 equiv) was
added. The mixture was stirred at r.t. for 3 d, then the reaction was
quenched with 2 M HCl (3.5 mL), extracted with Et2O (4 × 10 mL),
dried over MgSO4 and evaporated. Purification by column chroma-
tography (silica; PE–EtOAc, 5:1) gave 22a.
13C NMR (100 MHz, CDCl3): d = –5.3 [Si(CH3)], –4.8 [Si(CH3)],
10.2 [CH(OSi)CCH3], 16.0 (COCCH3), 16.2 (CH2CH2CCH3), 18.0
[SiC(CH3)3], 20.5 [CH(CH3)2], 21.0 (OCOCH3), 21.3 [CH(CH3)2],
25.4 (CHCHCH2), 25.5 (CH2CH2CCH3), 25.7 [3 × C, SiC(CH3)3],
29.4 [CH(CH3)2], 38.9 (CH2CH2CCH3), 42.8 (CHCHCH2), 53.9
(CHCHCH2), 61.2 (CHCH2O), 79.4 [CH(OSi)CCH3], 118.7
(CHCH2O), 127.4 (CHCH2CH2), 134.6 (COCCH3), 136.6
[CH(OSi)CCH3], 140.8 (CHCH2CHCH), 141.5 (CH2CH2CCH3),
171.0 (OCOCH3), 200.4 (CO).
MS (EI): m/z (%) = 476 (2) [M+], 419 (24), 359 (23), 325 (20), 266
(19), 265 (100), 209 (25), 207 (23), 165 (18), 133 (64), 117 (22), 93
(25), 75 (26), 73 (53).
HRMS (EI): m/z [M+] calcd for C28H48O428Si: 476.3322; found:
476.3298.
Yield: 380 mg (84%); colorless crystals; mp 79–81 °C; Rf = 0.32
(silica; PE–EtOAc, 5:1); [a]D25 –28.9 (c 1.03, CHCl3).
IR (ATR): 3482 (br), 2959 (m), 2931 (m), 2895 (m), 2858 (m), 1659
(s), 1469 (w), 1436 (w), 1368 (m), 1250 (m), 1111 (w), 1082 (s),
1068 (s), 1043 (s), 1012 (s), 874 (m), 836 (s), 777 (s), 706 (w), 669
(w), 573 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = –0.07 [s, 3 H, Si(CH3)], –0.06 [s,
3 H, Si(CH3)], 0.83 [s, 9 H, SiC(CH3)3], 0.85 [d, 3J = 6.6 Hz, 3 H,
3
CH(CH3)2], 0.85 [d, J = 6.7 Hz, 3 H, CH(CH3)2], 1.41–1.50 (m,
1 H, CHCHCH2), 1.52–1.62 [m, 1 H, CH(CH3)2], 1.62 [d,
UV (MeOH): lmax (log e) = 202 (4.18), 236 (3.80), 323 nm (2.22).
4J = 0.9 Hz, 3 H, CH(OSi)CCH3], 1.77 (ddd, 4J = 2.7 Hz,
5
2
5J = 1.4 Hz, J = 1.4 Hz, 3 H, COCCH3), 2.21 (ddd, J = 19.7 Hz,
Synthesis of 29
3J = 1.5 Hz, 3J = 3.4 Hz, 1 H, CHCHCH2), 2.44–2.53 (m, 1 H,
Ester 29a (3.00 g, 6.30 mmol, 1.00 equiv) was dissolved in THF/
H2O (1:1, 20.0 mL) and LiOH (756 mg, 31.5 mmol, 5.00 equiv)
was added. After stirring at r.t. for 3 d, sat. NH4Cl (15 mL) was add-
ed and the solution was extracted with Et2O (4 × 20 mL). The or-
ganic phase was dried over MgSO4 and the residue obtained after
evaporation of the solvent was purified by column chromatography
(silica; PE–EtOAc, 5:1) to give 29.
CHCHCH2), 2.66 (dd, J = 2.3 Hz, 3J = 9.6 Hz, 1 H, CHCHCH2),
3
4.19–4.29 (m, 2 H, CHCH2OH), 4.32 [d, 3J = 9.6 Hz, 1 H,
CH(OSi)CCH3], 5.60–5.63 (m, 1 H, CHCH2OH), 6.48–6.50 (m,
1 H, CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = –5.2 [Si(CH3)], –4.7 [Si(CH3)],
10.5 [CH(OSi)CCH3], 16.1 (COCCH3), 18.1 [SiC(CH3)3], 20.5
[CH(CH3)2], 21.2 [CH(CH3)2], 25.6 (CHCHCH2), 25.7 [3 × C,
SiC(CH3)3], 29.3 [CH(CH3)2], 42.6 (CHCHCH2), 53.8
(CHCHCH2), 59.1 (CHCH2OH), 78.8 [CH(OSi)CCH3], 127.2
(CHCH2OH), 134.7 (COCCH3), 139.1 [CH(OSi)CCH3], 141.2
(CHCH2CHCH), 200.1 (CO).
MS (EI): m/z (%) = 366 (1) [M+], 348 (3), 309 (17), 215 (30), 159
(40), 85 (44), 75 (100), 73 (90).
HRMS (EI): m/z [M – H2O]+ calcd for C21H36O228Si: 348.24847;
found: 348.24740.
Yield: 2.69 g (98%); colorless oil; Rf = 0.42 (silica; PE–EtOAc,
5:1); [a]D25 –33.3 (c 0.10, CHCl3).
IR (ATR): 3436 (m), 2954 (m), 2926 (m), 2892 (m), 2856 (m), 1668
(m), 1472 (w), 1462 (w), 1434 (w), 1387 (w), 1364 (m), 1249 (m),
1186 (w), 1082 (m), 1058 (s), 1005 (m), 939 (w), 879 (m), 835 (s),
815 (m), 774 (s), 705 (w), 667 (m) cm–1.
1H NMR (400 MHz, CDCl3): d = –0.10 [s, 3 H, Si(CH3)], –0.08 [s,
3 H, Si(CH3)], 0.82 [s, 9 H, SiC(CH3)3], 0.85 [d, 3J = 6.8 Hz, 3 H,
3
CH(CH3)2], 0.85 [d, J = 6.6 Hz, 3 H, CH(CH3)2], 1.38–1.42 (m,
1 H, CHCHCH2), 1.51–1.61 [m, 4 H, CH(CH3)2, CH(OSi)CCH3],
1.68 (s, 3 H, CH2CH2CCH3), 1.76–1.77 (m, 3 H, COCCH3), 2.07–
2.22 (m, 5 H, CHCHCH2, CH2CH2CCH3, CH2CH2CCH3), 2.41–
UV (MeOH): lmax (log e) = 201 (3.87), 240 (3.75), 328 nm (2.26).
(5R,6S)-6-[(1R,2E,6E)-1-(tert-Butyldimethylsilyloxy)-8-hy-
droxy-2,6-dimethylocta-2,6-dienyl]-5-isopropyl-2-methylcyclo-
hex-2-enone (29) via 29a
3
2.50 (m, 1 H, CHCHCH2), 2.64 (dd, J = 2.0 Hz, 3J = 9.8 Hz, 1 H,
CHCHCH2), 4.16 (d, 3J = 6.8 Hz, 2 H, CHCH2OH), 4.24 [d,
3J = 9.8 Hz, 1 H, CH(OSi)CCH3], 5.34–5.38 (m, 1 H, CHCH2CH2),
5.41–5.45 (m, 1 H, CHCH2OH), 6.45–6.47 (m, 1 H,
CHCH2CHCH).
13C NMR (100 MHz, CDCl3): d = –5.3 [Si(CH3)], –4.8 [Si(CH3)],
10.2 [CH(OSi)CCH3], 16.0 (COCCH3), 16.0 (CH2CH2CCH3), 18.0
[SiC(CH3)3], 20.5 [CH(CH3)2], 21.3 [CH(CH3)2], 25.5
(CHCHCH2), 25.6 (CH2CH2CCH3), 25.7 [3 × C, SiC(CH3)3], 29.4
[CH(CH3)2], 38.9 (CH2CH2CCH3), 42.7 (CHCHCH2), 53.9
(CHCHCH2), 59.3 (CHCH2OH), 79.4 [CH(OSi)CCH3], 123.8
(CHCH2OH), 127.6 (CHCH2CH2), 134.6 (COCCH3), 136.5
[CH(OSi)CCH3], 138.9 (CH2CH2CCH3), 141.0 (CHCH2CHCH),
200.5 (CO).
Alcohol 26 (7.00 g, 19.3 mmol, 1.00 equiv) was dissolved in DMF
(18.5 mL) and imidazole (2.89 g, 42.5 mmol, 2.20 equiv) was add-
ed. After 10 min, TBSCl (3.76 g, 25.1 mmol, 1.30 equiv) was added
and the resulting solution was stirred for 16 h at r.t. H2O (50 mL)
was added and the solution was extracted with Et2O (4 × 30 mL).
The organic phase was dried over MgSO4, filtered and the solvent
was evaporated. The residue obtained was purified by column chro-
matography (silica; PE–EtOAc, 12:1) to give silyl ether 29a.
Yield: 7.76 g (85%); colorless oil; Rf = 0.35 (silica; PE–EtOAc,
10:1); [a]D25 –19.8 (c 0.18, CHCl3).
IR (ATR): 2955 (m), 2927 (m), 2892 (m), 2856 (m), 1740 (s), 1679
(s), 1472 (w), 1462 (w), 1436 (w), 1386 (w), 1364 (m), 1230 (s),
1186 (w), 1082 (m), 1060 (s), 1023 (s), 978 (w), 956 (w), 879 (m),
835 (s), 815 (m), 774 (s), 708 (w), 667 (m), 607 (w) cm–1.
MS (EI): m/z (%) = 434 (1) [M+], 377 (7), 359 (9), 335 (4), 309 (8),
283 (28), 265 (30), 225 (12), 209 (28), 165 (20), 133 (54), 123 (18),
93 (25), 91 (28), 75 (56), 73 (100).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3952
E. Schöttner et al.
PAPER
HRMS (EI): m/z [M+] calcd for C26H46O328Si: 434.32162; found:
purified by column chromatography (silica; PE–EtOAc, 6:1) to give
434.32188.
31.
UV (MeOH): lmax (log e) = 202 (4.17), 236 (3.81), 331 nm (2.15).
Yield: 1.76 g (70%); colorless oil; Rf = 0.38 (silica; PE–EtOAc,
5:1); [a]D25 –24.2 (c 1.37, CHCl3).
(8R,2E,6E)-8-(tert-Butyldimethylsilyloxy)-8-[(1S,6R)-6-isopro-
pyl-3-methyl-2-oxocyclohex-3-enyl]-3,7-dimethylocta-2,6-
dienyl Diethyl Phosphate (30)
IR (ATR): 3389 (br), 2954 (m), 2926 (m), 2930 (m), 2858 (m), 1701
(m), 1461 (w), 1385 (w), 1365 (w), 1252 (m), 1087 (m), 1052 (s),
1006 (m), 881 (m), 836 (s), 811 (m), 774 (s), 679 (w), 666 (w) cm–1.
Alcohol 29 (868 mg, 2.00 mmol, 1.00 equiv) was dissolved under
N2 in anhydrous pyridine (10.0 mL) and ClP(O)(OEt)2 (0.58 mL,
4.00 mmol, 2.00 equiv) was added at 0 °C. The solution was al-
lowed to warm to r.t. and stirred for 2.5 h. 2 M HCl (20 mL) was
added and the solution was extracted with Et2O (4 × 15 mL). The
organic phase was washed with H2O (2 × 25 mL) and brine (25
mL), dried over MgSO4 and the solvent was evaporated. Quick col-
umn filtration (silica; PE–EtOAc, 6:4) gave 30.
1H NMR (400 MHz, CDCl3): d = –0.03 [s, 3 H, Si(CH3)], 0.01 [s,
3 H, Si(CH3)], 0.82 [d, 3J = 6.8 Hz, 3 H, CH(CH3)2], 0.84 [d,
3J = 6.9 Hz, 3 H, CH(CH3)2], 0.88 [s, 9 H, SiC(CH3)3], 1.09 (d,
3J = 6.9 Hz, 3 H, COCHCH3), 1.32–1.43 (m, 3 H, CHCHCH2CH2,
CHCHCH2CH2, OH), 1.47 [s, 3 H, CH(OSi)CCH3], 1.54–1.60 (m,
1 H, CHCHCH2CH2), 1.69 (s, 3 H, CH2CH2CCH3), 1.72–1.77 (m,
1 H, CHCHCH2CH2), 1.92–2.09 [m, 4 H, CH(CH3)2,
CHCHCH2CH2,
CH2CH2CCH3],
2.12–2.25
(m,
3 H,
Yield: 1.07 mg (94%); colorless oil; Rf = 0.55 (silica; PE–EtOAc,
1:1); [a]D25 –17.7 (c 0.57, CHCl3).
CH2CH2CCH3, COCHCH3), 2.38–2.41 (m, 1 H, CHCHCH2CH2),
3
3
4.15 (d, J = 6.8 Hz, 2 H, CHCH2OH), 4.79 [d, J = 3.6 Hz, 1 H,
CH(OSi)CCH3], 5.42–5.44 (m, 1 H, CHCH2OH), 5.46–5.49 (m,
1 H, CHCH2CH2C).
IR (ATR): 2956 (m), 2928 (m), 2895 (m), 2856 (m), 1678 (m), 1472
(w), 1462 (w), 1444 (w), 1388 (w), 1365 (m), 1256 (m), 1186 (w),
1166 (w), 1060 (s), 1032 (s), 1006 (s), 978 (s), 880 (m), 835 (s), 775
(s), 708 (w), 666 (w), 635 (w), 618 (w) cm–1.
13C NMR (100 MHz, CDCl3): d = –5.1 [Si(CH3)], –4.7 [Si(CH3)],
13.6 [CH(OSi)CCH3], 16.1 (COCHCH3), 16.2 (CH2CH2CCH3),
16.6 [CH(CH3)2], 18.2 [SiC(CH3)3], 21.1 [CH(CH3)2], 22.5
(CHCHCH2CH2), 25.7 (CH2CH2CCH3), 25.9 [3 × C, SiC(CH3)3],
28.4 [CH(CH3)2], 31.5 (CHCHCH2CH2), 39.2 (CH2CH2CCH3),
44.7 (CHCHCH2CH2), 45.0 (COCHCH3), 58.2 (CHCHCH2CH2),
59.4 (CHCH2OH), 76.1 [CH(OSi)CCH3], 123.7 (CHCH2OH),
1H NMR (400 MHz, CDCl3): d = –0.11 [s, 3 H, Si(CH3)], –0.09 [s,
3 H, Si(CH3)], 0.82 [s, 9 H, SiC(CH3)3], 0.85 [d, 3J = 6.7 Hz, 3 H,
CH(CH3)2], 0.85 [d, 3J = 6.7 Hz, 3 H, CH(CH3)2], 1.34 (dt,
3J = 7.1 Hz, 4J = 0.9 Hz, 6 H, POCH2CH3), 1.38–1.40 (m, 1 H,
CHCHCH2), 1.50–1.61 [m, 4 H, CH(CH3)2, CH(OSi)CCH3], 1.71
(d, 4J = 0.8 Hz, 3 H, CH2CH2CCH3), 1.75–1.76 (m, 3 H, COCCH3),
2.08–2.21 (m, 5 H, CHCHCH2, CH2CH2CCH3, CH2CH2CCH3),
2.40–4.49 (m, 1 H, CHCHCH2), 2.64 (dd, 3J = 2.0 Hz, 3J = 9.8 Hz,
1 H, CHCHCH2), 4.11 (dq, 3J = 7.1 Hz, 3J = 14.2 Hz, 4 H,
126.0
(CHCH2CH2C),
134.9
[CH(OSi)CCH3],
139.3
(CH2CH2CCH3), 213.4 (CO).
MS (EI): m/z (%) = 436 (2) [M+], 361 (23), 293 (23), 265 (24), 225
(48), 151 (28), 133 (43), 75 (83), 73 (100).
HRMS (EI): m/z [M+] calcd for C26H48O328Si: 436.33727; found:
3
POCH2CH3), 4.25 [d, J = 9.8 Hz, 1 H, CH(OSi)CCH3], 4.56 (dd,
3
3J = 7.5 Hz, J = 7.5 Hz, 2 H, CHCH2OP), 5.33–5.36 (m, 1 H,
434.33644.
CHCH2CH2), 5.40–5.44 (m, 1 H, CHCH2OP), 6.45–6.47 (m, 1 H,
CHCH2CHCH).
UV (MeOH): lmax (log e) = 204 (4.05), 232 nm (2.85).
13C NMR (100 MHz, CDCl3): d = –5.2 [Si(CH3)], –4.7 [Si(CH3)],
10.2 [CH(OSi)CCH3], 16.1 (COCCH3), 16.1 (d, 3J = 6.8 Hz, 2 × C,
POCH2CH3), 16.3 (CH2CH2CCH3), 18.1 [SiC(CH3)3], 20.5
[CH(CH3)2], 21.4 [CH(CH3)2], 25.5 (CHCHCH2), 25.5
(CH2CH2CCH3), 25.7 [3 × C, SiC(CH3)3], 29.4 [CH(CH3)2], 38.9
(CH2CH2CCH3), 42.8 (CHCHCH2), 53.9 (CHCHCH2), 63.6 (d,
2J = 5.8 Hz, 2 × C, POCH2CH3), 63.9 (d, 2J = 5.6 Hz, CHCH2OP),
79.4 [CH(OSi)CCH3], 119.4 (d, 3J = 6.9 Hz, CHCH2OP), 127.3
(CHCH2CH2), 134.7 (COCCH3), 136.8 [CH(OSi)CCH3], 140.9
(CHCH2CHCH), 141.9 (CH2CH2CCH3), 200.4 (CO).
MS (FAB): m/z (%) = 593 (7) [M + Na]+, 571 (5) [M + H]+, 513 (5),
439 (10), 419 (14), 359 (32), 285 (100), 265 (75), 229 (12), 211
(18).
HRMS (FAB): m/z [M + H]+ calcd for C30H56O628SiP: 571.3584;
found: 571.3567.
(8R,2E,6E)-8-(tert-Butyldimethylsilyloxy)-8-[(1S,3S,6R)-6-iso-
propyl-3-methyl-2-oxocyclohexyl]-3,7-dimethylocta-2,6-dienyl
Diethyl Phosphate (32)
Under N2, alcohol 31 (795 mg, 1.82 mmol, 1.00 equiv) was dis-
solved in anhydrous CH2Cl2 (3.0 mL). Pyridine (0.18 mL,
2.18 mmol, 1.20 equiv) and ClP(O)(OEt)2 (0.29 mL, 2.00 mmol,
1.1 equiv) were added at 0 °C. After 1 h at 0 °C the reaction was
quenched with 1 M HCl (3 mL) and extracted with Et2O (4 × 5 mL).
The organic phase was washed with 1 M HCl (2 × 10 mL), sat.
NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4 and evap-
orated. The residue was purified by quick column filtration (silica;
PE–EtOAc, 2:1) to give 32.
Yield: 560 mg (54%); colorless oil; Rf = 0.35 (silica; PE–EtOAc,
1:1); [a]D25 –55.9 (c 0.98, CHCl3).
IR (ATR): 2957 (m), 2930 (m), 2858 (w), 1710 (m), 1461 (w), 1389
(w), 1366 (w), 1256 (m), 1163 (w), 1031 (s), 1005 (s), 978 (s), 869
(m), 836 (s), 808 (m), 774 (s), 665 (w), 536 (w) cm–1.
HRMS (FAB): m/z [M + Na]+ calcd for C30H55O628SiPNa:
593.3403; found: 593.3391.
UV (MeOH): lmax (log e) = 202 (4.18), 236 (3.79), 324 nm (2.13).
1H NMR (300 MHz, CDCl3): d = –0.08 [s, 3 H, Si(CH3)], –0.02 [s,
3 H, Si(CH3)], 0.80 [s, 9 H, SiC(CH3)3], 0.81 [d, 3J = 6.6 Hz, 3 H,
CH(CH3)2], 0.88 [d, 3J = 6.4 Hz, 3 H, CH(CH3)2], 0.98 (d,
3J = 6.4 Hz, 3 H, COCHCH3), 1.22–1.28 (m, 1 H, CHCHCH2CH2),
1.34 (dt, 3J = 7.1 Hz, 4J = 1.0 Hz, 6 H, POCH2CH3), 1.38–1.48 [m,
2 H, CHCHCH2CH2, CH(CH3)2], 1.53–1.54 [m, 3 H,
CH(OSi)CCH3], 1.67–1.72 (m, 1 H, CHCHCH2CH2), 1.72 (m, 3 H,
CH2CH2CCH3), 1.77–1.85 (m, 1 H, CHCHCH2CH2), 1.88–1.95 (m,
1 H, CHCHCH2CH2), 2.08–2.24 (m, 4 H, CH2CH2CCH3,
CH2CH2CCH3), 2.60 (qd, 3J = 6.2 Hz, 3J = 12.6 Hz, 1 H,
COCHCH3), 2.69 (d, 3J = 10.4 Hz, 1 H, CHCHCH2CH2), 4.07–4.16
(m, 4 H, POCH2CH3), 4.47 [d, 3J = 10.4 Hz, 1 H, CH(OSi)CCH3],
(2S,3R,6S)-2-[(1R,2E,6E)-1-(tert-Butyldimethylsilyloxy)-8-hy-
droxy-2,6-dimethylocta-2,6-dienyl]-3-isopropyl-6-methylcyclo-
hexanone (31)
To a solution of 29 (2.50 g, 5.76 mmol, 1.00 equiv) in EtOH
(33.0 mL), BiCl3 (907 mg, 2.88 mmol, 0.5 equiv) was added at
0 °C. After 5 min at 0 °C, NaBH4 (876 mg, 23 mmol, 4.00 equiv)
was added slowly and the reaction was stirred for 4.5 h at 0 °C. The
reaction was quenched with H2O (15 mL) and filtered. The residue
was washed with H2O (2 × 10 mL), sat. NH4Cl (2 × 10 mL) and
CH2Cl2 (2 × 10 mL). The aqueous phase was extracted with CH2Cl2
(4 × 30 mL), dried over MgSO4 and evaporated. The residue was
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3953
4.54–4.59 (m, 2 H, CHCH2OP), 5.34–5.40 (m, 1 H, CHCH2CH2C),
5.41–5.46 (m, 1 H, CHCH2OP).
HRMS (ESI): m/z [M + Na]+ calcd for C52H94O428Si2Na: 861.6588;
found: 861.6586.
13C NMR (75 MHz, CDCl3): d = –5.5 [Si(CH3)], –4.4, [Si(CH3)],
10.1 [CH(OSi)CCH3], 14.5 (COCHCH3), 16.1 (d, 3J = 6.8 Hz, 2 ×
C, POCH2CH3), 16.3 (CH2CH2CCH3), 17.9 [SiC(CH3)3], 20.5
[CH(CH3)2], 21.4 [CH(CH3)2], 22.8 (CHCHCH2CH2), 25.6 [3 × C,
SiC(CH3)3], 25.6 (CH2CH2CCH3), 27.3 [CH(CH3)2], 32.2
(CH2CH2CHCH), 38.9 (CH2CH2CCH3), 41.8 (COCHCH3), 45.8
Data for 34
1H NMR (400 MHz, CDCl3): d = –0.07 [s, 3 H, Si(CH3)], –0.02 [s,
3 H, Si(CH3)], 0.79 [s, 9 H, SiC(CH3)3], 0.81 [d, 3J = 6.7 Hz, 3 H,
CH(CH3)2], 0.88 [d, 3J = 6.4 Hz, 3 H, CH(CH3)2], 0.98 (d,
3J = 6.4 Hz, 3 H, COCHCH3), 1.24–1.28 (m, 1 H, CHCHCHCH2),
1.35–1.43 [m, 2 H, CHCHCHCH2CH2, CH(CH3)2], 1.52 (m, 3 H,
CH3CCHCH2CH2), 1.58 (m, 3 H, CH3CCHCH3), 1.60 (m, 3 H,
CH3CCHCH3), 1.66–1.70 (m, 1 H, CHCHCHCH2), 1.79–1.85 (m,
1 H, CHCHCHCH2), 1.87–1.93 (m, 1 H, CHCHCHCH2CH2),
2.04–2.09 (m, 2 H, CH2CH2C), 2.11–2.18 (m, 2 H, CH2CH2C),
2.55–2.65 (m, 1 H, COCHCH3), 2.67 (d, 3J = 10.5 Hz, 1 H,
2
(CHCHCH2CH2), 57.9 (CHCHCH2CH2), 63.6 (d, J = 5.8 Hz, 2 ×
C, POCH2CH3), 63.9 (d, 2J = 5.5 Hz, CHCH2OP), 80.3
[CH(OSi)CCH3], 119.4 (d, 3J = 7.0 Hz, CHCH2OP), 128.4
(CHCH2CH2C), 135.9 [CH(OSi)CCH3], 141.9 (CH2CH2CCH3),
213.5 (CO).
MS (ESI): m/z (%) = 595/596 (100/30) [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C30H57O628SiPNa: 595.3560;
3
CHCHCHCH2), 4.47 (d, J = 10.5 Hz, 1 H, CHCHCHCH2), 5.24–
5.19 (m, 1 H, CH3CCHCH3), 5.34–5.38 (m, 1 H, CHCH2CH2C).
13C NMR (100 MHz, CDCl3): d = –5.6 [Si(CH3)], –4.4 [Si(CH3)],
10.0 (CH3CCHCH2CH2), 13.4 (CH3CCHCH3), 14.5 (COCHCH3),
15.4 (CH3CCHCH3), 18.0 [SiC(CH3)3], 20.5 [CH(CH3)2], 21.4
[CH(CH3)2], 22.8 (CHCHCHCH2), 25.6 [3 × C, SiC(CH3)3], 25.8
(CH3CCHCH2CH2), 27.3 [CH(CH3)2], 32.3 (CHCHCHCH2CH2),
39.0 (CH3CCHCH2CH2), 41.7 (COCHCH3), 45.8 (CHCHCHCH2),
57.9 (CHCHCHCH2), 80.4 (CHCHCHCH2), 118.8 (CH3CCHCH3),
129.3 (CH3CCHCH2CH2), 135.1 (CH3CCHCH3), 135.1
(CH3CCHCH2CH2), 213.7 (CO).
found: 595.3570.
UV (MeOH): lmax (log e) = 204 (4.13), 288 nm (2.03).
Homodimer 33
Samarium (864 mg, 5.74 mmol, 6.60 equiv) and diiodoethane
(1.472 g, 5.22 mmol, 6.00 equiv) were stirred in anhydrous and de-
gassed THF (52.0 mL). After 3 h, 32 (500 mg, 0.87 mmol,
1.00 equiv) dissolved in THF (50.0 mL) was dropped into the blue
SmI2 solution and stirred for 16 h. The reaction was quenched with
1 M HCl (80 mL) and extracted with Et2O (4 × 50 mL). The organic
phase was washed with sat. Na2S2O3 (100 mL), H2O (100 mL) and
brine (100 mL), dried over MgSO4 and evaporated. The crude prod-
uct was purified by column chromatography on silica (PE–EtOAc,
40:1 → 20:1) to give dimer 33 (142 mg, 0.17 mmol, 39%) as a col-
orless oil along with a mixture of two isomers 34 and 35 (55 mg,
0.13 mmol, 15%) in a ratio of 10:1. Isomer 35 was a 1:1 mixture of
two diastereomers.
Data for 35
1H NMR (400 MHz, CDCl3): d = –0.07 [s, 3 H, Si(CH3)], –0.06 [s,
3 H, Si(CH3)], –0.01 [s, 6 H, Si(CH3)], 0.80 [s, 18 H, SiC(CH3)3],
0.80–0.82 [m, 6 H, CH(CH3)2], 0.87 [d, 3J = 6.6 Hz, 6 H,
CH(CH3)2], 0.97–0.99 (m, 6 H, COCHCH3), 0.99–1.02 (m, 6 H,
CH3CHCHCH2), 1.27–1.30 (m, 2 H, CHCHCHCH2), 1.33–1.37
(m, 4 H, CCHCH2CH2), 1.39–1.43 [m, 4 H, CHCHCHCH2CH2,
CH(CH3)2], 1.52 (m, 6 H, CH3CCHCH2CH2), 1.65–1.73 (m, 2 H,
CHCHCHCH2), 1.79–1.87 (m, 2 H, CHCHCHCH2), 1.87–1.93 (m,
2 H, CHCHCHCH2CH2), 1.99–2.09 (m, 4 H, CCHCH2CH2), 2.09–
2.18 (m, 2 H, CH3CHCHCH2), 2.55–2.63 (m, 2 H, COCHCH3),
2.66–2.69 (m, 2 H, CHCHCHCH2), 4.46–4.50 (m, 2 H,
CHCHCHCH2), 4.92–4.93 (m, 1 H, CH3CHCHCH2), 4.94–4.95
(m, 2 H, CH3CHCHCH2), 4.98–5.00 (m, 1 H, CH3CHCHCH2),
5.34–5.42 (m, 2 H, CCHCH2CH2), 5.65–5.75 (m, 2 H,
CH3CHCHCH2).
Rf = 0.46 (silica; PE–EtOAc, 20:1); [a]D25 –73.8 (c 0.29, CHCl3).
IR (ATR): 2957 (m), 2930 (m), 2889 (m), 2858 (m), 1711 (s), 1461
(m), 1387 (w), 1363 (w), 1250 (m), 1159 (w), 1094 (m), 1054 (s),
1006 (w), 964 (w), 870 (m), 835 (s), 808 (m), 773 (s), 733 (w), 665
(w), 586 (w) cm–1.
1H NMR (400 MHz, CDCl3): d = –0.07 [s, 6 H, Si(CH3)], –0.02 [s,
6 H, Si(CH3)], 0.80 [s, 18 H, SiC(CH3)3], 0.81 [d, 3J = 6.5 Hz, 6 H,
CH(CH3)2], 0.87 [d, 3J = 6.4 Hz, 6 H, CH(CH3)2], 0.98 (d,
3J = 6.4 Hz, 6 H, COCHCH3), 1.24–1.27 (m, 2 H, CHCHCHCH2),
1.33–1.46 [m, 4 H, CHCHCHCH2CH2, CH(CH3)2], 1.53 (s, 6 H,
CH3CCHCH2CH2C), 1.61 (s, 6 H, CH2CH2CCH3), 1.67–1.70 (m,
2 H, CHCHCHCH2), 1.79–1.85 (m, 2 H, CHCHCHCH2), 1.87–
1.93 (m, 2 H, CHCHCHCH2CH2), 2.02–2.09 (m, 8 H,
CH2CH2CCH3, CH2CCHCH2), 2.11–2.18 (m, 4 H, CH2CH2CCH3),
2.55–2.63 (m, 2 H, COCHCH3), 2.67 (d, 3J = 10.4 Hz, 2 H,
13C NMR (100 MHz, CDCl3): d = –5.6 [Si(CH3)], –5.5 [Si(CH3)], –
4.4 [Si(CH3)], –4.4 [Si(CH3)], 10.1 (CH3CCHCH2CH2), 10.1
(CH3CCHCH2CH2), 14.5 (2 × C, COCHCH3), 18.0 [2 × C,
SiC(CH3)3], 20.0 (CH3CHCHCH2), 20.2 (CH3CHCHCH2), 20.6
[2 × C, CH(CH3)2], 21.4 [2 × C, CH(CH3)2], 22.9 (2 × C,
CHCHCHCH2), 25.3 (2 × C, CH3CCHCH2CH2), 25.6 [6 × C,
SiC(CH3)3], 27.4 [2
CHCHCHCH2CH2), 36.1 (2
×
C, CH(CH3)2], 32.3 (2
×
C,
3
CHCHCHCH2), 4.47 (d, J = 10.4 Hz, 2 H, CHCHCHCH2), 5.15–
5.17 (m, 2 H, CH2CCHCH2), 5.37–5.40 (m, 2 H, CHCH2CH2C).
×
C, CH3CCHCH2CH2), 37.4
(CH3CHCHCH2), 37.4 (CH3CHCHCH2), 41.8 (2 × C, COCHCH3),
45.9 (2 × C, CHCHCHCH2), 58.0 (2 × C, CHCHCHCH2), 80.5
13C NMR (100 MHz, CDCl3): d = –5.5 [2 × C, Si(CH3)], –4.4
[2 × C, Si(CH3)], 10.1 (2 × C, CH3CCHCH2CH2C), 14.5 (2 × C,
COCHCH3), 15.9 (2 × C, CH2CH2CCH3), 18.0 [2 × C, SiC(CH3)3],
20.6 [2 × C, CH(CH3)2], 21.5 [2 × C, CH(CH3)2], 22.9 (2 × C,
CHCHCHCH2), 25.6 [6
CH2CH2CCH3), 27.3 [2
CH2CCHCH2), 32.3 (2 × C, CHCHCHCH2CH2), 39.1 (2 × C,
CHCH2CH2C), 41.8 (2
CHCHCHCH2), 57.9 (2 × C, CHCHCHCH2), 80.4 (2 × C,
CHCHCHCH2), 124.6 (2 × C, CH2CCHCH2), 129.2 (2 × C,
CHCH2CH2C), 134.7 (2 × C, CHCH2CH2C), 135.2 (2 × C,
CHCCHCH2CH2), 213.6 (2 × C, CO).
(2
×
C, CHCHCHCH2), 112.8 (CH3CHCHCH2), 112.8
(CH3CHCHCH2),
(CH3CCHCH2CH2),
(CH3CCHCH2CH2),
129.5
135.1
144.4
(CH3CCHCH2CH2),
(CH3CCHCH2CH2),
(CH3CHCHCH2),
129.5
135.4
144.4
×
×
C, SiC(CH3)3], 26.1 (2
C, CH(CH3)2], 28.3 (2
×
×
C,
C,
(CH3CHCHCH2), 213.5 (2 × C, CO).
Mixture of 34 and 35
Rf = 0.58 (silica; PE–EtOAc, 20:1).
× C, COCHCH3), 45.8 (2 × C,
IR (ATR): 2957 (m), 2929 (m), 2890 (m), 2859 (m), 1711 (s), 1461
(m), 1386 (w), 1364 (w), 1250 (m), 1159 (w), 1094 (m), 1056 (s),
1006 (w), 964 (w), 946 (w), 886 (m), 835 (s), 808 (m), 773 (s), 733
(w), 665 (w), 584 (w) cm–1.
MS (EI): m/z (%) = 420 (1) [M+], 405 (3), 363 (98), 267 (100), 209
(39), 135 (36), 75 (51), 73 (69).
MS (ESI): m/z (%) = 861/862 (100/61) [M + Na]+.
UV (MeOH): lmax (log e) = 203 nm (4.42).
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3954
E. Schöttner et al.
PAPER
HRMS (EI): m/z [M – Me]+ calcd for C25H45O228Si: 405.31888;
found: 405.31845.
CH3CCHCH2CH), 5.10–5.13 (m, 1 H, CHCH2CH2C), 5.31 (d,
3J = 2.6 Hz, 1 H, CHCHCHCH2).
UV (MeOH): lmax (log e) = 203 (4.01), 286 nm (1.89).
13C NMR (150 MHz, CDCl3): d = –5.2 [Si(CH3)], –5.1 [Si(CH3)],
11.5 (COCHCH3), 12.7 (CH3CCHCH2CH2), 15.4 (CH2CH2CCH3),
18.2 [SiC(CH3)3], 19.7 [CH(CH3)2], 22.1 [CH(CH3)2], 25.2
(CH2CH2CCH3), 25.9 [3 × C, SiC(CH3)3], 28.0 (CHCHCHCH2),
29.3 (CH3CCHCH2CH), 30.4 [CH(CH3)2], 37.2 (CH3CCHCH2CH),
39.9 (CHCHCHCH2), 40.0 (CH2CH2CCH3), 45.4 (CH3CHCO),
(1R,3E,7E,9R,10S,12S,14R)-9-(tert-Butyldimethylsilyloxy)-14-
isopropyl-4,8,12-trimethylbicyclo[8.2.2]tetradeca-3,7-dien-11-
one (36)
Samarium (475 mg, 3.16 mmol, 6.08 equiv) was stirred under ar-
gon in anhydrous, degassed THF (26.3 mL) and diiodoethane
(742 mg, 2.63 mmol, 5.06 equiv) was added. After 4 h, 30 (300 mg,
0.52 mmol, 1.00 equiv), dissolved in THF (53.0 mL), was dropped
into the blue SmI2 solution and the mixture was stirred for 1 h at r.t.
The reaction was quenched with 1 M HCl (50 mL) and extracted
with Et2O (4 × 40 mL). The organic phase was washed with sat.
Na2S2O3 (60 mL), H2O (60 mL) and brine (60 mL) and dried over
MgSO4. After evaporation, the residue was purified by column
chromatography (silica; PE → PE–EtOAc, 40:1 → 20:1) to give
the bicycle 36.
61.2
(CHCHCHCH2),
127.7
73.7
(CHCHCHCH2),
(CH3CCHCH2CH2),
123.2
136.5
(CH3CCHCH2CH),
(CH3CCHCH2CH2), 136.8 (CH2CH2CCH3), 214.6 (CO).
MS (EI): m/z (%) = 418 (2) [M+], 361 (8), 269 (2), 198 (100), 141
(84), 73 (31).
HRMS (EI): m/z [M+] calcd for C26H46O228Si: 418.3267; found:
418.3264.
UV (MeOH): lmax (log e) = 203 nm (3.93).
X-ray Structure Determinations
Yield: 100 mg (46%); colorless oil; Rf = 0.19 (silica; PE–EtOAc,
20:1); [a]D25 +102.7 (c 0.60, CHCl3).
Numerical details are presented in Table 2. Data collection: Crys-
tals were mounted in inert oil on glass fibers and transferred to the
cold gas stream of the diffractometer (Oxford Diffraction Nova O
for 15 and 16, Oxford Diffraction Xcalibur S for 22a). Absorption
corrections based on multiple scans were performed. Structure re-
finement: The structures were refined anisotropically against F2 us-
ing the program SHELXL-97.21 Hydroxy hydrogens were refined
freely; other H atoms were included using a riding model or ideal-
ized rigid methyl groups. In all cases, the absolute configuration
was confirmed by the Flack parameter. Compounds 15 and 16 are
essentially isotypic. Complete crystallographic data (excluding
structure factors) have been deposited at the Cambridge Crystallo-
graphic Data Centre under the numbers CCDC 727147 (15),
727148 (16) and 727149 (22a).
IR (ATR): 2954 (m), 2929 (m), 2856 (m), 1702 (m), 1461 (w), 1387
(w), 1366 (w), 1254 (m), 1076 (m), 1057 (s), 1036 (s), 1036 (s),
1005 (s), 896 (s), 859 (w), 834 (s), 814 (m), 774 (s), 677 (w), 589
(w), 547 (w) cm–1.
1H NMR (600 MHz, CDCl3): d = 0.01 [s, 3 H, Si(CH3)], 0.02 [s,
3 H, Si(CH3)], 0.88 [s, 9 H, SiC(CH3)3], 0.93 [d, 3J = 6.5 Hz, 3 H,
CH(CH3)2], 0.97 [d, 3J = 6.5 Hz, 3 H, CH(CH3)2], 1.11 (d,
3J = 6.7 Hz, 3 H, COCHCH3), 1.50–1.54 (m, 1 H, CHCHCHCH2),
1.54 (s, 3 H, CH2CH2CCH3), 1.60 (s, 3 H, CH2CH2CHCCH3),
1.69–1.74 (m, 1 H, CHCHCHCH2), 1.90–2.03 [m, 5 H, CH(CH3)2,
CHCHCHCH2, CH2CH2CCH3, CH2CH2CCH3, CH3CCHCH2CH],
2.08–2.15 (m, 2 H, CH2CH2CCH3, CH3CCHCH2CH), 2.29–2.36
(m, 2 H, CH2CH2CCH3, CHCHCHCH2), 2.41–2.46 (m, 1 H,
CH3CCHCH2CH), 2.61 (dd, 3J = 6.9 Hz, 3J = 13.6 Hz, 1 H,
COCHCH3), 4.68 (m, 3J = 4.3 Hz, 3J = 11.5 Hz, 1 H,
Table 2 Details of X-ray Structure Analyses
Compound
Formula
Mr
15
16
22a
C17H24O2
260.36
C17H22O2
258.35
C21H38O3Si
366.60
Habit
colorless tablet
0.2 × 0.15 × 0.08
Cu Ka
colorless tablet
0.3 × 0.2 × 0.2
Cu Ka
colorless plate
0.45 × 0.4 × 0.02
Mo Ka
Crystal size (mm)
Radiation
l (Å)
1.54184
1.54184
0.71073
Crystal system
Space group
Cell constants:
a (Å)
orthorhombic
P212121
orthorhombic
P212121
monoclinic
P21
5.6405(3)
14.7723(4)
18.4186(5)
90
5.7520(2)
14.6744(3)
17.5551(3)
90
10.0162(4)
11.9025(4)
10.3783(4)
90
b (Å)
c (Å)
a (°)
b (°)
90
90
118.464(4)
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of a Rearranged Eunicellane Diterpenoid
3955
Table 2 Details of X-ray Structure Analyses (continued)
Compound
g (°)
15
16
22a
90
90
90
V (Å3)
1534.7
4
1481.8
4
1087.7
2
Z
Dx (Mg m–3)
m (mm–1)
F(000)
1.127
0.56
1.158
0.58
1.119
0.12
404
568
560
T (°C)
–180
142
–173
142
–173
57.4
99.6%
2qmax
Completeness
No. of reflections:
Measured
Independent
Rint
99% to 135°
96% to 135°
21914
2868
19946
2690
0.021
178
30716
5566
0.028
239
0.021
179
Parameters
Flack parameter
wR(F2, all refl.)
R[F, >4s(F)]
S
–0.02(17)
0.074
0.028
1.08
0.04(19)
0.074
0.029
1.08
0.01(6)
0.068
0.027
1.02
max. Dr/e Å–3
0.17
0.20
0.32
Overman, L. E.; Pennington, L. D. J. Am. Chem. Soc. 2003,
125, 6650. (e) Crimmins, M. T.; Brown, B. H. J. Am. Chem.
Soc. 2004, 126, 10264. (f) Kim, H.; Lee, H.; Kim, J.; Kim,
S.; Kim, D. J. Am. Chem. Soc. 2006, 128, 15851. (g) Clark,
J. S.; Hayes, S. T.; Wilson, C.; Gobbi, L. Angew. Chem. Int.
Ed. 2007, 46, 437. (h) Becker, J.; Bergander, K.; Fröhlich,
R.; Hoppe, D. Angew. Chem. Int. Ed. 2008, 47, 1654.
(i) Molander, G. A.; Jean, D. J. S. Jr.; Haas, J. J. Am. Chem.
Soc. 2004, 126, 1642.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
Support by the Deutsche Forschungsgemeinschaft (DFG, Li 597/4-1)
is gratefully acknowledged.
(5) For leading references, see: (a) Gilmour, R.; Prior, T. J.;
Burton, J. W.; Holmes, A. B. Chem. Commun. 2007, 3954.
(b) Ellis, J. M.; Crimmins, M. T. Chem. Rev. 2008, 108,
5278.
(6) For cyclization of cembranoids to eunicellanoids, see:
Shpatov, A. V.; Shakirov, M. M.; Raldugin, V. A. Russ. J.
Org. Chem. 2000, 36, 1163; and references cited therein.
(7) Araki, S.; Hatano, M.; Ito, H.; Butsugan, Y. J. Organomet.
Chem. 1987, 333, 329.
References
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Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York

3956
E. Schöttner et al.
PAPER
between any of the diastereotopic protons 5a-H/5b-H and
(12) (a) Shing, T. K. M.; Tang, Y.; Malone, J. F. J. Chem. Soc.,
Chem. Commun. 1989, 1294. (b) Shing, T. K. M.; Zhu,
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Navarro, I.; Gris, A. Tetrahedron 2006, 62, 3266.
(14) The high value for 3JOH–7H (11–12 Hz) in all eight examples
reflects the antiperiplanar arrangement of the two protons.
The 3J3H–7H coupling constants are very small (1–2 Hz) as
expected for cis-fused six-membered rings. 3J3H–4H coupling
constants show values between 11 and 12 Hz due to diaxial
arrangement.
3-H rules out axial positioning of 3-H. 3J coupling constants
between 8 and 10 Hz are consistent with an antiperiplanar
arrangement of 3-H and the carbinol-H of the side chain.
(16) Ren, P.-D.; Pan, S.-F.; Dong, T.-W.; Wu, S.-H. Synth.
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3
(15) JOH–CH Coupling constants vary from 3 to 9 Hz indicating
that hydrogen-bridged six-membered rings are not as
dominant as in the cyclohexanone case. The 3J3H–4H coupling
constants of cyclohexenone-type carvones reach values
between 2 and 5 Hz. The absence of NOESY correlations
(21) Sheldrick, G. M. Acta Crystallogr., Sect A 2008, 64, 112.
Synthesis 2009, No. 23, 3941–3956 © Thieme Stuttgart · New York