Synthesis of the c1-c14 fragment of sarcoglaucol-16-one via z -selective ando-type horner-wadsworth-emmons olefination

Article abstract of DOI:10.1055/s-0029-1218825

A synthetic strategy involving a Z-selective Horner-Wadsworth-Emmons olefination was developed for the preparation of the sarcoglaucolone precursor methyl (2Z,6E)-8-(methoxymethoxy)-6-methyl-2-[(3E)-4-methyl-5-oxopent-3-enyl]-9- [(trimethylsilyl)methyl]deca-2,6,9-trienoate. The target compound was isolated in a E/Z ratio of 17:83 Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1218825

PAPER
2643
Synthesis of the C1–C14 Fragment of Sarcoglaucol-16-one via Z-Selective
Ando-Type Horner–Wadsworth–Emmons Olefination
Synthesis of the
S
h
arcoglaucol
r
one C1–
i
C14 Fra
s
gment toph Gastl, Sabine Laschat*
Institut für Organische Chemie, Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax +49(711)68564285; E-mail: sabine.laschat@oc.uni-stuttgart.de
Received 26 March 2010; revised 12 April 2010
stereogenic centres at C-6 and C-9. The results are report-
ed below.
Abstract: A synthetic strategy involving a Z-selective Horner–
Wadsworth–Emmons olefination was developed for the preparation
of the sarcoglaucolone precursor methyl (2Z,6E)-8-(methoxymeth-
oxy)-6-methyl-2-[(3E)-4-methyl-5-oxopent-3-enyl]-9-[(trimethyl-
silyl)methyl]deca-2,6,9-trienoate. The target compound was
isolated in a E/Z ratio of 17:83
In our retrosynthetic approach, which is shown in
Scheme 1, a ring-closing metathesis (RCM)10,11 of macro-
cyclic methacrylate 2 was planned as the final step. Meth-
acrylate 2 should be obtained from allylic alcohol
derivative 3 via deprotection and esterification. Macrocy-
clization towards 3 should be achieved via intramolecular
Sakurai reaction12,13 of enal 4 which, in turn, could arise
from the C7–C14 fragment 5 via deprotection of the pri-
mary alcohol, oxidation to the corresponding aldehyde,
followed by Horner–Wadsworth–Emmons olefination
with phosphonate 6 (i.e., C1–C6 fragment). We hoped to
establish the stereogenic centre at C-9 via a Noyori-type
addition14 of an organozinc species derived from isopro-
penyl bromide 8 to the a,b-unsaturated aldehyde 7.
Key words: Ando-type reaction, olefination, cembranolide, natural
product, macrocycles
Cembranolides are macrocyclic diterpenes of marine ori-
gin that possess a variety of interesting biological activi-
ties, such as cytotoxic, anti-inflammatory, anti-bacterial
and anti-viral activities, which make these natural prod-
ucts promising targets for synthetic approaches1–3 as pio-
neered by Marshall.4 In 2004, Wright and König reported
the isolation of the cembranolide sarcoglaucol-16-one (1)
from a soft coral species belonging to the genus Sarcophy-
ton (Scheme 1).5 The structure of 1 was established by
NMR analysis and the absolute stereochemistry was de-
termined by the modified Mosher method. It was further
shown that compound 1 displayed promising cytotoxic
activity against MCF7 tumor cell lines.5 From a synthetic
point of view, sarcoglaucol-16-one (1) possesses the fol-
lowing structural features: (a) a 14-membered macrocycle
with attached g-butenolide unit,6 (b) two stereogenic cen-
tres at C-6 and C-9 and (c) a methyl ester at a branching
position of the diterpenoid, the latter being rather uncom-
mon among the various cembranolides. Whereas the car-
bon skeleton of 1 can be biogenetically traced back to
geranylacetone or geranylgeraniol,1 results by Dorta on
furanocembranolides revealed that a genus-specific oxi-
dation cascade leads from a methyl group to a carboxylic
acid or ester.2e However, the regioselective C–H oxidation
of the branching methyl groups in a terpene precursor is
rather difficult to achieve by chemical means,7 and even
treatment of terpene derivatives with isolated cytochrome
P450 monooxygenases often yields complex product mix-
tures with competing or sometimes strongly favoured ep-
oxide formation rather than allylic oxidation.8,9 In order to
develop a total synthesis of sarcoglaucol-16-one (1), we
decided to first establish the C1–C14 carbon skeleton of
the macrocycle 1 with correct configuration of the C=C
double bonds, and to focus later on the installation of the
O
O
O
O
9
14
RCM
1
CO2Me
CO2Me
6
7
OH
OH
sarcoglaucol-16-one
OR1
1
2
1) deprotection
2) esterification
OR1
TMS
Sakurai
CO2Me
CO2Me
O
OH
4
3
1) deprotection
2) oxidation
3) HWE olefination
organozinc
addition
OR1
O
R4O
R4O
TMS
5
7
O
(R2O)2P
CO2R3
Br
TMS
8
O
6
Scheme 1
SYNTHESIS 2010, No. 15, pp 2643–2651
x
x.
x
x
.
2
0
1
0
Advanced online publication: 18.06.2010
DOI: 10.1055/s-0029-1218825; Art ID: Z07810SS
© Georg Thieme Verlag Stuttgart · New York

2644
C. Gastl, S. Laschat
PAPER
The synthesis of the C7–C14 fragment commenced with and 82% ee. However, when enal 7a was treated with eth-
protection of 5-hydroxypentan-2-one (9) with triethylsilyl yl{1-[(trimethylsilyl)methyl]vinyl}zinc20 in the presence
chloride (TESCl) in the presence of triethylamine at room of ligand 14 under similar conditions, allylic alcohol 5a
temperature in 96% yield, followed by olefination with was isolated in 54% yield in racemic form. Then, the ad-
phosphonate 10a in the presence of 1,8-diazabicyc- dition was performed with ligand 1521 instead of N-mor-
lo[5.4.0]undec-7-ene (DBU) and lithium chloride in ace- pholinoisoborneol 14, yielding the allylic alcohol 5a in
tonitrile at room temperature according to the procedure 54% yield with a disappointing 6% ee (see also Support-
by Roush,15 to yield the a,b-unsaturated ester 11 in 68% ing Information for further experiments). Due to these un-
yield (E/Z = 74:26; Scheme 2). Reduction of 11 to the cor- expected difficulties, we decided to continue the synthetic
responding allylic alcohol 12 was achieved with diisobu- efforts with the racemic material 5a, which was protected
tylaluminum hydride (DIBAL-H)16 in tetrahydrofuran with chloromethyl methyl ether (MOMCl) in dichlo-
(THF) at –78 °C, from which the pure E-isomer 12 could romethane in the presence of Hünig’s base at room tem-
be obtained after flash chromatography in 61% yield.
perature to give the O-MOM-derivative 5b in 97% yield.
Subsequent deprotection of the TES group with tetrabutyl-
ammonium fluoride (TBAF) in THF at 0 °C gave 5c in
85% yield, which was oxidised with TPAP and NMO in
dichloromethane at room temperature to yield aldehyde
16 in 70% yield.
1) TESCl, py
r.t., 12 h, 96%
HO
TESO
CO2Me
O
O
2)
10a
9
11 (E/Z = 74:26)
(MeO)2P CH2CO2Me
DBU, LiCl, MeCN
r.t., 96 h, 68%
DIBAL-H, THF
–78 °C, 2 h, 61%
For the synthesis of the C1–C6 fragment 6a, the Ando
phosphonate 10b22 was deprotonated with sodium hydride
in dimethylsulfoxide (DMSO) at room temperature, fol-
lowed by addition of 4-bromobut-1-ene at 40 °C to yield
the phosphonate derivative 17a in 79% based on recov-
ered starting material 10b (Scheme 3).
TPAP, NMO
O
CH2Cl2
TESO
TESO
OH
10 °C, 30 min
61%
7a
12
EtZn
EtZn
toluene
0 °C, 1 h
TMS
, 14
, 15
Compound 17a was submitted to ozonolysis, the progress
of which was monitored by addition of Sudanred III,23 fol-
lowed by reductive work-up with triphenylphosphane to
give the aldehyde 18a in 76% yield. Treatment with stabi-
lized ylide 1924 in a (3:1) mixture of benzene and toluene
under reflux gave the enal-substituted phosphonate 6a in
65% yield. Compound 6a was protected either with 2,2-
dimethoxypropane in the presence of 10-camphorsulfonic
acid (CSA) in methanol at room temperature to give the
dimethylacetal 20a in 98% yield, or with 1,3-pro-
panedithiol and Montmorillonite K10 in dichloromethane
at room temperature to give the corresponding dithioace-
tal 20b in 88% yield. Phosphonate 20a was deprotonated
with sodium hydride in the presence of sodium iodide in
THF at room temperature, followed by addition of the
enal 16 in THF at –20 °C and warming to room tempera-
ture according to the procedure by Pikho,25,26 to give the
desired olefin 21a in 79% crude yield, predominantly as
the Z-isomer (E/Z = 17:83). Due to the fact that the crude
product 21a already contained 15% of enal 4a, the mix-
ture was treated with Dowex 50 × 8 ion-exchange resin in
dichloromethane at room temperature in order to hydro-
lyze the dimethyl acetal; enal 4a was isolated in 78% yield
(E/Z = 17:83). Dithioacetal 20b was treated in a similar
manner with aldehyde 16 as described for phosphonate
20a, and the corresponding olefin 21b was isolated in
47% yield (E/Z = 17:83).
OH
OH
TESO
TESO
TMS
13 78%, 82% ee
54%, 6% ee
5a
MOMCl, i-Pr2NEt
CH2Cl2, r.t., 36 h, 97%
O
OMOM
N
RO
TMS
OH
5b R = TES
14
TBAF, THF
0 °C, 10 min, 85%
O
5c R = H
OH
TPAP, NMO, CH2Cl2
r.t., 1 h, 70%
N
OMOM
15
O
TMS
16
Scheme 2
Subsequent oxidation with tetrapropylammonium perru-
thenate (TPAP) and N-methylmorpholine N-oxide
(NMO) in dichloromethane at 10 °C, yielded enal 7a in
61% yield. Next, Noyori-type 1,2-additions14,17 of an or-
ganozinc species to enal 7a were investigated in order to
establish the stereochemistry at C-9 of sarcoglaucol-16-
one (1). In a preliminary experiment, when enal 7a was
treated with ethylisopropenylzinc,18 employing N-mor-
pholinoisoborneol 1419 as chiral ligand, in toluene at 0 °C,
the desired allylic alcohol 13 was isolated in 78% yield
In order to check whether the Ando phosphonates 20a and
20b are required for the Z-selective Horner–Wadsworth–
Emmons olefination, the structurally related diethyl phos-
phonate 22 was deprotonated with sodium hydride in the
presence of sodium iodide in THF, followed by addition
of aldehyde 16, and the corresponding alkenes 23 were
isolated in 80% yield as a mixture of Z- and E-isomers
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

PAPER
Synthesis of the Sarcoglaucolone C1–C14 Fragment
2645
OMOM
1) NaH, DMSO
r.t., 30 min
O
O
(ArO)2P
CO2Me
(ArO)2P
CO2Me
TMS
2) Br(CH2)2CH=CH2
r.t., 1 h; 40 °C, 16 h
79%
10b Ar = o-tolyl
CO2Et
O
O
17a
(EtO)2P
CO2Et
1) O3, Sudanred III
CH2Cl2, –78 °C
2) Ph3P, r.t., 3 h
76%
(Z)-23
1) NaH, NaI, THF
r.t., 15 min
O
2) 16, THF, 0 °C
4 h; r.t., 8 h, 86%
(E/Z = 50:50)
O
O
O
OMOM
Ph3P
O
O
19
(ArO)2P
CO2Me
(ArO)2P
CO2Me
O
TMS
C6H6–toluene
(3:1), reflux
24 h, 65%
22
O
EtO2C
18a
6a
O
(E)-23
HS(CH2)3SH, K10, CH2Cl2
r.t., 6 h, 88%
Me2C(OMe)2
CSA, MeOH
O
75 °C, 3 h, 98%
Scheme 4
O
O
(ArO)2P
CO2Me
OMe
(ArO)2P
CO2Me
S
Melting points were measured with a Mettler-Toledo DSC822e cal-
orimeter and are uncorrected. IR spectra were recorded with a Bruker
Vector 22 FT-IR spectrometer. 1H and 13C NMR spectra were
recorded with a Bruker Avance 300 or a Bruker Avance 500 spec-
trometer with TMS as an internal standard. Mass spectra were re-
corded with a Finnigan MAT 95 (CI) instrument with ammonia as
reactant gas, a Varian MAT 711 (EI, 70 eV) and a Bruker Daltonics
microTOF-Q (ESI) spectrometer with nitrogen as carrier gas. Flash
chromatography was performed using Kieselgel 60, 40–63 mm
(Fluka). All solvents were dried, and reactions were performed in
dried glassware using standard Schlenk techniques. Reaction mon-
itoring was performed with a Trace GC 2000 Ultra Optima 5-MS
column (30 m × 0.25 mm) with hydrogen as carrier gas using differ-
ent temperature programs. The enantioselectivity was detected by
gas chromatography on chiral stationary phases.
OMe
S
20a
20b
1) NaH, NaI, THF, r.t., 15 min
2) 16, THF, –20 °C to r.t., 7 h
OMOM
TMS
OMOM
TMS
CO2Me
CO2Me
OMe
OMe
S
S
21a 79% (crude) (E/Z = 17:83)
21b
47%
(E/Z = 17:83)
Dowex 50x8
CH2Cl2, r.t., 15 min, 78%
The following compounds were prepared according to literature
procedures: 10b,22 11,4d 19,24 diisopropenylzinc18 and 2-bromo-3-
trimethylsilylprop-1-ene.20 For details of the preparation of ligand
15 and phosphonate 22, see the Supporting Information.
OMOM
4
9
7
5
8
6
3
TMS
1
2
10
CO2Me
(2E)-3-Methyl-6-[(triethylsilyl)oxy]hex-2-en-1-ol (12)
5'
1'
4'
3'
To a solution of 11 (4.27 g, 15.7 mmol) in THF (80 mL), was drop-
wise added DIBAL-H (52 mL, 62.7 mmol, 1.2 M in toluene) at
–78 °C and the mixture was stirred for 2 h. Sat. Seignette salt solu-
tion (20 mL) was added at –78 °C, and the mixture was warmed to
r.t., the layers were separated, the aqueous layer was extracted with
Et2O (5 × 100 mL) and the combined organic layers were dried over
Na2SO4 and evaporated. The crude product was purified by flash
chromatography on SiO2 (hexanes–EtOAc, 5:1) to yield 12.
O
2'
4a (E/Z = 17:83)
Scheme 3
(50:50, Scheme 4). It should be noted that the Still–
Gennari olefination27 was not considered as an alternative
method due to the use of expensive (bistrifluoroeth-
yl)phosphonate and [18]crown-6-ether.
Yield: 2.32 g (61%); pale-yellow oil; 100% E by 1H NMR analysis;
Rf = 0.34 (hexanes–EtOAc, 5:1).
FTIR (ATR): 3340 (w), 2952 (s), 2912 (s), 2876 (s), 1669 (w), 1458
(m), 1415 (m), 1382 (m), 1299 (w), 1238 (m), 1193 (w), 1095 (vs),
1003 (vs), 960 (s), 804 (s), 775 (m), 724 (vs), 669 (m) cm–1.
1H NMR (250 MHz, CDCl3): d = 0.58 (q, J = 7.9 Hz, 6 H, CH2,
TES), 0.96 (t, J = 7.9 Hz, 9 H, CH3, TES), 1.34 (br s, OH), 1.59–
1.72 (m, 2 H, H-4), 1.68 (d, J = 1.3 Hz, 3 H, CH3), 2.03–2.11 (m,
2 H, H-5), 3.68 (t, J = 6.6 Hz, 2 H, H-6), 4.15 (dq, J = 6.9, 0.7 Hz,
2 H, H-1), 5.42 (tq, J = 6.9, 1.3 Hz, 1 H, H-2).
In conclusion, the acyclic C1–C14 carbon skeleton 4a of
sarcoglaucol-16-one (1) has been established by a conver-
gent approach in ten steps (for the longest linear se-
quence) and 4.7% overall yield from hydroxyketone 9,
employing a Z-selective Ando-type Horner–Wadsworth–
Emmons olefination of 20a and aldehyde 16 as the key
step. Attempts to improve the enantioselectivity of the
1,2-addition of isopropenylzinc derivatives to enal 7a to
gain access to the enantiomerically pure target molecule
4a are currently in progress in our laboratories.
13C NMR (125 MHz, CDCl3): d = 2.9 (CH3, TES), 5.3 (CH2, TES),
14.7 (C-4), 29.4 (C-5), 34.2 (CH3), 57.9 (C-3), 60.9 (C-1), 121.8 (C-
2), 138.1 (C-3).
GC/MS (EI): m/z (%) = 340 (6), 307 (10), 294 (4), 266 (8), 262 (3),
239 (4), 220 (2), 215 (7), 199 (3), 191 (22), 180 (23), 165 (4), 153
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

2646
C. Gastl, S. Laschat
PAPER
(4E)-5-Methyl-8-[(triethylsilyl)oxy]-2-[(trimethylsilyl)meth-
(8), 147 (9), 134 (86), 119 (44), 106 (38), 103 (41), 93 (42), 90 (38),
87 (7), 73 (100, TMS), 67 (7), 59 (10), 51 (13).
yl]octa-1,4-dien-3-ol (5a)
To a solution of 2-bromo-3-trimethylsilylprop-1-ene (80 mg,
0.41 mmol) in Et2O (1 mL), was added t-BuLi (565 mL, 0.85 mmol,
1.5 M in toluene) at –78 °C. The mixture was warmed to –20 °C
over 1 h and re-cooled to –78 °C. Then, ZnCl2 (207 mL, 0.21 mmol,
1 M in Et2O) was added and the mixture was warmed to r.t. over 3
h, followed by sequential addition of diethylzinc (22 mL,
0.21 mmol) and 7a (97 mg, 0.4 mmol) in Et2O (1 mL). After 1 h, the
reaction mixture was hydrolyzed by addition of sat. NH4Cl (10 mL).
The layers were separated and the organic layers were extracted
with EtOAc (3 × 10 mL), dried (Na2SO4) and evaporated. The
crude product was purified by flash chromatography on SiO2 (hex-
anes–EtOAc, 10:1) to give 5a.
Anal. Calcd for C13H28O2Si: C, 63.87; H, 11.56. Found: C, 63.78;
H, 11.45.
(2E)-3-Methyl-6-[(triethylsilyl)oxy]hex-2-enal (7a)
To a solution of 12 (500 mg, 2.04 mmol) in CH2Cl2 (30 mL), were
added powdered molecular sieves 4 Å (1.00 g), NMO (1.44 g,
12.3 mmol) and TPAP (30 mg, 0.08 mmol) at 0 °C. After 10 min,
the mixture was warmed to r.t., filtered through SiO2, evaporated
and purified by flash chromatography (hexanes–EtOAc, 2:1) to
yield aldehyde 7a.
Yield: 302 mg (61%); colourless oil; Rf = 0.30 (hexane–EtOAc,
10:1).
Yield: 38 mg (54%); pale-yellow oil; Rf = 0.55 (hexanes–EtOAc,
10:1); 6% ee (by GC on Bondex a un b).
FTIR (ATR): 2953 (s), 2912 (s), 2876 (s), 1673 (vs), 1634 (m), 1458
(m), 1414 (m), 1383 (m), 1239 (m), 1192 (m), 1097 (vs), 1008 (s),
956 (m), 863 (m), 799 (s), 725 (vs), 670 (m), 599 (w), 551 (w), 516
(w) cm–1.
1H NMR (300 MHz, CDCl3): d = 0.59 (q, J = 7.9 Hz, 6 H, CH2,
TES), 0.96 (t, J = 7.9 Hz, 9 H, CH3, TES), 1.67–1.79 (m, 2 H, H-5),
2.18 (d, J = 1.2 Hz, 3 H, H-7), 2.25–2.33 (m, 2 H, H-4), 3.63 (t,
J = 6.2 Hz, 2 H, H-6), 5.89 (ddd, J = 8.0, 2.3, 1.2 Hz, 1 H, H-2),
10.00 (d, J = 8.0 Hz, 1 H, H-1).
FTIR (ATR): 3370 (w), 2952 (s), 2912 (s), 2877 (s), 2568 (w), 2373
(w), 2181 (w), 1973 (m), 1635 (w), 1458 (m), 1415 (m), 1382 (m),
1247 (s), 1157 (m), 1096 (s), 1005 (s), 962 (m), 882 (s), 839 (vs),
796 (s), 724 (vs), 693 (s), 670 (m), 633 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 0.58 (q, J =
7.9 Hz, 6 H, CH2, TES), 0.95 (t, J = 7.9 Hz, 9 H, CH3, TES), 1.38
(ddd, J = 14.0, 1.1, 0.3 Hz, 1 H, Ha-10), 1.45 (d, J = 3.5 Hz, 1 H,
OH), 1.59 (dd, J = 14.0, 1.1 Hz, 1 H, Hb-10), 1.63–1.69 (m, 2 H, H-
7), 1.73 (d, J = 1.4 Hz, 3 H, H-9), 2.06–2.09 (m, 2 H, H-6), 3.59 (t,
J = 6.7 Hz, 2 H, H-8), 4.65 (dq, J = 1.3, 1.04 Hz, 1 H, Ha-1), 4.65–
4.69 (m, 1 H, H-3), 4.98 (t, J = 1.4 Hz, 1 H, Hb-1), 5.15 (dq, J = 8.8,
1.4 Hz, 1 H, H-4).
13C NMR (125 MHz, CDCl3): d = 4.5 (CH3, TES), 6.8 (CH2, TES),
16.5 (C-5), 31.5 (C-4), 41.9 (C-7), 59.6 (C-6), 125.2 (C-2), 135.1
(C-3), 202.2 (C-1).
GC/MS (EI): m/z (%) = 224 (3), 182 (4), 165 (3), 149 (8), 134 (12),
131 (7), 120 (10), 115 (22, TES), 108 (43), 105 (38), 102 (8), 92
(88), 83 (62), 75 (22), 73 (100, TMS), 59 (36), 50 (24).
HRMS (ESI): m/z [M + Na]+ calcd for C13H26NaO2Si+: 265.1594;
13C NMR (125 MHz, CDCl3): d = 0.9 (TMS), 4.8 (CH3, TES), 7.1
(CH2, TES), 17.1 (C-9), 22.9 (C-10), 31.2 (C-7), 36.2 (C-6), 62.8
(C-8), 72.2 (C-3), 106.7 (C-1), 126.7 (C-4), 139.7 (C-5), 145.5 (C-
2).
found: 265.1587.
GC/MS (EI): m/z (%) = 338 (4) [M+ – H2O], 206 (10), 191 (6), 180
(24), 165 (9), 134 (39), 119 (34), 117 (26), 115 (18) [TES], 106 (15),
103 (16), 93 (20), 79 (6), 73 (100) [TMS], 59 (12).
HRMS (EI, 70 eV): m/z [M]+ calcd for C19H40O2Si2: 356.2567;
found: 356.2578.
(3R,4E)-2,5-Dimethyl-8-[(triethylsilyl)oxy]octa-1,4-dien-3-ol
(13)
To a solution of diethylzinc (127 mL, 1.24 mmol) in toluene (3 mL),
were added at r.t. over 15 min, diisopropenylzinc (413 mL, 0.41
mmol, 1 M in toluene) and ligand 14 (165 mL, 16.5 mmol, 0.1 M in
toluene) and the mixture was cooled to 0 °C. Then, 7a (100 mg, 0.41
mmol) was added and the reaction mixture was stirred for 1 h at
0 °C, hydrolyzed with sat. NH4Cl (10 mL) and diluted with Et2O (10
mL). The organic layer was separated, dried (Na2SO4), evaporated
and the crude product was purified by flash chromatography on
SiO2 (hexanes–EtOAc, 12:1) to give 13.
Anal. Calcd for C19H40O2Si2: C, 63.98; H, 11.30. Found: C, 63.97;
H, 11.31.
Triethyl[{(4E)-6-(methoxymethoxy)-4-methyl-7-[(trimethylsi-
lyl)methyl]octa-4,7-dienyl}oxy]silane (5b)
To an ice-cooled solution of alcohol 5a (243 mg, 0.68 mmol) in
CH2Cl2 (20 mL) were added sequentially DIPEA (2.56 mL,
14.3 mmol) and MOMCl (363 mL, 4.78 mmol). After 10 min, the
mixture was warmed to r.t., stirred for 36 h and then diluted with
H2O (20 mL). The layers were separated and the aqueous layer was
extracted with EtOAc (3 × 50 mL). The combined organic layers
were washed with 1.5 N HCl (20 mL), sat. NaHCO3 (20 mL), dried
(Na2SO4) and the solvent was evaporated. The crude product was
purified by flash chromatography on SiO2 (hexanes–EtOAc, 10:1)
to give 5b.
Yield: 91 mg (78%); colourless oil; Rf = 0.26 (hexanes–EtOAc,
10:1); 82% ee (by GC on Bondex a un b); [a]D20 –36 (c = 1, CHCl3).
FTIR (ATR): 3340 (m), 2939 (m), 2903 (m), 2876 (m), 2702 (w),
2548 (w), 2346 (w), 2189 (w), 1942 (m), 1651 (m), 1465 (m), 1415
(m), 1382 (m), 1335 (w), 1232 (m), 1095 (s), 1005 (s), 960 (m), 895
(m), 832 (m), 725 (vs), 670 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.61 (q, J = 7.9 Hz, 6 H, CH2,
TES), 0.96 (t, J = 7.9 Hz, 9 H, CH3, TES), 1.54 (d, J = 3.9 Hz, 1 H,
OH), 1.6–1.71 (m, 2 H, H-7), 1.65 (dd, J = 1.2, 0.8 Hz, 3 H, H-10),
1.73 (d, J = 1.4 Hz, 3 H, H-9), 1.97–2.13 (m, 2 H, H-6), 4.04–4.07
(m, 1 H, H-3), 4.17–4.19 (m, 2 H, H-8), 4.84–4.85 (m, 1 H, Ha-1),
4.94–4.95 (m, 1 H, Hb-1), 5.36 (tq, J = 6.5, 1.4 Hz, 1 H, H-4).
13C NMR (125 MHz, CDCl3): d = 4.5 (CH3, TES), 6.8 (CH2, TES),
16.4 (C-10), 17.6 (C-9), 32.9 (C-7), 35.5 (C-6), 59.7 (C-8), 75.6 (C-
3), 111.2 (C-1), 124.5 (C-4), 136.9 (C-5), 147.4 (C-2).
HRMS (ESI, positive): m/z [M + Na]+ calcd for C16H32O2SiNa:
307.2064; found: 307.2073.
Yield: 265 mg (97%); pale-yellow oil; Rf = 0.60 (hexanes–EtOAc,
10:1).
FTIR (ATR): 2952 (s), 2912 (m), 2877 (s), 1665 (w), 1637 (w),
1459 (m), 1416 (m), 1383 (m), 1247 (s), 1213 (m), 1149 (s), 1094
(vs), 1035 (vs), 958 (s), 917 (m), 884 (s), 840 (vs), 797 (s), 740 (vs),
726 (vs), 694 (s), 671 (m), 633 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 0.59 (q, J =
7.9 Hz, 6 H, CH2, TES), 0.96 (t, J = 7.9 Hz, 9 H, CH3, TES), 1.39
(dd, J = 14, 1 Hz, 1 H, Ha-3¢), 1.57 (dd, J = 14, 1 Hz, 1 H, Hb-3¢),
1.64–1.70 (m, 2 H, H-9), 1.72 (d, J = 1.3 Hz, 3 H, CH3), 2.06–2.1
(m, 2 H, H-8), 3.36 (s, 3 H, H-1), 3.58 (t, J = 6.9 Hz, 2 H, H-10),
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

PAPER
Synthesis of the Sarcoglaucolone C1–C14 Fragment
2647
4.56 (dd, J = 6.7, 0.3 Hz, 1 H, Ha-3), 4.61 (d, J = 6.7 Hz, 1 H, Hb-3),
4.62–4.65 (m, 1 H, H-5), 4.68 (ddd, J = 3.7, 1.8, 1.1 Hz, 1 H, Ha-1¢),
4.96–4.97 (m, 1 H, Hb-1¢), 5.07 (dq, J = 9.1, 1.3 Hz, 1 H, H-6).
13C NMR (125 MHz, CDCl3): d = –1.1 (TMS), 4.4 (CH3-TES), 6.8
(CH2-TES), 16.7 (CH3), 22.6 (C-3¢), 31.0 (C-9), 35.9 (C-8), 55.4
(C-1), 62.6 (C-10), 74.6 (C-5), 93.1 (C-3), 108.1 (C-1¢), 124.1 (C-
6), 140.2 (C-7), 146.4 (C-2¢).
GC/MS (EI): m/z (%) = 338 (2) [M+ – OMOM], 309 (2), 266 (2),
237 (6), 210 (4), 206 (8), 179 (14), 165 (7), 148 (4), 146 (9), 133
(72), 118 (43), 115 (21) [TES], 105 (34), 92 (46), 90 (37), 88 (32),
75 (26), 73 (100) [TMS], 59 (28).
2 H, H-3), 2.56–2.60 (m, 2 H, H-2), 3.35 (s, 3 H, OCH3), 4.57 (dd,
J = 6.5, 6.0 Hz, 2 H, H-2¢), 4.68–4.69 (m, 1 H, Ha-8), 4.95 (dt, J =
2.9, 1.0 Hz, 1 H, Hb-8), 5.1 (dq, J = 9.0, 1.4 Hz, 1 H, H-5), 9.77 (t,
J = 1.7 Hz, 1 H, H-1).
13C NMR (125 MHz, CDCl3): d = –1.1 (TMS), 16.8 (CH3), 22.4
(CH2TMS), 31.7 (C-3), 41.9 (C-2), 55.4 (OCH3), 74.6 (C-6), 93.2
(C-2¢), 108.5 (C-8), 125.1 (C-5), 138.2 (C-4), 146 (C-7), 201.9 (C-
1).
GC/MS (EI): m/z (%) = 222 (5), 204 (5), 187 (5), 181 (6), 165 (4),
149 (7), 135 (14), 132 (10), 117 (48), 106 (53), 95 (10), 93 (30), 92
(84), 90 (62), 88 (28), 79 (13), 74 (33), 73 (100) [TMS], 64 (8), 58
(33).
HRMS (EI, 70 eV): m/z [M]+ calcd for C21H44O3Si2: 400.2829;
found: 400.2810.
HRMS (ESI): m/z [M + Na]+ calcd for C15H28O3SiNa+: 307.1700;
found: 307.1702.
(4E)-6-(Methoxymethoxy)-4-methyl-7-[(trimethylsilyl)meth-
yl]octa-4,7-dienal (16)
Methyl 2-[Di(o-tolyl)oxyphosphoryl]hex-5-enoate (17a)
NaH (216 mg, 8.98 mmol, 60% suspension in mineral oil) was add-
ed to a solution of phosphonate 10b (3.00 g, 8.98 mmol) in DMSO
(5 mL). After stirring for 30 min at r.t., 4-bromobut-1-ene (1.05 mL,
10.3 mmol) was added dropwise and stirring was continued for 1 h.
The mixture was warmed to 40 °C and stirred for 16 h. After cool-
ing to r.t., sat. NH4Cl (50 mL) was added, the layers were separated
and the aqueous layer was extracted with EtOAc (3 × 50 mL). The
organic layer was dried (Na2SO4), evaporated and the residue was
purified by flash chromatography on SiO2 (hexanes–EtOAc, 2:1) to
yield 10b (705 mg, 2.11 mmol, 24%) and 17a (2.08 g, 79% based
on recovered 10b).
To a solution of 5b (151 mg, 0.38 mmol) in THF (2 mL) was added
dropwise a solution of TBAF·H2O (125 mg, 0.39 mmol) in THF (1
mL) at 0 °C, and the reaction mixture was stirred for 10 min. Then,
sat. NH4Cl (10 mL) was added, the mixture was warmed to r.t. and
the organic layer was extracted with EtOAc (3 × 10 mL), dried
(Na2SO4) and evaporated. The crude product was purified by flash
chromatography on SiO2 (hexanes–EtOAc, 10: 1) to give 5c.
Yield: 98 mg (90%); pale-yellow oil; Rf = 0.35 (hexanes–EtOAc,
10:1).
FTIR (ATR): 3346 (w), 2949 (m), 2884 (m), 2554 (w), 2367 (w),
1996 (w), 1636 (w), 1442 (w), 1417 (w), 1383 (w), 1247 (m), 1213
(w), 1145 (m), 1094 (m), 1033 (s), 957 (w), 917 (w), 884 (m), 839
(s), 771 (w), 726 (w), 694 (m), 634 (w) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 1.38 (dd, J =
14.1, 1.0 Hz, 1 H, CH2TMSa), 1.58 (dd, J = 14.1, 1.0 Hz, 1 H,
CH2TMSb), 1.68–1.76 (m, 2 H, H-2), 1.73 (d, J = 1.4 Hz, 3 H, CH3),
2.13 (td, J = 7.6, 1.3 Hz, 2 H, H-3), 3.36 (s, 3 H, OCH3), 3.62–3.66
(m, 2 H, H-1), 4.58 (dd, J = 6.7, 0.3 Hz, 1 H, Ha-2¢), 4.62 (d, J =
6.7 Hz, 1 H, Hb-2¢), 4.63–4.65 (m, 1 H, H-6), 4.68 (ddd, J = 3.7, 1.8,
1.1 Hz, 1 H, Ha-8), 4.96 (dd, J = 1.8, 1.1 Hz, 1 H, Hb-8), 5.08 (dq,
J = 9.2, 1.3 Hz, 1 H, H-5).
13C NMR (125 MHz, CDCl3): d = –1.1 (TMS), 16.6 (CH3), 22.5
(CH2TMS), 30.6 (C-2), 36.1 (C-3), 55.4 (OCH3), 62.7 (C-1), 74.8
(C-6), 93.3 (C-2¢), 108.2 (C-8), 124.5 (C-5), 139.9 (C-4), 146.3 (C-
7).
MS (EI): m/z (%) = 225 (3) [M+ – OMOM], 180 (4), 165 (3), 152
(5), 141 (6), 136 (12), 126 (5), 118 (36), 110 (14), 106 (25), 96 (16),
93 (58), 90 (48), 88 (18), 84 (12), 73 (100) [TMS], 66 (10), 58 (17).
Yellow oil; Rf = 0.35 (hexanes–EtOAc, 2:1).
FTIR (ATR): 3064 (w), 2952 (w), 1966 (m), 1737 (s), 1641 (w),
1585 (m), 1490 (s), 1461 (m), 1435 (m), 1336 (m), 1274 (s), 1222
(s), 1182 (s), 1163 (s), 1106 (s), 1043 (m), 929 (vs), 833 (m), 843
(m), 756 (vs), 708 (m), 601 (m) cm–1.
1H NMR (250 MHz, CDCl3): d = 2.07–2.48 (m, 4 H, H-2, H-4), 2.18
(s, 3 H, ArCH3), 2.24 (s, 3 H, ArCH3¢), 3.34 (ddd, J = 23.4, 10.8,
3.3 Hz, 1 H, H-2), 3.76 (s, 3 H, OCH3), 5.02 (dd, J = 1.2, 0.3 Hz,
1 H, Ha-6), 5.05–5.11 (m, 1 H, Hb-6), 5.68–5.85 (m, 1 H, H-5),
7.05–7.11 (m, 4 H, H-4¢, H-5¢, H-4¢¢, H-5¢¢), 7.11–7.2 (m, 2 H, H-
3¢), 7.21–7.35 (m, 2 H, H-6¢).
13C NMR (125 MHz, CDCl3): d = 16.3 (ArCH3), 26.2 (d, J = 3.9 Hz,
C-4), 32.3 (d, J = 16 Hz, C-3), 45.2 (d, J = 135.3 Hz, C-2), 52.6
(OCH3), 116.62 (C-5), 120.16 (d, J = 2.5 Hz, C-6¢), 120.24 (d, J =
2.5 Hz, C-9¢), 125.15 (C-4¢), 125.17 (C-4¢¢), 127.04 (d, J = 1.3 Hz,
C-5¢), 127.06 (d, J = 1.3 Hz, C-5¢¢), 129.22 (d, J = 1.3 Hz, C-2¢),
129.32 (d, J = 1.3 Hz, C-2¢¢), 131.41 (C-3), 131.43 (C-3¢¢), 136.3 (d,
J = 0.5 Hz, C-6), 148.9 (d, J = 1 Hz, C-1¢), 149.1 (d, J = 1 Hz, C-
1¢¢), 168.3 (d, J = 5.5 Hz, C-1).
HRMS (ESI): m/z [M + Na]+ calcd for C15H30O3SiNa+: 309.1856;
found: 309.1858.
31P NMR (202 MHz, CDCl3): d = 15.17–15.38 (m).
To a solution of 5c (72 mg, 0.24 mmol) in CH2Cl2 (10 mL) were se-
quentially added powered 4 Å molecular sieves (250 mg), NMO
(170 mg, 1.43 mmol) and TPAP (6 mg, 0.02 mmol) at 0 °C. The re-
action mixture was stirred for 1.5 h then warmed to r.t., filtered over
a plug of SiO2 and evaporated. The crude product was purified by
flash chromatography (hexane–EtOAc, 7:1) to yield 16.
GC/MS (EI): m/z (%) = 388 (14) [M]+, 357 (16), 347 (100), 334 (8),
315 (43), 302 (16), 287 (19), 249 (11), 227 (15), 192 (10), 180 (23),
165 (9), 153 (10), 133 (7), 115 (11), 108 (48) [o-cresyl], 107 (22),
91 (78) [tolyl], 77 (21), 64 (19), 55 (22).
HRMS (ESI): m/z [M + Na]+ calcd for C21H25O5PNa+: 411.1332;
found: 411.1337.
Yield: 50 mg (70%); colourless oil; Rf = 0.35 (hexanes–EtOAc,
6:1).
Methyl 2-[Di(o-tolyl)oxyphosphoryl]-5-oxopentanoate (18a)
A solution of 17a (768 mg, 1.98 mmol) and Sudanred III (3 mg) in
CH2Cl2 (70 mL) was cooled to –78 °C. Then, ozone was bubbled
through the solution until it turned colourless, followed by bubbling
argon through the solution for 5 min. Ph3P (648 mg, 2.47 mmol)
was added and the reaction mixture was warmed to r.t. over 7 h.
Evaporation of the solvent followed by flash chromatography on
SiO2 (hexanes–EtOAc, 1:1) yielded 18a.
FTIR (ATR): 2952 (m), 2890 (m), 2821 (w), 2721 (w), 2563 (w),
2367 (w), 2181 (w), 1965 (w), 1725 (s), 1668 (m), 1636 (m), 1444
(m), 1416 (m), 1386 (m), 1348 (w), 1247 (s), 1212 (w), 1148 (s),
1093 (s), 1031 (vs), 976 (m), 957 (m), 916 (m), 883 (s), 838 (vs),
772 (m), 723 (w), 693 (m), 621 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 1.36 (dd, J =
14.1, 1.0 Hz, 1 H, CH2TMSa), 1.57 (dd, J = 14.1, 1.1 Hz, 1 H,
CH2TMSb), 1.74 (d, J = 1.4 Hz, 3 H, CH3), 2.38 (td, J = 7.5, 1.4 Hz,
Yield: 586 mg (76%); yellow oil; Rf = 0.30 (hexanes–EtOAc, 1:1).
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

2648
C. Gastl, S. Laschat
PAPER
Methyl (5E)-2-[Di(o-tolyl)oxyphosphoryl]-7,7-dimethoxy-6-
FTIR (ATR): 2953 (w), 2728 (w), 1965 (w), 1735 (s), 1585 (m),
1490 (s), 1461 (m), 1436 (m), 1385 (w), 1328 (w), 1271 (s), 1222
(s), 1181 (m), 1162 (s), 1106 (s), 1043 (m), 930 (vs), 852 (m), 806
(m), 757 (s), 708 (m), 599 (m), 562 (m), 530 (m), 518 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 2.2 (s, 3 H, ArCH3), 2.24 (s, 3 H,
ArCH3¢), 2.45–2.55 (m, 2 H, H-4), 2.63–2.8 (m, 2 H, H-3), 3.44
(ddd, J = 29.9, 8.8, 5.6 Hz, 1 H, H-2), 3.76 (s, 3 H, OCH3), 7.03–
7.17 (m, 4 H, H-5¢, H-5¢¢, H-4¢, H-4¢¢), 7.15–7.20 (m, 2 H, H-3¢, H-
3¢¢), 7.22–7.25 (m, 1 H, H-6¢), 7.28–7.32 (m, 1 H, H-6¢¢), 9.75 (s,
1 H, H-5).
13C NMR (125 MHz, CDCl3): d = 16.3 (ArCH3), 19.7 (d, J = 4.8 Hz,
C-4), 41.8 (d, J = 13.1 Hz, C-3), 44.8 (d, J = 134.6 Hz, C-2), 52.8
(OCH3), 120.1 (d, J = 2.4 Hz, C-6¢), 120.2 (d, J = 2.1 Hz, C-6¢¢),
125.3 (C-4¢), 127.1 (C-5¢), 129.2 (d, J = 4.3 Hz, C-2¢), 129.3 (d, J =
4.3 Hz, C-2¢¢), 131.5 (d, J = 3.9 Hz, C-3¢), 148.8 (d, J = 9.6 Hz, C-
1¢), 168.3 (d, J = 5.5 Hz, C-1), 203 (C-5).
methylhept-5-enoate (20a)
To a solution of 6a (250 mg, 0.53 mmol) in MeOH (8 mL) were
added dimethoxypropane (1 mL, 8.16 mmol) and CSA (12 mg, 0.05
mmol) and the mixture was distilled to remove MeOH and acetone.
Filtration through basic Al2O3 and evaporation gave 20a.
Yield: 257 mg (98%); pale-yellow oil.
FTIR (ATR): 3475 (w), 2974 (m), 2932 (m), 2829 (m), 1962 (w),
1738 (s), 1651 (m), 1585 (m), 1491 (s), 1453 (m), 1438 (m), 1382
(w), 1333 (m), 1273 (m), 1223 (s), 1181 (s), 1163 (s), 1106 (vs),
1071 (s), 1042 (s), 931 (vs), 859 (m), 806 (m), 757 (vs), 708 (m),
601 (m), 561 (m) cm–1.
1H NMR (500 MHz, CDCl3): d = 1.58 (d, J = 1.4 Hz, 3 H, CH3),
2.14–2.40 (m, 3 H, H-2, H-4), 2.19 (s, 3 H, ArCH3), 2.24 (s, 3 H,
ArCH3¢), 3.27 (s, 3 H, OCH3), 3.28 (s, 3 H, OCH3¢), 3.35 (ddd, J =
23.2, 11.2, 3.2 Hz, 1 H, H-2), 3.77 (d, J = 0.7 Hz, 3 H, CO2CH3),
4.45 (d, J = 0.6 Hz, 1 H, H-7), 5.53 (t, J = 6.7 Hz, 1 H, H-5), 7.02–
7.12 (m, 4 H, H-5¢, H-5¢¢, H-4¢, H-4¢¢), 7.14–7.19 (m, 2 H, H-3¢, H-
3¢¢), 7.21–7.24 (m, 1 H, H-6¢), 7.27–7.30 (m, 1 H, H-6¢¢).
13C NMR (125 MHz, CDCl3): d = 11.2 (CH3), 16.3 (ArCH3), 16.4
(ArCH3¢), 26.1 (d, J = 16.1 Hz, C-3), 26.6 (d, J = 4.8 Hz, C-4), 45.5
(d, J = 133.9 Hz, C-2), 52.7 (CO2CH3), 53.5 (OCH3), 53.6 (OCH3¢),
107.4 (C-7), 120.1 (d, J = 2.6 Hz, C-6¢), 120.2 (d, J = 2.1 Hz, C-6¢¢),
125.1 (C-4¢), 125.2 (C-4¢¢), 126.8 (C-5), 127.0 (d, J = 1.3 Hz, C-5¢),
127.1 (d, J = 1.3 Hz, C-5¢¢), 129.3 (d, J = 4.5 Hz, C-2¢), 129.3 (d,
J = 4.4 Hz, C-2¢¢), 131.4 (C-3¢), 131.5 (C-3¢¢), 134.2 (C-6), 148.9 (d,
J = 1.5 Hz, C-1¢), 149 (d, J = 1.4 Hz, C-1¢¢), 168.6 (d, J = 5.8 Hz, C-
1).
31P NMR (202 MHz, CDCl3): d = 14.03–14.38 (m).
GC/MS (EI): m/z (%) = 391 (2) [M + H]+, 359 (6), 335 (11), 315
(24), 302 (18), 283 (100), 273 (5), 252 (26), 244 (7), 227 (28), 212
(14), 195 (10), 179 (23), 165 (12), 153 (15), 131 (12), 120 (6), 108
(61) [o-cresyl], 105 (13), 91 (74) [tolyl], 77 (32), 65 (26), 55 (17).
HRMS (ESI): m/z [M + H]+ calcd for C20H23O6PH+: 391.1305;
found: 391.1301.
Anal. Calcd for C20H23O6P: C, 61.54; H, 5.94. Found: C, 61.62; H,
5.89.
Methyl (5E)-2-[Di(o-tolyl)oxyphosphoryl]-6-methyl-7-oxohept-
5-enoate (6a)
A solution of 18a (200 mg, 0.51 mmol) and ylide 19 (236 mg,
0.72 mmol) in benzene (3 mL) and toluene (1 mL) was heated at re-
flux for 15 h. Evaporation of the solvent followed by flash chroma-
tography (hexanes–EtOAc, 1:1) yielded 6a.
31P NMR (202 MHz, acetonitrile-d3): d = 15.77–16.14 (m).
GC/MS (EI): m/z (%) = 444 (12), 405 (3), 386 (2), 354 (3), 293 (4),
285 (2), 222 (7), 198 (3), 182 (36), 171 (5), 166 (5), 150 (12), 137
(3), 123 (100), 111 (22), 91 (22) [tolyl], 79 (18), 77 (17), 65 (4), 55
(6), 53 (10).
Yield: 144 mg (65%); pale-yellow oil; Rf = 0.50 (hexanes–EtOAc,
1:1).
HRMS (ESI): m/z [M + Na]+ calcd for C25H33O7PNa+: 499.1856;
found: 499.1849.
FTIR (ATR): 3060 (w), 2952 (w), 2864 (w), 2825 (w), 2714 (w),
2359 (w), 2339 (w), 1736 (s), 1683 (s), 1645 (m), 1585 (m), 1490
(s), 1460 (m), 1436 (m), 1382 (w), 1336 (m), 1273 (s), 1223 (s),
1164 (vs), 1107 (vs), 1042 (s), 934 (vs), 853 (m), 806 (s), 759 (vs),
708 (m), 602 (m), 561 (m), 520 (s), 507 (s) cm–1.
1H NMR (250 MHz, CDCl3): d = 1.74 (d, J = 1.4 Hz, 3 H, CH3),
2.19 (s, 3 H, ArCH3), 2.25 (s, 3 H, ArCH3¢), 2.45–2.68 (m, 4 H, H-
2, H-4), 3.35 (ddd, J = 23.9, 10.2, 4 Hz, 1 H, H-2), 3.78 (d,
J = 0.6 Hz, 3 H, OCH3), 6.42 (tq, J = 7.2, 1.4 Hz, 1 H, H-5), 7.04–
7.12 (m, 4 H, H-5¢, H-5¢¢, H-4¢, H-4¢¢), 7.13–7.22 (m, 2 H, H-3¢, H-
3¢¢), 7.23–7.32 (m, 2 H, H-6¢, H-6¢¢), 9.42 (s, 1 H, H-7).
13C NMR (125 MHz, CDCl3): d = 9.3 (CH3), 16.31 (ArCH3), 16.33
(ArCH3¢), 25.8 (d, J = 4.5 Hz, C-4), 27.5 (d, J = 15.9 Hz, C-3), 45.4
(d, J = 134.9 Hz, C-2), 52.8 (OCH3), 120.1 (d, J = 2.5 Hz, C-6¢),
120.2 (d, J = 2.5 Hz, C-6¢¢), 125.34 (d, J = 1 Hz, C-4¢), 125.35 (d,
J = 1 Hz, C-4¢¢), 127.11 (d, J = 1.4 Hz, C-5¢), 127.14 (d, J = 1.4 Hz,
C-5¢¢), 129.18 (d, J = 5.9 Hz, C-2¢), 129.24 (d, J = 5.9 Hz, C-2¢¢),
131.51 (d, J = 0.7 Hz, C-3¢), 131.53 (d, J = 0.7 Hz, C-3¢¢), 140.79
(C-6), 148.82 (d, J = 1.3 Hz, C-1¢), 148.9 (d, J = 1.3 Hz, C-1¢¢),
151.1 (C-5), 168.4 (d, J = 5.8 Hz, C-1), 194.9 (d, J = 2.2 Hz, C-7).
Methyl (5Z)-2-[Di(o-tolyl)oxyphosphoryl]-6-(1,3-dithian-2-
yl)hept-5-enoate (20b)
To a solution of 6a (100 mg, 0.21 mmol) in CH2Cl2 (10 mL), was
added 1,3-propanedithiol (64 mL, 0.63 mmol) and Montmorillonite
K10 (20 mg) and the mixture was stirred at r.t. for 6 h. Evaporation
of the solvent yielded 20b.
Yield: 96 mg (88%); pale-yellow oil.
FTIR (ATR): 2948 (w), 2898 (w), 1738 (s), 1491 (s), 1461 (m),
1435 (m), 1274 (s), 1226 (s), 1166 (s), 1108 (s), 947 (s), 633 (s), 607
(w) cm–1.
1H NMR (500 MHz, CDCl3): d = 1.78 (s, 3 H, CH3), 1.84 (dtt, J =
14, 12.2, 3.2 Hz, 1 H, Ha-2¢), 2.10 (dtt, J = 14, 4.4, 2.5 Hz, 1 H, Hb-
2¢), 2.15–2.26 (m, 2 H, Ha-1¢), 2.19 (d, J = 0.4 Hz, 3 H, Ar-CH3),
2.24 (d, J = 0.4 Hz, 3 H, Ar-CH3¢), 2.3–2.38 (m, 2 H, Hb-1¢), 2.82–
2.88 (m, 2 H, H-3), 2.90–2.98 (m, 2 H, H-4), 3.36 (ddd, J = 23.4, 11,
3.1 Hz, 1 H, H-2), 3.77 (d, J = 0.4 Hz, 3 H, OCH3), 4.56 (d, J =
0.4 Hz, 1 H, H-7), 5.31 (tdd, J = 6.3, 1.3, 0.4 Hz, 1 H, H-5), 7.02–
7.07 (m, 2 H, H-5¢¢, H-5¢¢¢), 7.08–7.13 (m, 2 H, H-4¢¢, H-4¢¢¢), 7.14–
7.18 (m, 2 H, H-3¢¢, H-3¢¢¢), 7.22–7.24 (m, 1 H, H-6¢¢), 7.27–7.29
(m, 1 H, H-6¢¢¢).
13C NMR (125 MHz, CDCl3): d = 15.1 (CH3), 16.4 (Ar-CH3), 16.4
(Ar-CH3¢), 25.4 (C-2¢), 26.5 (d, J = 4.8 Hz, C-4), 26.6 (d, J =
16.2 Hz, C-3), 31.5 (C-1¢), 45.2 (d, J = 132 Hz, C-2), 52.7 (OCH3),
55.1 (C-7), 120.2 (d, J = 2.6 Hz, C-6¢¢), 120.3 (d, J = 2.6 Hz, C-6¢¢¢),
125.15 (d, J = 1.3 Hz, C-4¢¢), 125.16 (d, J = 1.3 Hz, C-4¢¢¢), 127.05
(d, J = 1.1 Hz, C-5¢¢), 127.06 (d, J = 1.1 Hz, C-5¢¢¢), 127.24 (C-5),
129.29 (d, J = 1.4 Hz, C-2¢¢), 129.34 (d, J = 1.1 Hz, C-2¢¢¢), 131.41
31P NMR (202 MHz, CDCl3): d = 14.35–14.65 (m).
GC/MS (EI): m/z (%) = 431 (22) [M + H], 412 (8), 402 (10), 365
(7), 347 (51), 335 (12), 315 (33), 303 (16), 287 (8), 263 (72), 253
(12), 241 (28), 209 (26), 190 (14), 184 (27), 178 (28), 168 (21), 152
(12), 137 (25), 126 (32), 124 (14), 108 (32) [o-cresyl], 91 (100)
[tolyl], 71 (28), 65 (18), 55 (38).
HRMS (ESI): m/z [M + H]+ calcd for C23H27O6PH+: 431.1618;
found: 431.1614.
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

PAPER
Synthesis of the Sarcoglaucolone C1–C14 Fragment
2649
(C-3¢¢, C-3¢¢¢), 135.42 (C-6), 148.92 (d, J = 3.0 Hz, C-1¢¢), 148.99 (d,
J = 3.0 Hz, C-1¢¢¢), 168.6 (d, J = 5.5 Hz, C-1).
31P NMR (202 MHz, CDCl3): d = 14.91–15.43 (m).
GC/MS (EI): m/z (%) = 520 (2) [M]+, 461 (88), 445 (3), 413 (6), 401
(4), 381 (24), 353 (8), 315 (5), 303 (2), 273 (2), 245 (2), 230 (3), 227
(5), 197 (3), 183 (5), 167 (8), 151 (11), 147 (4), 127 (100), 111 (13),
99 (23), 91 (42), 79 (54), 77 (16), 65 (12), 60 (10), 55 (14).
crude product was purified by flash chromatography on SiO2 (hex-
anes–EtOAc, 5: 1) to yield 21b.
Yield: 20 mg (47%); colourless oil (E/Z = 17:83 by 1H NMR anal-
ysis); Rf = 0.50 (hexanes–EtOAc, 5:1).
FTIR (ATR): 2949 (m), 2897 (m), 2559 (w), 2371 (w), 2184 (w),
1966 (w), 1715 (s), 1683 (m), 1637 (w), 1506 (w), 1435 (m), 1379
(w), 1246 (s), 1195 (m), 1148 (s), 1093 (m), 1033 (vs), 977 (m), 957
(m), 914 (m), 881 (m), 839 (vs), 770 (m), 693 (m), 634 (w), 621 (w),
528 (w), 511 (w) cm–1.
HRMS (ESI): m/z [M + H]+ calcd for C26H33O5PS2H+: 521.1589;
found: 521.1580.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 1.38 (ddd, J =
13.9, 1.1, 0.3 Hz, 1 H, CH2TMS-Ha), 1.58 (ddd, J = 14.1, 1.1,
0.3 Hz, 1 H, CH2TMS-Hb), 1.71 (d, J = 1.4 Hz, 3 H, CH3¢), 1.75 (dt,
J = 1.4, 0.8 Hz, 3 H, CH3), 1.78–1.87 (m, 1 H, Ha-8¢), 2.07–2.13 (m,
1 H, Hb-8¢), 2.14–2.18 (m, 4 H, H-5, H-1¢), 2.26–2.30 (m, 2 H, H-
2¢), 2.56–2.62 (m, 2 H, H-4), 2.82–2.87 (m, 2 H, H-7¢), 2.91–2.98
(m, 2 H, H-7¢), 3.36 (s, 3 H, OCH3), 3.74 (s, 3 H, CO2CH3), 4.55 (s,
1 H, H-5¢), 4.59 (dd, J = 26.2, 7.1 Hz, 2 H, H-2¢¢), 4.62–4.65 (m,
1 H, H-8), 4.68 (dd, J = 1.8, 0.8 Hz, 1 H, H-10a), 4.97 (dd, J = 1.8,
1.1 Hz, 1 H, H-10b), 5.09 (dq, J = 9.2, 1.3 Hz, 1 H, H-7), 5.6 (tdd,
J = 7.2, 1.4, 0.7 Hz, 1 H, H-3¢), 5.87 (tt, J = 7.3, 1 Hz, 1 H, H-3).
13C NMR (125 MHz, CDCl3): d = –1.1 (TMS), 15.1 (CH3¢), 16.5
(CH3), 22.5 (CH2TMS), 25.5 (C-8¢), 27.7 (C-1¢), 27.8 (C-4), 31.6
(C-7¢), 34.1 (C-2¢), 39.2 (C-5), 51.2 (CO2CH3), 55.3 (C-5¢), 74.5 (C-
8), 93.1 (C-2¢¢), 108.1 (C-10), 124.7 (C-7), 128.7 (C-3¢), 131.1 (C-
4¢), 133.8 (C-2), 139.6 (C-6), 142.6 (C-3), 146.3 (C-9), 168.2 (C-1).
Methyl (2Z,6E)-8-(Methoxymethoxy)-6-methyl-2-[(3E)-4-me-
thyl-5-oxopent-3-enyl]-9-[(trimethylsilyl)methyl]deca-2,6,9-
trienoate (4a)
To a solution of 20a (109 mg, 0.23 mmol) in THF (8 mL) were add-
ed NaI (45 mg, 0.29 mmol) and NaH (8 mg, 0.34 mmol) at 0 °C and
the mixture was stirred at r.t. for 15 min. The yellow solution was
cooled to –20 °C and a solution of 16 (65 mg, 0.23 mmol) in THF
(2 mL) was added dropwise. The reaction mixture was warmed to
r.t. over 7 h and quenched by addition of aqueous NaH2PO4/NaOH
buffer (0.1 M, 5 mL, pH 7). The aqueous layer was extracted with
CH2Cl2 (3 × 50 mL) and the combined organic layers were washed
with brine (50 mL), dried (Na2SO4) and evaporated. The crude
product was purified by flash chromatography on Florisil (hexanes–
EtOAc, 6:1) to yield 21a (86 mg, 79% crude) as a colourless oil
1
(E/Z = 17:83 by H NMR analysis), which contained 4a (15% as-
sessed by 1H NMR analysis). The product mixture was dissolved in
CH2Cl2 (10 mL), Dowex 50 × 8 (30 mg) was added and the mixture
was stirred at r.t. for 10 min to give 4a after filtration and evapora-
tion.
GC/MS (CI, CH4): m/z (%) = 526 (5) [M]+, 495 (4), 481 (12), 465
(32), 375 (6), 359 (8), 285 (5), 225 (4), 179 (24), 173 (11), 149 (6),
119 (10), 106 (25), 89 (34), 73 (100) [TMS], 61 (32), 45 (62).
HRMS (ESI): m/z [M + H]+ calcd for C27H46O4S2Si+: 527.2680;
found: 527.2670.
Yield: 78 mg (78%); colourless oil.
FTIR (ATR): 2951 (m), 2927 (m), 2709 (w), 2571 (w), 2365 (w),
2187 (w), 1967 (w), 1714 (s), 1686 (vs), 1643 (m), 1506 (w), 1436
(m), 1378 (m), 1246 (s), 1195 (s), 1149 (s), 1117 (s), 1093 (s), 1035
(s), 975 (m), 959 (m), 917 (w), 839 (vs), 770 (m), 694 (m), 634 (w),
525 (w) cm–1.
1H NMR (500 MHz, CDCl3): d = 0.04 (s, 9 H, TMS), 1.38 (dd, J =
5.0, 1.1 Hz, 1 H, CH2TMS-Ha), 1.57 (dd, J = 5.0, 1.1 Hz, 1 H,
CH2TMS-Hb), 1.71 (d, J = 1.4 Hz, 3 H, 4¢-CH3), 1.72 (d, J = 1.4 Hz,
3 H, 6-CH3), 2.15 (td, J = 7.5, 0.9 Hz, 2 H, H-5), 2.41–2.39 (m, 4 H,
H-1¢, H-2¢), 2.58–2.63 (m, 2 H, H-4), 3.36 (s, 3 H, OCH3), 3.75 (s,
3 H, CO2CH3), 4.58 (dd, J = 25.1, 6.6 Hz, 2 H, H-2¢¢), 4.67–4.68 (m,
1 H, H-8), 4.96 (dd, J = 1.9, 1.2 Hz, 2 H, H-10), 5.08 (dq, J = 9.2,
1.4 Hz, 1 H, H-7), 5.93 (tt, J = 7.3, 2.1 Hz, 1 H, H-3), 6.44 (tq, J =
7.3, 1.4 Hz, 1 H, H-3¢), 9.39 (s, 1 H, H-5¢).
Ethyl (2Z,6E)-2-[2-(1,3-Dioxan-2-yl)ethyl]-8-(methoxymeth-
oxy)-6-methyl-9-[(trimethylsilyl)methyl]deca-2,6,9-trienoate
(23)
A solution of 22 (43 mg, 0.16 mmol) in THF (1 mL) was added
dropwise to a suspension of NaH (4 mg, 0.16 mmol) in THF (3 mL)
at 0 °C and the mixture was stirred for 30 min. Then 16 (50 mg,
0.18 mmol) in THF (50 mL) was added and the mixture was kept at
0 °C for 4 h, then warmed to 15 °C over 8 h, hydrolyzed with sat.
NH4Cl (10 mL) and diluted with EtOAc (20 mL). After warming to
r.t. and extracting with EtOAc (3 × 20 mL), the organic layer was
washed with brine (20 mL), dried (Na2SO4) and evaporated. The
crude product was purified by flash chromatography (hexanes–
EtOAc, 3:1) to yield 23.
13C NMR (125 MHz, CDCl3): d = –1.2 (TMS), 9.2 (CH3¢), 16.5
(CH3), 22.6 (CH2TMS), 27.8 (C-1¢), 28.7 (C-4), 33.4 (C-2¢), 39.1
(C-5), 51.4 (CO2CH3), 55.3 (OCH3), 74.5 (C-8), 93.1 (C-2¢¢), 108.2
(C-10), 124.9 (C-7), 130.5 (C-2), 139.3 (C-6), 139.9 (C-4¢), 143.2
(C-3), 146.2 (C-9), 153.2 (C-3¢), 167.8 (C-1), 195.2 (C-5¢).
Yield: 59 mg (86%); colourless oil (E/Z = 50:50 by 1H NMR anal-
ysis); Rf = 0.48 (hexanes–EtOAc, 3:1).
FTIR (ATR): 2953 (m), 2849 (m), 1960 (w), 1708 (s), 1638 (m),
1447 (m), 1378 (m), 1243 (s), 1192 (s), 1138 (vs), 1091 (s), 1032
(vs), 976 (m), 945 (m), 917 (m), 885 (m), 839 (vs), 769 (m), 724
(w), 694 (m), 634 (m), 588 (w), 565 (w), 546 (m), 526 (m) cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C24H40NaO5Si+: 459.6467;
found: 459.6470.
(2Z)-23
1H NMR (500 MHz, CDCl3): d = 0.4 (s, 9 H, TMS), 1.28 (t, J =
7.1 Hz, 3 H, CO2CH2CH3), 1.33 (dq, J = 13.5, 1.3 Hz, 1 H, Ha-6¢),
1.39 (ddd, J = 14.1, 5.1, 1.0 Hz, 1 H, CH2TMS-Ha), 1.58 (dd, J =
14.1, 1.0 Hz, 1 H, CH2TMS-Hb), 1.68–1.71 (m, 2 H, H-2¢), 1.71 (d,
J = 1.3 Hz, 3 H, CH3), 2.02–2.11 (m, 1 H, Hb-6¢), 2.12–2.2 (m, 2 H,
H-5), 2.56–2.61 (m, 4 H, H-1¢, H-4), 3.36 (s, 3 H, OCH3), 3.70–3.77
(m, 2 H, Ha-5a¢, Ha-5b¢), 4.06–4.11 (m, 2 H, Hb-5a¢, Hb-5b¢), 4.18
(q, J = 7.1 Hz, 2 H, CO2CH2), 4.47 (t, J = 5.3 Hz, 1 H, H-3¢), 4.56
(dd, J = 6.7, 1.7 Hz, 1 H, Ha-2¢¢), 4.62 (dd, J = 6.7, 4.1 Hz, 1 H, Hb-
2¢¢), 4.62–4.66 (m, 1 H, H-8), 4.68 (dd, J = 1.9, 0.8 Hz, 1 H, H-10a),
4.96 (dd, J = 1.9, 1.2 Hz, 1 H, H-10b), 5.11 (dq, J = 9.2, 1.3 Hz, 1 H,
H-7), 5.86 (tt, J = 7.4, 1.1 Hz, 1 H, H-3).
Methyl (2Z,6E)-2-[(3E)-4-(1,3-Dithian-2-yl)pent-3-enyl]-8-
(methoxymethoxy)-6-methyl-9-[(trimethylsilyl)methyl]deca-
2,6,9-trienoate (21b)
To a solution of 20b (56 mg, 0.09 mmol) in THF (5 mL) were added
NaI (12 mg, 0.08 mmol) and NaH (2 mg, 0.09 mmol) at 0 °C and
the mixture was stirred for 10 min. After warming to r.t. for 20 min,
the yellow solution was cooled to –20 °C and a solution of 16
(23 mg, 0.09 mmol) in THF (3 mL) was added dropwise. The mix-
ture was warmed to r.t. over 7 h and diluted with sat. NH4Cl (10
mL). The layers were separated and the aqueous layer was extracted
with EtOAc (3 × 20 mL). The combined organic layers were
washed with brine (20 mL), dried (Na2SO4) and evaporated. The
Synthesis 2010, No. 15, 2643–2651 © Thieme Stuttgart · New York

2650
C. Gastl, S. Laschat
PAPER
13C NMR (125 MHz, CDCl3): d = 14.3 (CO2CH2CH3), 16.5 (CH3),
22.6 (C-10), 25.8 (C-6¢), 26.6 (C-1¢), 27.8 (C-4), 34.3 (C-18), 39.3
(C-5), 55.4 (OCH3), 60.4 (CO2CH2), 66.9 (C-20, C-22), 74.5 (C-8),
93.2 (C-12), 101.7 (C-19), 108.3 (C-11), 124.7 (C-7), 131.7 (C-2),
139.6 (C-6), 141.5 (C-3), 146.3 (C-9), 167.8 (C-1).
J. Nat. Prod. 2008, 71, 1189. (g) Kamel, H. N.; Ferreira, D.;
Garcia-Fernandez, L. F.; Slattery, M. J. Nat. Prod. 2007, 70,
1223. (h) Wang, L.-T.; Wang, S.-K.; Soong, K.; Duh, C.-Y.
Chem. Pharm. Bull. 2007, 55, 766. (i) Yan, X.-H.;
Gavagnin, M.; Cimino, G.; Guo, Y.-W. Tetrahedron Lett.
2007, 48, 5313. (j) Nieto, M. I.; Gonzalez, N.; Rodriguez, J.;
Kerr, R. G.; Jimenez, C. Tetrahedron 2006, 62, 11747.
(k) Su, J.-H.; Ahmed, A. F.; Sung, P.-J.; Chao, C.-H.; Shen,
J.-H. J. Nat. Prod. 2006, 69, 1134. (l) Jia, R.; Guo, Y.-W.;
Mollo, E.; Gavagnin, M.; Cimino, G. J. Nat. Prod. 2006, 69,
819.
MS (ESI): m/z = 486.21, 407.26, 361.22, 331.21, 305.19, 285.17,
259.16, 213.13, 185.13, 159.12, 131.09, 113.06.
HRMS (ESI): m/z [M + Na]+ calcd for C25H44O6SiNa+: 491.2799;
found: 491.2800.
(2E)-23
(3) For recent synthetic approaches, see: (a) Tietze, L. F.;
Brazel, C. C.; Hölsken, S.; Magull, J.; Ringe, A. Angew.
Chem. Int. Ed. 2008, 47, 5246; Angew. Chem. 2008, 120,
5324. (b) Schweizer, E.; Gaich, T.; Brecker, L.; Mulzer, J.
Synthesis 2007, 3807. (c) Wipf, P.; Grenon, M. Can. J.
Chem. 2006, 84, 1226. (d) Katsuyama, I.; Fahmy, H.;
Zjawiony, J. K.; Khalifa, S. I.; Kilada, R. W.; Konoshima,
T.; Takasahi, M.; Tokuda, H. J. Nat. Prod. 2002, 65, 1809.
(4) (a) Marshall, J. A.; Van Devender, E. A. J. Org. Chem. 2001,
66, 8037. (b) Marshall, J. A.; Gung, B. W. Isr. J. Chem.
1991, 31, 199. (c) Marshall, J. A.; Markwalder, J. A.
Tetrahedron Lett. 1988, 29, 4811. (d) Marshall, J. A.;
DeHoff, B. S. J. Org. Chem. 1986, 51, 863.
1H NMR (500 MHz, CDCl3): d = 0.42 (s, 9 H, TMS), 1.28 (t, J =
7.1 Hz, 3 H, CO2CH2CH3), 1.33 (dq, J = 13.5, 1.3 Hz, 1 H, Ha-6¢),
1.39 (ddd, J = 14.1, 5.1, 1.0 Hz, 1 H, CH2TMS-Ha), 1.58 (dd, J =
14.1, 1.0 Hz, 1 H, CH2TMS-Hb), 1.68–1.71 (m, 2 H, H-2¢), 1.73 (d,
J = 1.3 Hz, 3 H, CH3), 2.02–2.11 (m, 1 H, Hb-6¢), 2.12–2.2 (m, 2 H,
H-5), 2.30–2.37 (m, 2 H, H-4), 2.39 (t, J = 0.8 Hz, 2 H, H-1¢), 3.37
(s, 3 H, OCH3), 3.7–3.77 (m, 2 H, Ha-5a¢, Ha-5b¢), 4.06–4.11 (m,
2 H, Hb-5a¢, Hb-5b¢), 4.19 (q, J = 7.1 Hz, 2 H, CO2CH2), 4.49 (t, J =
5.3 Hz, 1 H, H-3¢), 4.56 (dd, J = 6.7, 1.7 Hz, 1 H, H-2a¢¢), 4.62 (dd,
J = 6.7, 4.1 Hz, 1 H, H-2b¢¢), 4.62–4.66 (m, 1 H, H-8), 4.68 (dd, J =
1.9, 0.8 Hz, 1 H, H-10a), 4.97 (dd, J = 1.9, 1.2 Hz, 1 H, H-10b),
5.08 (dq, J = 9.2, 1.3 Hz, 1 H, H-7), 6.73 (tt, J = 7.4, 1.1 Hz, 1 H, H-
3).
(5) Gross, H.; Wright, A. D.; Beil, W.; König, G. M. Org.
13C NMR (125 MHz, CDCl3): d = 14.3 (CO2CH2CH3), 16.6 (CH3),
21.4 (C-1¢), 22.5 (CH2TMS), 25.8 (C-6¢), 29.1 (C-4), 34.5 (C-2¢),
38.6 (C-5), 55.3 (OCH3), 60.2 (CO2CH2), 66.9 (C-5¢a, C-5¢b), 74.5
(C-8), 93.1 (C-2¢¢), 101.7 (C-3¢), 108.1 (C-10), 124.9 (C-7), 132.1
(C-2), 139.2 (C-6), 142.0 (C-3), 146.2 (C-9), 167.6 (C-1).
Biomol. Chem. 2004, 2, 1133.
(6) For an excellent review on a-methylene-g-butyrolactones,
see: Kitson, R. R. A.; Millemaggi, A.; Taylor, R. J. K.
Angew. Chem. Int. Ed. 2009, 48, 9426; Angew. Chem. 2009,
121, 9590.
(7) Umbreit, M. A.; Sharpless, K. B. J. Am. Chem. Soc. 1977,
99, 5526.
Supporting Information for this article is available online at
(8) Watanabe, Y.; Laschat, S.; Budde, M.; Affolter, O.;
Shimada, Y.; Urlacher, V. B. Tetrahedron 2007, 63, 9413.
(9) Seifert, A.; Vormund, S.; Grohmann, K.; Kriening, S.;
Urlacher, V. B.; Laschat, S.; Pleiss, J. ChemBioChem 2009,
10, 853.
http://www.thieme-connect.de/ejournals/toc/synthesis.
Acknowledgment
(10) For reviews, see: (a) Hoveyda, A. H.; Malcolmson, S. J.;
Meek, S. J.; Zhugralin, A. R. Angew. Chem. Int. Ed. 2010,
49, 434; Angew. Chem. 2010, 122, 38. (b) Nicolaou, K. C.;
Bulger, P. G.; Sarlah, D. Angew. Chem. Int. Ed. 2005, 44,
4490; Angew. Chem. 2005, 117, 4564. (c) Fürstner, A.
Angew. Chem. Int. Ed. 2000, 39, 3012; Angew. Chem. 2000,
112, 3140.
(11) For a recent example, see: Fuwa, H.; Naito, S.; Goto, T.;
Sasaki, M. Angew. Chem. Int. Ed. 2008, 47, 4737; Angew.
Chem. 2008, 120, 4815.
We gratefully acknowledge the Deutsche Forschungsgemeinschaft
(SFB 706), the Institute for Physical Chemistry and the Ministerium
für Wissenschaft, Forschung und Kunst des Landes Baden-Würt-
temberg (Landesgraduierten fellowship for C.G.) for generous fi-
nancial support. We would like to thank Prof. Pikho, Helsinki
University of Technology for helpful discussions and suggestions
and Daniel Pötzsch and Markus Mansueto for skillful technical as-
sistance.
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Synthesis of the Sarcoglaucolone C1–C14 Fragment
2651
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