Synthesis of a putative advanced intermediate en route to elisabethin A

Article abstract of DOI:10.1016/j.tet.2016.06.022

The first generation synthesis of an advanced intermediate en route to elisabethin A is described.

Full text of DOI:10.1016/j.tet.2016.06.022

Accepted Manuscript
Synthesis of a putative advanced intermediate en route to elisabethin A
Sebastian Steiner, Peter Gärtner, Valentin S. Enev
PII:
S0040-4020(16)30535-X
10.1016/j.tet.2016.06.022
TET 27836
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 2 March 2016
Revised Date: 31 May 2016
Accepted Date: 6 June 2016
Please cite this article as: Steiner S, Gärtner P, Enev VS, Synthesis of a putative advanced intermediate
en route to elisabethin A, Tetrahedron (2016), doi: 10.1016/j.tet.2016.06.022.
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Synthesis of a putative advanced
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intermediate en route to Elisabethin A
Sebastian Steiner, Peter Gärtner and Valentin S. Enev*
Institute of Applied Synthetic Chemistry, Vienna University of Technology, 1060 Vienna, Austria

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of a putative advanced intermediate en route to Elisabethin A
Sebastian Steiner, Peter Gärtner and Valentin S. Enev
Institute of Applied Synthetic Chemistry, Vienna University of Technology, 1060 Vienna, Austria
ARTICLE INFO
ABSTRACT
Article history:
Received
The first generation synthesis of an advanced intermediate en route to elisabethin A is described.
.
Received in revised form
Accepted
2009 Elsevier Ltd. All rights reserved
.
Available online
Keywords:
elisabethin A
natural products synthesis
Claisen rearrangement
ring-closing metathesis
1. Introduction
The constitution of the carbon framework and the relative
configuration of elisabethin A were assigned on the basis of
exhaustive spectroscopic studies and X-ray diffraction which did
not allow establishing the absolute configuration of the natural
compound. The complex tricyclic cis,trans-fused 5,6,6 ring
system of elisabethin A together with a fully substituted enedione
functionality and six contiguous stereogenic centers present a
considerable challenge for total synthesis.
Due to their rich functionalization and diverse biological
activities marine terpenoids from gorgonian corals of the genus
Pseudopterogorgia have received enormous attention over the
past decade.
In 1998 Rodriguez and coworkers reported the isolation
of small quantities (0.0089% dry weight) of the marine
diterpenoid elisabethin A (1) from West Indian sea whip
Pseudopterogorgia
elisabethae.1
Subsequent
chemical
Although the syntheses of compounds 2 and 3 were reported
by several groups,4 so far only three attempts towards the total
synthesis of elisabethin A have been published by Mulzer’s5 and
Rawal’s6 groups. Both groups used an intramolecular Diels-Alder
reaction (IMDA) to construct the tricyclic core of the molecule
but unfortunately, this approach gave two different diastereomers
of elisabetine A and it was not possible to convert them to the
target molecule.7 Challenged by this situation, we decided to
develop an alternative approach based on the proposed
biosynthesis from serrulatane precursor 4.1
investigations of this gorgonian specimen revealed the presence
of structurally related compounds elisapterosin B (2)2 and
colombiasin A (3)3 (Fig.1).
Fig.1.
———
Corresponding author. Tel.: +43 1 58801 163734; fax: +43 1 58801 16399; e-mail: valentin.enev@tuwien.ac.at

2
Tetrahedron
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Scheme 1. Retrosynthetic analysis.
2. Results and discussion
attention to the inverted sequence of rearrangements (Scheme 3).
Although this way would give a 1:1 mixture of diastereomers we
hoped that after RCM we can equilibrate the undesired cis isomer
to the trans product.
Our retrosynthetic plan is shown in Scheme 1. Guided by the
suggested biosynthetic pathway we intended to construct the five
membered ring of elisabethin A via an intramolecular para-C-
alkylation8 or via a Pd or Ir catalyzed intramolecular ipso-
Friedel-Crafts alkylation9,10a,b, of serrulatane intermediates 5a and
5b, respectively. Both intermediates could be obtained from
corresponding (R)- or (S)- alcohol 6 which in turn could be
synthesized from aldehyde 7. Further disconnection gives the key
intermediate 811 which was planned to be formed by ring-closing
metathesis (RCM) of diene 9. The latter could be assembled by
two successive Claisen rearrangement of 10 and 11, respectively
which can be easily obtained from the known compound 12.12
This highly biomimethic approach necessitates efficient
syntheses of bicyclic compound 8 and here we present our first
results towards elaboration of compound 12 to aldehyde 8.
Starting from 12 would allow us to install and rearrange
the “northern” and the “southern” allyl ethers independently.
Since the “northern” allylether in 10 is prochiral, we were
interested to see whether there would be influence of C3 chiral
centre (from the first rearrangement) on the stereochemical
outcome of the second Claisen rearrangement.
Our synthesis commenced with TBS13 deprotection of 12
(TBAF/THF) followed by coupling of the obtained phenol 13
with alcohol 1414 under modified Mitsunobu conditions15 to give
allyl ether 15 in 79% yield. Treatment of 15 with
trimethylaluminium in n-hexane at room temperature resulted in
clean and virtually quantitative rearrangement to compound 16.
Protection of phenol 16 as isopropyl ether, cleavage of MOM
group and subsequent installation of the allyl ether functionality
set the scene for the second Claisen rearrangement. Unfortunately
all our attempts to perform the rearrangement failed. Heating in
DMF or N,N-dimethylaniline only produced a complex mixture,
while the Lewis acids (trimethylaluminium, BF3 and Eu(fod)3)
(vide supra) failed to produce any conversion at all. Therefore
this approach was abandoned and we turned our
Scheme 2.“Southern” approach.
To remove the MOM group, compound 12 was treated with
TMSBr and the obtained phenol was coupled with allyl bromide
1816 to give allylether 22 in 75% yield together with a small
amount of SN2’ product (Scheme 3). The first Claisen
rearrangement of 22 was achieved by heating at 210° C in

3
To our delight, treatment of 35 with Grubbs 2nd generation
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catalyst (4 mol %) yielded bicyclic compound in 88 % yield.
Subsequent MOM protection of OH group enabled us to separate
the two diastereomers chromatographically. The stereochemistry
of both diastereomers was proven by NOESY experiments.
Scheme 3. “Northern” approach – synthesis of 28.
Scheme 5. Synthesis of 28 via relay ring closing metathesis.
N,N-dimethylaniline to give 23 in high yield. Protection of 23
(BuLi/MOMCl) followed by TBS cleavage and subsequent
reaction with alcohol 14 afforded allylether 26 in a 76% yield.
With compounds 28 in hand we turned our attention to the next
step - reduction of the double bond and simultaneous cleavage of
Bn group (Scheme 6). Thus, exposure of cis diastereomer 28b to
hydrogen (4 bars) in presence of Pd/C gave after 30 min alcohol
36 in 76% yield. To our surprise, prolonged reaction times led to
partial, yet selective cleavage of the “northern” MOM group (as
confirmed by NOESY) to give 37.
Next, we turned our attention to the second rearrangement
which proved to be much more challenging than we expected.
Initial attempts to perform the reaction in the presence of
trimethylaluminium failed and only starting material were
recovered. Thermal rearrangement similar to the first Claisen
rearrangement with both conventional and microwave heating
17
also failed. Finally, treatment with Eu(fod)3 in toluene at
elevated temperatures led to a 1:1 mixture of the desired product
and phenol 25. The rearrangement product was protected
(BuLi/MOMCl), setting the stage for the following ring closing
metathesis. In view of the steric hindrance of the diene 27 we
expected some problems for the RCM. In fact, attempts to
perform the reaction in presence of 2nd generation Grubbs or
Grubbs-Hoveyda catalyst in different solvents and at different
temperatures failed. Finally, using catalyst G-318 the desired
product 28 was obtained although in a moderate yield and with
high catalyst loading (17 mol %).
To circumvent this reactivity issue we decided to step
back and to try the ring formation via relay ring closing
metathesis (RRCM).19
Scheme 6. Synthesis of 8 and 39.
Under the same conditions hydrogenation of trans
diastereomer 28a, took much longer (3 h) to give 38 in 78 %
yield.20 It also underwent MOM cleavage to a certain extent
dependent on the overall reaction time. Interestingly, when the
reaction time was extended to 5 hours, we detected a small
quantity of undesired cis diastereomer 37. Most probably, the
observed epimerization occurs via double bond migration and
subsequent hydrogenation from the sterically less hindered face
resulted in a formation of cis diastereomer 37.
Scheme 4. Preparation of 33.
Finally, both alcohols 36 and 38
were oxidized
(DMP/CH2Cl2) to give aldehyde 8 and 39 in 84% and 81% yield
respectively (Scheme 6). The cis isomer 39 was treated with
tBuOK in tBuOH to give after 30 min a 1:1 mixture of both
isomers in a 76% yield thus increasing the yield of desired trans
aldehyde.
Hence, the required allyl ether 33 was synthesized in a
four step sequence as it is shown in Scheme 4 and reacted with
phenol 25 to give ether 34 in a good yield (Scheme 5).
Compound 34 was subjected to Claisen rearrangement in
presence of Eu(fod)3 to yield triene 35 in 55% yield (73% brsm).

4
Tetrahedron
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3. Conclusion
HR/MS: Measured at Vienna University of Technology,
Institute of Chemical Technology and Analytics by Prof. Erwin
Rosenberg. Samples were dissolved in CH3CN and measured
with a LC-IT-TOF-MS, EI, APCI in positive- and negative-ion-
mode.
We have synthesized the desired trans aldehyde 8 in 11 steps
and 10 % overall yield. The main features of our synthesis
include two sequential Lewis acid mediated Claisen
rearrangements for introducing of two branched allylic chains
followed by relay ring closing metathesis (RRCM) to create the
B ring of elisabethin A. Although this first generation synthesis
of the key intermediate 8 suffers from lack of selectivity in the
first Claisen rearrangement (and as a consequence significantly
reduces the overall yield) the information obtained in this
approach provides valuable insight into the reactivity of the
compounds in this sequence. The knowledge gained from this
work helped us to develop a second generation enantio and
diastereoselective synthesis of 8 which will be presented soon.
4.2. Experimental procedures
(R)-2-((Allyloxy)methyl)oxirane (30)
Sodium hydride (3.0 g; 60% dispersion in mineral oil; 75.0
mmol; 1.1 equiv.) was suspended in 250 mL of dry DMF. Allyl
bromide (6.4 mL; 74.2 mmol; 1.1 equiv.) was added and the
mixture was placed in an ice bath. (S)-(-)-Glycidol (5.1 g; 68.8
mmol) was added slowly, the ice bath was removed and the
mixture was stirred overnight. After TLC confirmed completion
the reaction was quenched with 20 mL of saturated ammonium
chloride solution and the resulting mixture was poured onto 250
mL of diethyl ether and 250 mL of n-pentane. After stirring for
20 minutes the layers were separated, the organic layer was
washed twice with water and once with brine, respectively, and
dried over sodium sulphate. The solution was carefully
concentrated at 40°C and ambient pressure, yielding 30 (12.7 g)
as clear colourless oil.* NMR analysis of the crude mixture
confirmed 90-95% yield.
1H-NMR (400 MHz, CDCl3): δ = 5.87-5.99 (1H, m); 5.31
(1H, d, J = 17.2 Hz); 5.22 (1H, d, J = 10.5 Hz); 4.00-4.13 (2H,
m); 3.75 (1H, dd, J = 11.0, 3.4 Hz); 3.43 (1H, dd, J = 11.4, 5.8
Hz); 3.15-3.22 (1H, m); 2.80-2.86 (1H, m) 2.64 (1H, dd, J = 5.0,
2.6 Hz).
13C-NMR (100 MHz, CDCl3): δ = 134.4 (d); 117.4 (t); 72.8
(t); 70.8 (t); 50.8 (d); 44.4 (t).
4. Experimental section
4.1. General experimental procedures
The following general procedures were used in all reactions
unless otherwise noted. Glassware was oven-dried at 115°C and
assembled while still hot. Schlenk flasks were flame-dried.
Oxygen and moisture sensitive reactions were carried out under a
slight argon overpressure using Schlenk techniques and in dry
solvents. Sensitive liquids and solutions were transferred via
double tipped cannula or syringes through rubber septa. All
reactions were stirred magnetically unless otherwise stated.
The solvents used were purified and dried according to
common procedures as follows. Dry methylene chloride and
diethyl ether were retrieved from an Innovative Technologies
PureSolv system. Dry tetrahydrofurane was pre-dried using an
Innovative Technologies PureSolv system, refluxed over
sodium/benzophenone ketyl and freshly distilled. Dry toluene
and hexane were p.a. and HPLC grade, respectively, refluxed
over sodium and freshly distilled. Dry DMF and DMSO were
used as purchased. Ethyl acetate, petroleum ether and diethyl
ether (technical grade) were distilled prior to use. Methylene
chloride (technical grade) was distilled from potassium carbonate
prior to use. All other solvents used were p.a. or HPLC grade. All
reagents were used as received, except diisopropylethylamine
(Hünig’s base) and N,N-dimethylaniline, which were freshly
distilled from CaH2, and chloromethyl methyl ether[42]
(MOMCl) as well as Dess-Martin periodinane which were
prepared according to literature procedures.
(R)-1-(Allyloxy)pent-3-yn-2-ol (32)
To
a cooled (10°C) suspension of lithium acetylide
ethylenediamine complex (2.6 g; 28 mmol; 1.2 equiv.) in DMSO
(50 mL) and THF (70 mL) a solution of epoxide 30 (2.7 g; 24
mmol) in of THF (10 mL) was added slowly. The mixture was
stirred for 2 hours. When TLC confirmed completion aqueous
HCl (5%) was added slowly until a pH of 4 was reached. Diethyl
ether (180 mL) was added and the layers were separated. The
aqueous layer was extracted four times with 50 mL of diethyl
ether. The combined organic layers were washed six times with
20 mL of water, once with saturated sodium bicarbonate and
once with brine, respectively, and dried over sodium sulphate.
The solvent was removed at 200 mbar and room temperature,
yielding 31 (93% according to NMR).
1H and 13C NMR spectra were recorded on a Bruker AC 200
at 200 and 50 MHz or on a Bruker AC 400 at 400 and 100 MHz,
using the solvent signal as reference. 13C NMR spectra were run
in proton-decoupled mode and multiplicities from APT were
referred to as s (singlet), d (doublet), t (triplet), q (quartet).
1
Multiplicities of H signals were referred to as s (singlet), d
The crude product was dissolved in 50 mL dry DMSO.
Potassium tert-butoxide (2.4 g, 21 mmol, 1 equiv.) was dissolved
in dry DMSO (15 mL) and added slowly and the mixture was
stirred at room temperature. After two hours† diethyl ether (200
mL) and solid ammonium chloride (1 g) were added and the
mixture was washed with five portions of water and one portion
(doublet), t (triplet), q (quartet), quin (quintet), sext (sextet), sept
(septet) and m (multiplet).
IR spectra were recorded on a Perkin Elmer Spectrum 65 FT
IR Spectrometer equipped with a specac MK II Golden Gate
Single Reflection ATR unit.
TLC-analysis was done with precoated aluminium-backed
plates (Silica gel 60 F254, Merck). Compounds were visualized
by submerging in an acidic phosphomolybdic acid / cerium
sulphate solution and heating. Column chromatography was
carried out with silica gel Merck 60. Specific rotations were
measured on an Anton Parr MCP 500 polarimeter in at 20°C and
589nm.
———
* Compound 30 is highly hygroscopic and was used in the next step
without further purification. For spectral characterization it was
distilled under reduced pressure to give colorless liquid.
† Longer reaction time or excess of potassium tert-butoxide
significantly reduce the yield due to the isomerization to the
corresponding vinyl ether.

5
of brine. After drying over sodium sulphate removal of the
solvent in vacuo gave 32 (2.6 g, 81%) as colorless oil that could
be used without further purification.
1H-NMR (400 MHz, CDCl3): δ = 5.83-5.95 (1H, m); 5.16-
5.31 (2H, m); 4.46-4.52 (1H, m); 4.05 (2H, d, J = 5.6 Hz); 3.56
(1H, dd, J = 9.8, 3.4 Hz); 3.44-3.50 (1H, m); 2.52 (1H, broad s);
1.82 (3H, d, J = 2.0 Hz).
A three-necked round bottomed flask with septum, dropping
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funnel and argon inlet was charged with phenol 21 (7.3 g; 25.9
mmol) in 300 mL of dry THF and cooled to -40°C in a liquid
nitrogen / acetone bath. n-Butyllithium solution (16.2 mL; 1.6 M
in hexanes; 25.9 mmol; 1 equiv.) was added slowly through the
septum, causing the solution to turn brightly yellow. The
temperature was held at -40°C for one hour. Then allyl bromide
18 (6.3 g; 25.9 mmol; 1 equiv.) in dry DMF (100 mL) was added
slowly via the dropping funnel. The solution turned greenish and
then orange. After the addition was complete the cooling bath
was removed and the mixture was stirred overnight. After TLC
confirmed completion the reaction was quenched with 10 mL of
saturated ammonium chloride solution and one spatula of solid
ammonium chloride. The mixture was concentrated to about 100
mL and partitioned between 100 mL of water and 180 mL of
diethyl ether. The layers were separated and the aqueous layer
was extracted with 180 mL of diethyl ether two more times. The
combined organic layers were washed with brine and dried over
sodium sulphate. The solvent was removed in vacuo and the
resulting crude yellow oil was purified via column
chromatography, yielding 22 (yellow oil, 8.6 g (75%).
13C-NMR (100 MHz, CDCl3): δ = 134.2 (d); 117.6 (t); 82.0
(s); 76.9 (s); 73.9 (t); 72.3 (t); 61.7 (d); 3.6 (q).
IR: ν = 3398, 2921, 2857, 2241, 1647, 1421, 1317, 1261,
1143, 1106, 1071, 1013, 926, 890, 802, 551, 538, 515 cm-1.
[α]20D = -13.6 (c = 0.98, CH2Cl2)
(R,E)-1-(Allyloxy)pent-3-en-2-ol (33).
To a suspension of LiAlH4 (1.8 g; 48 mmol; 2 equiv.) in dry
THF (20 mL) was added slowly a solution of 32 (3.4 g; 24 mmol)
in THF (20 mL) and the mixture was heated to 65°C for 2 hours.
After cooling to room temperature the completion was confirmed
by NMR.
1H-NMR (400 MHz, CDCl3): δ = 7.40-7.27 (m, 5H); 6.64 (d,
1H, J = 8.76 Hz); 6.47 (d, 1H, J = 8.76 Hz); 6.05-5.93 (m, 2H);
4.54 (s, 2H); 4.52-4.46 (m, 2H); 4.12-4.06 (m, 2H); 3.76 (s, 3H);
2.18 (s, 3H); 1.42-1.14 (m, 2H); 1.03 (s, 9H); 0.94-0.65 (m, 3H);
0.18 (s, 3H).
13C-NMR (100 MHz, CDCl3): δ = 151.7 (s); 150.1 (s); 143.2
(s); 138.3 (s); 129.3 (d); 128.8 (d); 128.5 (d, 2C); 127.9 (d, 2C);
127.8 (d); 121.6 (s); 117.3 (d); 107.3 (d); 72.4 (t); 70.2 (t); 68.7
(t); 60.1 (q); 26.4 (q, 3C); 18.9 (s); 9.4 (q); 7.6 (q); 4.9 (t); -6.5
(q).
The mixture was cooled on ice and slowly hydrolyzed with
ice-cold water. Diethyl ether (100 mL) and saturated solution of
Rochelle salt (25 mL) were added and the slurry was stirred
overnight. The layers were then separated and the aqueous layer
was extracted with diethyl ether five times. The combined
organic layers were washed with water, saturated ammonium
chloride and brine, respectively, and dried over sodium sulphate.
The solution was carefully concentrated in vacuo, and the crude
product was purified via column chromatography yielding 33
(3.1 g, 91%).
1H-NMR (400 MHz, CDCl3): δ = 5.94-5.81 (m, 1H); 5.80-
5.68 (m, 1H); 5.42 (ddd, 1H, J = 15.38, 6.67, 1.50 Hz); 5.24 (dd,
1H, J = 17.23, 1.38 Hz); 5.16 (dd, 1H, J = 10.30, 0.86 Hz); 4.27-
4.18 (m, 1H); 3.99 (d, 2H, J = 5.64 Hz); 3.42 (dd, 1H, J = 9.68,
3.32 Hz); 3.28 (dd, 1H, J = 9.42, 8.42 Hz); 1.66 (d, 3H, J = 6.56
Hz).
IR: ν = 2955, 2930, 2857, 1483, 1417, 1252, 1100, 1031,
1004, 967, 882, 834, 781, 735, 697 cm-1.
HRMS for C26H38O4Si: [M+H]+ calcd. 443.2612, found:
443.2618
6-(1-(Benzyloxy)but-3-en-2-yl)-4-((tert-butyl (ethyl) (methyl)
silyl) oxy)-3-methoxy-2-methylphenol (23)
13C-NMR (100 MHz, CDCl3): δ = 134.5 (d); 129.5 (d); 128.6
A glass pressure tube with magnetic stirring bar was charged
with allyl ether 22 (2.5 g; 5.7 mmol) in of N,N-dimethylaniline
(10 mL), purged with argon and screwed shut. The solution was
heated to 220°C in an oil bath for 3.5 hours. After TLC
confirmed completion the mixture was transferred to a separating
funnel with 80 mL of diethyl ether and washed with 60 mL of 1N
HCl (0.9 equivalents in respect to the dimethylaniline) in several
small portions. The organic layer was then washed with saturated
sodium bicarbonate and brine, respectively, and dried over
sodium sulphate. The solvent was removed in vacuo and the
resulting crude brown oil was purified via column
chromatography, yielding 23 (2.1 g, yellow oil, 85%)
1H-NMR (400 MHz, CDCl3): δ = 7.40-7.26 (m, 5H); 6.49 (s,
1H); 6.14-6.01 (m, 1H); 5.23 (d, 1H, J = 10.56 Hz); 5.11 (d, 1H,
J = 17.45 Hz); 4.61 (dd, 2H, J = 20.59 Hz, J = 12.06 Hz); 3.93
(dd, 1H, J = 12.64, 7.92 Hz); 3.79 (s, 3H); 3.76-3.70 (m, 2H);
2.21 (s, 3H); 1.04 (s, 9H); 1.02-0.85 (m, 3H); 0.85-0.65 (m, 2H);
0.18 (s, 3H).
(d); 117.4 (t); 74.3 (t); 72.2 (t); 71.3 (d); 17.9 (q).
IR: ν = 3419, 2857, 1647, 1450, 1421, 1378, 1349, 1248,
1092, 1063, 1001, 965, 922, 558, cm-1.
[α]20D = -19.2 (c 0.98, CH2Cl2)
4-((tert-Butyl(ethyl)(methyl)silyl)oxy)-3-methoxy-2-
methylphenol (21)
A Schlenk flask was charged with 12 (4.7 g; 14.5 mmol) in
dry methylene chloride and cooled to -20°C in a liquid nitrogen /
acetone bath. Bromotrimethylsilane (4.8 mL; 36.3 mmol; 2.5
equiv.) was added slowly causing the mixture to turn to a dark
orange. The reaction was held at about 4°C for six hours (TLC
control) and subsequently quenched with 50 mL of saturated
sodium bicarbonate. The layers were separated, the aqueous layer
was extracted with dichloromethane and the combined organic
layers were washed with brine and dried over sodium sulphate.
The solvent was removed in vacuo and the resulting crude
reddish brown oil was purified via column chromatography to
give 21 (3.4 g 84%). Spectroscopic data are identical to those
reported in the literature.12
13C-NMR (100 MHz, CDCl3): δ = 148.8 (s); 147.7 (s); 142.0
(s); 137.1 (s); 136.9 (d); 128.6 (d, 2C); 128.1 (d); 127.9 (d, 2C);
123.5 (s); 120.7 (s); 118.2 (d); 116.2 (t); 74.9 (t); 73.8 (t); 60.1
(q); 45.2 (d); 26.4 (q, 3C); 18.8 (s); 9.7 (q); 7.6 (q); 4.9 (t); -6.5
(q).
(E)-(4-((4-(Benzyloxy)but-2-en-1-yl)oxy)-2-methoxy-3-methyl-
phenoxy)(tert-butyl)(ethyl)(methyl)silane (22).

6
Tetrahedron
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IR: ν = 3316, 2955, 2929, 2858, 1639, 1604, 1481, 1455,
added in this order under vigorous stirring and the cooling bath
1421, 1361, 1341, 1296, 1251, 1208, 1093, 1062, 1004, 959, 916,
was removed. Then the reaction was stirred overnight. After TLC
confirmed completion the mixture was diluted with n-hexane (20
mL) and the tributylphosphine oxide precipitate was filtered off.
The solvent was removed in vacuo and the resulting crude yellow
oil was purified via column chromatography, yielding 34 (0.44 g,
54%) as an inseparable mixture of diastereomers.
879, 827, 783, 736, 697, 662 cm-1.
HRMS for C26H38O4Si: [M+H]+ calcd. 443.2612, found:
443.2622.
(5-(1-(Benzyloxy)but-3-en-2-yl)-2-methoxy-4-
(methoxymethoxy) -3-methylphenoxy) (tert-butyl) (ethyl)
(methyl)silane (24).
1H-NMR (400 MHz, CDCl3): δ = 7.36-7.21 (m, 5H); 6.68-
6.61 (m, 1H); 6.08-5.84 (m, 2H); 5.76-5.64 (m, 1H); 5.53-5.41
(m, 1H); 5.33-5.01 (m, 4H); 4.93-4.85 (m, 2H); 4.67 (quin, 1H, J
= 5.92 Hz); 4.57-4.46 (m, 2H); 4.16-4.08 (m, 1H); 4.08-4.03 (m,
2H); 3.82 (s, 3H); 3.72-3.56 (m, 4H); 3.58 (s, 3H); 2.22 (s, 3H);
1.68-1.61 (m, 3H).
13C-NMR (100 MHz, CDCl3): δ = 148.4 (s); 148.3 (s); 147.7
(s); 147.6 (s); 147.6 (s); 147.5 (s); 139.2 (d); 139.2 (d); 138.4 (s);
134.8 (d); 134.7 (d); 130.3 (d); 130.1 (d); 129.1 (s); 129.1 (s);
128.3 (d, 2C); 128.0 (d); 127.8 (d); 127.6 (d, 2C); 127.5 (d, 2C);
127.5 (d); 127.5 (d); 125.6 (s); 125.5 (s); 116.9 (t); 115.7 (t);
115.6 (t); 114.6 (d); 114.2 (d); 100.0 (t); 79.4 (d); 79.2 (d); 73.5
(t); 73.0 (t); 72.9 (t); 72.3 (t); 60.3 (q); 60.2 (q); 57.5 (q); 41.9
(d); 41.9 (d); 17.8 (q); 10.5 (q).
A Schlenk flask was charged with phenol 23 (0.5 g; 1.2 mmol)
in dry THF (8 mL) and cooled to -40°C in a liquid nitrogen /
acetone bath. n-Butyllithium solution (800 µL; 1.6 M in hexanes;
1.3 mmol; 1.1 equiv.) was added slowly and the mixture was
stirred for 30 minutes. Then N,N-dimethylformamide (2.5 mL)
and chloromethyl methyl ether (135 µL, 1.7 mmol, 1.5 equiv.)
were added. The cooling bath was removed and the solution was
slowly warmed to room temperature. After one hour TLC
(toluene : EA 12:1) confirmed completion. The reaction was
quenched with 1 mL of trimethylamine and 1 mL of saturated
sodium bicarbonate. After stirring for 5 minutes the mixture was
transferred to a separating funnel and extracted twice with 40 mL
of toluene. The combined organic layers were washed with brine
and dried over sodium sulphate. Removal of the solvent in vacuo
yielded 24 (0.56 g, 99%) as a colourless oil which could be used
without further purification.
IR: ν = 2857, 2248, 1637, 1588, 1482, 1453, 1434, 1399,
1336, 1236, 1204, 1158, 1058, 966, 909, 729, 698, 648, 609, 562,
549, 538, 522, 502 cm-1.
5-(1-(Benzyloxy)but-3-en-2-yl)-2-methoxy-4-
HRMS for C29H38O6: [M+Na]+ calcd. 505.2561, found:
(methoxymethoxy)-3-methylphenol (25).
505.2603.
To a solution of silyl ether 24 (1.8 g; 3.8 mmol) in dry THF
(20 mL) was added TBAF solution (4.2 mL; 1 M in THF; 4.2
mmol; 1.1 equiv.) and the mixture was stirred for 15 minutes at
ambient temperature. After TLC confirmed completion the
reaction was quenched with saturated ammonium chloride
solution (20 mL). The mixture was extracted two times with 50
mL of diethyl ether, the combined organic layers were washed
with 20 mL of water and brine, respectively, and dried over
sodium sulphate. The solvent was removed in vacuo and the
resulting crude brown oil was purified via column
chromatography to give 25 (1.2 g, 92%) as a pale yellow oil.
1H-NMR (400 MHz, CDCl3): δ = 7.38-7.23 (m, 5H); 6.67 (s,
1H); 6.02 (ddd, 1H, J = 17.18 Hz, J = 10.37 Hz, J = 6.81 Hz);
5.72 (s, OH); 5.18-5.02 (m, 2H); 4.93 (dd, 2H, J = 8.04 Hz, J =
5.80 Hz); 4.54 (s, 2H); 4.17-4.07 (m, 1H); 3.75 (s, 3H); 3.71-3.57
(m, 2H); 3.61 (s, 3H); 2.28 (s, 3H).
2-((S,E)-5-(Allyloxy)pent-3-en-2-yl)-3-(1-(benzyloxy)but-3-en-
2-yl)-6-methoxy-4-(methoxymethoxy)-5-methylphenol (35).
A Schlenk flask was charged with allyl ether 34 (0.33 g, 676
µmol) and Eu(fod)3 (0.11 g, 101 µmol, 0.15 equiv.) in degassed
dry toluene (25 mL) and heated to 100°C for 8 hours. Afterwards
the mixture was filtered over a plug of silica and the solvent was
removed in vacuo. Purification via column chromatography gave
35 (0.17 g, 52%) as an inseparable mixture of diastereomers and
25 (0.15 g, 44%).
1H-NMR (400 MHz, CDCl3): δ = 7.36-7.23 (m, 5H); 6.32-
6.18 (m, 1H); 6.18-6.06 (m, 1H); 5.98-5.84 (m, 1H); 5.68-5.62
(m, 1H); 5.60-5.38 (m, 1H); 5.31-5.08 (m, 3H); 5.05-4.94 (m,
1H); 4.91-4.79 (m, 2H); 4.60-4.44 (m, 3H); 4.00-3.88 (m, 5H);
3.80-3.53 (m, 8H); 2.24 (s, 3H); 1.35 (dd, 3H, J = 6.50 Hz, J =
4.46 Hz).
13C-NMR (100 MHz, CDCl3): δ = 147.9 (s); 145.0 (s); 139.6
(d); 138.6 (s); 138.5 (s); 137.9 (d); 137.5 (d); 135.1 (d); 129.4 (s);
129.2 (s); 128.4 (d, 2C); 128.4 (d, 2C); 128.3 (s); 128.0 (s); 127.8
(d, 2C); 127.6 (d); 127.6 (d); 125.6 (d); 125.3 (d); 122.4 (s);
122.3 (s); 117.0 (t); 115.4 (s); 115.0 (s); 100.1 (t); 73.4 (t); 73.3
(t); 73.0 (t); 71.0 (t); 71.0 (t); 70.8 (t); 70.7 (t); 60.8 (q); 60.8 (q);
57.6 (q); 18.9 (q); 10.9 (q).
13C-NMR (100 MHz, CDCl3): δ = 147.5 (s); 145.6 (s); 144.3
(s); 139.0 (d); 138.4 (s); 130.9 (s); 128.3 (d, 2C); 127.7 (d, 2C);
127.5 (d); 124.9 (s); 116.0 (t); 112.0 (d); 100.2 (t); 73.4 (t); 73.0
(t); 60.7 (q); 57.5 (q); 42.1 (d); 10.8 (q).
IR: ν = 3397, 2940, 2863, 2249, 1637, 1594, 1482, 1454,
1431, 1401, 1361, 1302, 1272, 1189, 1158, 1098, 1050, 972, 907,
727, 698, 648 cm-1.
IR: ν = 3407, 2961, 2920, 2851, 1633, 1603, 1455, 1422,
1401, 1362, 1263, 1208, 1157, 968, 922, 803, 737, 698 cm-1.
HRMS for C21H26O5: [M+Na]+ calcd. 381.1672, found:
381.1670.
HRMS for C29H38O6: [M+Na]+ calcd. 505.2561, found:
505.2562.
1-(((S,E)-1-(Allyloxy)pent-3-en-2-yl)oxy)-5-(1-(benzyloxy)but-
3-en-2-yl)-2-methoxy-4-(methoxymethoxy)-3-methylbenzene
(34).
(1S,4S)-1-((Benzyloxy)methyl)-6-methoxy-5,8-bis(methoxy-
methoxy)-4,7-dimethyl-1,4-dihydronaphthalene (28a) and (1R,
4S)-1-((benzyloxy)methyl)-6-methoxy-5,8-bis
(methoxy
A Schlenk flask was charged with phenol 25 (0.60 g, 1.69
mmol) and allyl alcohol 33 (0.31 g, 2.19 mmol, 1.3 equiv.) in dry
benzene (10 mL) and cooled to about 4°C in a water bath. Tri-n-
butylphosphine (630 µL, 2.53 mmol, 1.5 equiv.) and 1,1′-
(azodicarbonyl)dipiperidine (0.64 g, 2.53 mmol, 1.5 equiv.) were
methoxy)-4,7-dimethyl-1,4-dihydronaphthalene (28b).
A three-necked round bottomed flask with argon inlet was
charged with 35 (0.16 g, 341 µmol) in 150 mL of dry
dichloromethane. The mixture was degassed by freeze-pump-

7
thaw cycling three times. Then Grubbs catalyst 2nd generation
IR: ν = 3031, 2927, 1597, 1455, 1434, 1422, 1398, 1328,
ACCEPTED MANUSCRIPT
(14.3 mg, 17 µmol, 2 mol%) was added and the solution was
heated to 35°C for one hour. TLC showed incomplete
conversion, therefore additional Grubbs catalyst (9.0 mg, 11
µmol, 2 mol%) was added and the mixture was stirred overnight.
After TLC confirmed completion the reaction was quenched by
bubbling air through the solution for 10 minutes. The resulting
mixture was concentrated to about 10 mL and filtered over a plug
of silica. After removal of the solvent in vacuo purification via
column chromatography yielded 0.14 g (88%) of product as an
inseparable mixture of diastereomers which was used directly for
the next step.
1246, 1207, 1158, 1072, 1035, 968, 928, 821, 799 cm-1.
((1S,4S)-6-methoxy-5,8-bis(methoxymethoxy)-4,7-dimethyl-
1,2,3,4-tetrahydronaphthalen-1-yl)methanol (38).
A Parr reaction vessel was charged with compound 28a (150.0
mg; 350.0 µmol) and palladium (10% on charcoal; 20mg) in 8
mL of ethyl acetate. The mixture was shaken under 4 bars of
hydrogen for two hours. After TLC confirmed completion, the
mixture was filtered over celite and the solvent was removed in
vacuo. Purification via column chromatography yielded 90.3 mg
(78%) of clear, yellow oil,
A Schlenk flask was charged with crude product (55.3 mg,
144 µmol, mixture of diastereomers) in 15 mL of dry THF and
cooled to -40°C in a liquid nitrogen / acetone bath. n-
Butyllithium solution (90 µL; 1.6 M in hexanes; 144 µmol; 1
equiv.) was added and the mixture was stirred for one hour. Then
DMF (1 mL) and chloromethyl methyl ether (16 µL, 216 µmol,
1.5 equiv.) were added subsequently, the cooling bath was
removed and the mixture stirred overnight. After TLC confirmed
completion the reaction was quenched with 0.5 mL of
trimethylamine and 1 mL of saturated sodium bicarbonate
solution. The resulting mixture was extracted two times with
diethyl ether and the combined organic layers were subsequently
washed with water and brine, dried over sodium sulphate and
concentrated in vacuo. Column chromatography of the crude
product yielded 28a (35.2 mg, 57%) and 28b (25 mg, 40%).
1H-NMR (400 MHz, CDCl3): δ = 5.05 (d, 1H, J = 6.0 Hz);
4.97 (d, 1H, J = 6.0 Hz); 4.91(d, 1H, J = 6.3 Hz); 4.86 (d, 1H, J =
J = 6.3 Hz); 3.68 (s, 3H); 3.51 (s, 3H); 3.46 (dd, 1H, J = 10.3, 8.4
Hz ); 3.14 (m, 1H,); 2.09 (s, 3H); 1.83 (m, 2H); 1.54 (m, 2H);
1.15 (d, 3H, J = 7.0 Hz).
13C-NMR (100 MHz, CDCl3): δ = 151.0 (s); 149.6 (s); 145.3
(s); 135.0 (s); 126.1 (s); 122.9 (s); 99.6 (t); 99.2 (t); 66.1 (t); 59.0
(q); 57.5 (q); 57.4 (q); 35.8 (d); 27.4 (d); 24.6 (t); 23.0 (t); 22.2
q); 18.8 (t); (10.2 (q).
[α]20D = +39.4 (c 1.1, CH2Cl2)
((1R,4S)-6-Methoxy-5,8-bis(methoxymethoxy)-4,7-dimethyl-
1,2,3,4-tetrahydronaphthalen-1-yl)methanol (36).
28a
A Parr reaction vessel was charged with compound 28b
(200.8 mg; 480.5 µmol) and palladium (10% on charcoal; 29.8
mg) in 10 mL of ethyl acetate. The mixture was shaken under 4
bar of hydrogen for 30 minutes. After TLC confirmed
completion, the mixture was filtered over celite and the solvent
was removed in vacuo. Purification via column chromatography
yielded 36 (120.6 mg, 76%) as clear, yellow oil.
1H-NMR (400 MHz, CDCl3): δ = 7.38-7.23 (m, 5H); 6.07 (dd,
1H, J = 10.28 Hz, J = 2.20 Hz); 5.84 (dd, 1H, J = 10.28 Hz, J =
2.32 Hz); 5.14 (d, H, J = 6.0 Hz); 5.03 (d, H, J = 6.0 Hz); 4.97 (d,
1H, J = 6.0 Hz); 4.89 (d, 1H, J = 6.0 Hz); 4.53 (d, 1H, J = 12.0
Hz); 4.43 (d, 1H, J = 12.0 Hz); 4.0 (dd, 1H, J = 8.4, 3.5 Hz );
3.80 (s, 4H); 3.67-3.56 (m, 1H); 3.61 (s, 3H); 3.59 (s, 3H); 3.29
(t, 1H, J = 8.48 Hz); 2.20 (s, 3H); 1.34 (d, 3H, J = 7.00 Hz).
1H-NMR (400 MHz, CDCl3): δ = 5.07 (d, H, J = 5.64 Hz);
4.95 (d, H, J = 5.68 Hz); 4.87 (d, 1H, J = 6.9 Hz), 4.78 (d, 1H, J
= 6.9 Hz), 3.83 (dd, 1H, J = 10.24 Hz, J = 5.92 Hz); 3.76 (s,
3H); 3.59 (s, 3H); 3.57 (s, 3H); 3.30 (m, 1H,); 3.22 (m, 1H,); 2.16
(s, 3H); 1.88-1.73 (m, 2H); 1.64-1.52 (m, 2H); 1.28 (d, 3H, J =
7.04 Hz).
13C-NMR (100 MHz, CDCl3): δ = 151.0 (s); 150.3 (s); 145.4
(s); 139.0 (s); 133.2 (s); 130.3 (d); 128.4 (d, 2C); 127.6 (d, 2C);
127.4 (d); 124.7 (d); 123.8 (s); 123.7 (s); 99.9 (t); 99.5 (t); 75.8
(t); 73.1 (t); 60.2 (q); 57.6 (q); 57.6 (q); 36.4 (d); 30.7 (d); 24.0
(q); 10.2 (q).
[α]20D = +165.1 (c 0.78, CH2Cl2)
13C-NMR (100 MHz, CDCl3): δ = 151.1 (s); 149.8 (s); 145.6
(s); 136.1 (s); 127.0 (s); 122.7 (s); 99.7 (t); 99.3 (t); 67.7 (t); 60.0
(q); 57.8 (q); 57.6 (q); 36.2 (d); 28.2 (d); 28.1 (t); 23.0 (t); 21.9
(q); 10.5 (q).
28b
1H-NMR (400 MHz, CDCl3): δ = 7.38-7.24 (m, 5H); 6.17 (dd,
1H, J = 9.84 Hz, J = 4.44 Hz); 6.05 (dd, 1H, J = 9.86 Hz, J =
4.94 Hz); 5.06 (d, H, J = 6.0 Hz); 4.96 (d, H, J = 6.0 Hz); 4.86 (d,
1H, J = 6.0 Hz); 4.75 (d, 1H, J = 6.0 Hz); 4.53 (d, 1H, J = 12.0
Hz); 4.43 (d, 1H, J = 12.0 Hz); 3.99-3.90 (m, 2H); 3.80 (s, 3H);
3.70 (quin, 1H, J = 6.21 Hz); 3.60 (s, 6H); 3.33 (t, 1H, J = 10.04
Hz); 2.20 (s, 3H); 1.31 (d, 3H, J = 6.96 Hz).
IR: ν = 3434, 2931, 2870, 1593, 1459, 1431, 1420, 1393,
1324, 1248, 1207, 1157, 1107, 1049, 1018, 969, 939, 797, cm-1.
[α]20D = -19.8 (c 1.04, CH2Cl2)
(1S,4S)-6-Methoxy-5,8-bis(methoxymethoxy)-4,7-dimethyl-
1,2,3,4-tetrahydronaphthalene-1-carbaldehyde (8).
13C-NMR (100 MHz, CDCl3): δ = 150.6 (s); 150.1 (s); 144.6
(s); 138.8 (s); 133.7 (s); 131.9 (d); 128.4 (d, 2C); 127.7 (d, 2C);
127.5 (d); 127.1 (d); 125.0 (s); 123.2 (s); 99.7 (t); 99.3 (t); 76.5
(t); 73.1 (t); 60.0 (q); 57.6 (q); 57.5 (q); 36.6 (d); 30.9 (d); 23.8
(q); 10.5 (q).
A round bottomed flask was charged with alcohol 38 (400 mg;
1 mmol) in dichloromethane (15 mL). Pyridine (1 mL) was
added, followed by Dess-Martin periodinane (790 mg; 1.6
equiv.) and the resulting yellowish solution was stirred for 10
minutes. After TLC confirmed completion the mixture was
filtered over silica with a mixture of petroleum ether and ethyl
acetate (4:1). Removal of the solvent in vacuo yielded 8 (300 mg,
(84%).
[α]20D = -84.9 (c 0.43, CH2Cl2)

8
Tetrahedron
ACCEPTED MANUSCRIPT
1H-NMR (400 MHz, CDCl3): δ = 9.63 (s, 1H); 5.08 (d, 1H,
Am. Chem. Soc. 2003, 125, 13022−13023.
Synthesis of Colombiasin A: (c) A: Nicolaou, K.
C.; Vassilikogiannakis, G.; Magerlein, W.;
Kranich, R. Angew. Chem., Int. Ed. 2001, 40,
2482-2486. (d) Nicolaou, K. C.;
Vassilikogiannakis, G.; Magerlein, W.; Kranich, R.
Chem. Eur. J. 2001, 7, 5359-5371. (e) Kim, A. I.;
Rychnovsky, S. D. Angew. Chem., Int. Ed. 2003,
42, 1267-1270. (f) Harrowven, D. C.; Pascoe, D.
D.; Demurtas, D.; Bourne, H. O. Total Synthesis of
(-)-Colombiasin A and (-)-Elisapterosin B,: (g)
Angew. Chem., Int. Ed. 2005, 44, 1221-1222. (h)
Boezio, A. A.; Jarvo, E. R.; Lawrence, B. M.;
Jacobsen, E. N., Angew. Chem., Int. Ed. 2005, 44,
6046-6050.
J = 5.51 Hz); 4.99 (d, 1H, J = 5.51 Hz); 4.87 (d, 1H, J = 5.82
Hz); 4.82 (d, 1H, J = 5.81 Hz) 3.78 (brd, 1H, J= 6.2 Hz); 3. 70 (s,
3H); 3.51 (s, 3H); 3.46 (s, 3H); 3.17 (m, 1H); 3.58 (s, 3H); 3.52
(s, 3H); 3.31-3.22 (m, 1H); 2.14 (m, 1H); 2.11 (s, 3H); 1.89 (m,
1H); 1.60-150 (m, 2H); 1.18 (d, 3H, J = 7.00 Hz).
13C-NMR (100 MHz, CDCl3): δ = 203.1 (d); 151.3 (s); 150.6
(s); 145.4 (s); 135.5 (s); 122.9 (s); 121.3 (s); 99.5 (t); 99.2 (t);
60.0 (q); 57.4 (q); 57.3 (q); 46.5 (d); 27.2 (t); 26.6 (d); 21.3 (q);
17.9 (t); 10.2 (q).
[α]20D = +47.2 (c 1.0, CH2Cl2)
6. a) Heckrodt, T.J.; Mulzer, J. J. Am. Chem. Soc.
2003,125, 4680-4681.b) Preindl, J.; Leitner, C.;
Baldauf, S.; Mulzer, J. Org. Lett. 2014, 16, 4276–
4279.
7. Waizumi, N.; Stankovic, A.R.; Rawal, V.H. J.
Am. Chem. Soc. 2003, 125, 13022-13023.
8. Zanoni, G.; Franzini, M. Angew. Chem. Int. Ed.
2004, 43, 4837–4841.
9. (a) Jackson, S. R.; Johnson, M. G.; Mikami, M.;
Shiokawa, S.; Carreira, E. M. Angew. Chem., Int.
Ed. 2001, 40, 2694. (b) Ritter, T.; Zarotti, P.;
Carreira, E. M. Org. Lett. 2004, 6, 4372-43743 and
citations therein.
10. a) Nemoto, T.; Ishige, Y.; Yoshida, M.; Kohno, Y.;
Kanematsu, M.; Hamada, Y. Org. Lett. 2010, 12,
5020-5023. b) Rousseaux, S.; Fortanet, J.;
Sanchez, M.; Buchwald, S. L. J. Am. Chem. Soc.
2011, 133, 9282-9285
(1R,4S)-6-Methoxy-5,8-bis(methoxymethoxy)-4,7-dimethyl-
1,2,3,4-tetrahydronaphthalene-1-carbaldehyde (39).
A
round bottomed flask was charged with in of
dichloromethane (4 mL). Three drops of pyridine were added
causing the periodinane to fully dissolve. Then alcohol was
transferred into the mixture with three portions of
dichloromethane (0.5 mL each) and the resulting yellowish
solution was stirred for 10 minutes. After TLC confirmed
completion the mixture was filtered over silica with a mixture of
petroleum ether and ethyl acetate (4:1). Removal of the solvent in
vacuo yielded 39 (180.5 mg, 81%).
11. For the synthesis of similar bicyclic compounds
see: a) O'Hora, P. S.; Incerti-Pradillos, C. A.,
Kabeshov, M. A.; Shipilovskikh, S. A.; Rubtsov,
A. E., Elsegood, M. R. J.; Malkov, A. V.. Chem.
Eur. J., 2015, 21: 4551–4555. b) Ying, W.; Barnes,
C. L.; Harmata, M.; Tetrahedron Lett. 2011, 52,
177–180. c) Kotha, S.; Mandal, K.; Tetrahedron
Lett. 2004, 52, 2585–2588.
12. Wu, Q.;W.; Liu, Zhuo, C.; Rong, Z.; Ye, K.; You.
S. Angew. Chem. Int. Ed. 2011, 50, 4455-4458.
13. Chen, J.; Chen, X.; Willot, M.; Zhu, J. Angew.
Chem. Int. Ed. 2006, 45, 8028–8032.
14. It should be noted that in our hands the synthesis
of 12 always gave a mixture of TBS and TBEMS
(tButylethylmethylsilyl) protected phenol. For
simplicity only TBS protected phenol is depicted.
15. Takano, S.; Sekiguchi, Y.; Sato, N.; Ogasawara, K.
Synthesis 1987, 139–141.
1H-NMR (400 MHz, CDCl3): δ = 9.43 (d, 1H, J = 4.20 Hz);
5.06 (d, 1H, J = 5.72 Hz); 4.99 (d, 1H, J = 5.72 Hz); 4.74 (d, 1H,
J = 6.02 Hz); 4.72 (d, 1H, J = 6.00 Hz); 3.78 (s, 3H); 3.62-3.55
(m, 1H); 3.58 (s, 3H); 3.52 (s, 3H); 3.31-3.22 (m, 1H); 2.17 (s,
3H); 1.87-1.71 (m, 4H); 1.26 (d, 3H, J = 7.00 Hz).
13C-NMR (100 MHz, CDCl3): δ = 201.8 (d); 151.4 (s); 150.8
(s); 145.6 (s); 135.5 (s); 123.2 (s); 121.9 (s); 99.4 (t); 99.3 (t);
60.1 (q); 58.0 (q); 57.6 (q); 48.7 (d); 28.3 (t); 27.5 (d); 21.3 (q);
19.1 (t); 10.4 (q).
[α]20D = -37.6 (c 0.91, CH2Cl2)
Acknowledgments
16. Kanematsu, M.; Soga, K.; Manabe, Y.; Morimoto,
S.; Yoshida, M.; Shishido, K. Tetrahedron 2011,
67, 4758–4766.
17. Donohoe, T. J.; O’Riordan, T. J. C.; Peifer, M.;
Jones, C. R.; Miles, T. J. Org. Lett. 2012, 14,
5460–5463.
This work is financially supported by the Austrian Science
Fund (FWF) (Project No P 25556-N28). We wish to thank
Ass.Prof. Dipl.-Ing. Dr.techn. Christian Hametner (Vienna
University of Technology) for performing the 2D NMR
measurements.
18. Trost, B. M.; Toste, F. D. J. Am. Chem.Soc. 1998,
120, 815-816.
19. Stewart, I. C.; Ung, T.; Pletnev, A. A.; Berlin, J.
M.; Grubbs, R. H.; Schrodi, Y. Org. Lett. 2007, 9,
1589–1592.
20. Hoye, T. R.; Jeffrey, C. S.; Tennakoon, M. A.;
Wang, J.; Zhao, H. J. Am. Chem. Soc. 2004, 126,
10210–10211.
21. Compounds 36 and 38 were used to determinate
the enantiopurity of our products. Accordingly,
both alcohols were transformed to the
References and notes
1. Rodríguez, A. D.; González, C.; Huang, S. D. J.
Org. Chem. 1998, 63, 7083–7091.
2. Rodriguez, A. D.; Ramirez, C.; Rodriguez, I. I.;
Barnes, C. L. J. Org. Chem. 2000, 65, 1390-1398.
3. Rodriguez, A. D.; Ramirez, Org. Lett. 2000, 2,
507-510.
corresponding Mosher’s esters and based on HPLC
and 19F NMR analysis, the enantiomeric excess
was proven to be 96%.
4. Review on the synthesis of Colombiasin A and
Elisapterosin B:
5. (a) Lynch, J. K.; Park, C.-M. Chemtracts 2005,
18(4),236−245. Synthesis of Elisapterosin B :(b)
Waizumi, N.; Stankovic, A. R.; Rawal, V. H. J.