A Metathesis Route to (+)-Orientalol F, a Guaiane Sesquiterpene from Alisma Orientalis

Article abstract of DOI:10.1002/ejoc.201601197

The synthesis of (+)-orientalol F (1) started with aldehyde 6, which is available from (R)-limonene in two steps. Wittig reaction of 6 with unsaturated ylide 7 to give a tetraene, and subsequent ring-closing metathesis yielded hydroazulene 4, selective ep

Full text of DOI:10.1002/ejoc.201601197

A Journal of
Accepted Article
Title: A Metathesis Route to (+)-Orientalol F, a Guaiane Sesquiterpene from Alisma
Orientalis
¨
Authors: Martin Zahel; Yuzhou Wang; Anne Jager; Peter Metz
This manuscript has been accepted after peer review and the authors have elected
to post their Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by using the Digital
Object Identifier (DOI) given below. The VoR will be published online in Early View as
soon as possible and may be different to this Accepted Article as a result of editing.
Readers should obtain the VoR from the journal website shown below when it is pu-
blished to ensure accuracy of information. The authors are responsible for the content
of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601197
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601197
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
A Metathesis Route to ()-Orientalol F, a Guaiane Sesquiterpene
from Alisma Orientalis
Martin Zahel,[a] Yuzhou Wang,[a] Anne Jäger,[a] and Peter Metz*[a]
Dedicated to Professor Jürgen Fabian on the occasion of his 80th birthday
Abstract: The synthesis of ()-orientalol F (1) commenced with
aldehyde 6 that is available from (R)-limonene in two steps. Wittig
reaction of 6 with unsaturated ylide 7 to give a tetraene and
subsequent ring-closing metathesis yielded hydroazulene 4,
selective epoxidation of which provided epoxy ester 3. After
generation of the requisite isopropyl unit and regioselective reductive
epoxide opening, the derived dienol 2 was utilized for installation of
the oxygen bridge through intramolecular oxymercuration followed
by oxidative demercuration. The resultant allylic alcohol epimers 15
and 16 were readily converted to the target natural product 1 by
oxidation/reduction sequences.
sesquiterpene 1. Dienol 2 in turn was traced back to epoxy ester
3, preparation of which was planned by selective epoxidation of
triene 4. In another key operation, the hydroazulene should be
constructed by ring-closing metathesis of tetraene 5, which was
to be assembled through carbonyl olefination from unsaturated
aldehyde 6. This aldehyde is readily accessible according to a
published procedure from (R)-limonene by chemoselective
ozonolysis followed by intramolecular aldol condensation.[6]
Figure 1. Structure of ()-orientalol F (1).
Scheme 1. Retrosynthetic plan for guaiane 1.
Introduction
Gratifyingly, with substrate
6 an efficient and completely
stereoselective Wittig reaction with stabilized ylide 7[7]
succeeded in contrast to its saturated cyclopentane analog that
was used for the synthesis of ()-englerin A (Scheme 2).[4] While
reflux in toluene was suitable for this process, simply heating the
reactants 6 and 7 neat to 100 °C provided an optimum 90% yield
of the (E)-configured enoate 5. Using the Grubbs I catalyst 8,
tetraene 5 cyclized smoothly to give hydroazulene 4, whereas
the Grubbs II catalyst was too reactive for selective conversion
of 5.[8] Removal of ruthenium residues by oxidation with small
amounts of lead tetraacetate and filtration over silica gel prior to
The guaiane ()-orientalol F (1) was isolated from the rhizome of
Alisma orientalis, which is used in traditional Chinese medicine
for the treatment of diabetes and as a diuretic.[1] First syntheses
of this sesquiterpene were achieved by the groups of
Echavarren[2] as well as Sun and Lin[3] with a maximum ee of
88%. Here we report a concise access to virtually enantiopure
()-1 from the commercially available monoterpene (R)-limonene.
Results and Discussion
flash chromatography was essential for isolation of
4 in
reproducibly high yield.[9,10] Shi epoxidation with catalyst 9[11]
turned out to be the method of choice for chemo- and
stereoselective epoxidation of only the isolated olefin of 4.[12]
Optimum conditions involved rigorous exclusion of atmospheric
oxygen and running the reaction at ambient temperature in order
to avoid formation of overoxidation products. Since we obtained
the required -epoxide 3 at room temperature with the D- (9)
and with the L-catalyst ent-9 in comparable yields, the
diastereoselectivity is completely controlled by the substrate
under these conditions. As already applied to the synthesis of
englerin A,[4] the ester function in 3 was transformed via a
Weinreb amide (10) into a methyl ketone (11). This compound
yielded suitable crystals for X-ray diffraction analysis, through
which the stereochemical outcome of the Shi epoxidation was
unequivocally proven in retrospect.[13,14]
Scheme 1 depicts our retrosynthetic plan for ()-orientalol F (1).
Similar to our recently communicated routes to the guaianes ()-
englerin A[4] and ()-oxyphyllol,[5] key steps are chemo- and
stereoselective oxidation reactions of polyolefins next to a ring-
closing metathesis event to generate the carbobicyclic
framework. Thus, an oxidative cyclofunctionalization of dienol 2
was envisaged for construction of the oxygen-bridged
[a]
Fachrichtung Chemie und Lebensmittelchemie,
Organische Chemie I, Technische Universität Dresden
E-mail: peter.metz@chemie.tu-dresden.de
http://www.chm.tu-dresden.de/oc1/
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
Scheme 3. Conversion of dienone 11 into allylic alcohols 15 and 16. Reagents
and conditions: (a) Ph3P=CH2, THF, room temp.; (b) H2, (PPh3)3RhCl (10 mol-
%), benzene, EtOH, room temp., 92% (2 steps); (c) LiAlH4, Et2O, 20 °C, 72%;
(d) Hg(O2C-CF3)2, CH2Cl2, MeOH, 78 °C, then NaCl, aq. NaHCO3, 78 °C to
room temp.; (e) O2, NaBH4, DMF, 0 °C to room temp., 93% (2 steps).
Scheme 2. Synthesis of dienone 11. Reagents and conditions: (a) 7, 100 °C,
91%; (b) 8 (3 mol-%), CH2Cl2, room temp., 90%; (c) oxone, 9 (30 mol-%),
MeCN, H2O, pH 10.5, room temp., 67%; (d) MeONHMe•HCl, i-PrMgCl, THF,
40 °C to room temp.; (e) MeLi, THF, 40 °C to room temp., 89% (2 steps).
Following the protocol of Echavarren,[2] oxidation of 15 with
Collins reagent gave rise to epoxy alcohol 17 (Scheme 4). This
compound was subsequently deoxygenated with a lower valent
tungsten halide[18] to yield ()-orientalol F (1) for the first time in
high enantiomeric purity, i. e. 98% ee as for the starting material
(R)-limonene. Pleasingly, the novel -epimer 16 could be
converted to the target molecule 1 as well. In this case, oxidation
with excess Collins reagent did not stop at the epoxy alcohol
stage but led directly to epoxy ketone[19] 18 that was smoothly
deoxygenated with molybdenum hexacarbonyl[20] to give the
known unsaturated ketone 19.[2] Again following the protocol of
Echavarren,[2] Luche reduction of 19 then provided ()-orientalol
F (1).
Wittig methylenation of ketone 11 gave conjugated triene 12
(Scheme 3). Hydrogenation of 12 in the presence of the
Wilkinson catalyst (PPh3)3RhCl enabled
a
completely
chemoselective conversion of only the terminal olefin to afford
epoxy diene 13.[15] Lithium aluminium hydride then effected a
regioselective reductive epoxide opening of 13 with formation of
tertiary alcohol 2. Noteworthily, compound 2 was described as a
natural product isolated from the soft coral Nephthea
chabrollii.[16] However, the data of synthetic 2 did not match the
values reported in the literature for the naturally occuring
sesquiterpene with respect to specific rotation and 1H NMR
shifts. Thus, revision of the purported structure for this natural
product is probably required. After considerable experimentation,
intramolecular
trifluoroacetate[17a,b] and subsequent ligand exchange with
sodium chloride eventually allowed an efficient
oxymercuration
using
mercury
cyclofunctionalization to give a single organomercury chloride 14.
Oxidative demercuration[17] of 14 proceeded in high yield, but
with complete allylic transposition to furnish a 1.1:1 mixture of
epimeric allyl alcohols 15 and 16. NOESY measurements
showed a strong NOE between the angular hydrogen atom and
the methyl group at the cyclopentane moiety of 15, whereas a
corresponding NOE was not observed for 16. The -hydroxy
epimer 15 was found to be identical to a late stage intermediate
used in the Echavarren synthesis of orientalol F.[2]
Scheme 4. Completion of the synthesis of ()-orientalol F (1). Reagents and
conditions: (a) CrO3•py2, 4 Å sieves, CH2Cl2, 10 °C to room temp., 60% 17
from 15, 71% 18 from 16; (b) WCl6/BuLi (1:2), THF, 78 °C to 45 °C, 73%; (c)
Mo(CO)6, DME, reflux, 90%; (d) NaBH4, CeCl3•7H2O, MeOH, room temp.,
79% (90% brsm).
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
141.0 (s, CH), 133.6 (s, CH), 131.6 (s, CH), 128.4 (d, JC,P = 11.5 Hz, CH),
111.7 (s, CH2), 50.0 and 48.7 (s, CH3), 31.2 (d, JC,P = 137.9 Hz, CH2)
ppm, 4-C not visible. MS (ESI, positive): m/z = 375 [MH].
Conclusions
In summary, a highly efficient ring-closing metathesis of tetraene
5 and selective oxidative transformations of polyenes 4 and 2
were used as the key operations in a straightforward synthesis
of the guaiane sesquiterpene 1 from (R)-limonene.
Tetraene 5: Aldehyde 6[6] (975 mg, 6.49 mmol) and ylide 7 (4.86 g, 12.9
mmol) were stirred for 3 d at 100 °C. Then the mixture was cooled to
room temperature and purified by column chromatography
(isohexane/ethyl acetate 10:1) to afford tetraene 5 (1.446 g, 90%) as a
1
colorless oil as a single diastereomer. []D20 = 22 (c = 1.19, CHCl3). H
NMR (500 MHz, CDCl3):  = 7.37 (s, 1 H), 5.76–5.85 (m, 1 H), 4.92–4.99
(m, 2 H), 4.66–4.69 (m, 1 H), 4.55 (d, J = 0.6 Hz, 1 H), 3.73 (s, 3 H),
3.46–3.48 (m, 1 H), 3.00–3.11 (m, 2 H), 2.38–2.48 (m, 1 H), 2.22–2.32
(m, 1 H), 2.00–2.10 (m, 1 H), 1.83 (s, 3 H), 1.64–1.73 (m, 1 H), 1.68 (s, 3
H) ppm. 13C NMR (125 MHz, CDCl3):  = 169.1 (C), 147.4 (C), 147.1 (C),
136.5 (CH), 135.1 (CH), 133.8 (C), 127.3 (C), 115.0 (CH2), 110.2 (CH2),
54.4 (CH), 51.8 (CH3), 37.4 (CH2), 31.7 (CH2), 29.2 (CH2), 20.7 (CH3),
15.6 (CH3) ppm. IR (ATR):  = 3078 (w), 2950 (m), 2840 (w), 1917 (w),
1844 (w), 1770 (w), 1709 (s), 1651 (m), 1636 (m), 1620 (m), 1435 (m),
1375 (m), 1265 (s), 1208 (s), 1124 (m), 1064 (m), 994 (m), 892 (s), 831
(m), 760 (m), 634 (m) cm1. MS (GC–MS, EI): m/z (%) = 246 (5) [M], 231
(11) [MCH3], 215 (6), 205 (89), 187 (26), 171 (35), 157 (17), 145 (100),
131 (51), 119 (39), 105 (31), 91 (46), 77 (29), 59 (12), 41 (21). HRMS:
calcd for C16H22O2 [M] 246.1620; found 246.1612.
Experimental Section
General Remarks: THF and DCM were dried and purified by passage
through a MB-SPS-800 device using molecular sieves. All commercially
available reagents were used as received. Reactions were performed
under argon atmosphere. Thin layer chromatography (TLC) was
performed on Merck silica gel 60 F254 0.2 mm precoated plates. Product
spots were visualized by UV light at 254 nm and subsequently developed
using anisaldehyde solution as appropriate. Flash column
chromatography was carried out using silica gel (Merck, particle size 40-
63 microns). Melting points were measured on a Wagner & Munz
PolyTherm A and are uncorrected. Optical rotations were measured on a
Perkin Elmer 341 LC polarimeter. NMR spectra were recorded on a
Bruker DRX500P (500.13 MHz 1H, 125.77 MHz 13C) or else on an
Avance-III-600 (600.16 MHz 1H, 150.92 MHz 13C) spectrometer.
Chemical shifts () are quoted in parts per million (ppm) downfield of
tetramethylsilane, using residual proton-containing solvent as internal
standard (CDCl3 at 7.27 ppm). Abbreviations used in the description of
resonances are: s (singlet), d (doublet), t (triplet), q (quartet), spt (septet),
br (broad). Coupling constants (J) are quoted to the nearest 0.1 Hz.
Infrared spectra were recorded on a THERMONICOLET Avatar 360
instrument using ATR. Mass spectra were recorded with an Agilent
5973N detector coupled with an Agilent 6890N GC (GC–MS, 70 eV) or
else with a Bruker Esquire-LC (direct injection as a methanolic NH4OAc
solution, ESI). HRMS spectra were recorded on a Finnigan MAT 95 (EI,
70 eV) or a Bruker Daltonic "Impact II" (ESI-TOF). Elemental analysis
was performed on a Hekatech EA 3000. The X-ray diffraction analysis
was carried out with a Bruker Kappa CCD diffractometer.
Hydroazulene 4: A solution of tetraene 5 (557 mg, 2.26 mmol) and
Grubbs II catalyst 8 (56 mg, 67 mol) in DCM (55 mL) was stirred for 2 h
with occasional short time evaporation for ethylene removal and
subsequently treated with Pb(OAc)4 (60 mg, 136 mol). After stirring
overnight, the mixture was filtered over a pad of silica gel and then
evaporated. Purification of the residue by column chromatography
(isohexane/ethyl acetate 10:1) yielded the air sensitive hydroazulene 4
20
(444 mg, 90%) as a brown oil. []D = 43 (c = 0.64, MeOH). 1H NMR
(500 MHz, CDCl3):  = 7.41 (d, J = 2.2 Hz, 1 H), 5.62–5.66 (m, 1 H), 4.08
(br s, 1 H), 3.73 (s, 3 H), 3.04–3.28 (m, 2 H), 2.22–2.53 (m, 2 H), 1.92–
2.10 (m, 2 H), 1.82 (s, 3 H), 1.74 (d, J = 1.3 Hz, 3 H) ppm. 13C NMR (125
MHz, CDCl3):  = 169.1 (C), 144.7 (C), 140.7 (C), 133.4 (CH), 132.8 (C),
126.3 (C), 123.2 (CH), 51.9 (CH3), 47.8 (CH), 38.1 (CH2), 25.3 (CH2),
24.7 (CH2), 21.0 (CH3), 14.5 (CH3) ppm. IR (ATR):  = 3018 (w), 2948
(w), 2909 (w), 2832 (w), 2056 (w), 1770 (w), 1701 (m), 1653 (m), 1622
(m), 1457 /m), 1433 (m), 1375 (m), 1245 (s), 1196 (s), 1170 (m), 1080
(m), 973 (m), 911 (m), 859 (m), 811 (m), 764 (m), 707 (m), 644 (m) cm1.
MS (GC–MS, EI): m/z (%) = 218 (41) [M], 203 (22 ) [MCH3], 189 (28),
171 (11), 159 (100), 143 (31), 128 (42), 115 (27), 105 (13), 91 (20), 77
(14), 59 (6), 39 (7). HRMS: calcd for C14H18O2 [M] 218.1307; found
218.1299.
But-3-en-1-yltriphenylphosphonium
Bromide:
4-Bromo-1-butene
(0.93 g, 6.89 mmol) and triphenyl phosphine (2.17 g, 8.27 mmol) were
dissolved in toluene (30 mL). The mixture was refluxed for 5 d and then
cooled to room temperature. The precipitate was filtered off and washed
with a small amount of toluene. Drying under vacuum afforded but-3-en-
1-yltriphenylphosphonium bromide (1.81 g, 66%) as a colorless solid.[7]
M.p. 221 °C. 1H NMR (500 MHz, CDCl3):  = 7.86–7.67 (m, 15 H), 5.99
(ddt, J = 16.9, 10.2, 6.5 Hz, 1 H), 5.04 (dd, J = 17.0, 1.2 Hz, 1 H), 4.98 (d,
J = 10.2 Hz, 1 H), 3.94 (m, 2 H), 2.47–2.40 (m, 2 H) ppm. 13C NMR (125
MHz, CDCl3):  = 135.0 (d, JC,P = 3.0 Hz, CH), 134.9 (d, JC,P = 14.8 Hz,
CH), 133.7 (d, JC,P = 10.0 Hz, CH), 130.5 (d, JC,P = 12.6 Hz, CH), 118.1
(d, JC,P = 85.9 Hz, C), 117.4 (s, CH2), 26.6 (d, JC,P = 3.7 Hz, CH2), 22.3 (d,
JC,P = 49.4 Hz, CH2) ppm. MS (ESI, positive): m/z = 317 [MBr].
Epoxide 3: To a solution of ketone 9 (18.1 mg, 70 mol), substrate 4
(51.0 mg, 234 mol) and a catalytic amount of tetrabutylammonium
hydrogen sulfate in MeCN (2.5 mL) was added 2.5 mL of a buffer (0.05 M
Na2B4O7 ∙ 10 H2O in 4 ∙ 10-4 M aqueous Na2(EDTA)). Subsequently were
added solutions of oxone (132 mg, 215 mol in 1 mL of 4 ∙ 10-4
M
M
aqueous Na2(EDTA)) and K2CO3 (125 mg, 908 mol in 1 mL of 4 ∙ 10-4
aqueous Na2(EDTA)) simultaneously over 20 min. The mixture was
diluted with ethyl acetate and washed with saturated aqueous NH4Cl
solution and brine. Drying over MgSO4 and evaporation of the solvents
Ylide 7: To a suspension of but-3-en-1-yltriphenylphosphonium bromide
(1.00 g, 2.52 mmol) in THF (2 mL) and toluene (4 mL) at 0 °C was added
dropwise a solution of NaHMDS in THF (2 M, 2.52 mL, 5.03 mmol). After
stirring for 20 min, the mixture was cooled to 78 °C and stirred for
another 10 min. Then methyl chloroformate (0.24 g, 2.52 mmol) was
added, and the mixture stirred for 1 h. After warming to room temperature
the solvents were removed under vacuum, and the residue was taken up
in ethyl acetate. Filtration and concentration of the filtrate yielded
phosphorus ylide 7 (0.81 g, 86%) as a brown solid.[7] M.p. 137 °C. 1H
NMR (600 MHz, CDCl3):  = 7.61–7.58 (m, 6 H), 7.53–7.51 (m, 3 H), 7.44
(s, 6 H), 5.81–5.79 (m, 1 H), 4.69–4.51 (m, 2 H), 3.58 and 3.12 (s, 3 H),
2.72–2.64 (m, 2 H) ppm. 13C NMR (150 MHz, CDCl3):  = 170.3 (s, C),
afforded
a residue, that was purified by column chromatography
(isohexane/ethyl acetate 5:1) to give epoxide 3 (36.6 mg, 67%) as a
1
colorless solid. M.p. 55 °C. []D20 = 93 (c = 0.56, CHCl3). H NMR (600
MHz, CDCl3):  = 7.53 (d, J = 2.3 Hz, 1 H), 3.78 (s, 3 H), 3.27–3.46 (m, 2
H), 3.07 (dd, J = 8.1, 6.6 Hz, 1 H), 2.34–2.64 (m, 3 H), 1.97–2.08 (m, 2
H), 1.89 (s, 3 H), 1.18 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3):  =
168.8 (C), 147.7 (C), 134.9 (CH), 132.8 (C), 123.9 (C), 63.1 (CH), 60.0
(C), 52.1 (CH3), 51.1 (CH), 38.7 (CH2), 27.8 (CH2), 22.2 (CH2), 17.2
(CH3), 15.7 (CH3) ppm. IR (ATR):  = 2952 (w), 2900 (w), 2830 (w), 2057
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
(w), 1844 (w), 1791 (w), 1771 (w), 1734 (w), 1688 (s), 1653 (m), 1624
(m), 1589 (m), 1457 (m), 1432 (m), 1378 (m), 1307 (w), 1245 (s), 1176
(m), 1107 (m), 1062 (m), 949 (m), 888 (m), 846 (m), 787 (m), 754 (m),
695 (m) cm1. MS (GC–MS, EI): m/z (%) = 234 (32) [M], 219 (6)
[MCH3], 205 (8), 191 (17), 175 (16), 159 (33), 145 (19), 131 (100), 115
(41), 105 (34), 91 (56), 77 (28), 43 (34). HRMS: calcd for C14H18O3 [M]
234.1256; found 234.1244.
(CH), 30.6 (CH2), 22.3 (CH2), 21.2 (CH3), 21.1 (CH3), 17.3 (CH3), 14.0
(CH3) ppm. IR (ATR):  = 2952 (m), 2926 (m), 2834 (m), 1440 (w), 1379
(m), 1362 (w), 1329 (w), 1297 (w), 1269 (w), 1231 (w), 1206 (w), 1179
(w), 1106 (w), 1057 (m), 1015 (m), 907 (w), 883 (s), 823 (s), 749 (s), 716
(w), 677 (w), 629 (w) cm1. MS (GC–MS, EI): m/z (%) = 218 (56) [M],
203 (19) [MCH3], 189 (33), 175 (47) [MC(CH3)2], 157 (39), 147 (67),
131 (71), 119 (54), 105 (98), 91 (100), 77 (51), 65 (23), 55 (28), 43 (66)
[C(CH3)2]. HRMS: calcd for C15H22O [M] 218.1671; found 218.1669.
Methyl Ketone 11: To a stirred solution of 3 (885 mg, 3.78 mmol) and
N,O-dimethylhydroxylamine hydrochloride (1.29 g, 13.23 mmol) in dry
THF (50 mL) at 40 °C was added isopropylmagnesium chloride (2 M in
THF, 11.3 mL, 22.68 mmol) over 15 min. After stirring for 75 min, the
reaction was quenched with saturated aqueous NH4Cl solution, and the
mixture was extracted 3 with ethyl acetate. The combined organic
layers were washed with brine and dried over MgSO4. Removal of the
solvents under vacuum yielded the crude Weinreb amide 10 as a
colorless oil (1.05 g).
Tertiary Alcohol 2: LiAlH4 (43 mg, 1.15 mmol) was suspended in diethyl
ether (2.5 mL). A solution of epoxide 13 (50.0 mg, 229 mol) in diethyl
ether (2.5 mL) was added dropwise at 0 °C, and the mixture warmed to
20 °C (not room temperature!) and stirred for 3 d at this temperature.
Afterwards Glauber's salt (750 mg) was added, and the suspension was
stirred for another 30 min. Subsequently the mixture was filtered through
a glass sintered funnel, and the filtrate was concentrated under vacuum.
Column chromatography (isohexane/ethyl acetate 2:1) of the residue
20
yielded alcohol 2 (36.2 mg, 72%) as a colorless oil. []D = 164 (c =
1
0.36, CHCl3). H NMR (500 MHz, CDCl3):  = 6.01 (s, 1 H), 3.04 (br s, 1
This crude product (1.05 g) was dissolved in dry THF (50 mL) and cooled
to 40 °C. A solution of methylmagnesium bromide (3 M in diethyl ether,
3.8 mL, 11.34 mmol) was added. The reaction mixture was warmed to
room temperature and stirred for 1 h. Then it was poured into saturated
aqueous NH4Cl solution, extracted 3 with DCM, and the combined
organic layers were dried over MgSO4. The solvent was removed under
reduced pressure, and the residue was purified by flash chromatography
(isohexane/ethyl acetate 5:1) to afford methyl ketone 11 (730 mg, 89%, 2
H), 2.42–2.53 (m, 1 H), 2.17–2.41 (m, 3 H), 1.84–2.03 (m, 3 H), 1.79–
1.83 (m, 2 H), 1.73 (d, J = 1.3 Hz, 3 H), 1.09 (s, 3 H), 1.04 (d, J = 6.6 Hz,
3 H), 1.03 (d, J = 6.6 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3):  =
148.2 (C), 136.6 (C), 133.2 (C), 117.8 (CH), 75.7 (C), 57.9 (CH), 44.3
(CH2), 38.1 (CH), 37.3 (CH2), 25.5 (CH2), 24.2 (CH2), 22.4 (CH3), 21.6
(CH3), 21.4 (CH3), 14.4 (CH3) ppm. IR (ATR):  = 3356 (w), 2958 (s),
2922 (s), 2871 (m), 2838 (m), 1458 (m), 1438 (m), 1373 (m), 1333 (w),
1291 (m), 1196 (m), 1093 (s), 1006 (m), 976 (w), 961 (w), 901 (s), 865
(m), 843 (m), 808 (w), 762 (w) cm1. MS (GC–MS, EI): m/z (%) = 220
(48) [M], 202 (26) [MH2O], 187 (40) [MH2OCH3], 177 (24), 159 (76),
147 (49), 131 (40), 119 (59), 105 (61), 91 (88), 79 (46), 55 (24), 43 (100)
[C(CH3)2]. HRMS: calcd for C15H24O [M] 220.1827; found 220.1826.
20
steps) as a colorless solid. M.p. 102 °C. []D = 58 (c = 0.46, CHCl3).
1H NMR (500 MHz, CDCl3):  = 7.34 (s, 1 H), 3.55 (dd, J = 15.4, 6.3 Hz,
1 H), 3.37 (br s, 1 H), 2.97 (dd, J = 8.2, 6.3 Hz, 1 H), 2.42–2.59 (m, 2 H),
2.39 (s, 3 H), 2.29 (dd, J = 15.6, 8.4 Hz, 1 H), 1.99–2.07 (m, 2 H), 1.90 (s,
3 H), 1.16 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3):  = 198.7 (C), 148.4
(C), 135.4 (CH), 133.6 (C), 133.2 (C), 63.0 (CH), 59.8 (C), 51.2 (CH),
38.9 (CH2), 25.6 (CH2), 25.4 (CH3), 22.2 (CH2), 17.2 (CH3), 14.8 (CH3)
ppm. IR (ATR):  = 2966 (m), 2926 (w), 2834 (w), 1734 (w), 1697 (w),
1653 (m), 1618 (m), 1583 (m), 1517 (w), 1474 (m), 1423 (m), 1379 (s),
1344 (m), 1307 (m), 1282 (m), 1245 (s), 1180 (s), 1151 (m), 1106 (m),
1054 (m), 998 (m), 968 (m), 886 (s), 821 (s), 745 (m), 638 (m), 616 (s)
cm1. MS (GC–MS, EI): m/z (%) = 218 (17) [M], 203 (3) [MCH3], 189
(5), 175 (31) [MCH3CO], 157 (8), 133 (21), 115 (17), 105 (22), 91 (4),
77 (15), 65 (8), 43 (100) [CH3CO]. HRMS: calcd for C14H18O2 [M]
218.1307; found 218.1306.
Formation of the Ether Bridge: Diene 2 (50.0 mg, 227 mol) was
dissolved in DCM (10 mL), and methanol (25.0 mg) was added. Then
Hg(O2CCF3)2 (116 mg, 272 mol) was added at 78 °C in one portion,
and the mixture was stirred for 15.5 h at this temperature. Thereafter
saturated aqueous solution of NaHCO3 (10 mL) and brine (10 mL) were
added, and the mixture was warmed to room temperature and stirred for
another 3.5 h. Afterwards the layers were separated and the aqueous
layer was extracted 3 with diethyl ether. The combined organic layers
were dried over MgSO4 and evaporated to yield the crude
organomercurial 14 (113.2 mg) as an off-white solid.
Isopropyl Derivative 13: Methyltriphenylphosphonium bromide (2.39 g,
6.69 mmol) was suspended in dry THF (15 mL), and NaHMDS (2 M in
THF, 3.0 mL, 6.02 mmol) was added. After 5 min ketone 11 (730 mg,
3.34 mmol) in dry THF (15 mL) was added dropwise to the above mixture.
After stirring for 5 min, the reaction was quenched with saturated
aqueous NH4Cl solution, and the mixture was extracted 3 with DCM.
The combined organic layers were dried over MgSO4 and filtered over a
pad of silica gel (elution with isohexane/ethyl acetate 5:1) to yield the
crude triene 12 (733 mg) as a colorless solid.
A solution of NaBH4 (48 mg, 1.27 mmol) in DMF (15 mL) was cooled to
0 °C. Oxygen was bubbled through this solution for 30 min, and a
solution of the above crude organomercurial 14 (113.2 mg) in DMF (3
mL) was added dropwise over 1 h. The mixture was warmed to room
temperature and stirred for another 30 min (oxygen bubbling was
continued until workup). Subsequently 1 N aqueous HCl was added, and
the suspension was filtered through a plug of celite (elution with DCM).
The filtrate was diluted with DCM and washed with brine, dried over
MgSO4 and concentrated under vacuum. Flash chromatography
(isohexane/ethyl acetate 3:1) of the residue afforded the allylic alcohols
15[2] and 16 (50.2 mg, 94%) as a 1.1:1 diastereomeric mixture.
The above crude triene 12 (733 mg) and (PPh3)3RhCl (304 mg, 0.33
mmol) were dissolved in ethanol (15 mL) and benzene (15 mL). The
resulting mixture was stirred under hydrogen (1 atm) for 2 h and
20
adsorbed
on
silica
subsequently.
Column
chromatography
Allylic Alcohol 15: []D = 27 (c = 0.28, CHCl3). 1H NMR (500 MHz,
(isohexane/ethyl acetate 10:1) yielded the isopropyl derivative 13 (646
CDCl3):  = 5.74 (d, J = 2.8 Hz, 1 H), 2.70–2.79 (m, 1 H), 1.88–1.96 (m, 2
H), 1.66–1.85 (m, 5 H), 1.42–1.49 (m, 1 H), 1.37 (s, 3 H), 1.36 (s, 3 H),
1.34–1.39 (m, 1 H), 0.98 (d, J = 7.3 Hz, 3 H), 0.98 (d, J = 7.3 Hz, 3 H)
ppm. 13C NMR (125 MHz, CDCl3):  = 150.1 (C), 119.1 (CH), 85.8 (C),
82.4 (C), 77.5 (C), 51.1 (CH), 41.3 (CH2), 38.6 (CH2), 34.0 (CH), 30.5
(CH2), 28.0 (CH3), 26.0 (CH3), 23.8 (CH2), 18.1 (CH3), 17.8 (CH3) ppm.
IR (ATR):  = 3430 (w), 2960 (m), 2872 (m), 1917 (w), 1844 (w), 1780 (s),
1727 (s), 1684 (w), 1651 (m), 1473 (m), 1441 (m), 1684 (w), 1651 (m),
20
mg, 91%, 2 steps) as a colorless solid. M.p. 57 °C. []D = 108 (c =
1
1.32, CHCl3). H NMR (500 MHz, CDCl3):  = 6.06 (s, 1 H), 3.29 (br s, 1
H), 2.97 (dd, J = 8.4, 6.5 Hz, 1 H), 2.59 (dd, J = 15.4, 8.2 Hz, 1 H), 2.48
(dd, J = 15.1, 6.3 Hz, 1 H), 2.37–2.44 (m, 1 H), 2.27–2.37 (m, 2 H), 1.93–
2.01 (m, 2 H), 1.74 (s, 3 H), 1.18 (s, 3 H), 1.05 (d, J = 6.6, 3 H), 1.02 (d, J
= 6.6 Hz, 3 H) ppm. 13C NMR (125 MHz, CDCl3):  = 141.3 (C), 135.3 (C),
133.0 (C), 118.8 (CH), 63.9 (CH), 60.4 (C), 51.7 (CH), 38.1 (CH2), 37.8
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
1472 (m), 1441 (m), 1373 (m), 1164 (s), 1122 (s), 1053 (m), 1018 (m),
999 (m), 951 (m), 904 (m), 862 (m), 753 (m), 663 (m), 623 (m) cm1. MS
(GC–MS, EI): m/z (%) = 218 (10) [MH2O], 203 (5) [MH2OCH3], 193
(8), 175 (10), 160 (43), 147 (50), 135 (16), 119 (19), 105 (33), 91 (37), 77
(21), 55 (14), 43 (100) [C(CH3)2].
1699 (w), 1684 (w), 1450 (w), 1389 (m), 1368 (m), 1305 (w), 1273 (w),
1183 (w), 1097 (m), 1070 (m), 1034 (m), 970 (m), 952 (m), 923 (w), 877
(s), 838 (m), 777 (m), 735 (m), 706 (w) cm1. MS (ESI, positive): 268.2
[MNH4], 518.2 [2MNH4]. HRMS: calcd for C15H26NO3 [M+NH4]+
268.1907; found 268.1913.
20
Allylic Alcohol 16: []D = 49 (c = 0.91, CHCl3). 1H NMR (500 MHz,
Enone 19: A solution of epoxy ketone 18 (90.0 mg, 0.36 mmol) and
molybdenum hexacarbonyl (109.2 mg, 0.414 mmol) in 1,2-
dimethoxyethane (3.5 mL) was stirred at 90 °C for 16 h. After removal of
the solvent under vacuum, the residue was purified by flash
chromatography (pentane/diethyl ether 20:1) to yield enone 19[2,3] (75.7
CDCl3):  = 5.67 (d, J = 2.5 Hz, 1 H), 3.02–3.10 (m, 1 H), 1.64–1.97 (m, 7
H), 1.41–1.48 (m, 1 H), 1.39 (s, 3 H), 1.36 (s, 3 H), 1.18–1.25 (m, 1 H),
0.98 (d, J = 6.9 Hz, 3 H), 0.98 (d, J = 6.9 Hz, 3 H) ppm. 13C NMR (125
MHz, CDCl3):  = 147.6 (C), 119.6 (CH), 85.6 (C), 82.5 (C), 77.2 (C),
50.2 (CH), 41.1 (CH2), 38.4 (CH2), 34.0 (CH), 30.5 (CH2), 26.1 (CH3),
25.6 (CH3), 23.1 (CH2), 18.1 (CH3), 17.9 (CH3) ppm. IR (ATR):  = 3391
(w), 2962 (s), 2928 (s), 2871 (m), 1666 (w), 1486 (w), 1458 (w), 1374 (m),
1304 (w), 1268 (w), 1224 (w), 1181 (m), 1121 (m), 1086 (s), 1055 (m),
1022 (m), 996 (w), 953 (w), 908 (m), 861 (m), 776 (w), 623 (w) cm1. MS
(GC–MS, EI): m/z (%) = 236 (3) [M], 218 (7) [MH2O], 203 (6)
[MH2OCH3], 193 (6), 175 (12), 160 (32), 147 (40), 133 (17), 119 (14),
105 (30), 91 (34), 77 (21), 55 (11), 43 (100) [C(CH3)2]. HRMS: calcd for
C15H24O2 [M] 236.1776; found 236.1784.
23
mg, 90%) as a colorless oil. []D = 27.8 (c = 0.96, CH2Cl2). 1H NMR
(500 MHz, CDCl3)  = 3.15–3.25 (m, 1 H), 2.39–2.58 (m, 1 H), 2.23–2.33
(m, 1 H), 2.17 (spt, J = 6.9 Hz, 1 H), 1.94–2.08 (m, 5 H), 1.84–1.92 (m, 1
H) 1.57–1.64 (m, 1 H), 1.42–1.50 (m, 1 H), 1.33–1.41 (m, 1 H), 1.31 (s, 3
H), 1.01 (d, J = 6.9 Hz, 3 H), 1.00 (d, J = 6.9 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3)  = 199.8 (C), 154.4 (C), 131.9 (C), 91.0 (C), 84.3 (C),
57.8 (CH), 38.8 (CH2), 33.2 (CH2), 30.5 (CH), 30.0 (CH2), 25.9 (CH2),
24.6 (CH3), 18.4 (CH3), 17.3 (CH3), 15.9 (CH3) ppm. IR (ATR):  = 2964
(m), 2926 (m), 2876 (m), 1734 (w), 1716 (w), 1688 (s), 1652 (m), 1625
(s), 1457 (m), 1434 (m), 1375 (m), 1268 (m), 1176 (w), 1143 (w), 1115
(m), 1076 (s), 1034 (m), 1005 (m), 975 (m), 929 (m), 900 (w), 883 (m),
800 (m), 769 (m) cm1. MS (ESI, positive): 235.3 [MH].
Epoxy Alcohol 17: Pyridine (353 l, 4.37 mmol) was added dropwise to
a suspension of chromium trioxide (218.6 mg, 2.18 mmol) and molecular
sieves 4 Å (330 mg) in dichloromethane (15 mL) cooled to 10 °C. The
mixture was warmed to room temperature and stirred for 1 h. After
cooling the mixture to 10 °C, a solution of allyl alcohol 15 (129.0 mg,
0.546 mmol) in dichloromethane (3 mL) was added, and the mixture was
warmed to room temperature and stirred for 6.5 h. The mixture was
diluted with diethyl ether (10 mL) and filtered over a pad of silica gel.
Following removal of the solvents under vacuum, the residue was
purified by flash chromatography (pentane/diethyl ether 8:2) to give
epoxy alcohol 17[2] (82.6 mg, 60%) as a colorless oil. []D23 = 33.9 (c =
1.02, CH2Cl2). 1H NMR (600 MHz, CDCl3):  = 4.09 (dd, J = 10.5, 1.1 Hz,
1 H), 2.25 (d, J = 10.5 Hz, 1 H), 2.07–2.12 (m, 1 H), 1.93–2.04 (m, 2 H),
1.86–1.92 (m, 2 H), 1.67 (tdd, J = 12.8, 3.8, 1.1 Hz, 1 H), 1.50 (s, 3 H),
1.47–1.55 (m, 1 H), 1.34–1.42 (m, 1 H), 1.21 (s, 3 H), 1.04 (d, J = 6.4 Hz,
3 H), 1.03 (d, J = 6.4 Hz, 3 H), 0.97–1.06 (m, 1 H) ppm. 13C NMR (150
MHz, CDCl3):  = 87.6 (C), 82.9 (C), 71.2 (C), 67.2 (CH), 65.0 (C), 50.3
(CH), 33.3 (CH), 32.9 (CH2), 31.4 (CH2), 28.1 (CH2), 24.3 (CH3), 20.1
(CH2), 18.2 (CH3), 17.3 (CH3), 15.2 (CH3) ppm. IR (ATR):  = 3484 (br w),
2963 (m), 2926 (m), 2876 (w), 1473 (m), 1456 (m), 1379 (m), 1314 (w),
1260 (m), 1230 (w), 1187 (m), 1111 (m), 1076 (s), 1057 (s), 1019 (s),
()-Orientalol F (1) from Epoxy Alcohol 17: To a suspension of
tungsten hexachloride (365.0 mg, 0.92 mmol) in THF (10 mL) cooled to
78 °C was added BuLi (2.2 M in hexane, 0.84 mL, 1.84 mmol). After
warming the mixture to room temperature over 1 h, it was cooled to 0 °C
and treated with a solution of epoxy alcohol 17 (116.0 mg, 0.46 mmol) in
THF (4 mL). The mixture was stirred for 30 min at room temperature and
30 min at 45 °C, and then the reaction was quenched by addition of an
aqueous solution of sodium potassium tartrate (1.5 M, 8 mL) and NaOH
(2 N, 8 mL). Following extraction with diethyl ether (3), the combined
organic layers were washed with brine and dried over MgSO4. Removal
of the solvents under vacuum and purification by flash chromatography
(pentane/ethyl acetate 15:1) afforded ()-orientalol F[1-3] (1, 79.3 mg,
73%) as a white solid.
()-Orientalol F (1) from enone 19: To a mixture of enone 19 (83.0 mg,
0.367 mmol) and cerium trichloride heptahydrate (136.7 mg, 0.367 mmol)
in methanol (7 mL) was added sodium borohydride (14.0 mg, 0.367
mmol). After stirring for 24 h at room temperature, the reaction was
quenched by addition of brine. The mixture was extracted with diethyl
ether (3), the combined organic layers were washed with brine and
dried over MgSO4, and the solvents were removed under vacuum. Flash
chromatography (pentane/diethyl ether 8:2) provided ()-orientalol F[1-3]
(1, 66.5 mg, 79%, 90% based on recovered starting material) as a white
solid and unreacted enone 19 (10.1 mg).
1007 (s), 935 (s), 871 (s), 782 (s), 768 (s), 702 (m), 653 (m), 606 (s) cm1
MS (ESI, positive): 270.1 [MNH4], 522.2 [2MNH4].
.
Epoxy Ketone 18: Pyridine (401 l, 4.96 mmol) was added dropwise to
a suspension of chromium trioxide (247.8 mg, 2.48 mmol) and molecular
sieves 4 Å (370 mg) in dichloromethane (18 mL) cooled to 10 °C. The
mixture was warmed to room temperature and stirred for 1 h. After
cooling the mixture to 10 °C, a solution of allyl alcohol 16 (117 mg,
0.495 mmol) in dichloromethane (3 mL) was added, and the mixture was
warmed to room temperature and stirred for 24 h. The mixture was
diluted with diethyl ether (10 mL) and filtered over a pad of silica gel.
Following removal of the solvents under reduced pressure, the residue
was purified by flash chromatography (pentane/diethyl ether 8:2) to give
()-Orientalol F (1): M.p. 38.2–39.5 °C. []D23 = 13.7 (c = 0.57, CH2Cl2)
23
from epoxy alcohol 17 and []D = 13.5 (c = 0.52, CH2Cl2) from enone
25
19; ref [2]: []D = 12.2 (c = 0.5, CH2Cl2) for 1 with 88% ee, ref [3]:
[]D23 = 7.88 (c = 0.5, CH2Cl2) for ent-1 with 67% ee. 1H NMR (600 MHz,
CDCl3):  = 4.40–4.45 (m, 1 H), 2.64–2.70 (m, 1 H), 2.28–2.36 (m, 1 H),
2.17–2.24 (m, 1 H), 1.94 (spt, J = 7.0 Hz, 1 H), 1.88 (s, 3 H), 1.76–1.82
(m, 2 H), 1.66–1.72 (m, 1 H), 1.59–1.64 (m, 1 H), 1.44 (d, J = 7.5 Hz, 1
H), 1.26–1.32 (m, 1 H), 1.17–1.25 (m, 1 H), 1.18 (s, 3 H), 1.03 (d, J = 7.0
Hz, 3 H), 1.01 (d, J = 7.0 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3):  =
133.5 (C), 133.0 (C), 86.6 (C), 84.4 (C), 73.9 (CH), 57.6 (CH), 39.0 (CH2),
31.7 (CH), 31.6 (CH2), 28.6 (CH2), 24.0 (CH2), 23.9 (CH3), 18.1 (CH3),
17.2 (CH3), 14.6 (CH3) ppm. IR (ATR):  = 2964 (m), 3450 (w), 3401 (w),
2965 (m), 2924 (m), 2878 (w), 2836 (w), 1473 (w), 1374 (m), 1313 (w),
1254 (w), 1176 (m), 1108 (m), 1066 (m), 1008 (s), 975 (w), 931 (m), 901
23
epoxy ketone 18 (88.0 mg, 71%) as a colorless oil. []D = 0.73 (c =
1.23, CH2Cl2). H NMR (600 MHz, CDCl3)  = 2.76 (d, J = 9.4 Hz, 1 H),
1
2.16 (spt, J = 7.2 Hz, 1 H), 2.03–2.12 (m, 2 H), 1.85–1.95 (m, 2 H), 1.69–
1.77 (m, 1 H), 1.61–1.70 (m, 1 H), 1.50–1.56 (m, 1 H), 1.41–1.50 (m, 1
H), 1.35 (s, 3 H), 1.32 (s, 3 H), 0.99 (d, J = 6.8 Hz, 3 H), 0.98 (d, J = 6.8
Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3)  = 202.0 (C), 90.9 (C), 84.5
(C), 74.9 (C), 71.4 (C), 55.3 (CH), 32.6 (CH2), 32.0 (CH2), 30.5 (CH2),
24.7 (CH3), 23.2 (CH2), 17.5 (CH3), 17.2 (CH3), 14.9 (CH3) ppm. IR
(ATR):  = 2979 (m), 2961 (m), 2929 (m), 2899 (w), 2877 (w), 1724 (s),
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
(m), 871 (w), 799 (m), 769 (w) cm1. MS (ESI, positive): 237.5 [MH],
219.5 [MHH2O].
[11] O. A. Wong, Y. Shi, Chem. Rev. 2008, 108, 3958–3987.
[12] J. Bian, M. Van Wingerden, J. M. Ready, J. Am. Chem. Soc. 2006, 128,
7428–7429.
[13] CCDC 1474984 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Keywords: Asymmetric synthesis • Metathesis • Natural
products • Oxidation • Terpenoids
Cambridge
www.ccdc.cam.ac.uk/data_request/cif.
[14] E. Keller, SCHAKAL 99, Computer Program for the Graphic
Crystallographic
Data
Centre
via
[1]
[2]
[3]
G.-P. Peng, G. Tian, X.-F. Huang, F.-C. Lou, Phytochemistry 2003, 63,
877–881.
A
Representation of Molecular and Crystallographic Models, University of
Freiburg, Germany, 1999.
E. Jiménez-Núñez, K. Molawi, A. M. Echavarren, Chem. Commun.
2009, 7327–7329.
[15] a) C. Ehret, G. Ourisson, Tetrahedron 1969, 25, 1785–1799; b) J. A.
Osborn, F. H. Jardine, J. F. Young, G. Wilkinson, J. Chem. Soc. (A)
1966, 1711–1732.
a) C.-L Wang, B.-F. Sun, S.-G. Chen, R. Ding, G.-Q. Lin, J.-Y. Xu, Y.-J.
Shang, Synlett 2012, 23, 263–266; b) C.-L Wang, B.-F. Sun, S.-G.
Chen, R. Ding, G.-Q. Lin, J.-Y. Xu, Y.-J. Shang, Synlett 2012, 23, 1266;
c) J. Wang, S.-G. Chen, B.-F. Sun, G.-Q. Lin, Y.-J. Shang, Chem. Eur.
J. 2013, 19, 2539–2547.
[16] M. R. Rao, K. V. Sridevi, U. Venkatesham, T. P. Rao, S. S. Lee, Y.
Venkatesvarlu, J. Chem. Res. (S) 2000, 245–247.
[17] a) J. Lee, K. A. Parker, Org. Lett. 2012, 14, 2682–2685; b) C. A. Broka,
Y.-T. Lin, J. Org. Chem. 1988, 53, 5876–5885; c) C. L. Hill, G. M.
Whitesides, J. Am. Chem. Soc. 1974, 96, 870–876.
[4]
M. Zahel, A. Keßberg, P. Metz, Angew. Chem. 2013, 125, 5500–5502;
Angew. Chem. Int. Ed. 2013, 52, 5390–5392.
[5]
[6]
M. Zahel, P. Metz, Beilstein J. Org. Chem. 2013, 9, 2028–2032.
a) A. Srikrishna, N. C. Babu, Tetrahedron Lett. 2001, 42, 4913–4914; b)
N. Zimmermann, R. Hilgraf, L. Lehmann, D. Ibarra, W. Francke,
Beilstein J. Org. Chem. 2012, 8, 1246–1255.
[18] a) M. A. Umbreit, K. B. Sharpless, Org. Synth. 1981, 60, 29–32; b) K. B.
Sharpless, M. A. Umbreit, M. T. Nieh, T. C. Flood, J. Am. Chem. Soc.
1972, 94, 6538–6540.
[19] a) Y. Chai, Z. Mou, M. C. McIntosh, Tetrahedron Lett. 2010, 51, 2393–
2395; b) P. Sundararaman, W. Herz, J. Org. Chem. 1977, 42, 813–819.
[20] a) A. Patra, M. Bandyopadhyay, D. Mal, Tetrahedron Lett. 2003, 44,
2355–2357; b) H. Alper, D. Des Roches, T. Durst, R. Legault, J. Org.
Chem. 1976, 41, 3611–3613.
[7]
K. C. Nicolaou, S. Ninkovic, F. Sarabia, D. Vourloumis, Y. He, H.
Vallberg, M. R. V. Finlay, Z. Yang, J. Am. Chem. Soc. 1997, 119,
7974–7991.
[8]
[9]
S. P. Nolan, H. Clavier, Chem. Soc. Rev. 2010, 39, 3305–3316.
L. A. Paquette, J. D. Schloss, I. Efremov, F. Fabris, F. Gallou, J.
Méndez-Andino, J. Yang, Org. Lett. 2000, 2, 1259–1261.
[10] G. C. Vougioukalakis, Chem. Eur. J. 2012, 18, 8868–8880.
This article is protected by copyright. All rights reserved

European Journal of Organic Chemistry
10.1002/ejoc.201601197
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Hydroazulene Synthesis
Martin Zahel, Yuzhou Wang, Anne
Jäger, Peter Metz*
Page No. – Page No.
A Metathesis Route to ()-Orientalol
F, a Guaiane Sesquiterpene from
Alisma Orientalis
A highly efficient ring-closing metathesis of a tetraene and selective oxidative
transformations of polyenes were used as the key operations in a straightforward
synthesis of the title guaiane sesquiterpene from (R)-limonene.
This article is protected by copyright. All rights reserved