Combined coinage metal catalysis in natural product synthesis: Total synthesis of (+)-varitriol and seven analogs

Article abstract of DOI:10.1039/c2ob25069a

A modular total synthesis of the natural product (+)-varitriol (1) and seven analogs was achieved by using combined coinage metal catalysis. Starting from enynol 13, reagent-controlled introduction of stereogenic centers and efficient center-to-axis-to-ce

Full text of DOI:10.1039/c2ob25069a

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PAPER
Combined coinage metal catalysis in natural product synthesis: total synthesis
of (+)-varitriol and seven analogs†‡
Tao Sun, Carl Deutsch and Norbert Krause*
Received 10th January 2012, Accepted 20th February 2012
DOI: 10.1039/c2ob25069a
A modular total synthesis of the natural product (+)-varitriol (1) and seven analogs was achieved by using
combined coinage metal catalysis. Starting from enynol 13, reagent-controlled introduction of stereogenic
centers and efficient center-to-axis-to-center chirality transfer via α-hydroxyallene 5 afforded (+)-varitriol
with 6.4% yield over 10 steps.
our approach are the reagent-controlled introduction of all stereo-
Introduction
genic centers and an efficient center-to-axis-to-center chirality
transfer using combined coinage metal catalysis.11,12
Natural products derived from marine sources continue to fasci-
nate due to their intriguing biological activities and their challen-
ging structures.1 The fungus Emericella variecolor was isolated
from a sponge collected in Venezuelan waters of the Caribbean
Sea.2 In 2002, Barrero and co-workers isolated (+)-varitriol (1)
from this fungus and disclosed its structure, including the rela-
tive configuration of the tetrahydrofuran ring.3 Varitriol shows a
more than 100-fold increased potency (over the mean toxicity)
toward RXF 393 (renal cancer), T-47D (breast cancer) and
SNB-75 (CNS cancer) cell lines and lower potency against pros-
tate cancer, leukemia, ovarian cancer, and colon cancer cell
lines.3 This is a remarkable activity for such a small molecule,
even though the mode of action remains to be elucidated.4
The retrosynthetic analysis of (+)-varitriol (1) is delineated in
Scheme 1. We envisaged that (+)-1 can be derived from the aro-
matic phosphonate 2 and the chiral aldehyde 3 utilizing a
Horner–Wadsworth–Emmons (HWE) olefination. The phospho-
nate 2 should be prepared from 3-methoxybenzoic acid by Kami-
kawa’s procedure.13 The aldehyde 3, in which all four chiral
centers are present, should be synthesized from 2,5-dihydrofuran
4, which should be accessible by a gold-catalyzed cycloisomeri-
zation of the α-hydroxyallene 5.11,14 A copper hydride-catalyzed
reduction of propargyl oxirane 611,15 should provide the key
intermediate 5.
Notwithstanding the trisubstituted aromatic ring, the real syn-
thetic challenge of varitriol is the richly substituted tetrahydro-
furan bearing four stereogenic centers. Previous syntheses of
(+)-varitriol,5–7 its enantiomer,7–9 and analogs thereof7,10 used
starting materials from the chiral pool (mannitol, dimethyl tar-
trate) and employed various olefination methods for attaching
the aromatic side chain. Even though these approaches were suc-
cessful, they render structural variations at the tetrahydrofuran
ring (e.g., different relative and/or absolute configuration at the
four chirality centers) difficult. Based on our interest in com-
bined coinage metal catalysis using functionalized allenes,11 we
now disclose a highly modular synthesis of (+)-varitriol, as well
as of seven analogs of this natural product. Important features of
Organic Chemistry, Dortmund University of Technology, D-44227-
Dortmund, Germany. E-mail: norbert.krause@tu-dortmund.de; Fax:
+49 231 7553884; Tel: +49 231 7553882
†This article is part of the Organic & Biomolecular Chemistry 10th
Anniversary issue.
‡Electronic supplementary information (ESI) available: Experimental
procedures and copies of NMR spectra. See DOI: 10.1039/c2ob25069a
Scheme 1
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desired propargyl oxirane 6 with 47% yield over 2 steps. Use of
L-(+)-DIPT instead of D-(−)-DET afforded ent-14 with 92% ee.
Thus, the precursors for both enantiomers of varitriol were at
hand with high enantioselectivity.
In the first of two consecutive coinage metal-catalyzed steps,
the propargyl oxirane 6 was converted into α-hydroxyallene 5 by
anti-stereoselective SN2′-reduction using an NHC-stabilized
copper hydride catalyst (Scheme 3).15,19 This was formed in situ
from copper(I) chloride, an imidazolium salt and sodium tert-
butoxide in the presence of polymethylhydridosiloxane (PMHS)
as stoichiometric hydride source. Among different NHC precur-
sors used in this reaction, IBiox12·HOTf20 and SIMes·HCl21
gave similar results, but the latter is more readily available. In
the presence of 3 mol% NHC–CuH and 1.2 eq. PMHS, allene 5
was obtained with 78% yield and complete center-to-axis chiral-
ity transfer.
Based on our continued interest in the stereoselective synthesis
and transformation of functionalized allenes, we had developed
the gold-catalyzed cycloisomerization of allenes bearing a
hydroxy, amino, or thiol group in the α- or β-position, to the cor-
responding five- or six-membered heterocycles, a method that
combines high reactivity and excellent axis-to-center chirality
Scheme 2
transfer with
a
tolerance towards many functional
groups.11,12,14,22 With this method the α-hydroxyallene 5 was
conveniently transformed into the desired 2,5-dihydofuran 4
(Scheme 3). The chirality transfer was virtually complete when
the reaction was catalyzed by 1 mol% gold(III)-chloride in THF
at 0 °C, giving 4 with 89% ee and 82% yield. At room tempera-
ture, partial epimerization22a was observed. Gold(I)-chloride in
the presence of pyridine or 2,2′-bipyridine22a can also be used,
but the reaction was much slower.
After successful introduction of two stereogenic centers under
reagent control, our intention was to install the remaining two
chirality centers of varitriol by reagent control as well. Here, the
Scheme 3
Results and discussion
The synthesis of the aromatic phosphonate 2 and its simpler
counterpart 12 is shown in Scheme 2. Reduction of ethyl 6-
chloromethyl-2-methoxybenzoate (7), which was prepared from
3-methoxybenzoic acid according to Kamikawa’s route,13 with
DIBAL-H followed by protection of 8 with TBSCl provided the
substituted benzyl chloride 9. This was treated with triethylpho-
sphite in an Arbuzov reaction to give the corresponding HWE
agent 2. The aromatic phosphonate 12, which is required for the
synthesis of analogs of varitriol, was obtained in the same way
(Scheme 2) starting from 2-hydroxymethylbenzyl chloride (10)
which was prepared from 1,2-phenylenedimethanol with high
yield (93%).16
The synthesis of 6 (Scheme 3) commenced with enyne 13.17
Catalytic Katsuki–Sharpless epoxidation18 with D-(−)-DET pro-
vided the oxirane 14 with 91% ee after 3 days at −23 °C. Instead
of the usual basic work up with aqueous NaOH,18b which
destroyed the product, the reaction mixture was worked up only
with ferrous sulfate and tartaric acid and the crude product was
directly used in the following benzylation which afforded the
Scheme 4
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Sharpless dihydroxylation23 is the method of choice, even
though (cyclic or acyclic) cis-1,2-disubstituted olefins are not the
best substrates for this transformation.24 Therefore, a ligand
screening with dihydrofuran 4 was carried out (Scheme 4).
Whereas (DHQD)2PHAL and (DHQD)2AQN were almost unse-
lective, affording ratios of diastereomeric diols 15 and 16 of
55 : 45 and 57 : 43, respectively, the ligand (DHQD)2PYR led to
a ratio of 78 : 22, a diastereoselectivity that we consider satisfac-
tory for this type of substrate. The dihydroxylation was carried
out with a loading of 1 mol% potassium osmate(VI) dihydrate
and 5 mol% (DHQD)2PYR and gave an almost quantitative
yield after 2 days at 0 °C.25
The mixture of 15 and 16 was treated with 2,2-methoxypro-
pane and PPTS to give the bicyclic acetals 17 and 18
(Scheme 4) which could be separated chromatographically. The
relative configuration of 17 was determined by an NOESY exper-
iment which shows cross peaks between H2/H3 and the methyl
group at the tetrahydrofuran ring, as well as a cross peak
between H3 and H2 (Fig. 1). Due to overlapping signals in the
1H NMR spectrum of diastereomer 18, we conducted the
NOESY experiment with the debenzylated product 20 (Fig. 1),
Cross peaks between H1 and H2, between H2 and H3, and
between H3 and H4 confirm the all-cis-configuration.
Scheme 5
Table 1 Specific rotation reported for varitriol (1)
Enantiomer
Specific rotation [α]D20
Reference
(+)-1
(+)-1
(+)-1
(+)-1
(+)-1
(−)-1
(−)-1
(−)-1
+40.3 (c 2.7, MeOH)
+18.5 (c 2.3, MeOH)
+19.4 (c 2.7, MeOH)
+43.4 (c 0.53, MeOH)
+40.0 (c 0.21, MeOH)
−42.2 (c 0.135, MeOH)
−18.2 (c 0.0033, MeOH)
−40.6 (c 1.6, MeOH)
Our value
3
5
6
7
7
8
9
Hydrogenative debenzylation26 of 17 provided the alcohol 19
which was sufficiently pure for the subsequent oxidation
(Scheme 4). Whereas Swern, Parikh–Doering, and IBX oxi-
dation failed, clean conversion of 19 to the desired aldehyde 3
was achieved with Dess–Martin periodinane (DMP).27 Gratify-
ingly, no epimerization of 3 was observed. Likewise, the all-cis-
substituted diastereomer 18 was converted into the correspond-
ing aldehyde 21 which was used for the synthesis of analogs of
(+)-varitriol.
The aldehyde 3 was used in the subsequent HWE-olefina-
tion28 without purification. Deprotonation of phosphonate 2 with
n-BuLi and addition of aldehyde 3 resulted in no reaction at
0 °C and only sluggish conversion at ambient temperature.
However, heating to 50 °C for 15 hours afforded the desired
coupling product 22 with 40% yield over 3 steps (debenzylation,
oxidation and HWE-reaction). Running the olefination in a
microwave29 at 80 °C for 1 hour gave a similar result (37% yield
of 22). In both cases, the E-isomer was formed exclusively.
Global deprotection of the olefin 22 with a standard pro-
cedure5,9,10 furnished the enantiomerically pure natural product
(+)-varitriol (1) as colorless needles after recrystallization from
cyclohexane–ethyl acetate (Scheme 5). All spectroscopic data
agree with those reported for the isolated product.3 The optical
rotation of [α]2D0 = +40.3 (c = 2.7, MeOH) measured for our
product matches well with the values reported by Gracza et al.,6
Ghosh and Pradhan,7 and Taylor et al.,9 but not with other litera-
ture values3,5,8 (Table 1). Thus, it seems that previously varitriol
was not always obtained in pure form.
With the natural product (+)-varitriol (1) and an optimized
procedure for the HWE-reaction in hand, we synthesized seven
analogs of the natural product7,10 using aldehydes 3 or 21 and
phosphonates 2, 12, 23, or 24 (Table 2). Whereas the latter is
commercially available, phosphonate 23 was obtained by
Arbuzov reaction from 3-methoxybenzyl chloride and triethyl-
phosphite. The HWE-olefination proceeded smoothly under the
conditions used for the synthesis of 22 and afforded the desired
products 25–31 with 31–49% yield over 3 steps (starting from
17 or 18). In all cases, the E-olefin was obtained exclusively.
The deprotection under the acidic conditions used for the syn-
thesis of (+)-1 was successful as well to furnish the varitriol
analogs 32–38 with 45–91% yield. Among these is the all-cis-
diastereomer 35 of the natural product. It was remarkable that
deprotection of compounds 28–31 which bear an all-cis-substi-
tuted tetrahydrofuran ring required a larger excess of HCl (1 M,
72–120 eq.) and longer reactions times (18–52 h) than substrates
25–27 (1 M HCl, 18 eq; 18–28 h).
Conclusions
A modular total synthesis of the marine-derived natural product
(+)-varitriol (1) was achieved from enynol 13 with 6.4% yield
over 10 steps. Key steps are the copper hydride-catalyzed SN2′-
reduction of propargyl oxirane 6 and the subsequent gold-cata-
lyzed cycloisomerization of α-hydroxyallene 5 to 2,5-dihydro-
furan 4. This combined coinage metal catalysis enables an
efficient center-to-axis-to-center chirality transfer. In contrast to
Fig. 1 NOESY experiments of 17 and 20.
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Table 2 Varitriol analogs 32–38 and their precursors 25–31
Aldehyde
Phosphonate
HWE-Product
Analog of Varitriol
3
3
21
21
21
12
23
24
previous ex-chiral-pool syntheses, the modularity and the
reagent-controlled introduction of all stereogenic centers renders
our approach particularly useful for the synthesis of analogs of
the natural product and hence for structure–activity studies. This
was demonstrated by the rapid and efficient preparation of
derivatives 32–38, including diastereomer 35 of varitriol. Like-
wise, the unnatural enantiomer (−)-1 and analogs thereof are
accessible from readily available oxirane ent-14. We are continu-
ing to expand the repertoire of coinage metal catalysis and to
apply these methods to target-oriented synthesis.
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After extraction with Et2O (4 × 6 mL), the organic layer was
dried with MgSO4 and concentrated under vacuum. The crude
was purified by column chromatography using cyclohexane–
AcOEt (20 : 1).
Experimental section
(2S,4S)-1-(Benzyloxy)hexa-3,4-dien-2-ol (5)
A mixture of CuCl (13 mg, 0.131 mmol), NaOt-Bu (38 mg,
0.392 mmol) and SIMes·HCl (45 mg, 0.131 mmol) in degassed
toluene (18 mL) was briefly heated in a hot water bath to 100 °C
and then allowed to cool to room temperature (ca. 40 min). To
this solution was added dropwise PMHS (315 mg, 5.24 mmol).
After stirring at room temperature for 5 min, the yellow solution
was cooled to 0 °C and 15 (880 mg, 4.36 mmol) was added
dropwise. The reaction mixture was stirred at 0 °C for 3 h and
further at room temperature for 19 h. To the solution was added
a solution of HF·Pyr (65% in pyridine, 2.65 g, 17.4 mmol) in
THF (400 mL) at 0 °C. After stirring at this temperature for 2 h,
the reaction was quenched with aq. saturated NaHCO3 solution
(120 mL). The aqueous phase was extracted with Et2O (4 ×
60 mL), the combined organic layers were dried with MgSO4
and concentrated under vacuum. The residue was purified by
column chromatography using cyclohexane–AcOEt (5 : 1) to
give 5 (693 mg, 3.39 mmol, 78%) as a yellow oil. [α]2D0 = +42.2
(c 1.2, CHCl3). IR (ν cm−1): 3430 (OH), 3030, 2859, 1968
tert-Butyl(2-methoxy-6-((E)-2-((3aR,4R,6S,6aS)-2,2,6-
trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)vinyl)benzyloxy)
dimethylsilane (22)
HWE-reaction according to the general procedure (reaction time:
15 h) of 2 (285 mg, 0.708 mmol) and 3 (crude product, 60 mg)
gave 22 (58 mg, 0.133 mmol, 40% for 3 steps) as a light yellow
oil. [α]2D0 = +19.9 (c 1.4, CHCl3). IR (ν cm−1): 2930, 2856,
1579, 1472, 1381, 1252, 1080, 837. 1H NMR (400 MHz,
CDCl3) δ: 7.08–7.22 (3H, m), 6.78 (1H, d, J 8.1), 6.19 (1H, dd,
J 15.9, 6.5, HCvC), 4.81 (2H, s), 4.55 (1H, dq, J 6.8, 5.0),
4.44–4.49 (1H, m), 4.33 (1H, dd, J 6.8, 4.8), 4.01–4.08 (1H, m),
3.81 (3H, s), 1.57 (3H, s), 1.36 (3H, d, J 6.7), 1.35 (3H, s), 0.89
(9H, s), 0.06 (6H, s). 13C NMR (100 MHz, CDCl3) δ: 157.4,
138.5 (2 C), 130.2, 129.3, 128.5 (3 CH), 126.5 (C), 118.7 (CH),
114.9 (C), 110.0 (CH), 86.2, 85.6, 84.8, 80.2 (4 CH), 55.9
(CH2), 55.6 (OCH3), 27.4 (CH3), 26.0 (C(CH3)3), 25.5, 19.1 (2
CH3), 18.4 (C(CH3)3), −5.3 (2CH3). ESI-HRMS m/z: found
452.2825, calcd for C24H42O5NSi (M + NH4)+: 452.2827.
1
(CvCvC), 1454, 1110, 737. H NMR (400 MHz, CDCl3) δ:
7.27–7.39 (5H, m), 5.22–5.30 (1H, m), 5.15–5.22 (1H, m), 4.58
(2H, s), 4.36 (1H, m), 3.56 (1H, dd, J 9.6, 3.6), 3.45 (1H, dd, J
9.6, 7.6), 2.56 (OH, brs), 1.70 (3H, dd, J 7.0, 3.3). 13C NMR
(100 MHz, CDCl3) δ: 203.9 (CvCvC), 137.8 (C), 128.4,
127.7 (5 CH), 91.0, 88.6 (2 CH, CvCvC), 74.1, 73.3 (2 CH2),
68.6 (CH), 14.1 (CH3). EI-HRMS m/z: found 227.1044, calcd
for C13H16O2Na (M + Na)+: 227.1043.
General procedure for deprotection of the HWE-product
To a solution of the HWE-product. (1 mmol) in THF (3.5 mL)
was added at room temperature HCl (1 M, 18–120 eq). After stir-
ring at room temperature for 18–52 h, the reaction mixture was
neutralized with aq. saturated NaHCO3 solution After extraction
with CH2Cl2, the organic layer was dried with MgSO4 and con-
centrated under vacuum. The residue was purified by column
chromatography using CH2Cl2–acetone (for triols) or cyclo-
hexane–AcOEt (for diols).
(2S,5S)-2-(Benzyloxymethyl)-5-methyl-2,5-dihydrofuran (4)
To a solution of 5 (681 mg, 3.33 mmol) in THF (33 mL) was
added AuCl3 (10.1 mg, 0.0333 mmol) at 0 °C. After being
stirred at 0 °C for 2 h, the reaction mixture was filtered through
silica gel and the residue was washed with Et2O–isohexane
(3 : 1, 110 mL). After being concentrated under vacuum, the
residue was purified by column chromatography using cyclo-
hexane–AcOEt (20 : 1) to give 4 (555 mg, 2.72 mmol, 82%) as a
light yellow oil. [α]D20 = −48.9 (c 1.6, CHCl3). IR (ν cm−1):
3030, 2857, 1453, 1366, 1094, 737. 1H NMR (400 MHz,
CDCl3) δ: 7.25–7.38 (5H, m), 5.85 (1H, d, J 5.9), 5.79 (1H, d, J
6.1), 4.91–4.99 (2H, m), 4.63 (1H, d, J 12.2), 4.58 (1H, d, J
12.2) (AB-system with doublet by 4.63), 3.50–3.53 (2H, m),
1.30 (3H, d, J 6.2). 13C NMR (100 MHz, CDCl3) δ: 138.2 (C),
132.8 (CH), 128.2 (2CH), 127.5 (2CH), 127.4, 126.8 (2 CH),
85.2, 82.2 (2 CH), 73.8, 73.2 (2 CH2), 22.7 (CH3). EI-HRMS m/
z: found 204.1137, calcd for C13H16O2 (M+): 204.1145.
(+)-Varitriol ((+)-1)
Deprotection of 22 (126 mg, 0.290 mmol) according to the
general procedure (5.4 mL 1 M HCl, 18 eq, 26 h) and column
chromatography using CH2Cl2–acetone (2 : 1) gave (+)-1
(63 mg, 0.225 mmol, 78%) as a colorless solid which became
colorless needles after recrystallization from cyclohexane–ethyl
acetate (1 : 1). Mp 108–110 °C. [α]2D0 = +40.3 (c 2.7, CH3OH).
IR (ν cm−1): 3383 (OH), 2969, 2928, 1578, 1472, 1384, 1264,
1
1093, 1003, 786, 746. H NMR (400 MHz, acetone-d6) δ: 7.22
(1H, t, J 8.0), 7.08–7.16 (2H, m), 6.89 (1H, d, J 8.1), 6.20 (1H,
dd, J 15.8, 6.7, HCvC), 4.71 (2H, s), 4.26–4.32 (1H, m), 3.90
(1H, t, J 5.5), 3.78–3.87 (1H, m), 3.81 (3H, s, OCH3), 3.69 (1H,
t, J 5.7), 3.01 (1H, brs, OH), 1.27 (3H, d, J 6.4). 13C NMR
(100 MHz, acetone-d6) δ: 158.9, 139.0 (2 C), 132.4, 129.3,
129.3 (3 CH), 127.9 (C), 119.3, 110.6 (2 CH), 85.3, 80.0, 77.1,
76.4 (4 CH), 56.0 (OCH3), 55.4 (CH2), 19.5 (CH3). ESI-HRMS
m/z: found 561.2688, calcd for C30H41O10 (2M + H)+:
561.2694.
General procedure for HWE-olefinations
To a solution of the phosphonate (1 mmol) in THF (3 mL) was
added dropwise at 0 °C n-BuLi (2.24 M in hexane, 0.45 mL,
1 mmol). After stirring at 0 °C for 15 min, a solution of the
crude aldehyde (0.455 mmol) in THF (1.5 mL) was added. The
mixture was stirred at 0 °C for 30 min, at room temperature for
1 h, and at 50 °C for 8–21 h. After cooling to room temperature,
H2O (3 mL) and aq. saturated NaCl (3 mL) solution were added.
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1997, 62, 8666; (c) C. David, L. Bischoff, B. P. Roques and M.-
C. Fournié-Zaluski, Tetrahedron, 2000, 56, 209.
Acknowledgements
18 (a) T. Katsuki and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 5974;
(b) J. G. Hill, K. B. Sharpless, C. M. Exon and R. Regenye, Org. Synth.,
1985, 63, 66; (c) Y. Gao, R. M. Hanson, J. M. Klunder, S. K. Ko,
H. Masamune and K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765;
(d) K. B. Sharpless, Tetrahedron, 1994, 50, 4235; (e) T. Katsuki and V.
S. Martin, Org. React., 1996, 48, 1.
Continuous support of our work by the Deutsche Forschungsge-
meinschaft and the European Community is gratefully
acknowledged.
19 (a) C. Deutsch, B. H. Lipshutz and N. Krause, Angew. Chem., Int. Ed.,
2007, 46, 1650; (b) C. Deutsch, B. H. Lipshutz and N. Krause, Org.
Lett., 2009, 11, 5010.
20 (a) G. Altenhoff, R. Goddard, C. W. Lehmann and F. Glorius, J. Am.
Chem. Soc., 2004, 126, 15195; (b) S. Palacin, D. N. Chin, E. E. Simanek,
J. C. MacDonald, G. M. Whitesides, M. T. McBride and
G. T. R. Palmore, J. Am. Chem. Soc., 1997, 119, 11807.
21 A. J. Arduengo, R. Krafczyk and R. Schmutzler, Tetrahedron, 1999, 55,
14523.
22 (a) C. Deutsch, B. Gockel, A. Hoffmann-Röder and N. Krause, Synlett,
2007, 1790; (b) J. Erdsack and N. Krause, Synthesis, 2007, 3741;
(c) Y. Sawama, Y. Sawama and N. Krause, Org. Biomol. Chem., 2008, 6,
3573.
References
1 J. W. Blunt, B. R. Copp, M. H. G. Munro, P. T. Northcote and M.
R. Prinsep, Nat. Prod. Rep., 2011, 28, 196, and references cited therein.
2 C. Christophersen, O. Crescente, J. C. Frisvad, L. Cram, J. Nielsen, P.
H. Nielsen and L. Rahbaek, Mycopathologia, 1999, 143, 135.
3 J. Malmstrøm, C. Christophersen, A. F. Barrero, J. E. Oltra, J. Justicia
and A. Rosales, J. Nat. Prod., 2002, 65, 364.
4 A. M. S. Mayer and K. R. Gustafson, Eur. J. Cancer, 2004, 40, 2676.
5 V. Kumar and A. K. Shaw, J. Org. Chem., 2008, 73, 7526.
6 M. Palík, O. Karlubíkoví, A. Lásiková, J. Koźíśek and T. Gracza,
Eur. J. Org. Chem., 2009, 709.
7 S. Ghosh and T. K. Pradhan, J. Org. Chem., 2010, 75, 2107.
8 R. T. Clemens and M. P. Jennings, Chem. Commun., 2006, 2720.
9 G. D. McAllister, J. E. Robinson and R. J. K. Taylor, Tetrahedron, 2007,
63, 12123.
23 (a) H. C. Kolb, M. S. VanNieuwenhze and K. B. Sharpless, Chem. Rev.,
1994, 94, 2483; (b) A. B. Zaitsev and H. Adolfsson, Synthesis, 2006,
1725.
24 (a) L. Wang and K. B. Sharpless, J. Am. Chem. Soc., 1992, 114, 7568;
(b) Z. M. Wang, K. Kakiuchi and K. B. Sharpless, J. Org. Chem., 1994,
59, 6895; (c) M. S. VanNieuwenhze and K. B. Sharpless, Tetrahedron
Lett., 1994, 35, 843.
25 A. K. Ghosh and J.-H. Kim, Tetrahedron Lett., 2003, 44, 3967.
26 S. Gupta, M. Rajagopalan, M. M. Alhamadsheh, L. M. V. Tillekeratne
and R. A. Hudson, Synthesis, 2007, 3512.
27 (a) D. B. Dess and J. C. Martin, J. Org. Chem., 1983, 48, 4155;
(b) M. Frigerio, M. Santagostino and S. Sputore, J. Org. Chem., 1999,
64, 4537; (c) R. E. Ireland and L. Liu, J. Org. Chem., 1993, 58, 2899.
28 (a) W. S. Wadsworth, Org. React., 1978, 25, 73; (b) B. E. Maryanoff and
A. Reitz, Chem. Rev., 1989, 89, 863; (c) K. C. Nicolaou, M. W. Harter, J.
L. Gunzner and A. Nadin, Liebigs Ann. Chem., 1997, 1283; (d) V.
N. Korotchenko, V. G. Nenajdenko, E. S. Balenkova and A. V. Shastin,
Russ. Chem. Rev. (Engl. Transl.), 2004, 73, 957.
10 A. Senthilmurugan and I. S. Aidhen, Eur. J. Org. Chem., 2010, 555.
11 (a) N. Krause, V. Belting, C. Deutsch, J. Erdsack, H.-T. Fan, B. Gockel,
A. Hoffmann-Röder, N. Morita and F. Volz, Pure Appl. Chem., 2008, 80,
1063; (b) N. Krause, Ö. Aksin-Artok, V. Breker, C. Deutsch, B. Gockel,
M. Poonoth, Y. Sawama, Y. Sawama, T. Sun and C. Winter, Pure Appl.
Chem., 2010, 82, 1529.
12 (a) F. Volz and N. Krause, Org. Biomol. Chem., 2007, 5, 1519;
(b) F. Volz, S. H. Wadman, A. Hoffmann-Röder and N. Krause, Tetrahe-
dron, 2009, 65, 1902.
13 Y. Yamagiwa, K. Ohashi, Y. Sakamoto, S. Hirakawa and T. Kamikawa,
Tetrahedron, 1987, 43, 3387.
14 N. Krause and C. Winter, Chem. Rev., 2011, 111, 1994.
15 C. Deutsch, N. Krause and B. H. Lipshutz, Chem. Rev., 2008, 108, 2916.
16 W. E. Lindsell, D. D. Palmer, P. N. Preston and G. M. Rosair, Organome-
tallics, 2005, 24, 1119.
29 (a) A. Teichert, K. Jantos, K. Harms and A. Studer, Org. Lett., 2004, 6,
3477; (b) E. Quesada and R. J. K. Taylor, Synthesis, 2005, 3193.
17 (a) U. Koop, G. Handke and N. Krause, Liebigs Ann., 1996, 1487;
(b) H. Dieks, M. O. Senge, B. Kirste and H. Kurreck, J. Org. Chem.,
5970 | Org. Biomol. Chem., 2012, 10, 5965–5970
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