A Highly Convergent and Biomimetic Total Synthesis of Portentol

Article abstract of DOI:10.1021/jacs.5b10009

An efficient total synthesis of the unusual polyketide portentol is reported. Three boron aldol reactions were used to assemble the linear carbon chain of the natural product, which contains two challenging anti-anti stereotriads. A biomimetic double cyclization cascade, triggered by an oxidation, then afforded portentol and its known dehydration product, anhydroportentol. The biosynthesis of portentol and the biosynthetic relevance of our key step are discussed.

Full text of DOI:10.1021/jacs.5b10009

Subscriber access provided by NEW YORK MED COLL
Communication
A Highly Convergent and Biomimetic Total Synthesis of Portentol
Bichu Cheng, and Dirk Trauner
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b10009 • Publication Date (Web): 16 Oct 2015
Downloaded from http://pubs.acs.org on October 16, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Biosynthetic Speculations
266x530mm (300 x 300 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Retrosynthesis of Portentol
119x106mm (300 x 300 DPI)
ACS Paragon Plus Environment

Page 3 of 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of Ketone Fragment 11
139x94mm (300 x 300 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of Aldehyde Fragment 12
140x101mm (300 x 300 DPI)
ACS Paragon Plus Environment

Page 5 of 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Fragment Coupling
141x77mm (300 x 300 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Total Synthesis of Portentol and Anhydroportentol
141x108mm (300 x 300 DPI)
ACS Paragon Plus Environment

Page 7 of 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
147x200mm (600 x 600 DPI)
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 13
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table of Contents artwork
51x13mm (300 x 300 DPI)
ACS Paragon Plus Environment

Page 9 of 13
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
A Highly Convergent and Biomimetic Total Synthesis of Por-
tentol
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bichu Cheng, Dirk Trauner*
Department of Chemistry and Center for Integrated Protein Science, Ludwig-Maximilians-Universität München, Bu-
tenandtstrasse 5-13, 81377 München Germany
Supporting Information Placeholder
which have enabled a short, highly convergent, and
stereoselective total synthesis of portentol.
ABSTRACT: An efficient total synthesis of the unu-
sual polyketide portentol is reported. Three boron
aldol reactions were used to assemble the linear
carbon chain of the natural product, which contains
two challenging anti, anti-stereotriads. A biomimetic
double cyclization cascade, triggered by an oxida-
tion, then afforded portentol and its known dehydra-
tion product, anhydroportentol. The biosynthesis of
portentol and the biosynthetic relevance of our key
step are discussed.
Scheme 1. Biosynthetic Speculations
(a) The structure of portentol and Overton's biosynthetic analysis:
O
O
Me
Me
Me
OH OH
O
Me
O
Me
O
OH
Me
HO
Me
Me Me
Me
O
2
portentol (1)
O
O
O
O
O
O
Portentol (1) is a complex polyketide that is unusu-
al in several respects. It was first isolated in 1967
from the lichen Roccella portentosa and subsequent-
ly found in a variety of other lichens and in extracts
from the Brazilian nut tree Gustavia hexapetala.1 Bio-
logical testing showed moderate growth inhibition
activity against several cancer cell lines.1j The mole-
cule has a unique and complex structure, which after
detailed NMR investigations and degradation studies
was ultimately secured by single crystal X-ray analy-
sis. Its densely functionalized spiro tricyclic core fea-
tures nine consecutive stereocenters, including two
adjacent tetrasubstituted ones, which renders por-
tentol a challenging target for total synthesis. To the
best of our knowledge, however, the synthesis of
portentol or a comparable polyketide has not been
reported to date.2
OH
11
7
1
3
(b) Our biosynthetic analysis:
Me
Me
11
Me
OH
Me
Me
OH
Me
O
7
O
Me
O
Me
O
Me
O
OH
1
O
O
Me
portentol (1)
Me
4
O
Me
O
OH OH
O
O
Me
H
Me Me Me Me
5
OH OH
Me 11
O
OH
O
O
1
Me
Me
7
Biosynthetically, it has been proposed that porten-
tol is formed from linear polyketide 3 via cyclohexa-
dienone intermediate 2 (Scheme 1a).1g Isotope-
labeling studies showed that acetate and malonate
were incorporated into the carbon chain of portentol.
While the terminal secondary methyl group originates
from the C2 of acetate, the remaining five methyl
groups are shown to come from methionine.3
SR
Me Me Me Me Me
6
(c) Our previous work on the shimalactones:
H
Me
O
Me
OH
Me
steps
H+
Me
O
O
O
O
Here, we report our own biosynthetic speculations
and synthetic efforts toward this natural product,
Me
O
O
O
Me
Me
O
Me
shimalactone A (9)
8
7
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 13
We propose that portentol is formed via a cationic Accordingly, our synthesis of ketone 11 started
1
2
3
4
5
6
7
8
cyclization cascade (Scheme 1b). The last bond for-
mation would involve the intramolecular nucleophilic
addition of an enolized β-keto-δ-lactone moiety onto
a cyclic oxocarbenium ion in intermediate 4.4 This
intermediate, in turn, would stem from precursor 5
via nucleophilic attack of the hydroxy group at C11
onto the C7 carbonyl, followed by protonation and
loss of water. Precursor lactone 5 would be assem-
bled by a type II polyketide synthetase (PKS) via the
fully linear enzyme-bound thioester 6. It is conceiva-
ble that the thioesterase domain of the PKS not only
catalyzes the β-keto-δ-lactone formation but also the
subsequent cationic cyclization to yield portentol.
Analogous chemistry was used in our biomimetic
synthesis of shimalactone A (Scheme 1c). It involved
the cyclization of β-keto-δ-lactone 7, triggered by a
protonation of its diene moiety, to yield oxabicy-
clo[2.2.1]heptane 8.5
from aldehyde 137 and ketone 148. Both were made
in two steps using slightly modified literature proce-
dures (supporting information). Paterson aldol reac-
tion of aldehyde 13 and ketone 14 then afforded the
corresponding aldol adducts with a 4:1 dr favoring
the desired anti diastereomer 17.9 It could be isolat-
ed by flash column chromatography in 65% yield.
Single crystal X-ray analysis of a derivative confirmed
the assigned configuration (supporting information).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Synthesis of Ketone Fragment 11.
TES
O
O
Me
H
b. TMSCl,
TMS2NH,
pyridine
TES
Me
Me
a. Cy2BCl,
Et3N
O
OH
O
13
+
OBz
dr ~ 4:1
(65%)
(99%)
O
Me Me
OBz
17
Our synthetic strategy towards portentol aimed to
mimic our proposed biosynthesis (Scheme 2). We
envisioned that the spirocyclic core of the natural
product could be formed by an intramolecular dou-
ble cyclization cascade starting from β-keto-δ-
lactone 10. This compound is a masked form of in-
termediate 5 in our proposed biosynthesis and con-
tains two anti-anti stereotriads.6 Triads of this type
are a challenge, even after decades of progress in
acyclic stereoselection.6 We envisioned that 10
could be synthesized by an anti aldol reaction of “left
hand” ketone 11 and “right hand” aldehyde 12, two
fragments of similar size and complexity. These
compounds, in turn, would be assembled using two
aldol reactions that would involve known ketones
and aldehydes.
Me
14
TMS
O
TMS
O
TES
Me
TES
Me
O
O
O
O
c. SmI2
(97%)
OBz
Me Me Me
Me Me
11
18
Reagents and conditions: (a) Cy2BCl, Et3N, Et2O,
−78 °C to 0 °C, then 13, −78 °C to −20 °C, 65%
(4:1 dr); (b) TMSCl, TMS2NH, pyridine, rt, 99%; (c)
SmI2, THF/MeOH, 0 °C, 97%.
Next, we protected the secondary alcohol of 17.
Reaction of 17 with tert-butyldimethylsilyl trifluoro-
methanesulfonate (TBSOTf) and triethylsilyl trifluoro-
methanesulfonate (TESOTf) afforded the correspond-
ing silyl ethers cleanly, but it was later ascertained
that these groups were difficult to remove at the final
stage of the synthesis. We then decided to protect
the alcohol as the trimethylsilyl (TMS) ether. After
screening several conditions, TMS ether 18 was
prepared in quantitative yield using hexamethyldisi-
lazane (TMS2NH) and TMSCl in pyridine.10 Reductive
removal of the α-benzoate with SmI2 then afforded
the “left hand” ketone 11 in good yield (Scheme 3).11
Scheme 2. Retrosynthesis of Portentol.
Me
O
Me
OH
oxocarbenium/
β-keto lactone
cyclization
Me
O
OR OR'
O
O
O
Me
Me
O
Me
O
Me
O
Me Me Me Me
10
O
aldol
PMB
Me
TMS
O
TES
Me
portentol (1)
O
O
O
O
O
+
H
N
O
The synthesis of “right-hand”-aldehyde 12 began
with an Evans syn aldol reaction12 of known alde-
hyde 15, derived from the (R)-Roche ester, with oxa-
zolidinone 16.13 The resulting aldol product 19 was
protected as p-methoxybenzyl (PMB) ether 20,14
and the protected primary alcohol was desilylated
and oxidized under Swern condition to give aldehyde
12 (Scheme 4).15
Me Me
Me Me
Bn
11
12
aldol
O
aldol
O
TES
O
O
TES
O
O
O
OBz
Me
N
+
+
O
Me
H
H
Me
Bn
Me
13
14
16
15
ACS Paragon Plus Environment

Page 11 of 13
Journal of the American Chemical Society
Scheme 4. Synthesis of Aldehyde Fragment 12. Scheme 5. Fragment Coupling.
1
2
3
4
5
6
7
8
TES
TMS
TES
Me
O
O
O
O
O
TES
OH
H
O
O
O
O
b. PMB-OC(NH)CCl3,
Sc(OTf)3
a. Bu2BOTf,
Et3N
15
Me
Me Me
TES TMS
Cy2BCl, Et3N, Et2O,
0 °C to rt; then 12,
−78 °C to −40 °C;
Me
OR
+
N
11
O
O
O
O
O
(52%, 2 steps)
O
O
Me Me
Bn
19
+
5
Me
N
then pH 7 buffer,
THF, H2O2.
O
PMB
Me Me Me Me
O
H
O
O
O
Bn
dr ~ 4:1, (71%)
9
21 R = PMB
22 R = H
DDQ,
DCM, rt
(84%)
16
N
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
Me Me
PMB
TES
PMB
O O
Bn
O
O
O
O
O
12
c. DMSO,
(COCl)2; Et3N
O
H
N
O
N
With the full carbon chain successfully assembled,
we began to investigate the double cyclization cas-
cade to complete the synthesis of portentol. After
extensive screening, oxidation of the β-hydroxy lac-
tone could be achieved under Swern condition with
trifluoroacetic anhydride (TFAA) as the activator.17
Once the oxidation was complete, methanol was
added to quench the reaction. To our delight, TLC
O
(94%)
Me Me
Bn
Me Me
Bn
20
12
Reagents and conditions: (a) Bu2BOTf, Et3N, DCM,
0 °C, then 15, −78 °C to 0 °C; (b) PMB-OC(NH)CCl3,
Sc(OTf)3 (1 mol%), toluene, rt, 52% (2 steps, unopti-
mised); (c) DMSO, (COCl)2, DCM, −78 °C to −25 °C;
Et3N, 94%.
1
and H NMR analysis of the crude reaction mixture
With both fragments 11 and 12 in hand, we start-
ed to investigate the key coupling reaction. The un-
ion of the two fragments followed a procedure re-
ported by Evans with slight modification.16 Stirring
ketone 11 with Cy2BCl and Et3N in diethyl ether for 1
hour at 0 °C and 2 hours at room temperature gave
a boron enolate, which was added to a suspension
of aldehyde 12 in diethyl ether at −78 °C. The reac-
tion mixture was then stirred at −40 °C for 1−2 days
until no aldehyde 12 remained, as determined by
thin layer chromatography (TLC) analysis. Although
the aldol product could be isolated, it was found that
the desired lactonization occurred spontaneously if
THF was added as a cosolvent during the workup.
Separation by flash column chromatography gave
analytically pure lactone 21 and recovered starting
showed that both portentol (1) and the known deriv-
ative anhydroportentol (23)1g were formed cleanly in
a 0.7:1 ratio. These two compounds were readily
separated by flash column chromatography (silica
gel). Portentol was thus isolated in 35% yield, and
anhydroportentol was isolated in 55% yield. Their
spectroscopic data were in accord with literature
values,1g, 1j and single crystal X-ray structures of both
compounds confirmed our assignment (Scheme 6).
Scheme 6. Total Synthesis of Portentol and An-
hydroportentol.
Me
Me
OH
Me
O
DMSO,
TFAA, DCM;
Et3N, −78 °C;
TES
TMS
Me
OH
O
O
O
O
O
1
Me
O
Me
material 11. A H NMR study of the H-H coupling
O
constant (3JH-H) on the lactone ring suggested that
the desired stereochemistry was obtained at C5.
Next, the PMB group was oxidatively cleaved with
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in
dichloromethane (DCM) to generate alcohol 22.
Adding water or pH 7 phosphate buffer to the reac-
tion lead to byproduct formation, presumably due to
the loss of silyl groups under these conditions
(Scheme 5).
Me
MeOH, rt
O
Me Me Me Me
Me
1 (35%)
22
+
Me
Me
O
Me
Me
O
Me
O
O
Me
23 (55%)
23
1
The proposed mechanism of this cascade is
shown in Scheme 7. Oxidation of alcohol 22 pre-
sumably gave the corresponding β-keto lactone 10
in equilibrium with its enol form. The acid generated
in situ during the workup removed the silyl protecting
groups and induced the formation of oxocarbenium
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 13
4, which is shown here as a mixture of two conform- aldol reactions, including one syn aldol reaction and
1
2
3
4
5
6
7
8
ers. One of them, 4a, undergoes C2-C7 cyclization
to yield portentol (1). Rotation along the C6-C7 bond
yields 4b, which cannot undergo cyclization fast
enough due to a steric clash of the C8 methyl group
and C9 hydroxy group with the C2 methyl group,
which is apparent in molecular models. Due to steric
hindrance, the formation of the C2-C7 bond is pre-
sumably a relatively slow process. Therefore, proton
transfer in 4, followed by elimination of water can
compete in the cascade, which yields the unsaturat-
ed oxocarbenium ion 24, again as a mixture of ro-
tamers. Among these, 24a undergoes cyclization to
afford anhydroportentol (23). Its rotamer 24b suffers
from a steric clash between the C2 and C8 methyl
groups and an unfavorable A1,3-strain between the
C6 and C8 methyl groups, which prevents rapid cy-
clization. Therefore, stereoisomers of portentol (1)
and anhydroportentol (23) with respect to C7 are not
observed. Given the high yield and ease of this cy-
clization process, we believe that a similar transfor-
mation occurs in Nature (as we proposed in Scheme
1b). Whether this happens spontaneously or requires
enzymatic catalysis remains to be determined. The
fact that anhydroportentol is easily formed but has
not yet been isolated as a natural product points to
the latter.
two anti aldol reactions, were used to assemble the
linear carbon chain. A double cyclization cascade
formed the spirocyclic core and afforded portentol.
Thus, this unusual and attractive natural product has
finally yielded to total synthesis.
ASSOCIATED CONTENT
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Supporting Information.
Experimental procedures and compound characteriza-
1
tion data, H, 13C NMR spectra of new synthetic com-
pounds and cif files for X-ray structures. This material is
available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
dirk.trauner@lmu.de
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank SFB 749 (Dynamics and Intermediates of
Molecular Transformations) for financial support, and
Dr. Peter Mayer (LMU Munich) for X-ray structure de-
termination. We also thank Mr. James Frank and Mr.
Benjamin Williams for helpful discussions during the
preparation of this manuscript.
Scheme 7. Proposed Mechanism of the Double
Cyclization Cascade.
Me
REFERENCES
(1) (a) Huneck, S.; Trotet, G. Z. Naturforsch., B: Chem. Sci.
1967, 22b, 363. (b) Huneck, S.; Follmann, G.; Weber, W. A.;
Trotet, G. Z. Naturforsch., B: Chem. Sci. 1967, 22b, 671–673.
(c) Huneck, S.; Follmann, G. Z. Naturforsch., B: Chem. Sci.
1967, 22b, 1185–1188. (d) Huneck, S.; Mathey, A.; Trotet, G. Z.
Naturforsch., B: Chem. Sci. 1967, 22b, 1367–1368. (e) Aber-
hart, D. J.; Overton, K. H. J. Chem. Soc., Chem. Commun.
1969, 162–163. (f) Ferguson, G.; Mackay, I. R. J. Chem. Soc.,
Chem. Commun. 1970, 665–666. (g) Aberhart, D. J.; Overton,
K. H.; Huneck, S. J. Chem. Soc. (C) 1970, 1612–1623. (h)
Huneck, S.; Roenneberg, H.; Liaaen-Jensen, S. Pharmazie
1982, 37, 866. (i) Quilhot, W.; Garbarino, J. A.; Gambaro, V. J.
Nat. Prod. 1983, 46, 594–595. (j) Pettit, G. R.; Zhang, Q. W.;
Pinilla, W.; Herald, D. L.; Doubek, D. L.; Duke, J. A. J. Nat. Prod.
2004, 67, 983–985.
OH
Me
11
Me
O
HO
O
oxidation
2
7
10
22
O
Me
desilylation
Me
Me
O
H+
– H2O
OH
Me
Me
Me
O
8
Me
7
Me
Me
O
9
Me
HO
Me
6
HO
HO
1
O
Me
4a
4b
O
Me
2
O
O
(2) Only one synthetic study on portenol has been reported by
Jacolot, M.; Jean, M.; Levoin, N.; van de Weghe, P. Org. Lett.
2012, 14, 58–61.
(3) Aberhart, D. J.; Corbella, A.; Overton, K. H. J. Chem. Soc.
Chem. Comm. 1970, 664–665.
(4) Schröckeneder, A. PhD thesis, University of Munich, 2012.
(5) Sofiyev, V.; Navarro, N.; Trauner, D. Org. Lett. 2008, 10,
149–152.
(6) Chen, M.; William R. Roush, W. R. J. Am. Chem. Soc.
2012, 134, 3925–3931, and references therein. We tried several
other ways to make similar compounds with anti-anti stereotri-
ads, but all failed. See ref. 4.
– H2O
Me
Me
O
Me
HO
8
O
O
Me
Me
Me
HO
6
23
O
Me
O
Me
24a
24b
2
O
In conclusion, we have achieved a total synthesis
of portentol that owes its brevity and efficiency to a
biomimetic key step and the convergent nature of
our synthetic plan. Three diastereoselective boron
ACS Paragon Plus Environment

Page 13 of 13
Journal of the American Chemical Society
(7) Scheidt, K. A.; Bannister, T. D.; Tasaka, A.; Wendt, M. D.;
Savall, B. M.; Fegley, G. J.; Roush, W. R. J. Am. Chem. Soc.
2002, 124, 6981–6990.
(8) Paterson, I.; Wallace, D. J.; Cowden, C. Synthesis 1998,
639–652.
(9) Paterson, I.; Wallace, D. J.; Velázquez, S. M. Tetrahedron
Lett. 1994, 35, 9083–9086.
(10) Sweeley, C. C.; Bentley, R.; Makita, M.; Wells, W. W. J.
Am. Chem. Soc. 1963, 85, 2497–2507.
(11) Molander, G.; Hahn, G.; J. Org. Chem. 1986, 51, 1135–
1138.
(15) Rodríguez, A.; Nomen, M.; Spur, B.; Godfroid, J. Tetrahe-
dron Lett. 1999, 40, 5161–5164.
(16) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Rieger, D. L. J. Am.
Chem. Soc. 1995, 117, 9073–9074.
(17) Sakai, N.; Ohfune, Y. J. Am. Chem. Soc. 1992, 114,
998–1010.
1
2
3
4
5
6
7
8
9
(12) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc.
1981, 103, 2127–2129.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(13) Smith, A. B. III; Brandt, B. M. Org. Lett. 2001, 3, 1685–
1688.
(14) Rai, A.; Basu, A. Tetrahedron Lett. 2003, 44, 2267–2269.
Insert Table of Contents artwork here
Me
Me
OH
O
TMS
TES
Me
Me
OH
O
one-pot
O
O
O
O
Me
≡
Me
O
Me
O
O
Me Me Me Me
Me
portentol
ACS Paragon Plus Environment