Spirastrellolide E: Synthesis of an advanced C(1)-C(24) southern hemisphere

Article abstract of DOI:10.1016/j.tetlet.2014.12.026

The synthesis of a C(1)-C(24) advanced southern hemisphere fragment towards the total synthesis of spirastrellolide E has been achieved. Highlights of the route include a highly convergent Type I Anion Relay Chemistry (ARC) tactic for fragment assembly, in conjunction with a directed, regioselective gold-catalyzed alkyne functionalization to generate the central unsaturated [6,6]-spiroketal.

Full text of DOI:10.1016/j.tetlet.2014.12.026

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Spirastrellolide E: synthesis of an advanced C(1)–C(24) southern
hemisphere
Alexander Sokolsky a, Xiaozhao Wang b, , Amos B. Smith III a,
⇑
a Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States
b Incyte Corporation, Wilmington, DE 19803, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of a C(1)–C(24) advanced southern hemisphere fragment towards the total synthesis of
spirastrellolide E has been achieved. Highlights of the route include a highly convergent Type I Anion
Relay Chemistry (ARC) tactic for fragment assembly, in conjunction with a directed, regioselective
gold-catalyzed alkyne functionalization to generate the central unsaturated [6,6]-spiroketal.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 21 November 2014
Revised 1 December 2014
Accepted 5 December 2014
Available online xxxx
Keywords:
Spirastrellolide
Anion Relay Chemistry
Brook rearrangement
Gold catalysis
Total synthesis
In 2003 Anderson and colleagues reported the isolation, partial
structural determination, and disclosure that spirastrellolide A (1;
Fig. 1) was a selective (1 nM) and extremely potent inhibitor of
phosphatase 2A.1 The complete connectivity of 1, however, was
not established until 2004,2 with the stereochemical relationship
and absolute configuration of the core remaining unknown until
the 2007 isolation and X-ray characterization of the closely related
spirastrellolide B (2; Fig. 1).3 Later that year, the complete stereo-
structure of 1–7, including the absolute configuration, was estab-
lished via chemical degradation of spirastrellolide D (4).4
was not amenable to advancing ample material for a successful
synthetic campaign. We therefore set out to design a second-gen-
eration route. Herein, we report the result of that effort, which has
now led to a significantly improved approach to a related southern
hemisphere congener for spirastrellolide E, featuring both
a
decrease in the longest linear step count and an increase in the
overall yield.
Our initial 2007 spirastrellolide venture highlighted the use of
Type II Anion Relay Chemistry (ARC)36 to construct advanced spir-
astrellolide A southern hemisphere intermediate 11 from frag-
ments 8–10 (Scheme 1). Unfortunately, this approach precluded
installation of the C(14) methyl group until after spiroketalization,
a tactic requiring three steps. Moreover, when attempting to install
the C(23)–C(25) fragment 15, the undesired stereoisomer predom-
inated, which required an oxidation/reduction/reprotection
sequence.
The combination of structural complexity, biological activity,
and, at the outset, unknown relative stereochemistry led to consid-
erable interest in the synthetic community,5–27 culminating in the
first total synthesis of spirastrellolide A (2008) by the Paterson28–31
group, and the total syntheses of spirastrellolide
F (2009,
2011)32–34 and later A (2013),35 both by Furstner and colleagues.
Our interest in the spirastrellolides began in 2007, resulting
early on in completed approaches to advanced fragments for a
southern hemisphere relevant to spirastrellolide A and B22,23 and
a northern hemisphere relevant to B and E.26 With these routes
established, we considered a total synthesis venture; however it
quickly became apparent that our first generation southern hemi-
sphere synthesis, totaling 33 steps for the longest linear sequence,
To address these shortcomings, we present here a second-gen-
eration synthetic analysis, now aimed at spirastrellolide
E
(Scheme 2). As a new subtarget, we selected C(1)–C(24) fragment
19 (Scheme 2A), guided by the observations of both the Patterson
and Furstner groups that union with northern hemispheres might
best be accomplished at C(24).8,20,21 A key strategic consideration
in our second generation analysis was to alter the bonds forged
by the ARC protocol, thus permitting incorporation of the C14
methyl group as part of an appropriately designed epoxide (24).
Thus, the revised strategy clearly showcases the flexibility inherent
in the ARC tactic (Scheme 2A).
⇑
Corresponding author. Tel.: +1 215 898 4860; fax: +1 215 898 5129.
E-mail address: smithab@sas.upenn.edu (A.B. Smith).
Present address.
http://dx.doi.org/10.1016/j.tetlet.2014.12.026
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Sokolsky, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.12.026

2
A. Sokolsky et al. / Tetrahedron Letters xxx (2014) xxx–xxx
(A)
RO
46
O
OMe
OTBS
OTBS
I
HO
24
O
38
O
O
O
14
O
TBS
O
O
27
OBn
O
Y
X
O
1
OH
25
O
O
O
TES
H
23
O
O
OMe
14
HO
S
HO
S
23
TBS
19
Z
OH
OMe
O
O
gold-catalyzed
spiroketalization
Type I
ARC
HO
15
OTBS
TBS
O
16,16
1
2)
Spirastrellolide A ( ): R=X=Z=H, Y=Cl, Δ
Spirastrellolide B ( : R=X=Y=Z=H
O
OTBS
TBS
I
TES
O
O
O
Spirastrellolide C (3): R=X=Y=H, Z=OH
22
Spirastrellolide D (4): R=Z=H, X=Y=Cl, Δ15,16
Spirastrellolide E (5): R=X=Y=Z=H, Δ15,16
Spirastrellolide F (6): R=X=Z=H, Y=Cl
14
O
TESO
OTES
TBS
CHO
OTES
OH
OMe
OMe
O
14
15,16
7
Spirastrellolide G ( ): X=Z=H, R=Me, Y=Cl, Δ
TBS
I
20
HO
21
Alkynylation
H
O
OPMB
R'
Figure 1. Spirastrellolides A-G.
R
(B)
R
OH
R'
O
O
OMe
R
OMe
H
TBS
O
R'
HO
1) n-BuLi/KOtBu
OH
S
O
S
O
S
O
S
S
Au
20
S
O
19
O
O
2)
OMe
A
S
S
8
Au
OMe
OBn
OMe
11
77%
O
TBS
3)
9
Scheme 2. Retrosynthetic analysis.
O
BnO
10
BnO
BnO
BnO
appeared as an ideal substrate for Type I Anion Relay Chemistry,36
employing TES–dithiane 23 with epoxides 2438 and 25.39
Our initial approach to aldehyde 22 is outlined in Scheme 3.
Treatment of TES–dithiane 23 with n-butyllithium, followed by
the addition of epoxide (À)-24 in a mixture of tetrahydrofuran
(THF) and ether (3:1), and in turn a solvent-mediated Brook rear-
rangement of the intermediate lithium alkoxide, triggered by the
OBPS
OBPS
OMe
O
O
O
O
6 steps
14
14
OMe
3 steps
H
OBn
12
13
OPiv
O
O
S
S
O
9 steps
22
O
O
S
S
R
OH
14
O
OMe
16
14
undesired!
15
1) nBuLi, Et2O
OTBS
2)
O
OPiv
O
S
S
OBn
NBS/AgClO4
( )-24
−
O
O
TES
H
O
S
O
22
S
S
2,6-lutidine
79%
S
23
3)
O
O
3 steps
3 steps
22
OTBS
14
O
OMe
OTES
OBn
R
OH
O
17
14
HO
63%
O
Southern Hemisphere (18)
33 steps LLS, 0.2% yield
(+)-26
( )-25
−
OTBS
OTBS
Scheme 1. First-generation analysis of the C(1)–C(26) fragment of the
1) Me4NBH(OAc)3
70%
spirastrellolides.
O
O
R = TBS, TES
2) TBSOTf
RO
O
OR
14
OTES
OBn
Moreover, inspired by our recent northern hemisphere synthe-
sis,26 we envisioned access to the southern hemisphere [6,6]-spi-
TBSO
HO
(+)-27
14
28
OBn
roketal via
a gold-catalysed cyclization. However, given the
1) Me4NBH(OAc)3
70%
2) MOMBr, TBAI
DCE, 50 °C, 74%
difficulties often encountered with control of regioselectivity in
gold-catalyzed spiroketalizations, we chose to exploit the method
of Aponick et al.,37 which employs a substrate propargylic carbinol
to direct the site of ring closure, via an intermediate allene
(Scheme 2B).
With this scenario in mind, the southern hemisphere 19 would
arise from an appropriately functionalized propargylic triol 20.
Inclusion of a carbinol directing group conveniently revealed an
aldehyde alkynylation retron, simplifying construction of 20 to
two fragments: alkyne 21 and aldehyde 22. Alkyne 21, in turn,
would be constructed in 8 steps using a strategy adapted from
the Patterson spirastrellolide A synthesis,30 while aldehyde 22
OTBS
OTBS
1) Pd(OH)2, H2
55-80%
O
MOM
O
O
MOM
O
2) TPAP, NMO
50-78%
OTES
OTES
OBn
14
MOMO
MOMO
( )-29
14
CHO
( )-22
−
−
Scheme 3. Synthesis of aldehyde 22.
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A. Sokolsky et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
addition of hexamethylphosphramide (HMPA) in the presence of
epoxide (À)-25, smoothly furnished the three component adduct
(+)-26 in 60–70% yield.
requirement for a planned Suzuki union of the Northern and
Southern hemispheres. In practice, however, the required use of
methanol as either a solvent or co-solvent for the spiroketalization,
along with a mild acid, leads to slow decomposition of the sub-
strate. Only traces of spiroketals were observed under a variety
of conditions.
Undaunted, we examined a differentially protected construct, in
which the two alcohols required for spiroketalization could be
revealed selectively without affecting the C(22) TES group. Such a
scenario would greatly facilitate optimization of the key cycliza-
tion tactic. This approach would also permit replacement of the
C(13) TES group, which had earlier led to significant difficulties
due to its lability.
The revised strategy is illustrated in Scheme 5. Here we target
differentially protected spiroketalization precursor 32. Impor-
tantly, the requisite advanced ARC adduct (35, Scheme 5) could
be accessed employing the same components as the previous route,
by merely changing the order of addition of the two epoxides,
again demonstrating the flexibility of Anion Relay Chemistry.
Implementation of the revised strategy is outlined is Scheme 6.
Pleasingly, the ARC union proceeded smoothly with the inverted
order of addition to furnish three component adduct (+)-35 in
68% yield. Dithiane hydrolysis as before then led to (+)-36.
With (+)-36 in hand, we now required a tactic to reduce the
C(11) ketone with concomitant differential protection of the
resulting diol. This requirement was conveniently achieved by
exploiting the Evans–Tishchenko reaction47 with benzaldehyde,
followed in turn by TBS protection of the remaining hydroxyl,
removal of the benzyl group, and oxidation of the resultant
hydroxyl48 to furnish aldehyde (+)-33. Notably, yields for the
TES-free synthetic route were uniformly excellent. Alkynylation
exploiting the previously established protocol then furnished a
mixture of diastereomeric alcohols (+)-32a and (+)-32b (1.4:1)
in 85% combined yield, which again could be readily separated
and subjected to a two stage deprotection to remove the benzoyl
and PMB groups to furnish spiroketalization precursors (+)-38a
and (+)-38b. At this stage, we were also able to confirm the
configurations of the C(15) hydroxyl group in 32a and 32b by
conversion of 38a to the bisacetonide, with concomitant removal
of the C(22) TES ether. The relative stereochemistry of the result-
ing bisacetal was determined by NMR, utilizing the method of
Rychnovsky.49
With the ARC product (+)-26 in hand, we turned to dithiane
removal, which proved to be non-trivial. A wide range of condi-
tions (cf. the Stork reagent,40 mercury salts, NCS/AgNO3,41 iodine/
sodium bicarbonate,42 methyl iodide43) led either to poor or incon-
sistent results. Eventually we discovered that a combination of
NBS, silver perchlorate, and 2,6-lutidine41,44 furnished a reliable
and reproducible yield of 70–80% of the desired ketone (+)-27.
Having established conditions for dithiane removal, we next
performed a stereocontrolled anti-reduction of the derived hydrox-
yketone to form the desired anti diol in 70% yield as the only
observed diastereomer (Scheme 3). At this stage, all that remained
was a series of functional group manipulations to arrive at the
aldehyde fragment; this however also proved non-trivial.
Attempted protection of the diol as a bis-TBS ether resulted in par-
tial migration of the C(13) TES group in 27. Unfortunately, the
resulting products proved inseparable by column chromatography.
Switching to bis-MOM protection (i.e., 29) alleviated this problem,
albeit the MOM protecting group was deemed not ideal from the
point of view of a total synthesis, given the harsh conditions typi-
cally required for removal. Notwithstanding these issues, we con-
tinued with the synthesis to validate several critical late stage
transformations. Removal of the benzyl group and oxidation to
aldehyde (À)-22 again proved troublesome due to TES migration
and partial deprotection. Nonetheless, the stage was set to attempt
the union via alkynylation.
Two observations proved important. First, at this stage of our
spirastrellolide synthetic venture, the required configuration of
the C(15) propargylic hydroxyl was unknown. Second, a number
of groups had reported a strong stereochemical dependence of
the propargylic stereogenic center on spiroketalizations.37,45 We
therefore decided to initially pursue a non-selective alkynylation,
separate the diastereomers, and then subject each to gold catalysis
(Scheme 4). To this end, treatment of alkyne (À)-2146 with lithium
diisopropylamide (LDA) in THF followed by addition of aldehyde
(À)-22 in THF, furnished a diastereomeric mixture of propargylic
alcohols [(+)-30a and (+)-30b (1.7:1)] in a combined yield of 75%.
Pleasingly, the diastereomers proved readily separable via routine
flash column chromatography. Each isomer in turn was subjected
to PMB removal to furnish the spiroketalization precursors (+)-
31a and (+)-31b.
With the differentially protected adducts 38a and 38b in hand,
we turned to the critical spiroketalization (Scheme 7). Treatment of
the cis isomer (+)-38a with cationic gold catalyst 39, first prepared
It quickly became evident that our originally designed spirocyc-
lization substrates were not optimal. We had anticipated that spi-
roketalization conditions could be found that would permit
simultaneous removal of both the C(13) TES group, a prerequisite
for spiroketalization, as well as removal of the C(22) TES group, a
OTBS
OTBS
TBS
I
24
14
O
O
O
OBn
O
OTBS
25
OTES
OMe
OTBS
MOM
I
1) Alkyne 21, LDA
O
O
TBS
O
H
34
O
O
14
O
2) 22
1.7:1 d.r.,
S
O
S
MOM
O
TBS
TESO
OTES
22
19
75% total yield
13
OR
OTBS
gold-catalyzed
spiroketalization
Type I
MOMO
13
OTES
O
ARC
OMe
MOMO
O
HO
DDQ
(−)-22
S
S
(+)-30a,b
(+)-31a,b
R = PMB
R = H
OTBS
TBS
I
35
O
O
OH
OTBS
MOM
14
O
I
TESO
various conditions
O
TBS
CH2OBn
OMe
OBz
OPMB
OMe
(+)-31a, b
O
O
14
OTES
22
OH
TBS
13
O
O
I
HO
32
21
Alkynylation
MOMO
OMe
OPMB
Scheme 4. First attempts at southern hemisphere end game.
Scheme 5. Revised retrosynthesis.
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A. Sokolsky et al. / Tetrahedron Letters xxx (2014) xxx–xxx
1) nBuLi, Et2O
OTBS
2)
OTBS
O
S
S
O
S
S
TBS
H
( )-25
−
NBS/AgClO4
O
34
OH
O
3)
2,6-lutidine
79%
TBSO
OBn
68%
OBn
(+)-35
( )-24
−
OTBS
OTBS
1) SmI2, PhCHO
68%, 4:1 d.r.
21
alkyne
LDA
2) TBSOTf, 95%
O
O
TBS
O
O
33
then
3) Pd(OH)2, H2, 93%
4) DMP, 86%
85%, 1.4:1 d.r.
OH
OBz
TBSO
TBSO
OBn
(+)-36
O
(+)-33
OTBS
I
O
TBS
(+)-32a,b
R1=Bz, R2=PMB
(+)-37a,b R1=H, R2=PMB
(+)-38a,b
O
DIBAL-H, 78%
DDQ, 77%
TESO
OR1
OR2
OMe
R1=R2=H
TBSO
HO
Scheme 6. Implementation of the revised retrosynthetic analysis.
OTBS
TBS
I
OTBS
I
O
H
TBS
O
O
H
O
39
TESO
OTES
OMe
OH
OH 81%
O
O
TBSO
O
OMe
TBS
HO
tBu
38a
19
R
H
13
Key nOe:
SbF6
O
H
I
tBu P Au N
21
O
OMe
39 =
OTES
H
Scheme 7. Completion of the southern hemisphere.
by Echavarren,50 employing methylene chloride as the solvent
proceeded smoothly to furnished the desired spiroketal (19). The
stereostructure of the spiroketal was assigned by extensive 2D
NMR analysis.51 Particularly important was observation of an
nOe between the hydrogens on C(13) and C(21), which provided
evidence both for the expected double carbinol addition to the
alkyne, as well as the stereochemistry at the ketal center. A similar
nOe was observed in a related system by Paterson.19 We were thus
confident that the spiroketalization had proceeded as predicted,
thereby signaling completion of the C(1)–C(24) southern hemi-
sphere fragment for a prospective total synthesis of spirastrellolide
E (5).
The anti isomer (+)-38b however did not lead to the anticipated
spiroketalization product under otherwise identical conditions.
Structural determination of the observed product, along with the
development of a rationale for the stereochemical dependence on
reaction efficiency, is currently under investigation.
hemispheres now available, efforts turned to the total synthesis
of spirastrellolide E, which will be reported in due course.
Acknowledgments
This Tetrahedron Letter is presented to honor and remember
Professor Harry Wasserman (Yale University), great friend, true
gentleman, and scientist par excellence: Harry, thank you for
everything.
Financial support for this work was provided by the National
Institutes of Health – United States, Grant G.M.-29028. The authors
would like to acknowledge Dr. George Furst for help in obtaining
NMR spectra, as well as Dr. Rakesh Kohli for providing high
resolution mass spectrometry spectra.
Supplementary data
In summary, we have achieved a significantly improved second
generation synthesis of a spirastrellolide E C(1)–C(24) southern
fragment, now involving the longest linear sequence of 19 steps
and an overall yield of 2%. With streamlined routes to both
Supplementary data (experimental procedures and character-
ization of new compounds, as well as detailed NMR analysis of
compound 19) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2014.12.026.
Please cite this article in press as: Sokolsky, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.12.026

A. Sokolsky et al. / Tetrahedron Letters xxx (2014) xxx–xxx
5
26. Wang, X.; Paxton, T. J.; Li, N.; Smith, A. B., III Org. Lett. 2012, 14, 3998–4001.
27. Yang, J.-H.; Liu, J.; Hsung, R. P. Org. Lett. 2008, 10, 2525–2528.
References and notes
28. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Genovino, J.; Maltas, P.;
Moessner, C. Angew. Chem., Int. Ed. 2008, 47, 3016–3020.
29. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Genovino, J.; Maltas, P.;
Moessner, C. Angew. Chem., Int. Ed. 2008, 47, 3021–3025.
30. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Maltas, P.; Loiseleur, O.;
Genovino, J.; Moessner, C. Org. Biomol. Chem. 2012, 10, 5861–5872.
31. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Maltas, P. Org. Biomol.
Chem. 2012, 10, 5873–5886.
32. O’Neil, G. W.; Ceccon, J.; Benson, S.; Collin, M.-P.; Fasching, B.; Fürstner, A.
Angew. Chem., Int. Ed. 2009, 48, 9940–9945.
33. Benson, S.; Collin, M.-P.; O’Neil, G. W.; Ceccon, J.; Fasching, B.; Fenster, M. D. B.;
Godbout, C.; Radkowski, K.; Goddard, R.; Fürstner, A. Angew. Chem., Int. Ed.
2009, 48, 9946–9950.
34. Benson, S.; Collin, M.-P.; Arlt, A.; Gabor, B.; Goddard, R.; Fürstner, A. Angew.
Chem., Int. Ed. 2011, 50, 8739–8744.
1. Williams, D. E.; Roberge, M.; Van Soest, R.; Andersen, R. J. J. Am. Chem. Soc. 2003,
125, 5296–5297.
2. Williams, D. E.; Lapawa, M.; Feng, X.; Tarling, T.; Roberge, M.; Andersen, R. J.
Org. Lett. 2004, 6, 2607–2610.
3. Warabi, K.; Williams, D. E.; Patrick, B. O.; Roberge, M.; Andersen, R. J. J. Am.
Chem. Soc. 2007, 129, 508–509.
4. Williams, D. E.; Keyzers, R. A.; Warabi, K.; Desjardine, K.; Riffell, J. L.; Roberge,
M.; Andersen, R. J. J. Org. Chem. 2007, 72, 9842–9845.
5. Chandrasekhar, S.; Rambabu, C.; Reddy, A. S. Org. Lett. 2008, 10, 4355–4357.
6. Chen, J. L.-Y.; Brimble, M. A. Chem. Commun. (Camb). 2010, 3967–3969.
7. Chen, J. L.-Y.; Brimble, M. A. J. Org. Chem. 2011, 76, 9417–9428.
8. Fürstner, A.; Fasching, B.; O’Neil, G. W.; Fenster, M. D. B.; Godbout, C.; Ceccon, J.
Chem. Commun. (Camb). 2007, 3045–3047.
9. Fürstner, A.; Fenster, M. D. B.; Fasching, B.; Godbout, C.; Radkowski, K. Angew.
Chem., Int. Ed. 2006, 45, 5510–5515.
10. Fürstner, A.; Fenster, M. D. B.; Fasching, B.; Godbout, C.; Radkowski, K. Angew.
Chem., Int. Ed. 2006, 45, 5506–5510.
11. Keaton, K. A.; Phillips, A. J. Org. Lett. 2008, 10, 1083–1086.
12. Liu, J.; Hsung, R. P. Org. Lett. 2005, 7, 2273–2276.
13. Liu, J.; Yang, J. H.; Ko, C.; Hsung, R. P. Tetrahedron Lett. 2006, 47, 6121–6123.
14. Pan, Y.; De Brabander, J. Synlett 2006, 853–856.
15. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Loiseleur, O.; Maltas, P.;
Moessner, C. Pure Appl. Chem. 2007, 79, 667–676.
16. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Genovino, J.; Lim, J. H.; Moessner, C.
Chem. Commun. (Camb). 2007, 1852–1854.
17. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Lim, J. H.; Maltas, P.; Moessner, C.
Chem. Commun. (Camb). 2006, 4186–4188.
18. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Loiseleur, O. Org. Lett. 2005, 7, 4121–
4124.
19. Paterson, I.; Anderson, E. A.; Dalby, S. M.; Loiseleur, O. Org. Lett. 2005, 7, 4125–
4128.
35. Arlt, A.; Benson, S.; Schulthoff, S.; Gabor, B.; Fürstner, A. Chem. Eur. J. 2013, 19,
3596–3608.
36. Smith, A. B., III; Wuest, W. M. Chem. Commun. (Camb). 2008, 5883–5895.
37. Aponick, A.; Li, C.-Y.; Palmes, J. A. Org. Lett. 2009, 11, 121–124.
38. Mori, K.; Iwasawa, H. Tetrahedron 1980, 36, 87–90.
39. Available in two steps from known alkene, see Ref.30
40. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287–290.
41. Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553–3560.
42. Russell, G. A.; Ochrymowycz, L. E. O. A. J. Org. Chem. 1969, 34, 3618–3624.
43. Fetizon, M.; Jurion, M. J. Chem. Soc., Chem. Commun. 1972, 382–383.
44. Nicolaou, K. C.; Patron, A. P.; Ajito, K.; Richter, P. K.; Khatuya, H.; Bertinato, P.;
Miller, R. A.; Tomaszewski, M. J. Chem. Eur. J. 1996, 2, 847–868.
45. Fang, C.; Pang, Y.; Forsyth, C. J. Org. Lett. 2010, 12, 4528–4531.
46. Prepared by
a modification of a route developed by Paterson. See the
Supporting information.
47. Evans, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1990, 112, 6447–6449.
48. Careful oxidation with DMP was necessary to avoid facile benzoate elimination
20. Paterson, I.; Dalby, S. M.; Maltas, P. Isr. J. Chem. 2011, 51, 406–419.
21. Paterson, I.; Maltas, P.; Anderson, E. A. Pure Appl. Chem. 2013, 85, 1133–1147.
22. Smith, A. B., III; Kim, D.-S. Org. Lett. 2007, 9, 3311–3314.
23. Smith, A. B., III; Smits, H.; Kim, D.-S. Tetrahedron 2010, 66, 6597–6605.
24. Wang, C.; Forsyth, C. J. Org. Lett. 2006, 8, 2997–3000.
25. Wang, C.-C.; Tang, Y.; Yang, K.; Li, X.-Y.; Wu, Y.-B.; Hsung, R. P. Tetrahedron
2013, 69, 8284–8290.
to give the corresponding a, b-unsaturated aldehyde, which was inseperable.
49. Rychnovsky, S. D.; Skalitzky, D. J. Tetrahedron Lett. 1990, 31, 945–948.
50. Nieto-Oberhuber, C.; Muñoz, M. P.; López, S.; Jiménez-Núñez, E.; Nevado, C.;
Herrero-Gómez, E.; Raducan, M.; Echavarren, A. M. Chemistry 2006, 12, 1677–
1693.
51. See Supporting information for NMR analysis.
Please cite this article in press as: Sokolsky, A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.12.026