Stereoselective Construction of Polyether trans-Pyran Ring System by Gold(I)-Catalyzed Cyclization

Article abstract of DOI:10.1055/s-0035-1562525

Many natural polyether toxins contain the trans-pyran ladder structure. We describe a synthesis of the polyether trans-pyran ring system by using cationic gold(I)-catalyzed cyclization. This gold(I)-catalyzed cyclization provided high diastereoselectivity and high turnover. This method is expected to be applicable to the synthesis of polyethers.

Full text of DOI:10.1055/s-0035-1562525

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2016, 27, 2731–2733
letter
2731
H. Yokoyama et al.
Letter
Synlett
Stereoselective Construction of Polyether trans-Pyran Ring Sys-
tem by Gold(I)-Catalyzed Cyclization
Hajime Yokoyama*
Megumi Matsuo
Masahiro Miyazawa
Yoshiro Hirai
H
H
H
H
H
OH
O
Ph3PAuCl, AgOTf
OH
OH
MS4A, CH2Cl2, THF
r.t.
O
O
OH
H
H
up 80% yield
highly diastereoselective
high turnover numbers
mild reaction conditions
Graduate School of Science and Engineering,
University of Toyama, Gofuku, Toyama 930-
8555, Japan
single diastereomer
hyokoyam@sci.u-toyama.ac.jp
Received: 26.05.2016
Accepted after revision: 04.07.2016
Published online: 01.08.2016
DOI: 10.1055/s-0035-1562525; Art ID: st-2016-u0363-l
HO
Me
Abstract Many natural polyether toxins contain the trans-pyran ladder
structure. We describe a synthesis of the polyether trans-pyran ring sys-
tem by using cationic gold(I)-catalyzed cyclization. This gold(I)-cata-
lyzed cyclization provided high diastereoselectivity and high turnover.
This method is expected to be applicable to the synthesis of polyethers.
H
O
K
H
O
H
J
H
O
Me
OH
I
H
Key words gold catalyst, cyclization, polyether, stereoselective, trans-
fused pyran system
H
H
H
O
H
O
H
H
Me
H
H
H
H
H
H
H
H
H
G
Me
O
O
O
NaO3SO
F
Many polyether toxins have been isolated from marine
origin. Their interesting ladder structures have attracted
the attention of synthetic chemists. Many reports and re-
views were accumulated for a few years.1,2 For example,
yessotoxin, which was isolated from digestive glands of the
scallops Patinopecten yessoensis (Figure 1),3 has a typical
trans-pyran ladder system. The key issue for synthetic stud-
ies is stereoselective ether construction, especially the con-
secutive trans-pyran ring system. We have been studying
the palladium(II)-catalyzed cyclization of allylic alcohols
with oxygen and nitrogen nucleophiles.4,5 In 2009, we re-
ported the novel synthesis of a trans-pyran ring system by
using palladium(II)-catalyzed cyclization of allylic alcohol.5e
On the other hand, homogeneous gold catalysts are
known to activate alkynes, allenes, and alkenes for intra-
molecular or intermolecular attack of the nucleophile.6
Aponick's group6a,b and Robertson's group6e reported the
interesting reaction by using gold(I) or gold(III) catalyst. Es-
pecially, they show the efficient and simple method by
gold(I) catalyst, which enables reduced catalyst loading and
provides excellent chiral transfer. Mechanistically, by the
estimation of DFT methods, this gold(I)-catalyzed cycliza-
tion proceeds via anti-addition and anti-elimination, and
A
B
C
D
E
O
Me
O
O
NaO3SO
Me
Figure 1 Yessotoxin, a natural polyether
interestingly, it seems to be facilitated by hydrogen bond-
ing.6d Recently, Widenhoefer's group also reported gold(I)-
catalyzed amination.7 Therefore we considered the stereo-
selective construction of the polyether trans-pyran ring
system might be achieved by gold(I)-catalyzed cyclization.
Aldehyde 4 was obtained from tri-O-acetyl D-glucal (1)
according to the reported method (Scheme 1).5e Reduction
of this material 1 with Et3SiH and BF3·OEt2 gave the diace-
tate in 99% yield. Deprotection of the diacetate with
NaOMe, followed by hydrogenation with Pd/C catalyst un-
der a hydrogen atmosphere afforded the diol 2 in 96% yield
from the diacetate. Protection of diol 2, followed by depro-
tection of primary alcohol, gave the monoalcohol in 96%
yield. Oxidation of this hydroxy moiety, followed by Wittig
reaction of resulting aldehyde, gave the terminal olefin 3 in
80% yields (two steps). Hydroboration–oxidation of this ter-
minal olefin 3 and oxidation with SO3Py afforded the alde-
hyde 45e,8 in 57% yield (two steps).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 2731–2733

2732
H. Yokoyama et al.
Letter
Synlett
H
OAc
H
1) BF3⋅OEt2, Et3SiH
H
H
H
H
H
H
OH
O
OH
OH
Ph3PAuCl, AgOTf
(99%)
OAc
OAc
OH
OH
2) NaOMe, MeOH
3) H2, Pd/C
(96%)
MS4A, CH2Cl2, THF
(80%)
O
O
OH
O
OR
O
H
H
H
O
H
7
2
9 R = H single isomer
1
10 R = Bn
OH
Ph3PAuCl, AgOTf
H
H
H
1) TBSCl, imidazole,
DMF (99%)
1) BH3, then H2O2,
NaOH (70%)
OTBS
CHO
OTBS
MS4A, CH2Cl2, THF
(95%)
OH
H
H
2) SO3Py (82%)
2) PPTS, MeOH,
CH2Cl2 (97%)
O
O
H
8
H
H
H
H
H
H
3
4
O
O
3) DMSO, (COCl)2,
then Et3N
4) Ph3PCH3I, nBuLi
+
O
OR
O
OR
89:11
H
H
(80%)
11 R = H
12 R = H
Scheme 1 Preparation of aldehyde 4
14 R = Bn
13 R = Bn
Scheme 3 Gold(I)-catalyzed cyclization
Aldehyde 4 was treated with lithio propargyl derivatives
in THF to afford a mixture of adducts 5 (33%) and 6 (46%) in
79% yield (Scheme 2). After acidic workup, careful column
chromatography afforded the two pure diastereoisomers.
The diastereomer 5 was deprotected and hydrogenation
with Lindlar catalyst under a hydrogen atmosphere to give
the triol 7 in 78% yields (two steps). The other diastereomer
6 was similarly treated to afford the triol 8 in 86% yields
(two steps).
The transition structures of this reaction in 7 are con-
sidered to be TSA and TSB, if this reaction proceeds via anti-
addition and anti-elimination, as suggested in the litera-
ture6d and involves a six-membered cyclic transition struc-
ture (Scheme 4), TSB suffers the steric repulsion between
the gold-catalyst-coordinated alkene moiety and hydroxyl
moieties. TSA would lead the desired pyran ring system 9.
On the contrary, in case of 8, the steric repulsion in TSD is
smaller than in TSB and that may be the reason why 11 and
12 are both formed.
H
OTBS
CHO
O
H
4
H
O
O
nBuLi, THF, –78 °C
(79%)
OTBS
< <
O
OH
O
OH
Au
O
H
7
Au
H
H
H
H
OTBS
OH
O
OTBS
OH
TSA
+
TSB
O
O
OTBS
OTBS
6
(46%)
5
(33%)
9
1) p-TsOH, MeOH
2) H2, Lindlar cat.
(86%)
1) p-TsOH, MeOH
2) H2, Lindlar cat.
(78%)
OH
Au
OH
H
O
O
H
H
H
H
O
<
O
O
H
OH
OH
Au
8
OH
OH
OH
O
O
OH
H
O
H
TSC
TSD
8
7
Scheme 2 Synthesis of the precursors 7 and 8
12
11
Next, the triol 7 was treated with 10 mol% Ph3PAuCl, 10
mol% AgOTf, and 4 Å molecular sieves at room temperature
under an argon atmosphere to afford the pyran ring com-
pound 9 in 80% yield as a single isomer (Scheme 3).9 The
other triol 8 afforded the pyran ring compounds in 95%
yield as a diastereomeric mixture (11/12 = 89:11).10 The
stereochemistry of the benzyl derivatives 10 and 13 were
determined by NMR spectra in comparison with literature
data.11
Scheme 4 Proposed transition structures of gold(I)-catalyzed cycliza-
tion
In conclusion, we have attained the synthesis of trans-
pyran ring system by using a gold(I)-catalyzed cyclization.
We are undergoing the synthesis of natural poylether by us-
ing this method.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 2731–2733

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H. Yokoyama et al.
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Acknowledgment
J. Tetrahedron Lett. 2009, 50, 189. (m) Uenishi, J.; Fujikura, Y.;
Kawai, N. Org. Lett. 2011, 13, 2350. (n) Borrero, N. V.; Aponick,
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H.; Aponick, A.; Ess, D. H. J. Org. Chem. 2013, 78, 7664.
We thank to the University of Toyama, for financial support.
(5) (a) Yokoyama, H.; Shouji, Y.; Kubo, T.; Miyazawa, M.; Hirai, Y.
Heterocycles 2015, 91, 1752. (b) Yokoyama, H.; Kubo, T.;
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Sumiyoshi, K.; Miyazawa, M.; Hirai, Y. Heterocycles 2014, 89,
353. (d) Yokoyama, H.; Hayashi, Y.; Nagasawa, Y.; Ejiri, H.;
Miyazawa, M.; Hirai, Y. Tetrahedron 2010, 66, 8458.
(e) Yokoyama, H.; Nakayama, S.; Murase, M.; Miyazawa, M.;
Yamaguchi, S.; Hirai, Y. Heterocycles 2009, 77, 211.
(f) Yokoyama, H.; Hirai, Y. Heterocycles 2008, 75, 2133.
(g) Yokoyama, H.; Kobayashi, H.; Miyazawa, M.; Yamaguchi, S.;
Hirai, Y. Heterocycles 2007, 74, 283. (h) Yokoyama, H.; Ejiri, H.;
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(k) Yokoyama, H.; Otaya, K.; Kobayashi, H.; Miyazawa, M.;
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H.; Otaya, K.; Yamaguchi, S.; Hirai, Y. Tetrahedron Lett. 1998, 39,
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562525.
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Dry CH2Cl2 (1 mL) was added to an aluminum-foil-covered two-
necked flask containing PPh3AuCl (16 mg, 0.03 mmol), AgOTf
(7.9 mg, 0.03 mmol), and activated MS4Å (26 mg). After stirring
for 10 min, a solution of triol 7 (51.3 mg, 0.25 mmol) in dry THF
(1 mL) was added. After the mixture was stirred for 7 d and 20
h, it was diluted with CH2Cl2, and the mixture was filtered
through a short plug of silica. The eluent was concentrated and
the residue was purified on silica gel column chromatography
(hexane–EtOAc = 70:30, v/v) to give the alcohol 9 (36.2 mg, 80%)
as a single isomer and a colorless oil.
Analytical Data of 9
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1HNMR (600 MHz, CDCl3): δ = 5.82 (ddd, J = 17.59, 10.62, 7.33
Hz, 1 H), 5.40 (d, J = 17.89 Hz, 1 H), 5.32 (d, J = 10.26 Hz, 1 H),
3.90–3.87 (m, 1 H), 3.56–3.54(m, 1 H), 3.44–3.40 (m, 1 H), 3.38–
3.31 (m, 1 H), 3.01–2.99 (m, 2 H), 2.38–2.35 (m, 1 H), 2.07–1.92
(m, 2 H), 1.73–1.69 (m, 2 H), 1.45–1.39 (m, 1 H). 13C NMR (150
MHz, CD3OD): δ = 135.7, 119.7, 83.9, 77.7, 76.8, 69.1, 68.0, 38.0,
29.3, 25.6. IR (nujol): 3395, 2925, 2865, 1460, 1090, 1029 cm–1
.
MS (EI): m/z = 184 [M+]. HRMS (EI): m/z calcd for C10H14O2 [M+ –
H2O]: 166.0994; found: 166.1000.
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2013, 69, 9086.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 2731–2733