Synthesis of Panal Terpenoid Core

Article abstract of DOI:10.1055/s-0036-1588104

Panal is a natural bicyclic cadalane-type sesquiterpenoid with an unusual combination of stereocenters. It was isolated in 1988 as an alleged biosynthetic precursor of luciferin (a light-emitting molecule) in a bioluminescent fungus Panellus stipticus. Herein we present the first approach to the synthesis of the terpenoid skeleton of panal, which includes construction of five stereocenters, one of which is easily epimerizable. The key steps in the synthetic approach presented are high-pressure Diels-Alder reaction disobeying the ‘endo rule’, Barbier reductive allylation, and cyclization of trans-decalin ring via ring-closing metathesis.

Full text of DOI:10.1055/s-0036-1588104

SYNLETT
0
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2
1
4
1
4
3
7
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0
9
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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
letter
A
M. S. Baranov et al.
Letter
Synlett
Synthesis of Panal Terpenoid Core
Mikhail S. Baranova,b
Zinaida M. Kaskovaa,b
Roman Gritсenkoa
Svetlana G. Postikovaa
Pavel E. Ivashkina
Alexander A. Kislukhina
Dmitrii I. Moskvinc
Konstantin S. Mineeva
Alexander S. Arsenieva
Yulii A. Labasd
O
CH3
HO CH3
H
HO
CH3
O
CH3
Barbier,
RCM
H
H
[4+2]
EtO
OTBDPS
BnO
EtO
+
O
O
OTBDPS
OTBDPS
O
H
O
H
H
OH
OH
BnO
O
O
O
O
O
O
H3C CH3
single stereoisomer
H3C CH3
H3C CH3
panal terpenoid core
panal
Ilia V. Yampolsky*a,b
a Institute of Bioorganic Chemistry, Russian Academy of
Sciences, Miklukho-Maklaya 16/10, Moscow 117997,
Russian Federation
ivyamp@ibch.ru
b Pirogov Russian National Research Medical University,
Ostrovitianov 1, Moscow 117997, Russian Federation
c N.D. Zelinsky Institure of Organic Chemistry, Russian,
Academy of Sciences, Leninsky Prospekt, 47, Moscow
119991, Russian Federation
d Institute of Biochemistry, Russian Academy of Sciences,
Leninsky Prospekt, 33 bld. 2, Moscow 119071, Russian
Federation
Received: 02.09.2016
Accepted after revision: 02.11.2016
Published online: 17.11.2016
HO CH3
H
DOI: 10.1055/s-0036-1588104; Art ID: st-2016-b0575-l
O
O
H
OH
Abstract Panal is a natural bicyclic cadalane-type sesquiterpenoid
with an unusual combination of stereocenters. It was isolated in 1988
as an alleged biosynthetic precursor of luciferin (a light-emitting mole-
cule) in a bioluminescent fungus Panellus stipticus. Herein we present
the first approach to the synthesis of the terpenoid skeleton of panal,
which includes construction of five stereocenters, one of which is easily
epimerizable. The key steps in the synthetic approach presented are
high-pressure Diels–Alder reaction disobeying the ‘endo rule’, Barbier
reductive allylation, and cyclization of trans-decalin ring via ring-closing
metathesis.
O
cadalane skeleton
panal (1)
Figure 1 Сadalane skeleton and panal (1)
ty of the panal structure, an unusual combination of five
chiral centers make its synthesis a sophisticated challenge.
Herein we report the first approach to the synthesis of
panal terpenoid skeleton.
Key words panal, cadinane, cadalane, fungal bioluminescence, ter-
penoid
Retrosynthetic analysis revealed three key transforms
(Scheme 1). The first one is masking of the fragile acrolein
fragment by diol acetonide8 and protection of the remain-
ing keto group to prevent epimerization of the stereogenic
center in α position. Formation of cycle A of the trans-deca-
lin system in intermediate I can be achieved using the sec-
ond key transformation – ring-closing metathesis (RCM).
Essential methacrylate moiety can be easily introduced via
Barbier reaction of compound II with methyl 2-(bro-
momethyl)acrylate. Cycle B, bearing four chiral centers, can
be created via formation of the carbocycle in the third cru-
cial transform: Diels–Alder reaction disobeying the ‘endo
rule’. Following this strategy we came to simple dienophile
III and diene IV as the starting materials.
Structure of panal (1), a possible precursor of a lumines-
cent compound (luciferin) from bioluminescent fungus
Panellus stipticus, was elucidated by Nakamura et al.1 in
1988 (Figure 1). As it was thought that panal could provide
an insight into the chemistry of fungal bioluminescence,2
its synthesis was highly demanded. However, no significant
attempts were made since then.
Panal is a bicyclic sesquiterpenoid belonging to the ca-
dinane subclass of cadalane-like terpenoids.3 Lots of com-
pounds of this type have been described, and new bioactive
cadinane sesquiterpenoids are still being isolated from fun-
gi,4 algae,5 plants,6 and corals.7 In spite of apparent simplici-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
M. S. Baranov et al.
Letter
Synlett
and in the case of IVa by X-ray crystallography (IVb is a liq-
uid). It is worth mentioning that diene IVa has a transoid
conformation according to X-ray data,14 so additional acti-
vation might be required for its participation in the [4+2]
cycloaddition, which requires transition into the cisoid
form.
HO CH3
HO
CH3
B
H
H
deprotection
oxidation
elimination
B
A
O
O
OPG
α
O
H
O
H
OR
OH
I
O
O
Diels–Alder reaction is a very powerful method in or-
ganic synthesis, allowing formation of six-membered cycles
with four stereocenters in one step with high diastereose-
lectivity.15 The reaction between dienophile III and dienes
IVa and IVb was only possible under very high pressures
(Scheme 3), while the attempts to conduct the reaction at
increased temperature were unsuccessful. Both Diels–Alder
adducts 6a and 6b were obtained in moderate yields,16 the
structure of 6b was additionally justified by X-ray crystal-
lography17 (6a is a liquid).
1 panal
H3C CH3
RCM,
Barbier reaction
O
CH3
O
CH3
Diels–Alder
reaction
H
RO
III
RO
+
OPG
OPG
II
IV
H
O
BnO
O
O
O
H3C CH3
H3C CH3
Next transformations allowed alkene 9 for metathesis
reaction (Scheme 4). The use of TBDMS-protected com-
pound 6b was ineffective due to instability, isomerization,
and low yields observed in further synthetic steps, so re-
agent 6a was chosen. Benzyl protecting group in 6a was
cleaved by hydrogenolysis, the resulting alcohol was sub-
jected to Grieco elimination18 to create a monosubstituted
ethylene 7. Selective transformation of ester 7 into aldehyde
8 by DIBAL-H was not possible: at low temperatures (–70 °C)
reaction did not proceed, while at higher temperatures
overreduction to alcohol took place. Thus the ester 7 was
first reduced by excess of DIBAL-H to alcohol, and the latter
was subsequently oxidized with Dess–Martin periodinane
(DMP) to aldehyde 8. To obtain 1,7-diene 9, Barbier reaction
between 8 and methyl 2-(bromomethyl)acrylate19 was im-
plemented with zinc, instead of costly indium.20 The di-
alkene 9, whose structure was confirmed by 2D NMR spec-
tra, was purified as an inseparable mixture of two diaste-
reomers, which were used in further transformations.
Scheme 1 Retrosynthetic analysis of panal (1)
Dienophile III was synthesized from 3-(benzyloxy)pro-
pan-1-ol (2) according to the known procedures9 via oxida-
tion to aldehyde followed by Wittig reaction (Scheme 2).
Diene IV was synthesized from diethylmalonate in five
steps. Protected alkyl chloride 4, also obtained by known
procedures,10 was transformed into the Grignard reagent
which was then reacted with (E)-but-2-enal. Resulting alco-
hol was oxidized to ketone 5 by pyridinium chlorochromate
(PCC). Compound 5 was then silylated under mild condi-
tions via formation of lithium enolate. Importantly, silyla-
tion step required significant optimizations to obtain only
the desired Z isomer in good yield. The major finding was
the use of hexamethylphosphoramide (HMPA) as a metal
chelating agent,11 which favored the formation of Z isomer12
(up to 99% of Z). Two silylated derivatives of the diene IV
were obtained: IVa with bulky TBDPS substituent and IVb
with TBDMS group.13 Structures of compounds IVa and IVb
were confirmed by NMR spectroscopy, mass spectrometry,
Scheme 2 Synthesis of dienophile III and diene IV
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
M. S. Baranov et al.
Letter
Synlett
Scheme 3 Diels–Alder reaction and X-ray crystal structure of product 6b
Alkene 9 was not active in metathesis reaction under
any conditions (Scheme 5). Reduction of the ester group
provided diol 10, for which the metathesis reaction condi-
tions were screened with different Grubbs catalysts. RCM
did not proceed with Grubbs first- and third-generation
catalyst, however, good yields were obtained using second-
generation catalyst.21 Reaction proceeded faster in case of
Hoveyda–Grubbs catalyst (6 h at 40 °C instead of 8 h at
80 °C), although undesired products of allylic isomerization
were also isolated along with the target RCM product. As a
result, a bicyclic compound 11 was obtained as a mixture of
two diastereomers 11a and 11b, which could be separated
by column chromatography.
Further, two-step oxidation of primary alcohol 11a to
aldehyde 12 and then to the target acid 14 were sought
(Scheme 6). Hypochlorite oxidation of aldehydes is very se-
lective and in our case gave only desired products with no
side aromatization. Of course, Barbier reaction to obtain
compound 9 could have been performed in diastereoselec-
tive manner; however, we found that the undesired isomer
OH
CH3
RCM under
H
O
various
O
CH3
O
CH3
conditions
no reaction
H
H
OCH3
1) H2, Pd/C
MeOH, rt
OTBDPS
EtO
EtO
H
O
OTBDPS
OTBDPS
2) o-NO2C6H4SeCN
Bu3P, THF, 0 °C
H
O
H
O
O
H3C
H3C
N
N
BnO
3) H2O2, Na2MoO4
acetone, rt
CH3
H3C
Cl
H3C CH3
H3C
CH3
O
O
9
Ru
Cl
H3C CH3
H3C CH3
Ph
PCy3
DIBAL-H
toluene
–50 °C
6a
7 73% (3 steps)
Grubbs II catalyst
1) DIBAL-H
toluene, –50 °C
2) DMP, CH2Cl2, rt
OH
H
CH3
CH3
X
Y
H
Grubbs II
catalyst
OH
H
CH3
O
CH3
O
Br
OH
H
C2H4Cl2
80 °C
O
OTBDPS
OTBDPS
H
H
O
H
OCH3
OH
OCH3
OTBDPS
OTBDPS
O
O
O
Zn, NH4Cl
THF/H2O
H
O
H
O
H3C CH3
H3C CH3
O
O
10 75%
11a X = OH, Y = H 57% (1.3:1)
11b X = H, Y = OH
H3C CH3
H3C CH3
8 78% (2 steps)
inseparable mixture
9 87%
inseparable mixture
can be separated
by column chromatography
Scheme 4 Synthesis of compound 9
Scheme 5 Metathesis reaction
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
M. S. Baranov et al.
Letter
Synlett
11b may also be used to obtain the target compound 14.
Oxidation of 11b proceeded further to allow ketone 13. Ke-
tone 13 was then oxidized into acid 15, which may be re-
duced to the desired product 14 by selective syn reductants,
for instance, L-Selectride.22 A few more routine steps of
deprotection and oxidation are required for the completion
of the synthesis of panal (1).
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Planta Med. 2011, 77, 2023.
CH3
CH3
X
Y
Y
X
H
H
DMP
CH2Cl2
OTBDPS
OTBDPS
H
O
H
O
OH
O
O
O
H3C CH3
H3C CH3
11a X = OH, Y = H
11b X = H, Y = OH
12 92% X = OH, Y = H
13 72% X,Y = O
deprotection
oxidation
elimination
CH3
HO
H
CH3
X
Y
H
NaClO2
t-BuOH/H2O
NaH2PO4
2-methylbut-2-ene
O
O
OTBDPS
O
H
O
H
OH
OH
O
O
H3C CH3
14 90% X = OH, Y = H
15 79% X,Y = O
panal (1)
syn
reduction
(7) (a) Rahelivao, M. P.; Gruner, M.; Lübken, T.; Islamov, D.;
Kataeva, O.; Andriamanantoanina, H.; Bauer, I.; Knölker, H.-J.
Org. Biomol. Chem. 2016, 14, 989. (b) Roy, P. K.; Ashimine, R.;
Miyazato, H.; Taira, J.; Ueda, K. Arch. Pharm. Res. 2016, 39, 778.
(c) Su, J.-H.; Huang, C.-Y.; Li, P.-J.; Lu, Y.; Wen, Z.-H.; Kao, Y.-H.;
Sheu, J.-H. Arch. Pharm. Res. 2012, 35, 779.
(8) (a) Harada, H.; Morie, T.; Hirokawa, Y.; Kato, S. Chem. Pharm.
Bull. (Tokyo) 1996, 44, 2205. (b) Castro, M. Á.; Miguel Del Corral,
J. M.; García, P. A.; Rojo, M. V.; De La Iglesia-Vicente, J.;
Mollinedo, F.; Cuevas, C.; San Feliciano, A. J. Med. Chem. 2010,
53, 983.
(9) (a) Heapy, A. M.; Brimble, M. A. Tetrahedron 2010, 66, 5424.
(b) Drzewinski, W.; Dabrowski, R.; Czuprynski, K. Pol. J. Chem.
2002, 76, 273. (c) Mondal, S.; Mohamed, R. K.; Manoharan, M.;
Phan, H.; Alabugin, I. V. Org. Lett. 2013, 15, 5650.
(10) (a) Dubois, J.; Fourès, C.; Bory, S.; Falcou, S.; Gaudry, M.;
Marquet, A. Tetrahedron 1991, 47, 1001. (b) Guzaev, A.;
Lonnberg, H. Synthesis 1997, 1281. (c) Iwata, C.; Maezaki, N.;
Hattori, K.; Fujita, M.; Moritani, Y.; Takemoto, Y.; Tanaka, T.;
Imanishi, T. Chem. Pharm. Bull. (Tokyo) 1993, 41, 339. (d) Lange,
K.; Schneider, M. P. Tetrahedron: Asymmetry 2004, 15, 2811.
(11) Ireland, R. E.; Wipf, P.; Armstrong, J. D. J. Org. Chem. 1991, 56,
650.
Scheme 6 Oxidation of compounds 11a and 11b
In conclusion, a method for the synthesis of the panal
terpenoid core has been developed for the first time. The
key feature of this synthesis is a combination a powerful
Diels–Alder reaction and ring-closing metathesis. Four key
stereocenters were created by [4+2]-cycloaddition against
the ‘endo rule’. This is the first example of using the Diels–
Alder and ring-closing metathesis combination for the con-
struction of cadinane-type sesquiterpenoid skeleton,23
which we hope will find use in the future syntheses of nu-
merous bioactive representatives of this important class of
natural products.3
Acknowledgment
We acknowledge financial support by Russian Science Foundation
grant 16-14-00052. This research was partially carried out using the
equipment provided by IBCH сore facility (CKP IBCH).
(12) Xie, L.; Isenberger, K. M.; Held, G.; Dahl, L. M. J. Org. Chem. 1997,
62, 7516.
(13) General Procedure for Silylation
Supporting Information
HMPA (300 mL) was mixed with THF (150 mL) under inert
atmosphere. The mixture was cooled to –78 °C, and the solution
of LiHMDS (1 M in THF, 60 mL, 60 mmol) was added. The solu-
tion of ketone (9.9 g, 50 mmol) in THF (75 mL) was added drop-
wise, and the mixture was stirred for 30 min. The solution of
chlorosilane (55 mmol) in THF (35 mL) was added slowly, and
the mixture was stirred for 1 h at –78 °C and gently warmed to
the r.t. (1–2 h). The mixture was dissolved in hexane (1000 mL),
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588104.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
References and Notes
(1) Nakamura, H.; Kishi, Y.; Shimomura, O. Tetrahedron 1988, 44,
1597.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

E
M. S. Baranov et al.
Letter
Synlett
washed with brine (3 × 100 mL), and dried over sat. Na2SO4. The
solvents were evaporated, and the product was purified by
column chromatography (EtOAc–hexane, 1:10).
Representative Analytical Data
tert-Butyl{[(1Z,3E)-1-(2,2-dimethyl-1,3-dioxan-5-yl)penta-
1,3-dien-2-yl]oxy}diphenylsilane (IVa)
White solid, mp 96–98 °С, yield: 14.1 g (64%). ESI-HRMS: m/z
calcd for C27H37O3Si+ [M + H]+: 437.2512; found: 437.2495. 1H
NMR (700 MHz, CDCl3): δ = 7.73 (4 H, d, J = 8.1 Hz), 7.44 (1 H, t,
J = 7.1 Hz), 7.39 (1 H, t, J = 7.2 Hz), 5.89 (1 H, dq, J = 15.2, 6.8 Hz),
5.70 (1 H, dq, J = 15.2, 1.5 Hz), 4.50 (1 H, d, J = 10.0 Hz), 3.40 (2
H, dd, J = 4.7, 11.5 Hz), 3.27 (2 H, dd, J = 11.5, 8.1 Hz), 2.718–2.67
(1 H, m), 1.57 (3 H, dd, J = 6.8, 1.5 Hz), 1.35 (3 H, s), 1.27 (3 H, s),
1.08 (9 H, s). 13C NMR (176 MHz, CDCl3): δ = 17.6 (CH3), 19.8,
21.7, 26.1, 26.7 (3 × CH3), 32.3, 63.8, 97.2, 106.3, 126.3, 127.6,
129.5, 129.8, 133.3, 135.3, 150.3.
1H NMR (700 MHz, CDCl3): δ = 7.36–7.28 (5 H, m), 4.66 (1 H, br
s), 4.48 (1 H, d, J = 12.0 Hz), 4.37 (1 H, d, J = 12.0 Hz), 4.18–4.12
(2 H, m), 4.00 (1 H, t, J = 11.5 Hz), 3.90 (1 H, t, J = 11.5 Hz), 3.71
(1 H, br d, J = 11.8 Hz), 3.56 (1 H, br d, J = 11.8 Hz), 3.41 (2 H, br
t, J = 6.4 Hz), 2.61–2.58 (1 H, m), 2.20–2.17 (1 H, m), 2.06–2.03
(1 H, m), 1.99 (1 H, dd, J = 11.3, 11.8 Hz), 1.75–1.71 (2 H, m),
1.65–1.62 (1 H, m), 1.45 (3 H, s), 1.39 (3 H, s), 1.27 (3 H, t, J = 7.3
Hz), 0.96 (9 H, s), 0.93 (3 H, d, J = 6.8 Hz), 0.18 (3 H, s), 0.14 (3 H,
s). 13C NMR (176 MHz, CDCl3): δ = –4.6, –4.2, 14.3, 17.9, 18.7,
20.7, 25.8, 29.5, 29.7, 31.9, 33.8, 38.4, 40.1, 50.8, 60.4, 64.4, 65.6,
67.9, 73.0, 97.7, 109.2, 127.6, 127.7, 138.3, 149.3, 175.6.
(17) CCDC 1492234 (6b) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
(18) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41,
1485.
(19) (a) Miura, K.; Wang, D.; Hosomi, A. J. Am. Chem. Soc. 2005, 127,
9366. (b) Sudhakar, G.; Reddy, K. J.; Nanubolu, J. B. Tetrahedron
2013, 69, 2419.
tert-Butyl{[(1Z,3E)-1-(2,2-dimethyl-1,3-dioxan-5-yl)penta-
1,3-dien-2-yl]oxy}dimethylsilane (IVb)
Colorless liquid, yield: 13.6 g (87%). ESI-HRMS: m/z calcd for
C
17H33O3Si+ [M + H]+: 313.2199; found: 313.2188. 1H NMR (700
MHz, CDCl3): δ = 5.85–5.81 (2 H, m), 4.41 (1 H, d, J = 9.6 Hz),
3.80 (2 H, dd, J = 4.9, 12.0 Hz), 3.59 (2 H, dd, J = 11.1, 11.5 Hz),
2.98–2.92 (1 H, m), 1.75 (3 H, d, J = 4.9 Hz), 1.45 (3 H, s), 1.41 (3
H, s), 1.01 (9 H, s), 0.13 (6 H, s). 13C NMR (176 MHz, CDCl3): δ =
–4.7, 17.5, 19.2, 21.1, 25.9, 27.8, 32.4, 63.9, 64.1, 97.3, 107.4,
125.8, 129.5, 150.5.
(20) Vorwerk, S.; Vasella, A. Angew. Chem. Int. Ed. 1998, 37, 1732.
(21) General Procedure for RCM Reaction
The alkene (1.77 g, 3 mmol) was dissolved in dry DCE (50 mL),
and the Grubbs II catalyst (255 mg, 0.3 mmol) was added under
inert atmosphere. The mixture was heated to 80 °C for 8 h, the
solvent was evaporated, and the product was purified by
column chromatography (EtOAc–hexane, 1:1).
(14) CCDC 1492233 (IVa) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
Representative Analytical Data
(1R,4aR,5S,8S,8aS)-6-[(tert-Butyldiphenylsilyl)oxy]-5-(2,2-
dimethyl-1,3-dioxan-5-yl)-3-(hydroxymethyl)-8-methyl-
1,2,4a,5,8,8a-hexahydronaphthalen-1-ol (11a)
(15) Fringuelli, F.; Taticchi, A. The Diels–Alder Reaction: Selected Prac-
tical Methods; John Wiley and Sons: Chichester, 2002.
(16) General Procedure for the Diels–Alder Reaction
The mixture of alkene (24.6 g, 100 mmol), diene (105 mmol),
and ionol (2,6-di-tert-butyl-4-methylphenol; 1 g, 4.5 mmol)
was dissolved in 50 mL of dry CH2Cl2 and degassed upon freez-
ing. The mixture was heated in an autoclave to 100 °C under
high pressure (1 GPa) for 1 week. The solvent was evaporated,
and the product was purified by column chromatography
(EtOAc–hexane, 1:4).
White powder, yield: 540 mg (32%). ESI-HRMS: m/z calcd for
C
34H47O5Si+ [M + H]+: 563.3193; found: 563.3197. 1H NMR (700
MHz, CDCl3): δ = 7.75 (2 H, d, J = 6.6 Hz), 7.65 (2 H, d, J = 6.6 Hz),
7.46–7.40 (4 H, m), 7.36 (2 H, t, J = 7.5 Hz), 5.49 (1 H, br s), 4.49
(1 H, d, J = 3.0 Hz), 4.16 (1 H, t, J = 11.5 Hz), 4.03 (1 H, t, J = 11.3
Hz), 4.14–4.10 (1 H, m), 4.04–3.96 (2 H, m), 3.76 (1 H, ddd, J =
11.5, 4.9, 1.9 Hz), 3.73 (1 H, ddd, J = 11.3, 4.9, 1.9 Hz), 2.52–2.48
(1 H, m), 2.38 (1 H, br d, J = 11.5 Hz), 2.36–2.31 (1 H, m), 2.27–
2.20 (1 H, m), 2.07–2.03 (1 H, m), 2.02–1.96 (1 H, m), 1.92 (1 H,
br t, J = 3.3 Hz), 1.86 (1 H, br d, J = 3.5 Hz), 1.47 (3 H, s), 1.39 (3 H,
s), 1.08 (9 H, br s), 1.04 (1 H, br t, J = 11.1 Hz), 0.75 (3 H, d, J = 6.8
Hz). 13C NMR (176 MHz, CDCl3): δ = 18.8, 19.2, 19.4, 26.8, 29.5,
30.0, 34.3, 34.6, 36.8, 42.2, 42.5, 64.3, 64.6, 66.0, 66.7, 97.8,
113.2, 124.4, 127.6, 127.6, 129.8, 132.3, 133.5, 135.4, 135.8,
148.7.
Representative Analytical Data
(1S,2S,5R,6R)-Ethyl 6-[2-(Benzyloxy)ethyl]-4-[(tert-butyldi-
phenylsilyl)oxy]-5-(2,2-dimethyl-1,3-dioxan-5-yl)-2-methyl-
cyclohex-3-enecarboxylate (6a)
Colorless liquid, yield: 37.7 g (55%). ESI-HRMS: m/z calcd for
C
41H55O6Si+ [M + H]+: 671.3768; found: 671.3761. 1H NMR (700
MHz, CDCl3): δ = 7.67 (2 H, d, J = 6.6 Hz), 7.57 (2 H, d, J = 6.8 Hz),
7.39–7.20 (11 H, m), 4.48 (1 H, d, J = 11.3 Hz), 4.37 (1 H, d, J =
11.3 Hz), 4.36 (1 H, br s), 4.08–4.00 (4 H, m), 3.71 (1 H, dd, J =
11.3, 3.2 Hz), 3.56 (1 H, dd, J = 11.3, 3.0 Hz), 3.31 (2 H, br t, J = 7.3
Hz), 2.21–2.18 (1 H, m), 2.03–2.01 (1 H, m), 2.00–1.93 (1 H, m),
1.86 (1 H, dd, J = 11.5, 10.3 Hz), 1.82–1.78 (1 H, m), 1.68–1.63 (1
H, m), 1.55–1.51 (1 H, m), 1.40 (3 H, s), 1.34 (3 H, s), 1.17 (3 H, t,
J = 7.3 Hz), 1.00 (9 H, s), 0.62 (3 H, d, J = 6.8 Hz). 13C NMR (176
MHz, CDCl3): δ = 14.3, 18.8, 19.2, 20.3, 26.7, 29.5, 29.7, 32.3,
33.6, 38.6, 40.0, 50.6, 60.3, 64.6, 65.8, 68.0, 73.0, 97.7, 111.2,
127.5, 127.6, 127.7, 127.8, 128.9, 129.8, 129.9, 132.0, 133.5,
135.4, 138.2, 148.8, 175.4.
(1S,4aR,5S,8S,8aS)-6-[(tert-Butyldiphenylsilyl)oxy]-5-(2,2-
dimethyl-1,3-dioxan-5-yl)-3-(hydroxymethyl)-8-methyl-
1,2,4a,5,8,8a-hexahydronaphthalen-1-ol (11b)
White powder, yield: 420 mg (25%). ESI-HRMS: m/z calcd for
C
34H47O5Si+ [M + H]+: 563.3193; found: 563.3200. 1H NMR (700
MHz, CDCl3): δ = 7.75 (2 H, d, J = 6.7 Hz), 7.65 (2 H, d, J = 6.7 Hz),
7.46–7.41 (4 H, m), 7.36 (2 H, t, J = 7.5 Hz), 5.35 (1 H, br s), 4.42
(1 H, d, J = 3.1 Hz), 4.11 (1 H, t, J = 11.6 Hz), 4.04 (1 H, t, J = 11.6
Hz), 4.06–3.97 (2 H, m), 3.85 (1 H, ddd, J = 11.6, 4.9, 2.0 Hz), 3.74
(1 H, ddd, J = 11.4, 5.1, 1.8 Hz), 3.64–3.58 (1 H, m), 2.38 (1 H, br
dd, J = 16.7, 4.4 Hz), 2.25–2.19 (1 H, m), 2.12–2.05 (1 H, m),
2.05–2.01 (1 H, m), 2.00–1.96 (2 H, m), 1.85 (1 H, br t, J = 3.5
Hz), 1.70 (1 H, br d, J = 3.8 Hz), 1.49 (3 H, s), 1.40 (3 H, s), 1.17 (1
H, br q, J = 9.5 Hz), 1.07 (9 H, br s), 1.00 (3 H, d, J = 6.7 Hz). 13C
NMR (176 MHz, CDCl3): δ = 18.8, 19.1, 23.4, 26.7, 29.4, 33.9,
34.1, 36.9, 42.5, 43.1, 44.9, 64.5, 65.8, 66.0, 74.1, 97.7, 113.8,
124.3, 127.6, 127.7, 129.8, 132.3, 133.5, 135.4, 137.5, 148.8.
(1S,2S,5R,6R)-Ethyl 6-[2-(Benzyloxy)ethyl]-4-[(tert-butyldi-
methylsilyl)oxy]-5-(2,2-dimethyl-1,3-dioxan-5-yl)-2-methyl-
cyclohex-3-enecarboxylate (6b)
Colorless solid, mp 67–69 °С, yield: 25.3 g (45%). ESI-HRMS: m/z
calcd for C31H50NaO6Si+ [M + Na]+: 569.3274; found: 569.3271.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

F
M. S. Baranov et al.
Letter
Synlett
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F