An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using ring closing metathesis (RCM)

Article abstract of DOI:10.1007/s12039-010-0066-z

An asymmetric route for the synthesis of highly functionalized 2,3-epoxy-syn-1,4-cyclohexane diol derivatives present in some polyketide natural products has been developed. The key step involves RCM of an appropriately constructed 1,7-dienol derived from

Full text of DOI:10.1007/s12039-010-0066-z

J. Chem. Sci., Vol. 122, No. 6, November 2010, pp. 791–800. © Indian Academy of Sciences.
An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives
using ring closing metathesis (RCM)
SOUMITRA MAITY and SUBRATA GHOSH*
Department of Organic Chemistry, Indian Association for the Cultivation of Science,
Jadavpur, Kolkata 700 032
e-mail: ocsg@iacs.res.in
MS received 16 August 2010; accepted 29 October 2010
Abstract. An asymmetric route for the synthesis of highly functionalized 2,3-epoxy-syn-1,4-
cyclohexane diol derivatives present in some polyketide natural products has been developed. The key
step involves RCM of an appropriately constructed 1,7-dienol derived from D-mannitol to cyclohexane-
1,4-diol followed by its stereoselective epoxidation.
Keywords. Asymmetric synthesis; epoxides; metathesis; Michael addition; natural products.
1. Introduction
namely (i) Diels-Alder reaction of a properly substi-
5a,f
tuted diene,
(ii) retro Diels–Alder reaction of
5b,c,i
functionalized masked cyclohexane derivatives
and (iii) transformation of naturally occurring func-
2,3-Epoxy-syn-1,4-cyclohexane diol structural motif
1 is frequently encountered in a large number of
compounds belonging to a growing family of poly-
5d,e
tionalized cyclohexane derivatives. Some of these
1
ketide natural products. Many of these compounds
approaches lack stereoselectivity requiring separa-
tion of undesired diastereoisomers. Initially, we
planned to develop a concise stereocontrolled proto-
col for the construction of the epoxy cyclohexane
derivative 6 which would be exploited for the syn-
thesis of natural products in the second phase. In
this paper we report the results of the preliminary
investigation.
possess interesting biological and pharmacological
properties. The varied substitution and polyoxygena-
tion pattern present in these molecules are reflected
in epoxy-cyclohexane natural products like eutypox-
2
ide A 2, eutypoxide B 3, asperpentyn 4 and inte-
2
3
4
grasone 5 to name a few.
This class of natural products exhibits interesting
biological activities such as antitumor, antibacterial,
antifungal, etc. The highly oxygenated structural
features coupled with the interesting biological
activities elicited considerable interest amongst bi-
ologists, pharmacologists, and synthetic chemists.
The densely functionalised cyclohexane frameworks
associated with these natural products prompted or-
ganic chemists to develop efficient routes for their
1,5
synthesis. Apart from the construction of highly
oxygenated cyclohexane rings, stereocontrol in the
synthesis of epoxy-cyclohexane natural products is
the major hurdle. Several syntheses of these com-
pounds in racemic as well as enantiomerically pure
form have been reported. The key step in the syn-
thetic strategies developed so far towards cyclohex-
ane epoxides can be classified into three categories
Figure 1. Naturally occurring epoxy-cyclohexane deri-
*For correspondence
vatives.
791

792
Soumitra Maity and Subrata Ghosh
isomer) 137⋅8, 134⋅7, 117⋅7, 117⋅2, 109⋅4, 77⋅0,
2. Experimental
68⋅4, 66⋅5, 43⋅5, 41⋅4, 38⋅4, 35⋅7, 34⋅6, 25⋅0, 23⋅7
+
(2C); HRMS (ESI): m/z [M + Na] calcd. for
Melting points were taken in open capillaries in sul-
furic acid bath and are uncorrected. Petroleum ether
refers to the fraction having b.p. 60–80°C. A usual
workup of the reaction mixture consists of extrac-
tion with diethyl ether, washing with brine, drying
over Na2SO4, and removal of the solvent in vacuo.
Column chromatography was carried out with silica
C16H26O3Na: 289⋅1780; found: 289⋅1782.
2.2 (S)-5-((S)-1,4-dioxaspiro[4.5]decan-2-
yl)cyclohex-3-enol (12)
A solution of dienols 11 (1⋅25 g, 4⋅70 mmol) in
CH2Cl2 (100 mL) was treated with Grubbs’ first
generation catalyst (193 mg, 0.23 mmol) under Ar-
gon atmosphere and stirred at room temperature for
6 h. The residual mass obtained after removal of
solvent was column chromatographed (30%
Et2O/petroleum ether) to afford an inseparable mix-
1
gel (60–120 mesh). Peak positions in H and
13
C
NMR spectra are indicated in parts per million
downfield from internal TMS in δ units. NMR spec-
1
tra were recorded at 300 MHz for H and 75 MHz
13
for C on Bruker-Avance DPX300 instrument. IR
spectra were recorded on Shimadzu FTIR-8300
instrument. Optical rotations were measured using
ture of cyclohexenols 12 (1⋅0 g, 90%) as a colour-
D
Jasco P-1020 digital polarimeter and [α] values are
25
less oil. [α]
–51⋅9 (c 5⋅3, CHCl3); Rf = 0⋅4 (30%
D
–1
2
–1
given in units of 10 deg cm g . Mass spectra were
measured in a QTOF I (quadrupole-hexapole-TOF)
mass spectrometer with an orthogonal Z-spray–
electrospray interface on Micro (YA-263) mass
spectrometer (Manchester, UK). Unless otherwise
indicated, all reactions were carried out under a
blanket of Ar.
EtOAc/petroleum ether); IR (KBr): 3403, 2931,
–1
1
1448, 1364 cm ; H NMR (300 MHz, CDCl3):
δ = (for the mixture) 5⋅78 (d, J = 10⋅2 Hz) and 5⋅65
(br s, total 2H), 4⋅08 (br s, 1H), 3⋅97–3⋅85 (m, 3H),
3⋅61 (t, J = 6⋅8 Hz, 1H), 2⋅42–2⋅27 (m, 3H), 2⋅03–
1⋅83 (m, 2H), 1⋅56 (br s, 4H), 1⋅52 (br s, 4H), 1⋅34
13
(br s, 2H); C NMR (75 MHz, CDCl3): δ = (for ma-
jor isomer) 127⋅1, 125⋅8, 109⋅7, 78⋅7, 67⋅0, 66⋅7,
40⋅0, 36⋅3, 35⋅0, 34⋅8, 32⋅0, 25⋅2, 24⋅0, 23⋅8; (for
minor isomer) 127⋅6, 124⋅8, 109⋅7, 79⋅0, 67⋅3, 64⋅3,
36⋅4, 36⋅0, 35⋅1, 34⋅9, 33⋅7, 25⋅1, 24⋅0, 23⋅8; HRMS
2.1 (S)-6-((S)-1,4-dioxaspiro[4.5]decan-2-yl)
octa-1,7-dien-4-ol (11)
+
(ESI): m/z [M + Na] calcd. for C14H22O3Na:
To a magnetically stirred solution of the aldehyde 10
(1⋅0 g, 4⋅46 mmol) in THF (20 mL) was added drop-
wise allylmagnesium chloride solution (2⋅7 mL,
261⋅1467; found: 261⋅1462.
5⋅35 mmol, 2⋅0 M in THF) at 0°C. After stirring for 2.3 (S)-5-((S)-1,4-dioxaspiro[4.5]decan-2-
2 h, the reaction was quenched with saturated aque- yl)cyclohex-3-enyl acetate (14)
ous NH4Cl solution (3 mL), and the whole mixture
To a magnetically stirred solution of the cyclohex-
enols 12 (570 mg, 2⋅40 mmol) in CH2Cl2 (20 mL) at
0°C was added drop-wise triethyl amine (0⋅67 mL,
4⋅78 mmol), acetic anhydride (0⋅34 mL, 3⋅60 mmol),
and 4-DMAP (cat). The reaction mixture was then
allowed to stir for 2 h at room temperature. Solvent
was evaporated, and the residual mass was extracted
with diethyl ether (2 × 20 mL). The ether layer was
then washed with water (2 mL) and brine. Removal
of solvent under reduced pressure followed by col-
umn chromatography (5% Et2O/petroleum ether)
was extracted with diethyl ether (3 × 25 mL). The
combined organic layer was washed with brine,
dried over Na2SO4, filtered and evaporated to give
crude product. Purification of the residue by column
chromatography (10% Et2O/petroleum ether) gave
an inseparable mixture of dienols 11 (1⋅0 g, 85%) as
25
a colourless liquid. [α] D + 24⋅0 (c 3⋅9, CHCl3);
Rf = 0⋅6 (20% EtOAc/petroleum ether); IR (KBr):
–1
1
3447, 3075, 2935, 1639, 1448 cm ; H NMR
(300 MHz, CDCl3): δ = (for both diastereoisomers)
5⋅82–5⋅57 (m, 2H), 5⋅12–5⋅02 (m, 4H), 4⋅09–3⋅89
(m, 2H), 3.61–3.56 (m, 2H), 2.46–2.42 (m, 1H),
2.31–2.26 (m, 1H), 2⋅18–2⋅08 (m, 4H), 1⋅54 (br s,
afforded the corresponding acetate 14 (640 mg,
27
95%) as a colourless oil. [α]
–47⋅3 (c 5⋅9,
D
13
4H), 1⋅52 (br s, 4H), 1⋅33 (br s, 2H); C NMR
CHCl3); Rf = 0⋅4 (30% EtOAc/petroleum ether); IR
–1
1
(KBr): 2935, 2860, 1734, 1448, 1365 cm ; H NMR
(300 MHz, CDCl3): δ = (for the mixture) 5⋅82–5⋅62
(m, 2H), 5⋅18–5⋅11 and 4⋅97–4⋅87 (m, total 1H),
(75 MHz, CDCl3): δ = (for major isomer) 137⋅5,
134⋅7, 117⋅8, 117⋅7, 109⋅2, 78⋅0, 68⋅0, 66⋅6, 43⋅4,
42⋅5, 38⋅0, 35⋅7, 34⋅8, 25⋅1, 23⋅8 (2C); (for minor

An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using RCM
793
3⋅90–3⋅88 (m, 2H), 3⋅63–3⋅58 (m, 1H), 2⋅43–2⋅28 Na2SO4, filtered and then concentrated in vacuo.
(m, 2H), 2⋅13–2⋅07 (m, 1H), 2⋅00 (s, 3H), 1⋅88–1⋅81 Purification of the crude residue by column chroma-
(m, 1H), 1⋅58 (br s, 4H), 1⋅54 (br s, 4H), 1⋅50–1⋅32 tography (70% Et2O/petroleum ether) afforded the
13
(m, 3H); C NMR (75 MHz, CDCl3): δ = (for major epoxy-alcohol 13 (120 mg, 85%) as a colourless oil.
26
isomer) 170⋅8, 127⋅6, 124⋅5, 109⋅7, 78⋅6, 67⋅7, 67⋅2, [α] –19⋅6 (c 6⋅5, CHCl3); Rf = 0⋅3 (50% EtOAc/
D
36⋅4, 36⋅0, 35⋅0, 30⋅4, 28⋅9, 25⋅2, 24⋅1, 23⋅9, 21⋅4; petroleum ether); IR (KBr): 3431, 2936, 2860, 1448,
–1 1
(for minor isomer) 170⋅6, 127⋅7, 125⋅0, 109⋅7, 78⋅5, 1365 cm ; H NMR (300 MHz, CDCl3): δ = (for the
70⋅0, 67⋅0, 40⋅0, 36⋅3, 35⋅1, 31⋅2, 30⋅5, 25⋅2, 24⋅0, mixture) 4⋅10–3⋅95 (m, 3H), 3⋅90 (br s, 1H), 3⋅74–
+
23⋅9, 21⋅4; HRMS (ESI): m/z [M + Na] calcd. for 3⋅58 (m, 1H), 3⋅37 and 3⋅27 (all s, 1H), 3⋅22–3⋅13
C16H24O4Na: 303⋅1572; found: 303⋅1577.
(m, 1H), 2⋅44–2⋅19 (m, 2H), 2⋅11–1⋅99 (m, 1H),
1⋅91–1⋅67 (m, 1H), 1⋅58 (br s, 4H), 1⋅55 (br s, 4H),
13
1⋅36 (br s, 2H), 1⋅27–1⋅13 (m, 1H); C NMR
2.4 (R)-5-((S)-1,4-dioxaspiro[4.5]decan-2-yl)-7-
oxabicyclo[4.1.0]heptan-3-yl acetate (15)
(75 MHz, CDCl3): δ = (for the mixture) 110⋅0,
109⋅6, 109⋅5, 77⋅0, 76⋅7, 67⋅6, 67⋅5, 67⋅2, 66⋅2, 64⋅2,
62⋅8, 54⋅2, 53⋅3, 53⋅1, 52⋅6, 51⋅4, 50⋅5, 40⋅0, 38⋅7,
36⋅5 (2C), 36⋅3, 35⋅2, 35⋅1, 35⋅0, 34⋅9, 34⋅2, 33⋅7,
33⋅0, 32⋅2, 29⋅4, 27⋅4, 25⋅2, 24⋅0 (2C), 23⋅8; HRMS
m-CPBA (273 mg, 1⋅58 mmol) was added in one
portion to a solution of the acetate 14 (222 mg,
0⋅79 mmol) in CH2Cl2 (10 mL) and stirred for 2 h at
room temperature. The mixture was treated with
saturated aqueous NaHCO3 and Na2SO3 (5 mL,
v/v = 1 : 1), and extracted with CH2Cl2 (2 × 10 mL).
The extract was washed with brine, dried over
Na2SO4 and concentrated to give crude product.
Purification of the crude product by column chroma-
tography (15% Et2O/petroleum ether) afforded the
+
(ESI): m/z [M + Na] calcd. for C14H22O4Na:
277⋅1416; found: 277⋅1417.
2.6 (4S,5S)-4-hydroxy-5-((S)-1,4-dioxaspiro[4.5]
decan-2-yl)cyclohex-2-enone (17) and (4R,5S)-4-
hydroxy-5-((S)-1,4-dioxaspiro[4.5]decan-2-yl)
cyclohex-2-enone (18)
title compound 15 (192 mg, 82%) as a colourless oil.
27
[α]
–30⋅1 (c 5⋅9, CHCl3); Rf = 0⋅6 (30% EtOAc/ To a solution of the epoxy-alcohols 13 (1⋅1 g,
D
petroleum ether); IR (KBr): 2935, 2860, 1736, 1446, 4⋅33 mmol) in CH2Cl2 (50 mL) at room temperature
–1
1
1365 cm ; H NMR (300 MHz, CDCl3): δ = (for the was added DMP (2⋅2 g, 4⋅76 mmol) portion-wise
mixture) 4⋅88–4⋅77 and 4⋅66–4⋅61 (m, total 1H), and the reaction mixture was allowed to stir for 2 h.
4.12–3.98 (m, 2 H), 3⋅67–3⋅61 (m, 1H), 3⋅38, 3⋅29, The reaction mixture was quenched with 10%
3⋅24, and 3⋅15 (all s, total 2H), 2⋅21–2⋅03 (m, 2H), Na2S2O3 solution (20 mL) doped with NaHCO3 at
2⋅00, 1⋅99, 1⋅97, and 1⋅96 (all s, total 3H), 1⋅79–1⋅66 ice-cold condition and stirred vigorously until the
(m, 1H), 1⋅57 (br s, 8H), 1⋅36 (br s, 3H), 1⋅27–1⋅10 organic layer became transparent. The organic layer
13
(m, 1H); C NMR (75 MHz, CDCl3): δ = (for the was washed with brine, dried over Na2SO4 and con-
mixture) 170⋅4, 170⋅3, 170⋅2, 110⋅2, 110.1, 109.6, centrated in vacuo. The crude mixture thus obtained
109.5, 76.9, 76.8, 76.7, 76.1, 68⋅5, 68⋅2, 67⋅7, 67⋅6, after chromatography over silica gel column (12%
67⋅2, 66⋅3, 65⋅7, 53⋅7, 53⋅2, 52⋅9, 52⋅7, 52⋅4, 50⋅8, EtOAc/petroleum ether) afforded cyclohexenone
50⋅7, 50⋅0, 39⋅0, 38⋅7, 37⋅0, 36⋅6, 36⋅5, 36⋅4, 36⋅3, derivatives 17 (640 mg, 58%) and 18 (210 mg,
25
35⋅1, 35⋅0, 34⋅2, 30⋅7, 30⋅0, 29⋅5, 29⋅3, 29⋅2, 27⋅4, 20%). Compound 17: colourless oil; [α] D –50⋅7 (c
25⋅7, 25⋅2, 24⋅3, 24⋅1 (2C), 24⋅0, 23⋅8, 21⋅4, 21⋅3, 1⋅5, CHCl3); Rf = 0⋅40 (30% EtOAc/petroleum
+ –1
21⋅2; HRMS (ESI): m/z [M + Na] calcd. for ether); IR (KBr): 3444, 2935, 2860, 1682, 1448 cm ;
1
C16H24O5Na: 319⋅1521; found: 319⋅1524.
H NMR (300 MHz, CDCl3): δ = 6⋅95 (dd, J = 10⋅0,
4⋅4 Hz, 1H), 5⋅98 (d, J = 10⋅0 Hz, 1H), 4⋅61 (br s,
1H), 4⋅21 (dd, J = 14⋅3, 7⋅1 Hz, 1H), 4⋅06 (t,
J = 6⋅8 Hz, 1H), 3⋅65 (t, J = 7⋅7 Hz, 1H), 2⋅44 (dd,
J = 17⋅3, 11⋅2 Hz, 1H), 2⋅30–2⋅20 (m, 2H), 1⋅83–
2.5 (R)-5-((S)-1,4-dioxaspiro[4.5]decan-2-yl)-7-
oxabicyclo[4.1.0]heptan-3-ol (13)
The acetate 15 (165 mg, 0⋅56 mmol) was dissolved 1⋅77 (m, 1H), 1⋅56 (br s, 4H), 1⋅53 (br s, 4H), 1⋅35
13
in CH3OH (4 mL) and cooled to –5°C. LiOH⋅H2O (br s, 2H); C NMR (75 MHz, CDCl3): δ = 197⋅8,
(35 mg, 0⋅83 mmol) was then added and stirred for 149⋅3, 129⋅7, 110⋅3, 75⋅1, 67⋅6, 65⋅0, 43⋅0, 36⋅5,
3 h. The reaction mixture was extracted with EtOAc 36⋅4, 35⋅1, 25⋅0, 24⋅0, 23⋅9; HRMS (ESI): m/z
+
(3 × 5 mL) and washed with brine, dried over [M + Na] calcd. for C14H20O4Na: 275⋅1259; found:

794
Soumitra Maity and Subrata Ghosh
275⋅1257; Compound 18: white solid; M.p. 80– δ = 6⋅92 (dd, J = 9⋅9, 5⋅6 Hz, 1H), 5⋅97 (d, J = 9⋅9 Hz,
25
78°C; [α]
+55⋅4 (c 1⋅5, CHCl3); Rf = 0.45 (30% 1H), 4⋅50 (dd, J = 4⋅8, 2⋅4 Hz, 1H), 4⋅15–4⋅09 (m,
D
EtOAc/petroleum ether); IR (KBr): 3462, 2935, 1H), 4⋅04 (dd, J = 7⋅9, 5⋅9 Hz, 1H), 3⋅60 (t,
–1 1
2858, 1674, 1448 cm ; H NMR (300 MHz, J = 7⋅8 Hz, 1 H), 2⋅59 (dd, J = 15⋅8, 12⋅8 Hz, 1H),
CDCl3): δ = 6⋅87 (d, J = 10⋅3 Hz, 1H), 5⋅95 (d, 2⋅16–2⋅01 (m, 2H), 1⋅57 (br s, 8H), 1⋅40 (br s, 2H),
13
J = 10⋅2 Hz, 1H), 4⋅60 (d, J = 7⋅1 Hz, 1H), 4⋅16– 0⋅87 (s, 9H), 0⋅15 (s, 3H), 0⋅11 (s, 3H); C NMR
4⋅10 (m, 2H), 3⋅72–3⋅65 (m, 1H), 2⋅30 (t, J = 6⋅3 Hz, (75 MHz, CDCl3): δ = 199⋅0, 148⋅1, 129⋅8, 109⋅6,
1H), 2⋅25–2⋅06 (m, 2H), 1⋅84–1⋅80 (m, 1 H), 1⋅63 74⋅7, 67⋅5, 63⋅0, 44⋅4, 36⋅7, 35⋅5, 35⋅0, 25⋅8 (3C),
13
(br s, 3H), 1⋅59 (br s, 5H), 1⋅39 (br s, 2H); C NMR 25⋅3, 24⋅1, 24⋅0, 18⋅2, –4⋅0, –4⋅7; HRMS (ESI): m/z
+
(75 MHz, CDCl3): δ = 196⋅6, 152⋅7, 128⋅0, 111⋅0, [M + Na] calcd. for C20H34O4SiNa: 389⋅2124;
79⋅4, 70⋅9, 67⋅9, 47⋅0, 37⋅9, 35⋅9, 34⋅9, 24⋅8, 24⋅0, found: 389⋅2122.
+
23⋅7; HRMS (ESI): m/z [M + Na] calcd. for
C14H20O4Na: 275⋅1259; found: 275⋅1258.
2.9 (1R,4S,5R)-4-(tert-butyldimethylsilyloxy)-
5-((S)-1,4-dioxaspiro[4.5]decan-2-yl)cyclohex-
2.7 (1R,4S,5R,9S)-4,9-dihydroxy-2-oxabicyclo
[3.3.1]nonan-7-one (20)
2-enol (22)
To a magnetically stirred solution of the cyclohexe-
A solution of cyclohexenone 18 (40 mg, 0⋅16 mmol) none derivative 21 (212 mg, 0⋅58 mmol) in methanol
in CDCl3 (0⋅60 mL) was kept for five days in room (5 mL) was added CeCl3⋅H2O (458 mg, 1⋅73 mmol)
temperature and then the whole mixture was col- and stirred for 5 min at room temperature. The reac-
lected with ethyl acetate. The residual mass obtained tion mixture was then cooled to –78°C and to it
after removal of solvent was column chromatogra- NaBH4 (66 mg, 1⋅73 mmol) was added portion-wise.
phed (50% EtOAc/petroleum ether) to afford the After stirring for 30 min at that temperature, the re-
cyclic ether 20 (22 mg, 80%) as crystalline solid. action mixture was quenched by drop-wise addition
27
M.p.: 112–110°C; [α] D + 26⋅8 (c 0⋅5, EtOH); IR of AcOH. Usual workup of the reaction mixture
–1 1
(KBr): 3404, 3385, 2907, 1695 cm ; H NMR afforded, after column chromatography (20% Et2O/
(300 MHz, CD3OD): δ = 4⋅11 (br s, 1H), 3⋅89–3⋅82 petroleum ether), the cyclohexenol derivative 22
25
(m, 2H), 3⋅60 (dd, J = 12⋅4, 5⋅9 Hz, 1H), 3⋅02 (t, (180 mg, 85%) as a colourless oil; [α]
–78⋅5 (c
D
J = 11⋅6 Hz, 1H), 2⋅85 (dd, J = 17⋅7, 4⋅6 Hz, 1H), 0⋅9, CHCl3); Rf = 0⋅3 (20% EtOAc/petroleum ether);
13
–1 1
IR (KBr): 3348, 2932, 1448 cm ; H NMR
2⋅63–2⋅57 (m, 3H), 2⋅42 (d, J = 17⋅8 Hz, 1H);
C
NMR (75 MHz, CD3OD): δ = 211⋅3, 72⋅7, 66⋅4, (300 MHz, CDCl3): δ = 5⋅80–5⋅72 (m, 2H), 4⋅21 (d,
65⋅5, 62⋅0, 41⋅5, 41⋅4, 34⋅3; HRMS (ESI): m/z J = 3⋅0 Hz, 1H), 4⋅14 (t, J = 7⋅5 Hz, 1H), 4⋅10–4⋅01
+
[M + Na] calcd. for C8H12O4Na: 195⋅0633; found: (m, 2H), 3⋅64 (t, J = 7⋅4 Hz, 1H), 1⋅64–1⋅54 (m, 9H),
195⋅0631.
1⋅40–1⋅31 (m, 3H), 1⋅23–1⋅18 (m, 1H), 0⋅86 (s, 9H),
13
0⋅07 (s, 3H), 0⋅06 (s, 3H); C NMR (75 MHz,
CDCl3): δ = 133⋅6, 130⋅2, 109⋅1, 75⋅5, 68⋅3, 67⋅6,
2.8 (4S,5R)-4-(tert-butyldimethylsilyloxy)-5-((S)-
1,4-dioxaspiro[4.5]decan-2-yl)cyclohex-2-enone
(21)
63⋅8, 43⋅3, 36⋅7, 35⋅3, 28⋅9, 26⋅0 (3C), 25⋅3, 24⋅1,
+
24⋅0, 18⋅2, –3⋅8, –4⋅7; HRMS (ESI): m/z [M + Na]
calcd. for C20H36O4SiNa: 391⋅2281; found: 391⋅2281.
To a magnetically stirred solution of the alcohol 17
(209 mg, 0⋅83 mmol) in CH2Cl2 (7 mL) at –40°C,
was added triethyl amine (0⋅12 mL, 0⋅91 mmol), fol-
lowed by t-butyldimethylsilyl triflate (0⋅23 mL,
0⋅10 mmol). The reaction mixture was allowed to
2.10 (1S,4S,5R)-4-(tert-butyldimethylsilyloxy)-5-
((S)-1,4-dioxaspiro[4.5]decan-2-yl)cyclohex-2-enol
(23)
stir at that temperature for 15 min. The crude mass To a solution of cyclohexenol 22 (120 mg,
obtained after evaporation of the solvent, was col- 0⋅32 mmol) in THF (2 mL) were added triphenyl-
umn chromatographed (5% Et2O/petroleum ether) to phosphine (214 mg, 0⋅82 mmol), diisopropyl
afford the silyl ether 21 (280 mg, 92%) as a colour- azodicarboxylate (0⋅13 mL, 0⋅65 mmol), and p-
27
less liquid; [α]
–86⋅1 (c 3⋅9, CHCl3); Rf = 0⋅8 nitrobenzoic acid (217 mg, 1⋅30 mmol), and the
D
(20% EtOAc/petroleum ether); IR (KBr): 2934, reaction mixture was stirred at room temperature for
–1 1
2856, 1682, 1462 cm ; H NMR (300 MHz, CDCl3): 2 h. After being diluted with Et2O (20 mL), the reac-

An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using RCM
795
tion mixture was washed with saturated aqueous was added 2,6-lutidine (0⋅07 mL, 0⋅60 mmol), fol-
NaHCO3 solution, water and brine, dried over lowed by t-butyldimethylsilyl triflate (0⋅08 mL,
Na2SO4, and concentrated under reduced pressure. 0⋅36 mmol) and allowed to stir for 10 min. The
The resulting crude residue was purified by column residual mass obtained after evaporation of the
chromatography (4% Et2O/petroleum ether) to give solvent, was column chromatographed (2% Et2O/
p-nitrobenzoate derivative (135 mg, 80%) as a col- petroleum ether) to afford the bis-silyl ether deriva-
25
ourless liquid; [α] D –164⋅4 (c 2⋅5, CHCl3); Rf = 0⋅6 tive 24 (136 mg, 95%) as a colourless liquid; [α]
24
D
(10% EtOAc/petroleum ether); IR (KBr): 2953, –117⋅3 (c 4⋅5, CHCl3); IR (KBr): 2932, 2856, 1471,
–1
1
–1
1
2856, 1724, 1608, 1531, 1464 cm ; H NMR 1362 cm ; H NMR (300 MHz, CDCl3): δ = 5⋅85
(300 MHz, CDCl3): δ = 8⋅27 (d, J = 8⋅8 Hz, 2H), (dd, J = 9⋅8, 5⋅2 Hz, 1H), 5⋅72 (dd, J = 9⋅7, 4⋅6 Hz,
8⋅16 (d, J = 8⋅8 Hz, 2H), 6⋅14 (dd, J = 9⋅8, 5⋅3 Hz, 1H), 4⋅23 (dd, J = 5⋅1, 3⋅2 Hz, 1H), 4⋅18–4⋅13 (m,
1H), 5⋅95 (dd, J = 9⋅7, 4⋅5 Hz, 1H), 5⋅51 (d, 1H), 4⋅11–4⋅02 (m, 2H), 3⋅59 (t, J = 7⋅1 Hz, 1H),
J = 4⋅1 Hz, 1H), 4⋅34 (dd, J = 5⋅2, 2⋅6 Hz, 1H), 4⋅13 2⋅05–1⋅98 (m, 1H), 1⋅84 (td, J = 12⋅9, 4⋅0 Hz, 1H),
(t, J = 7⋅2 Hz, 1H), 4⋅07 (dd, J = 7⋅5, 6⋅1 Hz, 1H), 1⋅59 (br s, 4H), 1⋅58 (br s, 4H), 1⋅38 (br s, 3H), 0⋅88
3⋅60 (t, J = 7⋅4 Hz, 1H), 2⋅10–1⋅97 (m, 2H), 1⋅61 (br (s, 9H), 0⋅86 (s, 9H), 0⋅09 (s, 3H), 0⋅06 (s, 3H), 0⋅05
13
s, 4H), 1⋅58 (br s, 4H), 1⋅39 (br s, 3H), 0⋅88 (s, 9H), (s, 3H), 0⋅04 (s, 3H); C NMR (75 MHz, CDCl3):
13
0⋅13 (s, 3H), 0⋅10 (s, 3H); C NMR (75 MHz, δ = 131⋅0, 130⋅7, 109⋅1, 75⋅6, 68⋅2, 64⋅2, 63⋅9, 39⋅3,
CDCl3): δ = 164⋅3, 150⋅6, 135⋅9, 135⋅3, 130⋅8 (2C), 36⋅7, 35⋅6, 28⋅7, 26⋅0 (6C), 25⋅5, 24⋅2, 24⋅0, 18⋅3,
125⋅4, 123⋅6 (2C), 109⋅4, 75⋅1, 68⋅3, 68⋅0, 63⋅2, 18⋅2, –3⋅8, –4⋅3, –4⋅6, –4⋅7; HRMS (ESI): m/z
+
40⋅2, 36⋅7, 35⋅3, 25⋅9 (3C), 25⋅3, 25⋅0, 24⋅2, 23⋅9, [M + Na] calcd. for C26H50O4Si2Na: 505⋅3145;
+
18⋅2, –3⋅9, –4⋅7; HRMS (ESI): m/z [M + Na] calcd. found: 505⋅3144.
for C27H39NO7SiNa: 540⋅2393; found: 540⋅2390.
The
p-nitrobenzoate
derivative
(190 mg,
2.12 ((1R,2R,3R,5S,6S)-3-((S)-1,4-dioxaspiro
[4.5]decan-2-yl)-7-oxabicyclo[4.1.0]heptane-2,5-
diyl)bis(oxy)bis(tert-butyldimethylsilane) (25)
0⋅36 mmol) was treated with LiOH.H2O (15 mg,
0⋅36 mmol) in methanol (2 mL) at 0°C for 1 h. After
being diluted with Et2O (20 mL), the reaction mix-
ture was washed with brine solution, dried over
Na2SO4, and concentrated under reduced pressure.
The crude residue was purified by column chroma-
tography (20% Et2O/petroleum ether) to provide the
To a solution of the bis-silyl ether 24 (45 mg,
0⋅09 mmol) in 1,2-dichloro ethane (2 mL) was added
m-CPBA (48 mg, 0⋅28 mmol), and the solution was
heated under reflux. After 2 h, the reaction mixture
was diluted with CH2Cl2 (5 mL), washed with satu-
rated aqueous NaHCO3 and Na2SO3 solution (v/v,
1 : 1), dried (Na2SO4), and evaporated. The residual
oil was purified by column chromatography (3%
title compound 23 (111 mg, 82%) as a colourless
26
liquid; [α]
–134⋅6 (c 1⋅5, CHCl3); Rf = 0⋅3 (30%
D
EtOAc/petroleum ether); IR (KBr): 3398, 2934,
–1
1
2856, 1531, 1448 cm ; H NMR (300 MHz,
CDCl3): δ = 5⋅93 (dd, J = 9⋅8, 5⋅1 Hz, 1H), 5⋅84 (dd,
J = 10⋅1, 4⋅5 Hz, 1H), 4⋅22–4⋅17 (m, 2H), 4⋅11–4⋅07
(m, 1H), 4⋅03 (t, J = 6⋅0 Hz, 1H), 3⋅64 (t, J = 7⋅4 Hz,
1H), 2⋅74 (br s, 1H), 1⋅91–1⋅83 (m, 2H), 1⋅57 (br s,
4H), 1⋅56 (br s, 4H), 1⋅40–1⋅30 (m, 3H), 0⋅85 (s,
Et2O/petroleum ether) to afford epoxide 25 (30 mg,
25
65%) as a colourless oil; [α]
–68⋅1 (c 1⋅0,
D
–1
1
CHCl3); IR (KBr): 2934, 2885, 1462 cm ; H NMR
(300 MHz, CDCl3): δ = 4.33 (t, J = 3⋅9 Hz, 1H),
4⋅29 (d, J = 2⋅2 Hz, 1H), 4⋅07 (dd, J = 14⋅1, 7⋅7 Hz,
1H), 3⋅97 (dd, J = 7⋅6, 6⋅1 Hz, 1H), 3⋅51 (t,
J = 7⋅6 Hz, 1H), 3⋅22 (t, J = 3⋅6 Hz, 1H), 3⋅01 (br s,
1H), 1⋅89–1⋅85 (m, 1H), 1⋅68 (td, J = 13⋅1, 2⋅8 Hz,
1H), 1⋅58 (br s, 4H), 1⋅56 (br s, 4H), 1⋅39 (br s, 3H),
0⋅92 (s, 9H), 0⋅90 (s, 9H), 0⋅16 (s, 3H), 0⋅12 (s, 3H),
13
9H), 0⋅09 (s, 3H), 0⋅05 (s, 3H); C NMR (75 MHz,
CDCl3): δ = 132⋅5, 129⋅8, 109⋅2, 75⋅5, 68⋅0, 63⋅8,
63⋅5, 39⋅2, 36⋅7, 35⋅6, 28⋅0, 25⋅9 (3C), 25⋅4, 24⋅2,
+
24⋅0, 18⋅2, –3⋅8, –4⋅7; HRMS (ESI): m/z [M + Na]
calcd. for C20H36O4SiNa: 391⋅2281; found: 391⋅2283.
13
0⋅08 (s, 3H), 0⋅07 (s, 3H); C NMR (75 MHz,
2.11 ((1S,4S,5R)-5-((S)-1,4-dioxaspiro[4.5]decan-
2-yl)cyclohex-2-ene-1,4-diyl)bis(oxy)bis(tert-butyl-
dimethylsilane) (24)
CDCl3): δ = 109⋅1, 74⋅8, 67⋅8, 66⋅0, 64⋅7, 55⋅3, 54⋅6,
38⋅1, 36⋅7, 35⋅4, 26⋅0 (3C), 25⋅9 (3C), 25⋅4, 24⋅6,
24⋅2, 24⋅0, 18⋅5, 18⋅2, –4⋅2, –4⋅6, –4⋅7, –4⋅8; HRMS
+
(ESI): m/z [M + Na] calcd. for C26H50O5Si2Na:
To a magnetically stirred ice-cold solution of the
alcohol 23 (110 mg, 0⋅30 mmol) in CH2Cl2 (4 mL),
521⋅3094; found: 521⋅3096.

796
Soumitra Maity and Subrata Ghosh
2.13 (1S,4S,5S)-5-((S)-1,2-dihydroxyethyl)
cyclohex-2-ene-1,4-diol (26)
2.15 ((1S,4S,5R)-5-((tert-butyldimethylsilyloxy)
methyl)cyclohex-2-ene-1,4-diyl)bis(oxy)bis
(tert-butyldimethylsilane) (28)
A solution of the cyclohexenol derivative 22
(200 mg, 0⋅54 mmol) in 80% aqueous acetic acid
(3 mL) was stirred at 70°C for 4 h. After cooling to
room temperature, the solvent was evaporated under
reduced pressure. Purification of the crude mass by
column chromatography (20% CH3OH/EtOAc) af-
Following the above described protocol a solution of
the triol 27 (30 mg, 0⋅21 mmol) was silylated with t-
butyldimethylsilyl triflate (0⋅21 mL, 0⋅93 mmol) in
DMF (1 mL) to afford, after column chromatogra-
phy (3% Et2O/petroleum ether), the trisilyl ether de-
forded the tetraol 26 (66 mg, 70%) as a colourless
rivative 28 (86 mg, 85%) as a colourless liquid;
24
25
[α] –107⋅5 (c 2⋅3, CHCl3); IR (KBr): 2930, 2884,
heavy oil; [α]
–201⋅6 (c 4⋅6, CH3OH); Rf = 0⋅2
D
D
–1
1
(20% CH3OH/EtOAc); IR (KBr): 3389, 3350,
1462 cm ; H NMR (300 MHz, CDCl3): δ = 5⋅71
(br s, 2H), 4⋅24 (d, J = 2⋅9 Hz, 2H), 3⋅75 (dd,
J = 10⋅0, 6⋅8 Hz, 1H), 3⋅46 (t, J = 9⋅7 Hz, 1H), 2⋅18–
2⋅08 (m, 1H), 1⋅97–1⋅88 (m, 1H), 1⋅51 (d, J = 13⋅1 Hz,
1H), 0⋅89 (s, 18 H), 0⋅87 (s, 9H), 0⋅07 (s, 6H), 0⋅04
–1
1
1435 cm ; H NMR (300 MHz, CD3OD): δ = 5⋅96
(dd, J = 9⋅8, 4⋅8 Hz, 1H), 5⋅88 (dd, J = 9⋅8, 4⋅2 Hz,
1H), 4⋅29 (t, J = 4⋅1 Hz, 1H), 4⋅16 (d, J = 2⋅3 Hz,
1H), 3⋅76–3⋅65 (m, 2H), 3⋅58 (dd, J = 10⋅3, 5⋅5 Hz,
1H), 2⋅07–1⋅98 (m, 1H), 1⋅90 (td, J = 13⋅3, 4⋅1 Hz,
13
(s, 12H); C NMR (75 MHz, CDCl3): δ = 131⋅6,
13
1H), 1⋅58 (d, J = 13⋅0 Hz, 1H); C NMR (75 MHz,
131⋅4, 65⋅7, 64⋅8, 63⋅1, 39⋅2, 30⋅5, 26⋅1 (3C), 26⋅0
(3C), 25⋅9 (3C), 18⋅4 (2C), 18⋅3, –4⋅0, –4⋅4, –4⋅5,
CD3OD): δ = 131⋅0, 130⋅5, 73⋅1, 64⋅3, 63⋅3 (2C),
+
36⋅0, 28⋅7; HRMS (ESI): m/z [M + Na] calcd. for
+
–4⋅7, –5⋅2 (2C); HRMS (ESI): m/z [M + Na] calcd.
C8H14O4Na: 197⋅0790; found: 197⋅0793.
for C25H54O3Si3Na: 509⋅3279; found: 509⋅3276.
2.14 (1S,4S,5R)-5-(hydroxymethyl)cyclohex-2-ene-
1,4-diol (27)
2.16 ((1R,2R,3R,5S,6S)-3-((tert-butyldimethyl-
silyloxy)methyl)-7-oxabicyclo[4.1.0]heptane-2,5-
diyl)bis(oxy)bis(tert-butyldimethylsilane) (29)
To a magnetically stirred ice-cold solution of the
tetraol 26 (100 mg, 0⋅57 mmol) in CH3OH/H2O
(3 : 1, 3 mL) was added NaIO4 (245 mg, 1⋅14 mmol)
in multiple portions. The reaction mixture was al-
lowed to stir at 0°C for 30 min. The precipitated
white solid was filtered off, after washing it thor-
oughly with ethyl acetate. Usual workup of the
filtrate afforded the corresponding aldehyde. To a
stirred solution of this crude aldehyde in CH3OH
(2 mL) was added NaBH4 (ca. 40 mg) in small por-
tions at 0°C, and the mixture was allowed to stir for
30 min. The reaction mixture was quenched with
AcOH. Usual workup of the residual mass obtained
after evaporation of methanol under reduced pres-
sure followed by column chromatography (5%
Following the above described protocol a solution of
the silyl ether 28 (30 mg, 0⋅21 mmol) was treated
with m-CPBA (0⋅21 mL, 0⋅93 mmol) in 1,2-dichlo-
roethane (1 mL) to afford, after column chromatog-
raphy (3% Et2O/petroleum ether), the epoxy
cyclohexene derivative 29 (86 mg, 85%) as a colour-
26
less liquid; [α]
–26⋅6 (c 1⋅6, CHCl3); IR (KBr):
D
–1
1
2955, 2856, 1464, 1255 cm ; H NMR (300 MHz,
CDCl3): δ = 4⋅24–4⋅18 (m, 2H), 3⋅64 (m, 1H), 3⋅36
(dd, J = 9⋅8, 7⋅9 Hz, 1H), 3⋅20 (t, J = 3⋅7 Hz, 1H),
3⋅05 (br s, 1H), 1⋅91–1⋅88 (m, 1H), 1⋅69–1⋅62
(m, 2H), 0⋅91 (s, 9H), 0⋅89 (s, 9H), 0⋅87 (s, 9H),
0⋅12 (s, 3H), 0⋅08 (s, 3H), 0⋅07 (s, 3H), 0⋅06 (s, 3H),
13
0⋅05 (s, 3H), 0⋅03 (s, 3H); C NMR (75 MHz,
CH3OH/EtOAc) afforded the triol 27 (56 mg, 68%)
25
CDCl3): δ = 65⋅9, 65⋅6, 63⋅3, 56⋅4, 55⋅1, 36⋅9, 29⋅8,
26⋅2 (3C), 26⋅0 (3C), 25⋅9 (3C), 18⋅4 (2C), 18⋅3,
–4⋅2, –4⋅7 (2C), –4⋅9, –5⋅2 (2C); HRMS (ESI): m/z
as a gummy liquid; [α]
–286⋅7 (c 4⋅0, CH3OH);
D
Rf = 0⋅4 (20% CH3OH/EtOAc); IR (KBr): 3367,
–1
1
3308, 2933, 1410 cm ; H NMR (300 MHz,
CD3OD): δ = 5⋅92 (dd, J = 9⋅9, 4⋅3 Hz, 1H), 5⋅86
(dd, J = 9⋅9, 3⋅7 Hz, 1H), 4⋅16 (br s, 2H), 3⋅73 (dd,
J = 10⋅7, 7⋅6 Hz, 1H), 3⋅50 (dd, J = 10⋅7, 6⋅6 Hz,
+
[M + K] calcd. for C25H54O4Si3K: 541⋅2967; found:
541⋅2966.
1H), 2⋅17–2⋅06 (m, 1H), 1⋅80 (td, J = 13⋅7, 4⋅5 Hz, 3. Results and discussion
13
1H), 1⋅58 (d, J = 13⋅7 Hz, 1H); C NMR (75 MHz,
In a retrosynthetic analysis, compound 6 could be
obtained from the cyclohexenol 7. The ketal moiety
would be the source of chirality as well as the
CD3OD): δ = 131⋅0, 130⋅8, 63⋅7, 63⋅1, 62⋅7, 37⋅0,
+
29⋅0; HRMS (ESI): m/z [M + Na] calcd. for
C7H12O3Na: 167⋅0684; found: 167⋅0685.

An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using RCM
797
masked carbonyl to be required for introduction of ratio of ca. 3 : 1 in 78% yield. The formation of the
the carbon chain for completion of the synthesis of hydroxy-enones could be attributed to the silica
the natural products. The cyclohexenol 7 would be induced facile opening of the oxirane rings in the
6
available by ring closing metathesis of the dienol 8, epoxy cyclohexanones 16. The gross structures of
which in turn would be available from the unsatu- these compounds were established through analysis
rated ester 9.
of their NMR spectra. The stereochemical assign-
The ester 9 was prepared from D-mannitol follow- ment to the newly generated stereogenic center in 18
ing the procedure developed earlier in this labora- was confirmed by its transformation to 20. When a
7
tory. The ester 9 was then transformed into the solution of 18 in CDCl3 was allowed to sit for five
known aldehyde 10 using a reduction–oxidation se- days at room temperature, the cyclic ether 20 was
8
quence. The aldehyde 10 on reaction with allyl- formed in excellent yield as a white crystalline solid,
magnesium chloride afforded in 85% yield, an mp 110–112°C. The structure of 20 was established
9
inseparable mixture of alcohols 11 (ca. 3 : 2) as through single crystal X-ray (figure 2). The forma-
13
revealed by C NMR spectra. We decided to pro- tion of 20 could be attributed as follows. Initially
ceed with this mixture as in a subsequent step this deketalization of 18 took place by trace amount of
stereogenic centre will be destroyed after oxidation HCl present in CDCl3 to provide the triol 19. The
of the hydroxy group. RCM of this dienol mixture triol 19 underwent in situ intramolecular oxy-
with Grubbs’ first generation catalyst, Cl2(PCy3)2 Michael addition to provide 20. With the establish-
Ru=CHPh (G 1) afforded a mixture of cyclohex- ment of the structure 19, the major and minor hy-
enols 12 in excellent yield. The cyclohexenols 12 droxy enones were assigned the structures 17 and 18
was then subjected to epoxidation with m-CPBA to respectively.
The hydroxyl group of 17 was then protected to
afford the silyl ether 21. Reduction of 21 using the
produce a mixture of oxiranes 13 in 50% yield. It
was thought that an appropriately protected hydroxyl
group might increase the yield of oxiranes. After
considerable experimentation, an acetoxy group was
found to be most effective for this purpose. The hy-
droxyl group was thus transformed to the acetate 14.
Epoxidation of the acetate 14 with m-CPBA pro-
ceeded smoothly to produce in 82% yield an insepa-
rable mixture of the oxiranes 15.
10
condition developed by Luche (NaBH4-CeCl3-
MeOH) led to the isolation of a single diastereo-
isomer in overall excellent yield. Reduction of the
carbonyl group in 21 was expected to proceed
exclusively from the side opposite to the C-5 sub-
stituent to provide 22. Indeed determination of the
structure of the reduction product through analysis
of its HSQC, COSY and NOESY spectra (figure 3)
showed the structure of the reduction product as 22.
Inversion of the stereochemistry of the C-1 hydroxyl
group was then required to have syn-1,4-hydroxy
The acetate 15 was then hydrolysed. The resulting
hydroxy-epoxides 13 were subjected to oxidation
with Dess–Martin periodinane (DMP). Interestingly,
purification of the resulting product through silica
gel column chromatography afforded, instead of the
keto-epoxide 16, the hydroxy enones 17 and 18 in a
11
group and was achieved via Mitsunobu reaction in
good yield. In order to introduce the oxirane ring
anti to the 1,4-dihydroxyl group, a unique character-
istic of this family of natural products, it was earlier
5f
demonstrated by other workers that an increase in
steric bulk of the substituents at the allylic positions
directed the electrophile to add from the opposite
face. The free hydroxyl groups of 23 were protected
as silyl ether by treating with TBSOTf to afford 24
in 95% yield. The cyclohexene derivative 24 was
then treated with m-CPBA in DCE under reflux and
the reaction was found to be highly stereoselective
to furnish the epoxide 25 as the only isolable pro-
duct in 65% yield. The stereochemical assignment to
25 followed from comparison of the coupling con-
stant of the C-2 H [δ 3⋅22 (1H, t, J = 3⋅6 Hz)] with
5f
that reported in literature for an analogous com-
Scheme 1. Retrosynthetic plan.
pound.

798
Soumitra Maity and Subrata Ghosh
Scheme 2. Synthesis of functionalized cyclohexenone derivative.
Deketalization of 25 appeared to be a tough job
12
under a variety of conditions. Thus, we decided to
change the reaction sequence. Compound 23 was
first subjected to deketalization with 80% aqueous
AcOH at 70°C to give the tetraol 26 in excellent
yield. The tetraol 26 was transformed to the triol 27
by cleavage of the vicinal diol unit with sodium
metaperiodate followed by reduction of the resulting
aldehyde with NaBH4. The cyclohexane derivative
28 with m-CPBA produced the oxirane 29 as a sin-
gle diastereoisomer in overall good yield. The silyl
ethers 25 and 29 represent the highly functionalized
epoxy-cyclohexane-1,4-diol skeletons present in the
natural products 2–5.
Figure 2. ORTEP drawing of 20.
4. Conclusions
We have developed a new stereocontrolled route for
the synthesis of the highly functionalized 2,3-epoxy-
Figure 3. COSY and NOESY analysis of 22.

An asymmetric route to 2,3-epoxy-syn-1,4-cyclohexane diol derivatives using RCM
799
Scheme 3. Synthesis of fully functionalized 2,3-epoxy-1,4-cyclohexane diol derivative.
5. (a) Defrancq E, Gordon J, Brodard A and Tabacchi R
1992 Helv. Chim. Acta 75 276; (b) Takano S, Moriya
M, Higashi Y and Ogasawara K 1993 J. Chem. Soc.,
Chem. Commun. 177; (c) Takano S, Moriya M and
Ogasawara K 1993 J. Chem. Soc., Chem. Commun.
614; (d) Barros M T, Maycock C D and Ventura M R
1997 J. Org. Chem. 62 3984; (e) Barros M T, May-
cock C D and Ventura M R 2000 Chem. Eur. J. 6
3991; (f) Shimizu H, Okamura H, Iwagawa T and
Nakatani M 2001 Tetrahedron 57 1903; (g) Mehta G
and Roy S 2004 Org. Lett. 6 2389; (h) Mehta G and
Pan S C 2004 Org. Lett. 6 3985; (i) Mehta G and Roy
S 2005 Chem. Commun. 3210; (j) Mehta G and Roy S
2005 Tetrahedron Lett. 46 7927 and the references
cited therein
syn-1,4-cyclohexane diol derivatives. The key step
involves ring closing metathesis of an appropriately
constructed 1,7-dienol derived from D-mannitol and
stereoselective epoxidation.
Acknowledgements
Financial support from the Department of Science
and Technology (DST), Government of India
through a Ramanna Fellowship to S G is gratefully
acknowledged. S M thanks Council of Scientific and
Industrial Research (CSIR), New Delhi for SRF.
Financial support from DST for the National Single
crystal X-ray Diffractometer facility at the Depart-
ment of organic Chemistry is gratefully acknow-
ledged.
6. For excellent accounts on RCM see: (a) Grubbs R H,
Miller S J and Fu G C 1995 Acc. Chem. Res. 28 446;
(b) Fürstner A 1997 Top. Catal. 4 285; (c) Schuster
M and Blechert S 1997 Angew. Chem. Int. Ed. 36
2036; (d) Grubbs R H and Chang S 1998 Tetrahedron
54 4413; (e) Armstrong S K 1998 J. Chem. Soc.,
Perkin Trans. 1 371; (f) Fürstner A 2000 Angew.
Chem. Int. Ed. 39 3012; (g) Deiters A and Martin S F
2004 Chem. Rev. 104 2199; (h) Nicolaou K C, Bulger
P G and Sarlah D 2005 Angew. Chem. Int. Ed. 44
4490; (i) Ghosh S, Ghosh S and Sarkar N 2006
J. Chem. Sci. 118 223; (j) Chattopadhyay S K, Kar-
makar S, Biswas T, Majumdar K C, Rahaman H and
Roy B 2007 Tetrahedron 63 3919
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800
Soumitra Maity and Subrata Ghosh
deposit@ccdc.cam.ac.uk). Crystal data for 20: C H O ,
9. X-ray crystallography: X-ray single crystal data were
8
12
4
collected using MoKα (λ = 0⋅7107 Å) radiation on a
BRUKER APEX II diffractometer equipped with
CCD area detector. Data collection, data reduction,
structure solution/refinement were carried out using
the software package of SMART APEX. The struc-
ture was solved by direct method and refined in a
routine manner. Non-hydrogen atoms were treated
anisotropically. All hydrogen atoms were geometri-
FM = 172⋅18, orthorhombic space group P2 2 2 (No.
1
1 1
19), a = 6⋅926(4), b = 9⋅196(5), c = 12⋅178(6) Å.
3
–3
V = 775⋅6(7) Å , T = 120 K, Z = 4. D = 1⋅475 g cm . F
c
–1
(000) = 368, λ (Mo–Kα) = 0⋅71073 Å, μ = 0⋅118 mm ,
2θ = 57⋅36°, 9358 collected reflections measured,
max
1988 observed (I > 2σ (I)) 111 parameters; R =
int
0⋅0436, R = 0⋅0335; wR = 0⋅0811 (I > 2σ (I)),
1
2
R = 0⋅0379; wR = 0⋅0831 (all data) with GOF = 1⋅051
1
2
cally fixed. CCDC (CCDC No: 759612) contains the 10. Luche J-L 1978 J. Am. Chem. Soc. 100 2226
supplementary crystallographic data for this paper. 11. Mitsunobu O 1981 Synthesis 1
These data can be obtained free of charge via www. 12. (a) Vijayasarandhi S, Singh J and Aidhen I S 2000
ccdc.cam.ac.uk/conts/retrieving.html (or from the Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB21EZ, UK; fax: (+44) 1223-336-033; or
Synlett. 1 110; (b) Babjak M, Zálupský P and Gracza
T 2005 ARKIVOC (v) 45; (c) Merino P, Jimenez P
and Tejero T 2006 J. Org. Chem. 71 4685