Hydroxyhalogenations of acyloxycyclohex-2-enes. Part 3. Iterative 1,2-hydroxyiodination of acetoxycyclohex-2-ene: Preparation of tetraacetyl conduritol D

Article abstract of DOI:10.1039/a709056k

Compound 22, the tetraacetyl derivative of conduritol D, has been synthesized by repeated hydroxyiodination reactions in nine steps from acetoxycyclohex-2-ene.

Full text of DOI:10.1039/a709056k

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Hydroxyhalogenations of acyloxycyclohex-2-enes. Part 3.1 Iterative
1,2-hydroxyiodination of acetoxycyclohex-2-ene: preparation of
tetraacetyl conduritol D
Johannes Bange, Alan F. Haughan, J. R. Knight and Joseph Sweeney*,†
Department of Chemistry, University of Reading, Reading, UK RG6 6AD
Compound 22, the tetraacetyl derivative of conduritol D, has been synthesized by repeated
hydroxyiodination reactions in nine steps from acetoxycyclohex-2-ene.
Oxidation of alkenes by means of addition of oxygen has been
an area of research of great interest to organic chemists
OAc
OAc
OH
throughout the history of the subject. In particular, of late the
i
study of asymmetric epoxidation2 and dihydroxylation3 reac-
tions of alkenes has provided many of the most-used reactions
of the modern synthetic chemist’s armoury. Our group has had
an interest in such oxygen addition reactions of alkenes for
some time, and we have aimed during that time to develop new
and useful synthetic methods of this type, with a view to enabl-
ing synthesis of cyclitols, such as the conduritol4 family
(conduritols A–F, 1–6). We here disclose in full5 the details of
I
7
ii
OAc
O
OH
OH
OH
8
OH
OH
OH
OH
OH
OH
OAc
OAc
OAc
I
I
OH
OH
OH
OH
+
+
1
2
3
OH
NOT OBSERVED
I
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Scheme 1 Reagents: i, N-iodosuccinimide, water, CH2Cl2; ii, DBU,
room temp.
diaxial ring-opening to give 7. Because of the trans-diaxial
requirement for ring-opening, iodonium ion 10 is the only
intermediate which can furnish 7 as the product of the reaction.
Since it is likely that the energetic barriers between the possible
iodonium ions are small, it is perhaps the case that there is a
neighbouring group effect in operation, whereby only iodonium
ion 10 may react via intramolecular trans-diaxial ring-opening.
Thus, even if ion 10 is not very much more stable than its coun-
terparts, once it is formed, reaction to give dioxolonium ion 11
is rapid, thereby distorting the conformer population by Le
Chatelier’s principle. Dioxolonium ion 11 would then react with
water to give 7, in which the acetate remains in an equatorial
position rather than migrating to an axial one. When the reac-
tion to produce 7 was repeated on a large scale, however, a small
amount of regioisomeric hydroxy iodide 12 was isolated, indi-
cating that the acetate migration is occurring, albeit to a small
extent (Scheme 3).
Given the appearance of this acetate-migrated isomer, we
were keen to investigate further to see whether other factors
could influence the product ratio of the reaction. When dichlo-
romethane was replaced as solvent by acetonitrile, the product
ratio 7:12 was improved to 34:1, although the reaction was
low-yielding. When THF was employed as solvent, the major
product was another isomeric hydroxy iodide 13, produced via
iodonium ion 14 as an intermediary (Scheme 4).
OH
OH
OH
4
5
6
Conduritols A–F (1–6, respectively)
our recent endeavours in this area of research which have
culminated in a synthesis of the peracetylated derivative of a
meso-conduritol, conduritol D 4.
Our work commenced with the investigation of the addition
of ‘I–OH’ to acetoxycyclohex-2-ene, a reaction which could
produce four compounds in two diastereomeric pairs (Scheme
1). In fact, a single product was obtained from this reaction, in
65% yield. Upon the basis of the values of H NMR chemical
shift and J coupling constants, the structure was tentatively
assigned as 7, an assignment reinforced by conversion of the
product of the reaction to cis-3-acetoxycyclohexene oxide 86
upon reaction with DBU.
The pronounced selectivity of this hydroxyiodination reac-
tion is rationalized by a mechanism involving the less stable7
conformer 9 of the cycloalkene (Scheme 2). Thus, the pre-
ponderance of 7 may be explained if one accepts that iodonium
ion 10, produced by addition of iodenium ion to the face of the
double bond distant from the ring substituent, is the predomin-
ant intermediate in the reaction. Compound 10 then reacts
regiospecifically with water due to the constraint for trans-
1
3
Having performed a brief examination of the solvent effect
upon product distribution in the hydroxyiodination reaction,
we next examined the role of the acyl substituent upon the
† E-Mail: j.b.sweeney@reading.ac.uk
J. Chem. Soc., Perkin Trans. 1, 1998
1039

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OAc
OAc
9
+
OAc
I
+
I
OAc
OAc
OAc
+
I
+
I
14
10
OAc
+
HO
O
H2O
O
OH
rather than
OAc
I
I
I
12
7
11
Scheme 2
reaction, the ratio of non-acyl migrated product 18 to acyl
migrated product 19 was slightly better than in the reaction
with NIS, and the yield was higher.
With this highly selective, previously unreported reaction in
hand, we immediately realized that an iterative hydroxyiodin-
ation procedure would, if similar regio- and stereo-selectivity
were exhibited, allow a conceptually unique synthesis of
tetraacetyl conduritol D, as described diagrammatically in
Scheme 7. Thus, we proposed to acetylate 7 and then eliminate
OAc
OAc
OH
OH
+
OAc
i
I
I
74% yield
4% yield
7
12
Scheme 3 Reagents: i, N-iodosuccinimide, water, CH2Cl2
OAc
OAc
OH
OAc
OAc
OAc
OAc
I
OH
OAc
OAc
OAc
OH
OAc
OAc
i
ii, iii
+
+
i
I
I
OH
7
12
13
Ι
i,ii,iii
20
21
CH2Cl2
74:4:0
CH3CN
Solvent
THF
OAc
7:12:13
34:1:0 17:0:54
OAc
OAc
Scheme 4 Reagents: i, N-iodosuccinimide, water, solvent
reaction. Thus, the acetyl sub-unit of the starting material was
replaced by a pivaloyl group. When this compound was exposed
to the reaction conditions previously referred to, the reaction
trend was repeated (Scheme 5), although yields were lower.
OAc
22
Scheme 7 Reagents: i, N-iodosuccinimide, water, CH2Cl2; ii, acetic
anhydride, pyridine, DMAP; iii, DBU, toluene, reflux
OCOC(CH3)3 OH
OCOC(CH3)3
OCOC(CH3)3
i
I
OH
+
OCOC(CH3)3
HI to give 1,2-diacetoxycyclohex-3-ene 20 which, we hoped,
would undergo a regio- and stereo-selective reaction with NIS
and water in a fashion analogous to the reaction of mono-
acetoxycyclohexene, to give hydroxy iodide 21. Double repetition
of the acetylation–elimination–hydroxy iodination protocol
would then eventually provide the desired cyclitol derivative 22.
To commence the realization of this synthetic concept, com-
pound 20 was prepared from 7 in 65% yield by reaction, firstly,
with acetic anhydride in pyridine and, secondly, DBU in reflux-
ing toluene. When 20 was reacted with NIS in dichloromethane
at room temperature, only two products were obtained; our
desired hydroxy iodide, 1,2-trans-2,3-cis-3,4-cis-3,4-diacetoxy-
2-hydroxy-1-iodocyclohexane, 21, and the undesired regio-
isomer 23 (Scheme 8). Although the reaction was reasonably
stereoselective, in as much as only two diastereoisomers were
produced, unfortunately, the undesired isomer 23 was the major
product of the reaction.
+
I
I
OH
15
16
17
Solvent
CH2
THF
7:0:50
15:16:17 51:4:0
Scheme 5 Reagents: i, N-iodosuccinimide, water, solvent
The same pivalate substrate was also reacted with NBS,
again repeating the trend observed earlier (Scheme 6). In this
OCOC(CH3)3
i
OCOC(CH3)3
OH
OH
OCOC(CH3)3
Br
+
Br
When a trace of acetic acid (1% v/v) was used in the reaction,
the product ratio was shifted in favour of 21, but the regioselec-
tivity of the process was still relatively poor (ca. 5:3 in favour of
21). As before, the use of acetonitrile as solvent proved bene-
83% yield
18
4% yield
19
Scheme 6 Reagents: i, N-bromosuccinimide, water, CH2Cl2
1040
J. Chem. Soc., Perkin Trans. 1, 1998

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OAc
OAc
OAc
OH
OAc
i
Me2N
N
P
N
P
NMe2
+
20
Me2N
P
N
N
P
NMe2
Ι
Me2N
NMe2
Ι
OH
Me2N
NMe2
21
23
NMe2
Yield 21
39%
Yield 23
52%
Solvent
CH2Cl2
27
46%
27%
CH2Cl2–AcOH
CH3CN
60%
6%
OAc
OAc
OAc
Scheme 8 Reagents: i, N-iodosuccinimide, water, solvent; ii, acetic
OAc
OAc
OAc
OAc
OAc
27
anhydride, pyridine, DMAP; iii, DBU, toluene, reflux
+
ficial and the product ratio of the reaction improved drastically
to lie heavily in favour of our desired regio- and diastereo-
isomer 21. To yield 21 and 23, iodonium ions 24a and 24b,
respectively, are implicated in the mechanism (Scheme 9).
O
I
25
26
Table 1
O
Yield (%)
+
I
OAc
AcO
Reaction
time/h
O
21
23
Reaction temp.
Solvent
25
26
22
6
7
6
18
6
Ϫ130 ЊC to rt
Ϫ100 ЊC to rt
Ϫ78 ЊC to rt
Ϫ78 ЊC
Pentane
THF
THF
THF
THF
THF
30
16
16
0
0
0
61
52
82
21
0*
0*
H2O:
I
+
24a
24b
Scheme 9
Ϫ40 ЊC
0 ЊC
Compound 21 was acylated in good yield and then dehydro-
halogenated to give 1,2-cis-2,3-cis-1,2,3-triacetoxycyclohex-4-
ene 25 in moderate overall yield (Scheme 10). The dehydrohalo-
* Decomposition observed.
a few hours when the reaction was performed from Ϫ78 ЊC
to room temperature in THF solvent, but under these con-
ditions the major product was epoxide 26, obtained in 82%
yield (Scheme 11).
Given this rather unexpected observation, we probed more
deeply the effect of reaction temperature upon the dehydro-
halogenation using the phosphazene base. The results of this
investigation are collated in Table 1.
OAc
OAc
OAc
OH
OAc
OAc
i, ii
63% yield
I
25
21
Thus, based on the results summarized in Table 1, it can be
concluded that the formation of our desired cycloalkene 25
using the P4-But base is only feasible at very low temperature,
and that even at these temperatures, the predominant product is
epoxide 26. This epoxide presumably arises via, firstly, deacyla-
tion caused by hydroxide ion generated by reaction of 27 with
trace amounts of water in the reaction mixture and, secondly, 3-
exo-tet ring-closure. Whatever the origin of epoxide 26, it is
clear that DBU provides a much more reliable means of obtain-
ing compound 25.
Scheme 10 Reagents: i, acetic anhydride, pyridine, DMAP; ii, DBU,
toluene, reflux
genation reaction was slightly irksome, in that it proceeded
slowly (although in good yield), taking 96 hours to reach com-
pletion for small-scale reactions (<30 mg substrate) and con-
siderably longer for larger-scale reactions (120 h on 200 mg
scale and 168 hours on > 800 mg scale). Furthermore, in the
longest reaction, an additional product, epoxide 26 began to
appear (Scheme 11).
Armed with sufficient quantities of 25 to bring a synthesis of
tetraacetyl conduritol D in sight, we proceeded to the crucial
final hydroxyiodination step. Thus, 1,2-cis-2,3-cis-1,2,3-
triacetoxycyclohex-4-ene 25 was treated with NIS and water in
dichloromethane at room temperature over a three-day period;
three products were obtained from the reaction, in a combined
yield of 60%, along with a small amount of unreacted starting
material (8%) (Scheme 12). These three (previously unreported)
compounds were identified as 1,2-cis-2,3-cis-3,4-cis-4,5-trans-
1,2,3-triacetoxy-5-iodocyclohexan-4-ol 28, the regioisomeric
1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3-triacetoxy-4-iodocyclo-
hexan-5-ol 29 and 1,2-cis-2,3-cis-3,4-trans-4,5-trans-1,2,3-
triacetoxy-4-iodocyclohexan-5-ol 30. Compounds 28 and 29
were obtained in a yield of 53% and could not be separated by
flash chromatography using a variety of solvents: these com-
pounds were formed in a ratio of approximately 2:3 (as judged
from 1H NMR spectra), while 30 was purified by flash chroma-
tography, after which it was obtained in 7% yield.
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
+
O
I
26
25
P4-But base, THF, –78 °C to rt
7 hours
16%
Reagents DBU, toluene, reflux
168 hours
51%
Time
Yield 25
Yield 26
82%
4%
Scheme 11
In an attempt to obviate these complications, we turned our
attention to a stronger base for dehydrohalogenation and,
accordingly, we next examined the use of Schwesinger’s P4-But
phosphazene base 27, a substance more basic than DBU by
a factor of 1018.8 Using this base, dehydrohalogenation was
much more rapid, with HI elimination being complete within
The conformational effects responsible for this product dis-
tribution are summarized diagrammatically in Scheme 13.
Since the major product of the reaction is 29, in which there has
J. Chem. Soc., Perkin Trans. 1, 1998
1041

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OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
+
Ι
AcO
25
OAc
Ι
31
32
i
i
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
+
+
OAc
OAc
OAc
OAc
I
HO
+
HO
+
I
I
OH
Ι
OAc
28
29
30
OAc
31
22
7% yield
53% yield
12%
59%
26%
(28 : 29 = 2.3)
Scheme 12 Reagents: i, N-iodosuccinimide, water, CH2Cl2
i
90% yield
O
AcO
I
AcO
O
Scheme 14 Reagents: i, DBU, toluene, reflux, 4 h
+
OAc
OAc
O
AcO
O
AcO
I
prepare 31 with greater selectivity as a pure compound, the final
dehydrohalogenation reaction of the iteration sequence would
be a very efficient reaction. The factors affecting the selectivity
of the last hydroxyiodination reaction of the above sequence
are the subject of close scrutiny in our laboratory at present.
+
AcO
I
+
H2O
H2O
H2O
Experimental
Ac
OAc
General
AcO
OAc
OAc
I
AcO HO
AcO
O
HO
Where appropriate, solvents and reagents were purified using
standard procedures. Light petroleum refers to the fraction
with the boiling range 40–60 ЊC.
OAc
OAc
I
I
OH
Melting points were recorded on either a Kofler hot-stage
apparatus and were corrected, or an Electrothermal melting
point apparatus and were uncorrected. Infra-red spectra were
recorded on a Perkin-Elmer 881 spectrophotometer. Mass spec-
tra were recorded on a Fisons Autospec spectrometer. NMR
spectra were recorded on a JEOL GX-270 spectrometer, a
JEOL GX-400 spectrometer or a JEOL Λ-300 spectrometer,
using tetramethylsilane or chloroform as the internal standard.
Chemical shifts in 1H NMR spectra are expressed as ppm down
field from tetramethylsilane, and in 13C NMR relative to the
internal solvent standard. Coupling constants (J) are quoted in
Hz.
Reactions involving chemicals or intermediates sensitive to
air and/or moisture were conducted under a nitrogen or argon
atmosphere in flame- or oven-dried apparatus. Column chro-
matography was performed using Merck Kieselgel 60 or Fluka
Kieselgel 60 silica gel. Preparative plate thin layer chroma-
tography was carried out using Kieselgel 60 PF254ϩ366. Ana-
lytical thin layer chromatography was carried out using either
precoated Merck Kieselgel 60 F254 glass backed plates, or pre-
coated Merck Kieselgel 60 F254 aluminium backed plates and
were visualized under UV at 346 nm and by staining with iodine
and an acidic ammonium molybdate stain [20% w/v ammo-
nium molybdate() tetrahydrate in 10% v/v sulfuric acid].
28
29
30
Scheme 13
been no anchimeric assistance to ring-opening of an iodonium
ion, we presume that the neighbouring group participation
which we proposed to explain our initial observations is of rela-
tively little importance when there is greater steric constraint
present in the substrate, so that the primary concern is to min-
imize axiality (both proper and pseudo). Thus, 28 and 29 are
favoured over 30 simply because they result from a reactive
conformation in which there is a pseudoequatorial rather than a
pseudoaxial allylic acetoxy substituent. Furthermore, the pres-
ence of 28 and 29 in roughly equal amounts implies a high-
energy barrier for interconversion of the iodonium ions leading
to 28 and 29, since intramolecular ring-opening of iodonium
might otherwise be expected to dominate the mechanism. There
is no trace of a product in which acetate has migrated, presum-
ably because such a process would incur a highly-disfavoured
1,3-diaxial interaction.
Although disappointed that 28 and 29 were not separable, we
proceeded with the mixture of regioisomers in the hope that
separation would be possible at a later stage. Thus, 28 and 29
were acylated in high yield, but even as the acetyl derivative the
mixture remained inseparable. Treatment of the mixture of
tetraacetates 31 and 32 with DBU in refluxing toluene induced
a rapid reaction yielding three products, which were isolated by
flash chromatography and proved to be unreacted tetraacetate
31, 1,3-diacetoxybenzene and conduritol D tetraacetate 229 in
12, 59 and 26% yields, respectively (Scheme 14). Although the
yield of 22 from this reaction was disappointing, when now-
pure tetraacetate 31 was re-exposed to the reaction conditions,
a 90% yield of 22 was obtained. Clearly, if we were able to
( )-1,2-cis-2,3-trans-1-Acetoxy-3-iodocyclohexan-2-ol 7 and
( )-1,2-cis-2,3-trans-2-acetoxy-3-iodocyclohexan-1-ol 12
To a solution of 1-acetoxycyclohex-2-ene10 (5.30 g, 37.81
mmol) in dichloromethane (100 ml) was added N-iodo-
succinimide (11.06 g, 49.15 mmol) and distilled water (5 ml).
The mixture was stirred at room temperature (24 h), washed
with saturated aqueous sodium thiosulfate (50 ml) and the
organic layer dried (MgSO4) and concentrated in vacuo. Purifi-
1042
J. Chem. Soc., Perkin Trans. 1, 1998

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cation by flash column chromatography (40% diethyl ether in
light petroleum) yielded hydroxy iodide 7 as a colourless solid
(8.00 g, 74%); Rf 0.37 (50% diethyl ether in light petroleum);
mp 56–58 ЊC (Found: C, 34.07; H, 4.59; I, 44.88. C8H13IO3
requires C, 33.82; H, 4.61; I, 44.67%); νmax(CCl4)/cmϪ1 3446
(OH), 1741 (CO); δH(270 MHz, CDCl3) 1.39–2.45 (6H, m,
3 × CH2), 2.11 (3H, s, CH3), 2.64 (1H, d, J 4.0, OH), 3.81 (1H,
ddd, J 9.2, 4.0, 3.3, CHOH), 4.35 (1H, ddd, J 10.6, 9.5, 4.4,
CHI), 5.26–5.30 (1H, m, CHOAc); δC(67.5 MHz, CDCl3) 170.6
(CO), 75.4 (CH), 71.6 (CH), 36.5 (CH2), 34.1 (CH), 28.3 (CH2),
21.9 (CH2), 21.2 (CH3); m/z (CI) 285 (MHϩ, 1.4%), 267 (12.0),
225 (74.0), 207 (24.0), 157 (10.0), 97 (100.0) [Found 284.9998.
C8H14IO3 (MHϩ) requires 284.9988]; and hydroxy iodide 12 as a
colourless oil (0.43 g, 4%); Rf 0.27 (50% diethyl ether in light
petroleum); νmax(CCl4)/cmϪ1 3614 (OH), 2948, 1753 (CO);
δH(270 MHz, CDCl3) 1.39–2.10 (6H, m, 3 × CH2), 2.16 (3H, s,
CH3), 2.36–2.43 (1H, m, OH), 4.14 (1H, m, CHOH), 4.42 (1H,
ddd, J 10.6, 9.8, 4.4, CHI), 5.01 (1H, dd, J 9.5, 2.6, CHOAc);
δC(67.5 MHz, CDCl3) 170.5 (CO), 78.4 (CH), 68.2 (CH), 34.8
(CH2), 30.3 (CH2), 27.1 (CH), 21.3 (CH3), 21.2 (CH2); m/z (CI)
225 (14.0%), 207 (11.0), 157 (M Ϫ I, 5.0) [Found 157.0867.
C8H13O3 (M Ϫ I)ϩ requires 157.0865].
aqueous layer was saturated with sodium chloride and
extracted with ethyl acetate (2 × 10 ml). The organic layers were
combined, dried (MgSO4) and concentrated in vacuo. Purifica-
tion by flash column chromatography (20% diethyl ether in light
petroleum) yielded: hydroxy iodide 15 as a colourless oil (184
mg, 51%); Rf 0.38 (20% diethyl ether in light petroleum)
(Found: C, 40.31; H, 5.99; I, 38.79. C11H19IO3 requires C, 40.50;
H, 5.87; I, 38.91%); νmax(CCl4)/cmϪ1 3572 (OH), 2954, 1730
(C᎐O); δ (270 MHz, CDCl , 1.23 [9H, s, C(CH ) ], 1.46–1.68
᎐
H
3
3 3
[3H, m, CH(H)CH2], 1.95–2.15 (2H, m, CH2), 2.45–2.47 [1H,
m, CH(H)], 2.46 (1H, d, J 4.4, OH), 3.81 (1H, ddd, J 9.7, 4.2,
3.1, CHOH), 4.29 (1H, ddd, J 11.3, 9.7, 4.3, CHI), 5.22–5.27
[1H, m, CH(OPiv)]; δC(67.5 MHz, CDCl3) 178.0 (CO), 75.9
(CH), 71.3 (CH), 39.1 (C), 37.1 (CH2), 34.4 (CH), 28.6 (CH2),
27.2 (CH3), 22.10 (CH2); m/z (CI) 327 (MHϩ, 57.3%), 309
(48.2), 225 (100.0), 199 (30.6), 131 (14.0) [Found 327.0463.
C11H20IO3 (MHϩ) requires 327.0457]; and hydroxy iodide 16 as a
colourless oil (14 mg, 4%); Rf 0.32 (20% diethyl ether in light
petroleum); νmax(CCl4)/cmϪ1 3617 (OH), 2953, 1737 (C᎐O);
᎐
δH(270 MHz, CDCl3) 1.28 [9H, s, C(CH3)3], 1.66–2.40 (6H, m,
3 × CH2), 4.12–4.17 (1H, m, CHOH), 4.44 (1H, ddd, J 10.3,
9.5, 4.2, CHI), 4.99 [1H, dd, J 9.4, 2.6, CH(OPiv)]; δC(75 MHz,
CDCl3) 177.07 (CO), 77.9 (CH), 68.0 (CH), 39.1 (C), 30.2
(CH2), 27.3 (CH2), 26.8 (CH), 21.3 (CH2), 19.1 (CH2); m/z (CI)
372 (MHϩ, 16.7%), 309 (44.5), 225 (57.3), 207 (62.2), 199 (31.9),
103 (41.0) [Found 327.0442. C11H20IO3 (MHϩ) requires
327.0457].
( )-1,2-cis-2,3-trans-1-Acetoxy-3-iodocyclohexan-2-ol 7 and
( )-1,2-cis-2,3-trans-1-acetoxy-2-iodocyclohexan-3-ol 13
To a solution of 1-acetoxycyclohex-2-ene (110 mg, 0.785 mmol)
in THF (2 ml) was added N-iodosuccinimide (265 mg, 1.178
mmol) and water (5 drops). The mixture was stirred at room
temperature (20 h) and then concentrated in vacuo. The residue
thus obtained was dissolved in dichloromethane (20 ml),
washed with saturated aqueous sodium thiosulfate (10 ml),
dried (MgSO4) and evaporated in vacuo. Purification by flash
column chromatography (50% diethyl ether in light petroleum)
yielded hydroxy iodide 7 (37 mg, 17%), data as before, and
hydroxy iodide 13 as a colourless oil (120 mg, 54%); Rf 0.29 (50%
diethyl ether in light petroleum) (Found: C, 33.73; H, 4.75.
C8H13IO3 requires C, 33.82; H, 4.61; I, 4.75%); νmax(CCl4)/cmϪ1
( )-1,2-cis-2,3-trans-1-(2,2-Dimethylpropionyloxy)-3-iodo-
cyclohexan-2-ol 15 and ( )-1,2-cis-2,3-trans-1-(2,2-dimethyl-
propionyloxy)-2-iodocyclohexan-3-ol 17
To a solution of 1-(2,2-dimethylpropionyloxy)cyclohex-2-ene
(150 mg, 0.823 mmol) in THF (3 ml) was added N-iodo-
succinimide (278 mg, 1.236 mmol) and water (8 drops). The
mixture was stirred at room temperature (23 h), concentrated
in vacuo, the residue dissolved in dichloromethane (10 ml) and
washed with saturated aqueous sodium thiosulfate (7 ml). The
organic layer was dried (MgSO4) and concentrated in vacuo.
Purification by flash column chromatography (40% diethyl
ether in light petroleum) yielded hydroxy iodide 15 (20 mg, 7%),
data as before, and hydroxy iodide 17 as a colourless oil (133 mg,
50%); Rf 0.28 (40% diethyl ether in light petroleum); νmax(CCl4)/
3568 (OH), 2947, 1747 (C᎐O); δ (270 MHz, CDCl ) 1.40–2.20
᎐
H
3
(6H, m, 3 × CH2), 2.13 (3H, s, CH3), 2.25 (1H, d, J 3.1, OH),
4.01 (1H, ddt, J 9.4, 4.2, 2.9, CHOH), 4.23 (1H, dd, J 9.2, 2.9,
CHI), 5.23–5.26 (1H, m, CHOAc); δC(75 MHz, CDCl3) 170.0
(CO), 73.7 (CH), 71.7 (CH), 43.4 (CH), 32.5 (CH2), 29.9 (CH2),
21.2 (CH3), 19.1 (CH2); m/z (EI) 284 (Mϩ, 3.3%), 224 (7.6), 180
(4.7), 157 [(M Ϫ I)ϩ, 4.8].
cmϪ1 3571 (OH), 2954, 1735 (C᎐O); δ (270 MHz, CDCl ) 1.27
᎐
H
3
[9H, s, C(CH3)3], 1.35–1.88 [5H, m, CH2CH2CH(H)], 2.17–2.23
[1H, m, CH(H)], 2.45 (1H, d, J 3.0, OH), 3.96–4.05 (1H, m,
CHOH), 4.23 (1H, dd, J 9.7, 2.9, CHI), 5.23–5.25 [1H, m,
CH(OPiv)]; δC(75 MHz, CDCl3) 177.14 (CO), 73.6 (CH), 71.8
(CH), 43.4 (CH), 39.2 (CH), 32.9 (CH2), 29.9 (CH2), 27.3
(CH3), 19.1 (CH2); m/z (CI) 327 (MHϩ, 4.6%), 309 (39.4), 225
(25.2), 207 (33.9), 199 (6.0) [Found 327.0452. C11H20IO3 (MHϩ)
requires 327.0457].
( )-cis-1-Acetoxy-2,3-epoxycyclohexane 8
To a solution of ( )-1,2-cis-2,3-trans-1-acetoxy-3-iodocyclo-
hexan-2-ol 7 (60 mg, 0.211 mmol) in toluene (1 ml) was added
DBU (0.04 ml, 0.267 mmol). The mixture was stirred at room
temperature (0.5 h), concentrated in vacuo and the residue dis-
solved in dichloromethane (10 ml). The organic layer was
washed with 5% hydrochloric acid (5 ml), saturated aqueous
sodium hydrogen carbonate (5 ml), dried (MgSO4) and concen-
trated in vacuo to yield epoxide 811 as a colourless oil (30 mg,
91%); νmax(CCl4)/cmϪ1 2946, 1741 (C᎐O), 1230; δ (270 MHz,
( )-1,2-cis-2,3-trans-3-Bromo-1-(2,2-dimethylpropionyloxy)-
cyclohexan-2-ol 18 and ( )-1,2-cis-2,3-trans-3-bromo-2-(2,2-
dimethylpropionyloxy)cyclohexan-1-ol 19
᎐
H
CDCl3) 1.24–1.88 (6H, m, 3 × CH2), 2.11 (3H, s, CH3), 3.28–
3.30 [2H, m, CH(OAc)CH(O)CH], 5.10–5.16 [1H, m,
CH(OAc)]; δC(67.5 MHz, CDCl3) 170.9 (CO), 70.9 (CH), 54.2
(CH), 52.8 (CH), 24.4 (CH2), 22.5 (CH2), 21.2 (CH3), 19.4
(CH2); m/z (CI) 157 (MHϩ, 2.8%), 153 (62.9), 97 (100.0) [Found
157.0861. C8H13O3 (MHϩ) requires 157.0865].
To a solution of 1-(2,2-dimethylpropionyloxy)cyclohex-2-ene
(150 mg, 0.823 mmol) in dichloromethane (3 ml) was added
N-bromosuccinimide (220 mg, 1.236 mmol) and water (5
drops). The mixture was stirred at room temperature (25 h) and
then washed with saturated aqueous sodium thiosulfate (5 ml),
dried (MgSO4) and concentrated in vacuo. Purification by flash
column chromatography (50% diethyl ether in light petroleum)
yielded hydroxy bromide 18 as a colourless oil (190 mg, 83%); Rf
0.37 (50% diethyl ether in light petroleum) (Found: C, 47.16; H,
6.79; Br, 28.31. C11H19BrO3 requires C, 47.32; H, 6.86; Br,
( )-1,2-cis-2,3-trans-1-(2,2-Dimethylpropionyloxy)-3-iodocyclo-
hexan-2-ol 15 and ( )-1,2-cis-2,3-trans-2-(2,2-dimethyl-
propionyloxy)-3-iodocyclohexan-1-ol 16
To a solution of 1-(2,2-dimethylpropionyloxy)cyclohex-2-ene
(210 mg, 1.097 mmol) in dichloromethane (5 ml) was added
N-iodosuccinimide (370 mg, 1.646 mmol) and water (8 drops).
The mixture was stirred at room temperature (26 h) and then
washed with saturated aqueous sodium thiosulfate (5 ml). The
28.62%); νmax(CCl4)/cmϪ1 3587 (OH), 2973, 2955, 1735 (C᎐O);
᎐
δH(270 MHz, CDCl3) 1.23 [9H, s, C(CH3)3], 1.60–1.66 (4H, m,
2 × CH2), 1.80–1.97 [1H, m, CH(H)], 2.30–2.39 [1H, m,
CH(H)], 2.38 (1H, d, J 3.7, OH), 3.77 (1H, ddd, J 9.4, 3.3, 3.3,
CHOH), 4.21 (1H, ddd, J 11.0, 9.3, 4.4, CHBr), 5.29–5.31 [1H,
J. Chem. Soc., Perkin Trans. 1, 1998
1043

View Article Online
m, CH(OPiv)]; δC(75 MHz, CDCl3) 177.8 (CO), 75.3 (CH), 71.6
(CH), 55.3 (CH), 39.1 (C), 34.9 (CH2), 28.4 (CH2), 27.2 (CH3),
20.9 (CH2); m/z (CI) 199 [(M Ϫ 79Br)ϩ, 15.0%], 179 (12.0), 131
(33.0), 115 (29.0) [Found 199.1333. C11H19O3 (M Ϫ 79Br)ϩ
requires 199.1334]; and hydroxy bromide 19 as a colourless oil
(10 mg, 4%); Rf 0.30 (50% diethyl ether in light petroleum);
νmax(CCl4)/cmϪ1 3613 (OH), 2955, 1737 (C᎐O); δ (270 MHz,
CDCl3) 1.27 [9H, s, C(CH3)3], 1.62–1.99 [5H, m, CH2CH2-
CH(H)], 2.27–2.37 [1H, m, CH(H)], 4.14–4.19 (1H, m,
CHOH), 4.35 (1H, ddd, J 9.5, 9.5, 4.2, CHBr), 4.99 [1H, dd, J
9.2, 2.8, CH(OPiv)]; δC(75 MHz, CDCl3) 177.7 (CO), 71.8
(CH), 68.5 (CH), 49.2 (CH), 39.1 (C), 34.7 (CH2), 30.1 (CH2),
27.2 (CH3), 20.0 (CH2); m/z (CI) 217 (0.15%), 207 (0.45), 199
[(M Ϫ 79Br)ϩ, 0.95], 149 (1.3), 137 (5.0), 131 (10.0), 123 (6.0).
(50% diethyl ether in light petroleum; foil covered column)
yielded hydroxy iodide 21 as a colourless solid (103 mg, 60%); Rf
0.29 (50% diethyl ether in light petroleum); mp 108–109 ЊC
(diethyl ether–light petroleum) (Found: C, 35.10; H, 4.46.
C10H15IO5 requires C, 35.11; H, 4.42; I, 37.09%); νmax(CCl4)/
cmϪ1 3577 (OH), 2956, 1753 (C᎐O); δ (270 MHz, CDCl ) 1.62–
᎐
H
3
1.68 [1H, m, 1H of CH(OAc)CH2], 1.74–1.89 [1H, m, 1H of
CH(OAc)CH2], 2.01 and 2.14 (6H, 2 × s, 2 × CH3), 2.04 (1H,
m, 1H of CHICH2), 2.43–2.53 (1H, m, 1H of CHICH2), 2.63
(1H, d, J 4.6, OH), 3.82 (1H, ddd, J 10.1, 4.6, 3.1, CHOH), 4.20
(1H, ddd, J 11.7, 10.2, 4.4, CHI), 4.91 [1H, ddd, J 11.4, 4.9, 2.7,
CH(OAc)CH2], 5.51 [1H, ddd, J 2.7, 2.7, 1.5, CH(OAc)-
CH(OAc)CHOH]; δC(67.5 MHz, CDCl3) 170.4 (CO), 170.1
(CO), 74.7 (CH), 70.9 (CH), 70.2 (CH), 32.9 (CH2), 31.2 (CH),
27.0 (CH2), 20.9 (CH3), 20.9 (CH3); m/z (CI) 343 (MHϩ, 2.0%),
342 (1.9), 325 (29.0), 283 (28.0), 223 (37.5), 143 (40.9), 97 (60.0)
[Found 341.9978. C10H15IO5 (Mϩ) requires 341.9964]; and
hydroxy iodide 23 as a colourless oil (10 mg, 6%); Rf 0.19 (50%
diethyl ether in light petroleum); νmax(CCl4)/cmϪ1 3598 (OH),
᎐
H
( )-cis-1,2-Diacetoxycyclohex-3-ene 2012
To a solution of ( )-1,2-cis-2,3-trans-1-acetoxy-3-iodocyclo-
hexan-2-ol 7 (7.39 g, 26.01 mmol) in pyridine (90 ml) was added
acetic anhydride (2.5 ml, 26.42 mmol) and DMAP (50 mg). The
mixture was stirred at room temperature (18 h), diluted with
ethyl acetate (100 ml), washed with saturated aqueous cop-
per() sulfate (2 × 100 ml) and water (80 ml). The organic layer
was separated, dried (MgSO4) and concentrated in vacuo. Puri-
fication by flash column chromatography (40% diethyl ether in
light petroleum) yielded ( )-1,2-cis-2,3-trans-1,2-diacetoxy-3-
iodocyclohexane as a colourless oil (7.18 g, 85%); Rf 0.70 (50%
diethyl ether in light petroleum) (Found: C, 36.85; H, 4.67; I,
38.65. C10H15IO4 requires C, 36.83; H, 4.64; I, 38.91%);
2958, 1752 (C᎐O); δ (270 MHz, CDCl ) 1.38–2.01 (4H, m,
᎐
H
3
2 × CH2), 1.99 and 2.19 (6H, 2 × s, 2 × CH3), 2.51 (1H, d, J 3.1,
OH), 3.96 (1H, dddd, J 10.6, 10.6, 4.8, 3.1, CHOH), 4.16 (1H,
dd, J 10.6, 2.6, CHI), 4.90 [1H, ddd, J 11.5, 5.5, 2.7, CH-
(OAc)CH2], 5.62 [1H, ddd, J 2.6, 2.6, 1.1, CHICH(OAc)]; m/z
(EI) 342 (Mϩ, 2.0%), 264 (2.6), 215 (31.2), 155 (46.1), 113 (46.6),
95 (56.9) [Found 341.9968. C10H15IO5 (Mϩ) requires 341.9964].
Method B. To a solution of ( )-cis-1,2-diacetoxycyclohex-3-
ene 20 (100 mg, 0.505 mmol) in dichloromethane (5 ml) was
added N-iodosuccinimide (147 mg, 0.653 mmol) and acetic acid
(0.06 ml, 1.04 mmol). The mixture was stirred at room temper-
ature (48 h), then washed with saturated aqueous sodium thio-
sulfate (3 ml), water (3 ml), dried (MgSO4) and concentrated in
vacuo. Purification by flash column chromatography (50%
diethyl ether in light petroleum) yielded hydroxy iodide 21 (80
mg, 46%), hydroxy iodide 23 (47 mg, 27%) and unreacted olefin
(10 mg, 8%).
νmax(CCl4)/cmϪ1 1744 (C᎐O); δ (270 MHz, CDCl ) 1.48–2.42
᎐
H
3
(6H, m, 3 × CH2), 2.08 and 2.085 (6H, 2 × s, 2 × CH3), 4.33
(1H, ddd, J 10.0, 4.4, CHI), 5.00 [1H, dd, J 9.9, 2.9, CH(OAc)-
CHI], 5.32–5.36 [1H, m, CH2CH(OAc)]; δC(67.5 MHz, CDCl3)
169.7 (CO), 169.5 (CO), 75.6 (CH), 69.2 (CH), 36.6 (CH2), 28.1
(CH2), 26.1 (CH), 21.7 (CH2), 20.9 (CH3), 20.7 (CH3); m/z (EI)
326 (Mϩ, 0.6%), 199 (57.0), 139 (31.9), 97 (100.0) [Found
199.0979. C10H15O4 (M Ϫ I)ϩ requires 199.0970].
To a solution of ( )-1,2-cis-2,3-trans-1,2-diacetoxy-3-iodo-
cyclohexane (5.53 g, 16.96 mmol) in toluene (40 ml) was added
DBU (5.1 ml, 34.10 mmol). The mixture was heated to reflux
Method C. To a solution of ( )-cis-1,2-diacetoxycyclohex-3-
ene 20 (100 mg, 0.505 mmol) in dichloromethane (5 ml) was
added N-iodosuccinimide (147 mg, 0.653 mmol) and water (3
drops). The mixture was stirred at room temperature (10 days),
then washed with saturated aqueous sodium thiosulfate (3 ml),
dried (MgSO4) and concentrated in vacuo. Purification by flash
column chromatography (50% diethyl ether in light petroleum)
yielded hydroxy iodide 21 (67 mg, 39%) and hydroxy iodide 23
(90 mg, 52%).
1
until the reaction had gone to completion as evinced by H
NMR spectroscopy (ca. 3 days). Toluene was removed in vacuo,
and the residue dissolved in dichloromethane (100 ml), washed
with 5% hydrochloric acid (60 ml), saturated aqueous sodium
hydrogen carbonate (60 ml), dried (MgSO4) and concentrated in
vacuo. Purification by flash column chromatography (30%
diethyl ether in light petroleum) yielded cyclohexene 20 as a
colourless oil (2.45 g, 73%); Rf 0.70 (50% diethyl ether in light
petroleum) (Found: C, 60.32; H, 7.39. C10H14O4 requires C,
60.59; H, 7.12%); νmax(CCl4)/cmϪ1 1743 (C᎐O), 1665 (C᎐C);
( )-1,2-cis-2,3-cis-3,4-trans-1,2,3-Triacetoxy-4-iodocyclohexane
To a solution of ( )-1,2-cis-2,3-cis-3,4-trans-1,2-diacetoxy-4-
iodocyclohexan-3-ol 21 (181 mg, 0.529 mmol) in pyridine (4 ml)
was added acetic anhydride (0.06 ml, 0.634 mmol) and DMAP
(10 mg). The mixture was stirred at room temperature (18 h),
then diluted with ethyl acetate (20 ml), washed with saturated
aqueous copper() sulfate (2 × 15 ml), water (15 ml) and the
organic layer dried (MgSO4) and concentrated in vacuo. Purifi-
cation by flash column chromatography (40–50% diethyl ether
in light petroleum) yielded ( )-1,2-cis-2,3-cis-3,4-trans-1,2,3-
triacetoxy-4-iodocyclohexane as a colourless solid (158 mg,
78%); Rf 0.57 (50% diethyl ether in light petroleum); mp 77–
78 ЊC (Found: C, 37.39; H, 4.83; I, 32.92. C12H17IO6 requires C,
᎐
᎐
δH(270 MHz, CDCl3) 1.75–2.35 (4H, m, 2 × CH2), 2.05 and
2.08 (6H, 2 × s, 2 × CH3), 5.10 [1H, ddd, J 10.4, 3.5, 3.5,
CH(OAc)CH ], 5.44–5.47 [1H, m, CH(OAc)CH᎐CHCH ], 5.68
᎐
2
2
[1H, dddd, J 9.9, 4.4, 2.2, 2.2, CH(OAc)CH᎐CHCH ], 5.99 [1H,
᎐
2
ddd, J 9.7, 3.3, 3.1, CH(OAc)CH᎐CHCH ]; δ (67.5 MHz,
᎐
2
C
CDCl3) 170.5 (CO), 170.4 (CO), 132.9 (CH), 123.3 (CH), 69.4
(CH), 66.5 (CH), 23.9 (CH2), 23.1 (CH2), 21.3 (CH3), 21.1
(CH3); m/z (CI) 199 (MHϩ, 1.8%), 158 (5.8), 139 (34.9), 97
(43.4), 79 (100.0) [Found 139.0760. C8H10O2 (M Ϫ CH3CO2)ϩ
requires 139.0759].
37.52; H, 4.46; I, 33.02%); νmax(CCl4)/cmϪ1 2943, 1755 (C᎐O);
᎐
( )-1,2-cis-2,3-cis-3,4-trans-1,2-Diacetoxy-4-iodocyclohexan-3-
ol 21 and ( )-1,2-cis-2,3-cis-3,4-trans-1,2-diacetoxy-3-iodo-
cyclohexan-4-ol 23
Method A. To a solution of ( )-1,2-cis-1,2-diacetoxy-
cyclohex-3-ene 20 (100 mg, 0.505 mmol) in acetonitrile (5 ml)
was added N-iodosuccinimide (147 mg, 0.653 mmol). The mix-
ture was stirred at room temperature (3 days), concentrated in
vacuo, dissolved in ethyl acetate (20 ml), washed with saturated
aqueous sodium thiosulfate (10 ml), dried (MgSO4) and evap-
orated in vacuo. Purification by flash column chromatography
δH(270 MHz, CDCl3) 1.65–1.95 [2H, m, CH2CH(OAc)], 2.05
(1H, m, 1H of CHICH2), 2.00, 2.07 and 2.15 (9H, 3 × s,
3 × CH3), 2.48–2.57 (1H, m, 1H of CHICH2), 4.17 (1H, ddd,
J 12.3, 11.2, 4.6, CHI), 4.94 [1H, ddd, J 11.4, 5.3, 2.7,
CH2CH(OAc)], 5.00 [1H, dd, J 11.2, 2.7, CHICH(OAc)], 5.44–
5.46 [1H, m, CH(OAc)CH(OAc)CH(OAc)]; δC(67.5 MHz,
CDCl3) 169.8 (CO), 169.7 (CO), 169.3 (CO), 75.0 (CH), 70.0
(CH), 69.5 (CH), 33.6 (CH2), 30.4 (CH), 27.1 (CH2), 23.0
(CH3), 20.8 (CH3), 20.7 (CH3); m/z (EI) 257 [(M Ϫ I)ϩ, 100.0%],
155 (45.8), 113 (44.7).
1044
J. Chem. Soc., Perkin Trans. 1, 1998

View Article Online
( )-1,2-cis-2,3-cis-1,2,3-Triacetoxycyclohex-4-ene 25
70.8 (CH), 68.8 (CH), 66.8 (CH), 37.8 (CH), 32.3 (CH2), 22.6
Method A. To a solution of ( )-1,2-cis-2,3-cis-3,4-trans-
1,2,3-triacetoxy-4-iodocyclohexane (270 mg, 0.703 mmol) in
toluene (20 ml) was added DBU (0.26 ml, 1.739 mmol). The
mixture was heated to reflux (5 days), after which time further
DBU (0.21 ml, 1.404 mmol) was added and reflux continued (24
h). The toluene was removed in vacuo, and the residue dissolved
in dichloromethane (20 ml), dried (MgSO4) and evaporated in
vacuo. Purification by flash column chromatography (30%
diethyl ether in light petroleum) yielded ( )-1,2-cis-2,3-cis-1,2-
diacetoxy-3,4-epoxycyclohexane 26 (5 mg, 3%) and cyclohexene
25 (91 mg, 51%) as a colourless oil; Rf 0.53 (50% diethyl ether in
light petroleum) (Found: C, 56.32; H, 6.19. C12H16O6 requires
(CH3), 20.8 (CH3), 20.7 (CH3); m/z (EI) 273 [(M Ϫ I)ϩ, 6.2%],
153 (1.6), 110 (7.1) [Found 273.0961. C12H17O7 (M Ϫ I)ϩ
requires 273.0974].
( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3,4-Tetraacetoxy-5-
iodocyclohexane 31 and ( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-
1,2,3,5-tetraacetoxy-4-iodocyclohexane 32
To a solution of a 40:60 mixture of ( )-1,2-cis-2,3-cis-3,4-cis-
4,5-trans-1,2,3-triacetoxy-5-iodocyclohexan-4-ol 28 and ( )-
1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3-triacetoxy-4-iodocyclo-
hexan-5-ol 29 (263 mg, 0.657 mmol) in pyridine (5 ml) was
added acetic anhydride (0.07 ml, 0.740 mmol) and DMAP (10
mg). The mixture was stirred at room temperature (18 h),
diluted with ethyl acetate (20 ml), washed with saturated aque-
ous copper() sulfate (2 × 10 ml), water (10 ml), dried (MgSO4)
and concentrated in vacuo. Purification by flash column chro-
matography (60% diethyl ether in light petroleum) yielded
tetraacetates 31 and 32 as a mixture and a colourless solid (279
mg, 93%); Rf 0.24 (50% diethyl ether in light petroleum); mp
115–119 ЊC (Found: C, 38.31; H, 4.52; I, 29.01. C14H19IO8
requires C, 38.02; H, 4.33; I, 28.70%); νmax(CCl4)/cmϪ1 1760
C, 56.24; H, 6.25%); νmax(CCl4)/cmϪ1 2932, 1752 (C᎐O), 1666
᎐
(C᎐C); δ (270 MHz, CDCl ) 2.04, 2.05 and 2.13 (9H, 3 × s,
᎐
H
3
3 × CH3), 2.39–2.44 (2H, m, CH2), 5.13 [1H, ddd, J 8.6, 7.0, 1.8,
CH2CH(OAc)], 5.51–5.60 [3H, m, CH(OAc)CH(OAc)-
CH᎐CH], 5.83–5.90 (1H, m, CH᎐CHCH ); δ (67.5 MHz,
᎐
᎐
2
C
CDCl3) 170.5 (CO), 170.2 (CO), 170.1 (CO), 127.5 (CH), 124.2
(CH), 68.2 (CH), 68.0 (CH), 67.9 (CH), 27.1 (CH2), 21.0 (CH3),
20.9 (2 × CH3); m/z (CI) 257 (MHϩ, 8.9%), 155 (41.0), 136
(14.6), 94 (100.0) (Found 257.1029. C12H17O6 requires
257.1025).
(C᎐O); δ (270 MHz, CDCl ) 1.78–1.89 (1H, m, H of CH2),
᎐
H
3
eq
Method B. To a solution of ( )-1,2-cis-2,3-cis-3,4-trans-1,2,3-
triacetoxy-4-iodocyclohexane (55 mg, 0.143 mmol) in THF (2
ml) at Ϫ78 ЊC was added dropwise a solution of phosphazene
base P4-But 27 (0.14 ml of a 1  solution in hexane, 0.143 mmol)
in THF (1 ml). The mixture was stirred at Ϫ78 ЊC (1.5 h) then at
room temperature (2 h). Solvent was then removed in vacuo and
diethyl ether (5 ml) added. The resulting precipitate was filtered
and washed with diethyl ether (5 × 5 ml). The combined fil-
trates were dried (MgSO4) and concentrated in vacuo. Purifica-
tion by flash column chromatography (50–70% diethyl ether in
light petroleum) yielded cyclohexene 25 (6 mg, 16%) and ( )-
1,2-cis-2,3-cis-1,2-diacetoxy-3,4-epoxycyclohexane 26 (25 mg,
82%).
2.08, 2.09, 2.12 and 2.15 (12H, 4 × s, 4 × CH3), 2.43–2.53 (1H,
m, Hax of CH2), 4.32 (0.7H, dd, J 7.9, 4.0, CHI of 31), 4.44
(0.3H, ddd, J 10.6, 10.1, 4.0, CHI of 32), 5.20–5.49 [4H, m,
4 × CH(OAc)]; m/z (EI) 323 (0.8%), 315 [(M Ϫ I)ϩ, 43.3], 213
(28.1), 153 (63.8), 111 (82.3) [Found 315.1090. C14H19O8
(M Ϫ I)ϩ requires 315.1080].
( )-1,2-cis-2,3-cis-3,4-cis-1,2,3,4-Tetraacetoxycyclohex-5-ene 22
(conduritol D tetraacetate)8
To a solution of a 40:60 mixture of 31 and 32 (150 mg, 0.339
mmol) in toluene (10 ml) was added DBU (0.10 ml, 0.669
mmol). The mixture was heated to reflux (4 h), then cooled and
dried (MgSO4) and concentrated in vacuo. Purification by flash
column chromatography (60% diethyl ether in petroleum ether)
yielded the following, in order of elution.
( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3-Triacetoxy-5-
iodocyclohexan-4-ol 28, ( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-
1,2,3-triacetoxy-4-iodocyclohexan-5-ol 29 and ( )-1,2-cis-2,3-
cis-3,4-trans-4,5-trans-1,2,3-triacetoxy-4-iodocyclohexan-5-ol
30
To a solution of ( )-1,2-cis-2,3-cis-1,2,3-triacetoxycyclohex-4-
ene 25 (360 mg, 1.405 mmol) in dichloromethane (10 ml) was
added N-iodosuccinimide (632 mg, 2.810 mmol) and water (10
drops). The mixture was stirred at room temperature (2 days),
washed with saturated aqueous sodium thiosulfate (5 ml), dried
(MgSO4) and concentrated in vacuo. Purification by flash col-
umn chromatography (50–70% diethyl ether in light petroleum;
foil covered column) yielded cyclohexene 25 (30 mg, 8%) and
hydroxy iodides 28 and 29 as an inseparable mixture and a col-
ourless solid (296 mg, 53%); Rf 0.29 (75% diethyl ether in light
petroleum); mp 141–143 ЊC; νmax(CCl4)/cmϪ1 3582 (OH), 2981,
1,3-Diacetoxybenzene. Colourless oil (39 mg, 59%); Rf 0.78
(50% diethyl ether in light petroleum); νmax(CCl4)/cmϪ1 1780
(C᎐O), 1569, 1439, 1369; δ (270 MHz, CDCl ) 2.28 (6H, 2 × s,
᎐
H
3
2 × CH3), 7.15–7.26 (4H, m, aromatic H); m/z (CI) 195 (MHϩ,
5.1%), 153 (100.0) [Found 195.0658. C10H11O4. (MHϩ) requires
195.0657].
( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3,4-Tetraacetoxy-5-
iodocyclohexane 31. Unreacted, as a colourless solid (18 mg,
12%); Rf 0.51 (50% diethyl ether in light petroleum); mp 133–
134 ЊC (corrected); νmax(CCl4)/cmϪ1 2931, 1754 (C᎐O), 1220;
᎐
δH(270 MHz, CDCl3) 2.02, 2.088, 2.094 and 2.12 (12H, 4 × s,
4 × CH3), 2.25–2.31 (1H, m, 1H of CH2), 2.60–2.66 (1H, m, 1H
of CH2), 4.44 (1H, ddd, J 10.6, 10.1, 4.0, CHI), 5.06–5.12 [2H,
m, CHICH(OAc) and CH2CH(OAc)CH(OAc)], 5.19–5.23 [1H,
m, CH2CH(OAc)], 5.51 [1H, ddd, J 3.3, 2.9, 0.9, CHICH-
(OAc)CH(OAc)]; δC(75 MHz, CDCl3) 169.8 (CO), 169.7 (CO),
169.6 (CO), 169.3 (CO), 73.6 (CH), 68.5 (2 × CH), 68.4 (CH),
36.1 (CH), 20.9 (CH3), 20.7 (2 × CH3), 20.6 (CH3), 18.2 (CH2);
m/z (CI) 383 (M Ϫ OAc, 100.0%), 341 (20.0), 315 (M Ϫ I, 16.0),
281 (18.0), 221 (28.0) [Found 315.1069. C14H19O8. (M Ϫ I)ϩ
requires 315.1080].
1755 (C᎐O); δ (270 MHz, CDCl ) 1.71–1.81 (1H, m, H of
᎐
H
3
eq
CH2), 2.03, 2.09 and 2.16 (9H, 3 × s, 3 × CH3), 2.36 (1H, d, J
2.9, OH), 2.39–2.48 (1H, m, Hax of CH2), 4.23–4.35 (2H, m,
CHOH and CHI), 5.14 [1H, m, CH(OAc)CH(OAc)CH(OAc)],
5.41–5.45 [1H, m, CH2CH(OAc)], 5.49–5.51 [1H, m,
CH2CH(OAc)CH(OAc)CH(OAc)]; m/z (EI) 400 (Mϩ, 1.2%),
340 (1.2), 273 (24.7), 213 (80.7), 110 (100.0) (Found 400.0048.
C12H17IO7 requires 400.0019). Also isolated was hydroxy iodide
30 as a colourless oil (37 mg, 7%); Rf 0.40 (75% diethyl ether in
light petroleum); νmax(CCl4)/cmϪ1 3582 (OH), 2955, 1760
Conduritol D tetraacetate 22.8 Colourless solid (18 mg, 26%);
Rf 0.20 (50% diethyl ether in light petroleum); mp 103–104 ЊC
(lit.,8 103–103.5 ЊC); νmax(CCl4)/cmϪ1 1752 (C᎐O), 1368, 1264,
᎐
1227; δH(270 MHz, CDCl3) 2.083 and 2.088 (12H, 2 × s,
4 × CH3), 5.37 [2H, d, J 5.1, CH(OAc)CH(OAc)CH(OAc)-
CH(OAc)], 5.58 [2H, dd, J 5.1, 1.5, CH(OAc)CH(OAc)-
(C᎐O); δ (270 MHz, CDCl ) 1.87–2.01 (1H, m, H of CH2),
᎐
H
3
eq
2.02, 2.09 and 2.16 (9H, 3 × s, 3 × CH3), 2.18–2.23 (1H, m, Hax
of CH2), 2.70 (1H, d, J 2.4, OH), 3.86–3.97 (1H, m, CHOH),
4.18 (1H, dd, 11.5, 10.3, CHI), 4.98 [1H, ddd, J 12.6, 4.6, 2.7,
CH2CH(OAc)], 5.08 [1H, dd, J 11.7, 2.7, CH(OAc)CHI], 5.40
[1H, ddd, J 2.6, 2.6, 1.5, CH2CH(OAc)CH(OAc)]; δC(67.5
MHz, CDCl3) 169.8 (CO), 169.7 (CO), 169.3 (CO), 72.1 (CH),
CH(OAc)CH(OAc)], 5.89 (2H, d, J 1.3, CH᎐CH); δ (75 MHz,
᎐
C
CDCl3) 170.0 (2 × CO), 127.5 (CH), 66.9 (CH), 65.7 (CH),
20.80 (CH3), 20.7 (CH3); m/z (CI) 315 (MHϩ, 2.2%), 255
(76.1), 153 (89.9), 111 (100.0) [Found 255.0866. C12H15O6.
(M Ϫ OAc)ϩ requires 255.0869].
J. Chem. Soc., Perkin Trans. 1, 1998
1045

View Article Online
Chem. Rev., 1995, 140, 189; D. J. Berrisford, C. Bolm, K. B.
( )-1,2-cis-2,3-cis-3,4-cis-1,2,3,4-Tetraacetoxycyclohex-5-ene 22
(conduritol D tetraacetate)8
Sharpless, Angew. Chem., Int. Ed. Engl., 1995, 34, 1059.
3 For pertinent reviews, see: K. B. Sharpless, Tetrahedron, 1994,
50, 4235; H. C. Kolb, M. S. Vannieuwenhze, K. B. Sharpless, Chem.
Rev., 1994, 94, 2483; B. B. Lohray, Tetrahedron: Asymmetry, 1992, 3,
1317.
To a solution of ( )-1,2-cis-2,3-cis-3,4-cis-4,5-trans-1,2,3,4-
tetraacetoxy-5-iodocyclohexane 31 (15 mg, 0.034 mmol) in
toluene (1 ml) was added DBU (0.01 ml, 0.067 mmol). The
mixture was heated to reflux (4 h), then cooled and dried
(MgSO4) and concentrated in vacuo. Purification of the crude
product by flash column chromatography (60% diethyl ether in
light petroleum) yielded conduritol D tetraacetate 228 (9.7 mg,
90%). Spectral properties were as reported previously.
4 M. Balci, Y. Sütbeyaz and H. Seçan, Tetrahedron, 1990, 46, 3715.
5 Preliminary communication: J. R. Knight and J. B. Sweeney,
Tetrahedron Lett., 1996, 37, 6579.
6 A. J. Pearson and S.-Y. Hsu, J. Org. Chem., 1986, 51, 2505.
7 A. Ouédraogo, M. T. P. Viet, J. K. Saunders, J. Lessard, Can. J.
Chem., 1987, 65, 1761.
8 R. Schwesinger and H. Schlemper, Angew. Chem., Int. Ed. Engl.,
1987, 26, 1167.
9 R. Criegee and P. Becher, Chem. Ber., 1957, 90, 2516.
10 A. Kötz and K. Richter, J. Prakt. Chem., 1925, 111, 373.
11 P. Chamberlain, M. C. Roberts and G. H. Whitham, J. Chem. Soc.
(B), 1970, 1374.
Acknowledgements
We acknowledge the financial support of the Nuffield Founda-
tion, the EPSRC (quota awards to A. F. H. and J. R. K.) and
Zeneca (award from the Strategic Research Fund to J. B. S.).
12 I. V. Machinskaya and V. A. Barkhash, Zh. Obshch. Khim., 1956,
26, 848.
References
1 For Part 2, see ref. 5.
Paper 7/09056K
Received 17th December 1997
Accepted 19th December 1997
2 For pertinent reviews, see: L. A. Campbell and T. Kodadek, J. Mol.
Cat., A, 1996, 113, 293; S. Pedragosamoreau, A. Archelas and
R. Furstoss, Bull. Soc. Chim. Fr., 1995, 132, 769; T. Katsuki, Coord.
1046
J. Chem. Soc., Perkin Trans. 1, 1998