The formation of 7-oxabicyclo[4.2.0]octanes and 6-oxabicyclo[3.2.1]octanes via cationic iodocyclization

Article abstract of DOI:10.1081/SCC-120021045

Several 2-cyclohexenemethanol derivatives were subjected to cationic iodocyclization. Two product types were formed: the fused 7-oxabicyclo[4.2.0]octane, and the bridged 6-oxabicyclo[3.2.1]octane. The degree of substitution in the alkenol determined the ratio of the products, with aromatic substituents leading to the formation of the fused system as the major product.

Full text of DOI:10.1081/SCC-120021045

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The Formation of 7-Oxabicyclo[4.2.0]octanes and 6-
Oxabicyclo[3.2.1]octanes via Cationic Iodocyclization
Christopher J. Nichols a
a Department of Chemistry , California State University , Chico, California, USA
Published online: 17 Aug 2006.
To cite this article: Christopher J. Nichols (2003) The Formation of 7-Oxabicyclo[4.2.0]octanes and 6-
Oxabicyclo[3.2.1]octanes via Cationic Iodocyclization, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:12, 2167-2179, DOI: 10.1081/SCC-120021045
To link to this article: http://dx.doi.org/10.1081/SCC-120021045
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 12, pp. 2167–2179, 2003
The Formation of 7-Oxabicyclo[4.2.0]octanes and
6-Oxabicyclo[3.2.1]octanes via Cationic
Iodocyclization
*
Christopher J. Nichols
Department of Chemistry, California State University,
Chico, California, USA
ABSTRACT
Several 2-cyclohexenemethanol derivatives were subjected to cationic
iodocyclization. Two product types were formed: the fused 7-oxa-
bicyclo[4.2.0]octane, and the bridged 6-oxabicyclo[3.2.1]octane. The
degree of substitution in the alkenol determined the ratio of the
products, with aromatic substituents leading to the formation of
the fused system as the major product.
Key Words: Oxabicyclooctane; Etherification; Oxetane.
*Correspondence: Christopher J. Nichols, Assistant Professor of Chemistry,
Department of Chemistry, California State University, 400 W. 1st St., Chico,
CA, USA 95929-0210; Fax: 1-530-898-5234; E-mail: cjnichols@csuchico.edu.
2167
DOI: 10.1081/SCC-120021045
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2168
Nichols
INTRODUCTION
The use of iodonium species to convert an alkenol to a cyclic
iodoether has been extensively studied.[1] Schauble and others have
shown that when homoallylic alcohols are treated with a source of Iþ
(either I(coll)2ClO4 or I2/NaHCO3), the major product is generally the
less strained 5-membered tetrahydrofuran ring, such as the compound 2
(Sch. 1).[2] This 5-endo cyclization is particularly favored in the case of
a 1,2-disubstituted alkene. An oxetane (compounds 4 or 6, formed via
a 4-exo cyclization) can only be obtained if either the proximal carbon is
substituted (as in the alcohol 3), or if extra alkyl groups are added to the
system (as in the dimethyl alcohol 5). This so-called geminal dialkyl
effect[3] has demonstrated the ability to greatly affect the course of a
cyclization, both in terms of relative reaction rates and regiochemistry.[4]
In a continuing investigation of the synthesis of oxetanes through iodo-
cyclization,[5] this research focused on the formation of bicyclic molecules
by treating derivatives of 2-cyclohexenemethanol 7a with a source of Iþ,
namely iodonium bis-sym-collidine perchlorate.[6]
RESULTS AND DISCUSSION
2-Cyclohexenemethanol 7a itself was made by literature methods in
two steps from benzoic acid.[7] The other homoallylic alcohols 7b–g were
made by treating 3-bromocyclohexene 8 with powdered metallic tin and
the appropriate aldehyde (Sch. 2). The use of benzaldehyde had been
found to lead to the formation of only one diastereomer of the alcohol
7f, but with aliphatic aldehydes (acetaldehyde and propionaldehyde) the
Scheme 1.

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Cationic Iodocyclization
2169
Scheme 2. Reagents and Conditions: (a) Sn, MeCHO or EtCHO, THF/NH4Cl
(aq.) 6 :1, 0ꢀC to rt, 2 d; (b) i. TPAP/NMO, CH2Cl2, 4 h, ii. MeLi or EtMgBr,
THF, À78ꢀC to rt, 20 h; (c) Sn, PhCHO, THF/NH4Cl (aq.) 6 :1, 65ꢀC, 20 h;
(d) PCC, CH2Cl2; (e) PhBr, Mg, ether, 0ꢀC t o rt , 20 h.
diastereoselectivity of the reaction which forms the products 7b and 7c is
less than 2:1.[8] Attempted direct formation of the geminal dialkyl or
diaryl derivatives 7d, 7e, and 7g through the addition of symmetrical
ketones to the stannylated bromide was unsuccessful. However, oxida-
tion of the monoalkylated species with either pyridinium chlorochromate
(PCC) or tetrapropylammonium perruthenate (TPAP) and N-methyl-
morpholine N-oxide,[9] followed by immediate treatment with an
appropriate alkyl anion (PhMgBr, CH3Li or EtMgBr) furnished the
disubstituted alcohols 7d, 7e, and 7g in a modestyield.
The first alkenol studied, the benzaldehyde derivative 7f, yielded two
different products upon treatment with iodonium bis-sym-collidine per-
chlorate (Sch. 3). These were identified as the 7-oxabicyclo[4.2.0]octane
10f and the 6-oxabicyclo[3.2.1]octane 11f, formed in 61% total yield and
in a 54:46 ratio. These products were separated by column chromatogra-
phy, and COSY and NOESY studies established the identity and relative
stereochemistry of the two products. This analysis also confirmed the
stereochemistry of the alcohol 7f, which had up to this point been
assigned based on literature reports.[8]
When other cyclohexenemethanols were treated in the same
fashion the differences in product ratios were striking (Table 1). The

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Scheme 3.
Table 1.
Starting
material
Ration of
10:11
Time for 90%
loss of 7
R1, R2
Yield (%)
7a
7d
7e
7f
H, H
Me, Me
Et, Et
0:100
30:70
26:74
54:46
62:38
40b
60c
81c
61c
68b
10 min
5 h
1 h
Ph, H
Ph, Ph
15 min
—
7g
aTypical procedure is as follows: To a solution of Ag(coll)2ClO4 (5 equiv.) in
CH2Cl2 is added I2 (5 equiv.) and the solution is stirred until the I2 has completely
reacted (typically 20–40 min). Then a CH2Cl2 solution of alkenol is added, and
the mixture is stirred for 18 h. Filtration of the AgI and washing of the organic
layer with aq. sodium thiosulfate, 1 M aq. HCl, and aq. sodium bicarbonate is
followed by removal of the solvent in vacuo and column chromatography to
isolate the products.
bIsolated yield.
cYield and productraito by NMR.
unsubstituted compound 7a (R1 ¼ R2 ¼ H) gave exclusively the bridged
bicyclic ether 11a. Iodocyclization in the presence of two geminal methyl
or ethyl groups (in 7d and 7e) still resulted in the bridged ethers 11d and
11e being predominant but now small amounts of the oxetanes 10d and
10e were also isolated. Having aromatic rings in the alkenol changed the
identity of the major product: for both the monophenyl (7f ) and diphenyl

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Cationic Iodocyclization
2171
(7g) alcohols the fused compounds 10f and 10g were the major products.
This is a similar effect to prior studies[2] as the addition of geminal dialkyl
groups led to a higher proportion of the oxetane product. In 7f, one
benzene ring causes more of the oxetane to be formed than do two
methyl or ethyl groups—this can be explained by unfavorable steric
interactions in the bicyclic product molecule 11f, where the large aro-
matic ring is in an endo position.
Kinetic studies using 1H NMR were also carried outat21 ꢀC on
the four alcohols 7a, 7d, 7e, and 7f. They were each treated with four
equivalents of I(coll)2ClO4 (to ensure complete reaction) in CDCl3 and
the formation of products followed by the appearance of characteristic
peaks (typically of those hydrogen atoms on carbons a to the oxygen
1
atoms) in the H NMR. The more substituents the alcohols possessed,
the more slowly the cyclizations occurred, which is in contrast to a
typical geminal dialkyl effect in which such substituents enhance the
rates of cyclization.[3] This is likely a steric effect, with the reaction
slowing as the nucleophilic oxygen is hindered by the extra alkyl
groups. The rates of reaction and relative ratios of products are
both governed by steric interactions but in different senses: the tertiary
alcohols slow the reaction down, but the presence of only one alkyl
group in position R2 (see Table 1) is enough to decrease the amount of
bridged compound formed.
EXPERIMENTAL
General
Unless otherwise stated, starting materials were obtained from com-
mercial suppliers (Aldrich Chemical, ACROS, Fisher Scientific) and used
without purification. THF was distilled over Na/benzophenone, and
CH2Cl2 was distilled over CaH2. NMR spectra were recorded on a
Varian Mercury VX300, exceptfor compounds 10f and 11f, which
were sent to the University of California, Santa Barbara for analysis
on their Varian UNITY-INOVA 500 MHz spectrometer. FT-IR spectra
were recorded on a Mattson Galaxy Series 3000. 2-Cyclohexene-
methanol 7a was synthesized in two steps from benzoic acid according
to the method of Walton.[7] Silver (I) bis-collidine perchlorate was
synthesized from silver nitrate, collidine, and sodium perchlorate.[8]
(1R*,10RS*)-1-Cyclohex-2-enylethanol (7b). To
a
solution of
3-bromocyclohexene (1.20 mL, 10.4 mmol) in THF (17 mL) and satu-
rated aqueous ammonium chloride (3 mL) cooled to 0ꢀC was added

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2172
Nichols
acetaldehyde (3.5 mL, 63 mmol) and powdered tin (1.17 g, 9.86 mmol),
and the solution was stirred for 44 h, allowing to warm to room tempera-
ture. Brine (10 mL) was added, and the mixture was extracted with ether
(3ꢁ: 20, 20, 50 mL). The combined extracts were dried over MgSO4 and
the solvent removed in vacuo. Column chromatography (SiO2, 15% ethyl
acetate/85% hexane) afforded 535.9 mg of 7b (4.25 mmol, 43%) as a
colorless oil, as a 2:1 mixture of two diastereomers.
1H NMR (300 MHz, CDCl3) ꢀ: mixture of 2 diastereomers, 5.5–5.9
(both isomers, 2H, m), 3.77 (major isomer, 1H, qd, J ¼ 6.3, 5.1 Hz), 3.67
(minor isomer, 1H, quin, J ¼ 6.2 Hz), 1.30–2.10 (both isomers, 8H, m),
1.22 (minor isomer, 3H, d, J ¼ 6.3 Hz), 1.20 (major isomer, 3H, d,
J ¼ 6.3 Hz). 13C NMR (75 MHz, CDCl3) ꢀ: major isomer: 130.5, 128.5,
70.9, 42.99, 25.5, 23.5, 21.5, 20.2; minor isomer: 129.9, 127.2, 71.7, 42.97,
25.7, 25.5, 21.9, 21.2; IR (neat) 3360 (br, s), 3024 (s), 2934 (br, s), 1448 (s),
1374 (s), 1086 (s) cmÀ1
.
(1R*,10RS*)-1-Cyclohex-2-enyl-propan-1-ol (7c). To a slurry of
powdered tin (1.24 g, 10.4 mmol) in THF (17 mL) and saturated aq.
NH4Cl (4 mL), cooled to 0ꢀC, was added 3-bromocyclohexene (1.11 mL,
9.6 mmol), followed by propionaldehyde (4.3 mL, 60 mmol). The solution
was stirred for 22 h, allowing to warm to room temperature, and the
THF was removed by rotary evaporation. Brine (20 mL) was added,
and the mixture was extracted with ether (3ꢁ: 40, 40, 100 mL). The
combined extracts were dried over MgSO4 and the solvent removed
in vacuo. Column chromatography (SiO2, 10% ethyl acetate/90%
hexane) afforded 0.52 g of 7c (3.71 mmol, 39%) as a 72:28 mixture of
two diastereomers.
1H NMR (300 MHz, CDCl3) ꢀ: mixture of two diastereomers, 5.86
(both isomers, 1H, m), 5.70 (minor isomer, 1H, dq, J ¼ 10.1, 2.5 Hz), 5.54
(major isomer, 1H, dqd, J ¼ 10.1, 2.2, 0.8 Hz), 3.49 (major isomer, 1H, dt,
J ¼ 7.5, 5.0 Hz), 3.36 (minor isomer, 1H, dt, J ¼ 8.4, 4.4 Hz), 2.22 (both
isomers, 1H, m), 1.98 (both isomers, 2H, m), 1.74 (both isomers, 2H, m),
1.50 (both isomers, 5H, m), 0.96 (both isomers, 3H, t, J ¼ 7.5 Hz);
13C NMR (75 MHz, CDCl3) ꢀ: major isomer: 130.7, 129.1, 76.2, 41.0,
26.8, 25.46, 22.8, 21.6, 10.7; minor isomer: 130.3, 127.1, 76.8, 41.1,
27.7, 26.2, 25.51, 22.0, 10.6; IR (neat) 3358 (br, s), 3023 (m), 2931 (s),
1456 (m), 1113 (m), 966 (s), 725 (m) cmÀ1
.
2-Cyclohex-2-enylpropan-2-ol (7d). To a solution of 7b (66.0 mg,
0.523 mmol) in CH2Cl2 (4 mL) was added solid N-methylmorpholine
N-oxide (195 mg, 1.66 mmol) and powdered molecular sieves (ca.
100 mg, 4A). Tetrapropylammonium perruthenate (39 mg, 0.111 mmol)
was then added, and the mixture stirred for 4 h. The solution was filtered
through Celite, and the solvent removed in vacuo. THF (5 mL) was

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Cationic Iodocyclization
2173
added, and the solution was cooled to À78ꢀC. Methyllithium (1.4 M,
1.5 mL, 2.1 mmol) was added slowly, and the solution was stirred for
16 h, allowing to warm to room temperature. Ether and water were
added, and the layers were separated. The aqueous layer was extracted
once more with ether, and the organic layers were combined, washed with
brine, dried over MgSO4, and the solvent removed in vacuo. Column
chromatography (SiO2, 10% ethyl acetate/90% hexane) afforded
27.3 mg of 7d (0.195 mmol, 37%) as a colorless oil.
1H NMR (300 MHz, CDCl3) ꢀ: 5.84 (1H, dq, J ¼ 10.6, 3.1 Hz), 5.74
(1H, dquin, J ¼ 10.5, 1.5 Hz), 2.15 (1H, m), 1.98 (2H, m), 1.82 (2H, m),
1.52 (2H, m), 1.32 (1H, td, J ¼ 11.2, 2.2 Hz), 1.21 (3H, s), 1.17 (3H, s);
13C NMR (75 MHz, CDCl3) ꢀ: 129.9, 127.7, 73.1, 47.1, 28.1, 26.4,
25.4, 24.7, 22.5; IR (neat): 3377 (br, s), 2973 (m), 2930 (m), 1147 (s),
1124 (s) cmÀ1
.
3-Cyclohex-2-enylpentan-3-ol (7e). To a solution of 7c (170.5 mg,
1.22 mmol) in CH2Cl2 (3 mL) was added solid N-methylmorpholine
N-oxide (210 mg, 1.79 mmol) and powdered molecular sieves (ca.
100 mg, 4A). Tetrapropylammonium perruthenate (24 mg, 0.068 mmol)
was then added, and the mixture stirred for 3 h. The solution was filtered
through Celite, and the solvent removed in vacuo. THF (5 mL) was
added, and the solution was cooled to À78ꢀC. Ethyl magnesium bromide
(1.0 M, 2.5 mL, 2.5 mmol) was added slowly, and the solution was stirred
for 16 h, allowing to warm to room temperature. Water (2 mL) and HCl
(1 M, 2.5 mL) were added, followed by ether (25 mL), and the layers were
separated. The aqueous layer was extracted once more with ether, the
organic layers were combined and washed with brine, dried over MgSO4,
and the solvent removed in vacuo. Column chromatography (SiO2, 8%
ethyl acetate/92% hexane) afforded 98.8 mg of 7e (0.587 mmol, 48%) as
a colorless oil.
1H NMR (300 MHz, CDCl3) ꢀ: 5.84 (1H, ddtd, J ¼ 10.4, 4.7, 2.4,
0.8 Hz), 5.71 (1H, ddq, J ¼ 10.4, 2.2, 1.6 Hz), 2.32 (1H, m), 1.96 (2H,
m), 1.77 (2H, m), 1.30–1.60 (7H, m), 0.87 (6H, 2 overlapping t,
J1 ¼ 7.4 Hz, J2 ¼ 7.6 Hz); 13C NMR (75 MHz, CDCl3) ꢀ: 130.2, 127.5,
76.1, 42.3, 28.9, 27.9, 25.4, 23.8, 22.6, 7.9, 7.8; IR (neat): 3476 (br, s),
3028 (m), 2966 (s), 2937 (s), 2881 (s), 1136 (s), 949 (s) cmÀ1
.
(1R*,10S*)-Cyclohex-2-enylphenylmethanol (7f ). To a solution of
3-bromocyclohexene (5.36 g, 33.3 mmol) in THF (35 mL) and saturated
aqueous ammonium chloride (6 mL) was added benzaldehyde (2.03 mL,
20.0 mmol) and powdered tin (3.57 g, 30.1 mmol). The solution was
heated to 65ꢀC for 20 h, and the THF was removed by rotary evapora-
tion. Brine (40 mL) was added, and the mixture was extracted with ether
(3ꢁ: 75, 75, 200 mL). The combined extracts were dried over MgSO4 and

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2174
Nichols
the solvent removed in vacuo. Column chromatography (SiO2, 8% ethyl
acetate/92% hexane) afforded 3.231 g of 7f (17.2 mmol, 86%) as a
colorless oil, and as a single diastereomer.
1H NMR (300 MHz, CDCl3) ꢀ: 7.25–7.36 (5H, m), 5.83 (1H, dq,
J ¼ 10.2, 3.2 Hz), 5.40 (1H, dq, J ¼ 10.2, 1.4 Hz), 4.60 (1H, d,
J ¼ 6.6 Hz), 2.52 (1H, m), 2.00 (2H, m), 1.85 (1H, br s), 1.75 (2H, m),
1.54 (2H, m); 13C NMR (75 MHz, CDCl3) ꢀ: 143.1, 130.7, 128.5, 128.2,
127.6, 126.7, 77.6, 43.2, 25.5, 24.1, 21.3; IR (neat): 3420 (br, s), 1739 (m),
1726 (m), 1459 (m), 1377 (m), 1240 (s), 1060 (m) cmÀ1
.
2-Cyclohexenyl phenyl ketone (9). To a solution of pyridinium chloro-
chromate (1.71 g, 7.93 mmol) in CH2Cl2 (10 mL) was added solid sodium
acetate (130 mg, 1.71 mmol) followed by a solution of 7f (995 mg,
5.28 mmol) in CH2Cl2 (5 mL), and the mixture was stirred for 2 h. The
mixture was diluted with ether, filtered through Celite, and the solvent
was removed in vacuo. Column chromatography (SiO2, 2% ethyl
acetate/98% hexane) afforded 467.0 mg of 9 (2.51 mmol, 47%) as a color-
less oil.
1H NMR (300 MHz, CDCl3) ꢀ: 7.96 (2H, dd, J ¼ 8.4, 1.3 Hz), 7.56
(1H, m), 7.47 (2H, m), 5.93 (1H, dtd, J ¼ 10.1, 4.0, 2.2 Hz), 5.74 (1H, dq,
J ¼ 10.1, 2.3 Hz), 4.09 (1H, m), 1.61–2.12 (6H, m); 13C NMR (75 MHz,
CDCl3) ꢀ: 202.1, 136.4, 133.1, 130.4, 128.9, 128.7, 125.0, 44.1, 26.1, 25.0,
21.2); IR (neat): 2937 (m), 1682 (s), 1447 (m), 1212 (s), 961 (m), 697 (s) cmÀ1
.
Cyclohex-2-enyldiphenylmethanol (7g). To a round-bottomed flask,
charged with Mg turnings (149.2 mg, 6.14 mmol) was added a solution
of bromobenzene (0.63 mL, 6.0 mmol), in ether (2 mL). The mixture was
treated with ultrasonic waves for 10 min, and then stirred an additional
20 min. The solution was cooled to 0ꢀC, and a solution of 9 (373 mg,
2.00 mmol) in ether (3 mL) was added, and the mixture stirred for 18 h,
allowing it to warm to room temperature. The reaction was quenched
with water, ether was added, and the layers were separated. The aqueous
layer was extracted twice more with ether, and the combined organic
extracts were washed with brine and dried over MgSO4. Column chro-
matography (SiO2, 2% ethyl acetate/98% hexane) afforded 251.5 mg of
7g (0.948 mmol, 47%) as a colorless oil.
1H NMR (300 MHz, CDCl3) ꢀ: 7.61 (2H, m), 7.49 (2H, m), 7.36–7.13
(6H, m), 5.98 (1H, dq, J ¼ 10.6, 3.2 Hz), 5.51 (1H, dq, J ¼ 10.6, 1.9 Hz),
3.44 (1H, m), 2.23 (1H, br s), 2.02 (2H, m), 1.79 (1H, m), 1.61–1.42 (3H,
m); 13C NMR (75 MHz, CDCl3) ꢀ: 147.1, 145.7, 134.0, 128.5, 128.2,
126.8, 126.6, 126.4, 126.3, 125.7, 79.6, 43.9, 25.5, 24.0, 22.2; IR (neat):
3553 (m), 3024 (w), 2972 (m), 1493 (m), 1447 (m) cmÀ1
.
(1R*, 5R*, 8R*)-8-Iodo-6-oxabicyclo[3.2.1]octane (11a). To a solu-
tion of silver (I) bis-collidine perchlorate (262 mg, 0.464 mmol) in

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Cationic Iodocyclization
2175
CH2Cl2 (8 mL) was added solid iodine (136 mg, 0.536 mmol), and the
solution was stirred for 60 min. To this mixture was added 2-cyclohex-
ene-1-methanol 7a (52.1 mg, 0.464 mmol), and the mixture was stirred
for 18 h. The solid silver iodide was filtered out, and the solution was
washed with sodium thiosulfate (10% aq.), dilute HCl (1 M), saturated
aq. sodium bicarbonate, dried over MgSO4, and the solvent removed
in vacuo. Column chromatography (SiO2, 5% ethyl acetate/95%
hexane) afforded 43.9 mg of 11a (0.184 mmol, 40%) as a slightly
yellow oil.
1H NMR (300 MHz, CDCl3) ꢀ: 4.20 (1H, m), 4.15 (1H, t, J ¼ 4.8 Hz),
3.87 (1H, s), 3.86 (1H, s), 2.28 (1H, m), 2.10 (1H, ddd, J ¼ 15.5, 13.8,
4.1 Hz), 1.97 (1H, m), 1.35–1.75 (4H, m); 13C NMR (75 MHz, CDCl3) ꢀ:
77.4, 69.9, 39.7, 30.0, 27.6, 26.9, 17.5; IR (neat): 2942 (s), 2873 (s), 1089
(m), 1066 (m), 980 (m), 750 (m) cmÀ1
.
(1R ,5S ,6S )-5-Iodo-8,8-dimethyl-7-oxabicyclo[4.2.0]octane
*
*
*
(10d)
*
*
*
and (1R ,5R ,8R )-8-iodo-7,7-dimethyl-6-oxabicyclo[3.2.1]octane (11d). To
a solution of silver (I) bis-collidine perchlorate (640 mg, 1.42 mmol) in
CH2Cl2 (5 mL) was added solid iodine (370 mg, 1.46 mmol), and the
solution was stirred for 40 min. To this mixture was added a solution
of 7d (39.0 mg, 0.278 mmol) in CH2Cl2 (2 mL), and the mixture was
stirred for 2d. The solid silver iodide was filtered out, and the solution
was washed with sodium thiosulfate (10% aq.), dilute HCl (1 M), satu-
rated aq. sodium bicarbonate, dried over MgSO4, and the solvent
removed in vacuo. Column chromatography (SiO2, 5% ethyl acet-
ate/95% hexane) afforded 13.6 mg of 10d (0.051 mmol, 18%) and
13.2 mg of 11d (0.050 mmol, 18%) as colorless oils.
1
10d: H NMR (300 MHz, CDCl3) ꢀ: 4.91 (1H, dd, J ¼ 8.3, 6.1 Hz),
4.32 (1H, ddd, J ¼ 9.2, 5.7, 4.4 Hz), 2.59 (1H, q, J ¼ 7.6 Hz), 2.17 (1H,
dtd, J ¼ 14.5, 6.1, 4.4 Hz), 1.42–1.92 (5H, m), 1.40 (3H, s), 1.26 (3H, s);
13C NMR (75 MHz, CDCl3) ꢀ: 84.8, 80.3, 41.7, 32.4, 30.5, 30.3, 25.2,
20.8, 18.4; IR (neat): 2943 (s), 1458 (m), 1369 (m), 1143 (s), 1000 (m),
947 (m) cmÀ1
.
1
11d: H NMR (300 MHz, CDCl3) ꢀ: 4.77 (1H, dd, J ¼ 5.7, 4.4 Hz),
4.26 (1H, dd, J ¼ 5.3, 4.4 Hz), 2.21 (1H, m), 2.09 (1H, m), 1.89 (1H, q,
J ¼ 3.4 Hz), 1.69–1.83 (3H, m), 1.49 (3H, s), 1.45 (1H, m), 1.27 (3H, m);
13C NMR (75 MHz, CDCl3) ꢀ: 81.0, 78.5, 47.8, 32.5, 32.4, 28.9, 25.3, 25.1,
17.5; IR (neat): 2936 (s), 1446 (m), 1277 (m), 1238 (m), 1090 (m), 1056
(m), 949 (s) cmÀ1
.
*
*
*
(1R ,5S ,6S )-8,8-Diethyl-5-iodo-7-oxabicyclo[4.2.0]octane (10e) and
*
*
*
(1R ,5R ,8R )-7,7-diethyl-8-iodo-6-oxabicyclo[3.2.1]octane (11e). To a
solution of silver (I) bis-collidine perchlorate (812 mg, 1.81 mmol)
in CH2Cl2 (7 mL) was added solid iodine (428 mg, 1.69 mmol), and

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2176
Nichols
the solution was stirred for 30 min. To this mixture was added a
solution of 7e (59.4 mg, 0.353 mmol) in CH2Cl2 (3 mL), and the mix-
ture was stirred for 22 h. The solid silver iodide was filtered out, and
the solution was washed with sodium thiosulfate (10% aq.), dilute HCl
(1 M), saturated aq. sodium bicarbonate, dried over MgSO4, and the
solventremoved in vacuo. Column chromaotgraphy (SiO 2, 3% ethyl
acetate/97% hexane) afforded 9.9 mg of 10e (0.034 mmol, 10%) and
30.4 mg of 11e (0.103 mmol, 29%) as colorless oils.
1
10e: H NMR (300 MHz, CDCl3) ꢀ: 4.88 (1H, dd, J ¼ 8.2, 6.6 Hz),
4.37 (1H, ddd, J ¼ 10.2, 6.6, 4.9 Hz), 2.62 (1H, q, J ¼ 8.2 Hz), 2.23 (1H,
quin of d, J ¼ 7.1, 4.9 Hz), 1.5–2.0 (9H, m), 0.88 (3H, t, J ¼ 7.4 Hz), 0.79
(3H, t, J ¼ 7.4 Hz); 13C NMR (75 MHz, CDCl3) d: 89.4, 80.6, 40.6, 32.6,
31.1, 30.2, 27.3, 21.0, 17.7, 7.6, 7.5; IR (neat): 2966 (s), 2941 (s), 2879 (m),
1460 (m), 1002 (m), 938 (m), 901 (m) cmÀ1
.
1
11e: H NMR (300 MHz, CDCl3) ꢀ: 4.80 (1H, t, J ¼ 5.1 Hz), 4.24
(1H, t, J ¼ 4.9 Hz), 2.23 (1H, m), 2.09 (1H, m), 1.94 (1H, q, J ¼ 3.3 Hz),
1.4–1.9 (8H, m), 0.92 (3H, t, J ¼ 7.6 Hz), 0.86 (3H, t, J ¼ 7.6 Hz);
13C NMR (75 MHz, CDCl3) d: 85.2, 77.2, 44.3, 32.2, 30.5, 28.3, 24.6,
23.9, 16.7, 9.8, 8.9; IR (neat) 2961 (s), 2941 (s), 2876 (m), 1467 (m),
1060 (s), 962 (m), 933 (s) cmÀ1
.
*
(1R ,5S*,6S*,8R*)-5-Iodo-8-phenyl-7-oxabicyclo[4.2.0]octane (10f )
and (1R*,5R*,7R*,8R*)-8-iodo-7-phenyl-6-oxabicyclo[3.2.1]octane (11f ).
To
a solution of silver (I) bis-collidine perchlorate (1010 mg,
2.25 mmol) in CH2Cl2 (12 mL) was added solid iodine (480 mg,
1.89 mmol), and the solution was stirred for 30 min. To this was
added a solution of 7f (258 mg, 1.35 mmol) in CH2Cl2 (3 mL), and the
solution was stirred for 18 h. The solid silver iodide was filtered out, and
the solution was washed with sodium thiosulfate (10% aq.), dilute HCl
(1 M), saturated aq. sodium bicarbonate, dried over MgSO4, and the
solventremoved in vacuo. Column chromaotgraphy (SiO 2, 1% ethyl
acetate/99% hexane) afforded two fractions, one containing 58.4 mg of
11f, and the other containing 187.2 mg of a 3:1 mixture of 10f and 11f
(Yield of 10f is 140.4 mg (0.447 mmol, 33%), yield of 11f is 105.2 mg
(0.335 mmol, 25%)).
10f: 1H NMR (500 MHz, CDCl3) ꢀ: 7.25–7.41 (5H, m), 5.85
(1H, d, J ¼ 6.7 Hz); 5.25 (1H, dd, J ¼ 6.4, 3.5 Hz); 4.60 (1H, q,
J ¼ 4.6 Hz); 3.25 (1H, tt, J ¼ 8.5, 6.4 Hz), 2.04 (1H, m), 1.96 (1H, m),
1.52 (1H, m), 1.40 (3H, m); 13C NMR (125 MHz, CDCl3) ꢀ: 139.5,
128.4, 127.4, 125.2, 81.4, 77.3*, 37.0, 31.4, 30.6, 20.0, 19.3; IR (neat):
3026 (m), 2940 (s), 2864 (m), 1494 (m), 1448 (s), 1077 (s), 1063 (s), 954
(s), 722 (s), 700 (s) cmÀ1. HRMS (EI, m/z): 313.0098, Calcd. for
C13H14IO (M À H)þ 313.0089.

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Cationic Iodocyclization
2177
1
11f: H NMR (500 MHz, CDCl3) ꢀ: 7.18–7.36 (5H, m), 5.19 (1H, d,
J ¼ 3.8 Hz), 4.54 (1H, t, J ¼ 4.8 Hz), 4.41 (1H, t, J ¼ 5.0 Hz), 2.56 (1H, t,
J ¼ 3.4 Hz), 2.18 (1H, ddd, J ¼ 14.1, 11.7, 6.8 Hz), 1.83 (1H, td, J ¼ 13.8,
6.8 Hz), 1.72 (1H, dt, J ¼ 13.7, 5.9 Hz), 1.35 (1H, m), 1.25 (1H, m), 1.08
(1H, dt, J ¼ 13.7, 6.5 Hz); 13C NMR (125 MHz, CDCl3) ꢀ: 139.5, 128.3,
126.9, 125.5, 80.0, 78.2, 43.4, 30.3, 27.6, 22.9, 16.4; IR (neat): 2937 (s),
2861 (m), 1448 (m), 1077 (s), 1065 (s), 954 (s), 764 (m), 721 (s), 700 (s)
cmÀ1. HRMS (EI, m/z): 313.0087, Calcd. for C13H14IO (M À H)þ
313.0089.
*
(1R ,5S*,6S*)-5-Iodo-8,8-diphenyl-7-oxabicyclo[4.2.0]octane
(10g)
and (1R*,5R*,8R*)-8-Iodo-7,7-diphenyl-6-oxabicyclo[3.2.1]octane (11g). To
a solution of silver (I) bis-collidine perchlorate (0.31 g, 0.69 mmol) in
CH2Cl2 (3 mL) was added solid iodine (173 mg, 0.68 mmol), and the
solution was stirred for 40 min. To this was added a solution of
7 g (36.1 mg, 0.136 mmol) in CH2Cl2 (2 mL) and the solution was
stirred for 18 h. The solid silver iodide was filtered out, and the solution
was washed with sodium thiosulfate (10% aq.), dilute HCl (1 M),
saturated aq. sodium bicarbonate, dried over MgSO4, and the solvent
removed in vacuo. Column chromatography (SiO2, 5% ethyl
acetate/95% hexane) afforded two fractions, one containing 12.9 mg of
10 g, and the other containing 13.2 mg of a 1:1 mixture of 10 g and 11 g
(Yield of 10 g is 19.5 mg (0.050 mmol, 37%), yield of 11 g is 6.6 mg
(0.017 mmol, 12%)).
1
10g: H NMR (300 MHz, CDCl3) ꢀ: 7.18–7.50 (10H, m), 5.06 (1H,
dd, J ¼ 7.0, 4.8 Hz), 4.56 (1H, dt, J ¼ 7.5, 4.8 Hz), 3.56 (1H, q, J ¼ 7.8 Hz),
1.3–2.1 (6H, m); 13C NMR (75 MHz, CDCl3) ꢀ: 146.9, 143.6, 128.5, 128.4,
127.3, 126.9, 125.4, 125.3, 89.4, 80.5, 43.2, 31.1, 30.8, 21.8, 20.0;
IR (neat): 3059 (m), 3025 (m), 2939 (s), 2867 (m), 1447 (s), 748 (m),
704 (s) cmÀ1
.
1
11g: H NMR (300 MHz, CDCl3) ꢀ: 7.12–7.60 (10H, m), 4.56 (1H,
m), 4.42 (1H, td, J ¼ 3.7, 1.7 Hz), 3.13 (1H, q, J ¼ 3.4 Hz), 2.25 (1H, ddd,
J ¼ 14.1, 11.8, 6.6 Hz), 1.3–2.1 (4H, m), 1.15 (1H, tt, J ¼ 14.1, 5.5 Hz);
13C NMR (75 MHz, CDCl3) ꢀ: 148.5, 144.1, 128.6, 128.2, 126.8, 126.6,
125.7, 124.8, 87.3, 78.2, 47.0, 30.0, 27.9, 24.1, 16.6. IR (neat): 3060 (m),
3027 (m), 2940 (s), 2867 (m), 1491 (m), 1448 (s), 908 (s), 734 (s) cmÀ1
.
CONCLUSION
Various 3-cyclohexenemethanol derivatives 7 were transformed into
mixtures of bicyclic ethers with Iþ. The presence of alkyl groups along

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2178
Nichols
the backbone between the double bond and the alcohol altered both
the rate and the stereoselectivity of the reactions. When benzene rings
were present, the major products were the oxetane-containing bicyclics
10f and 10g.
ACKNOWLEDGMENTS
This work was supported by the Department of Chemistry at
California State University, Chico. Summer support was provided by
the CSU Chico Research Foundation Summer Scholars Program. The
departmental Varian Mercury VX300 NMR spectrometer was obtained
through an NSF-CCLI grant by Prof. David B. Ball. Thanks also go to
Will Chrisman at the University of California, Santa Barbara, for 2D
NMR of compounds 10f and 11f.
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©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.
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Received in the USA October 28, 2002

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