Trans dialkoxylation of cyclic alkenes: A Prevost-type reaction

Article abstract of DOI:10.1055/s-2005-865333

Reaction of anhydrous silver perchlorate, sym-collidine, and iodine (2:1:1 molar ratio) with cyclic alkenes and an excess of an alcohol in CH ₂Cl₂ affords trans-1,2-dialkoxycycloalkanes in high yields and purity. The reaction occurs via initial formation of the trans-iodoethers, which undergo Ag-assisted iodide abstraction to give the trans-diethers. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865333

PAPER
1333
Trans Dialkoxylation of Cyclic Alkenes: A Prévost-Type Reaction
Trans
D
ia
l
koxylation o
H
f
Cyclic
A
lkenes erman Schauble,*1 Edward A. Trauffer,2 Prashant P. Deshpande,3 Robert D. Evans4
Department of Chemistry, Villanova University, Villanova, PA 19085, USA
Fax +1(610)5197167; E-mail: j.herman.schauble@villanova.edu
Received 20 August 2004; revised 4 January 2005
ate or tetrafluoroborate, weak nucleophiles, and by strong
acids and polar solvents. It was thus considered likely that
the diether 3a and ring-contracted acetal 4 were being
formed via the iodoether 2 by concerted methoxyl- and
Abstract: Reaction of anhydrous silver perchlorate, sym-collidine,
and iodine (2:1:1 molar ratio) with cyclic alkenes and an excess of
an alcohol in CH2Cl2 affords trans-1,2-dialkoxycycloalkanes in
high yields and purity. The reaction occurs via initial formation of
the trans-iodoethers, which undergo Ag-assisted iodide abstraction Ag-assisted iodide abstraction to give the oxiranium-tet-
to give the trans-diethers.
rafluoroborate ion pair. The ion-pair then undergoes rear-
side attack by MeOH to give the diether 3a, or dissociates
and rearranges to the oxocarbenium ion, which is trapped
by methanol to give acetal 4.
Keywords: alkenes, iodoalkoxylation, dialkoxylation, silver per-
chlorate, collidine
It should be noted (Scheme 1) that two molar equivalents
of silver tetrafluoroborate per equivalent of alkene and io-
dine are required for complete conversion of cyclohexene
to the diether 3a and acetal 4; the first equivalent reacting
with iodine to form cyclohexene iodiranium tetrafluoro-
borate and AgI. The second equivalent of silver salt is re-
quired for Ag-assisted abstraction of iodide from the
intermediate iodoether, leading to formation of 3a and 4.
Since the amount of silver tetrafluoroborate employed in
our initial study was only half of that required for com-
plete conversion of cyclohexene to 3a and 4, their forma-
tion as major products indicated that iodide abstraction
from the iodoether 2 occurred more rapidly than the initial
iodoetherification step.
A variety of reactions have been described for the stereo-
selective iodoesterification and diesterification of alk-
enes. In contrast to the Prévost-type reactions for
conversion of alkenes to trans-1,2-diesters via intermedi-
ate 1,2-iodoesters, analogous procedures for dietherifica-
tion of alkenes via vic-iodoethers have apparently not
been developed. Herein, we report the facile trans-di-
alkoxylation of cyclic alkenes using silver perchlorate,
sym-collidine, iodine (2:1:1 molar ratio relative to the al-
kene), plus an excess of the appropriate alcohol in CH2Cl2
solution.
An initial attempt to develop a one-step dialkoxylation of
alkenes in our lab involved reaction of cyclohexene with
silver tetrafluoroborate and iodine (1:1:1 molar ratio),
plus MeOH (20 mol equiv) in CH2Cl2, resulting in a mix-
ture of trans-1-fluoro-2-iodocyclohexane (1), trans-1-
iodo-2-methoxycyclohexane (2), trans-1,2-dimethoxycy-
clohexane (3a), and (dimethoxymethyl)cyclopentane (4),
in relative yields of 24%, 13%, 21% and 42%.
I
I
AgBF4, I2
+ HB(OMe)F3
BF4
F
1
MeOH
+ AgI
Proposed pathways for formation of the major products
are shown in Scheme 1. Initial formation of cyclohexene
iodiranium ion followed by anti-mode nucleophilic attack
by either tetrafluoroborate (with transfer of fluoride ion),5
or by MeOH provides the iodofluoride 1 and intermediate
iodoether 2. The paths for methanolysis of iodoether 2 to
the diether 3a and acetal 4 are based on results of studies
on Ag+-assisted solvolyses of alkyl halides by Pocker and
Kevill and coworkers,6,7 Vona and Steigman,8 and others.7
Such reactions appear to occur via alkyl halide–silver salt
complexes, followed by iodide abstraction by silver ion to
give ion-paired species, which then undergo either nu-
cleophilic displacement by SN2Ag-type processes, or dis-
sociate to free carbocations, followed by nucleophile
trapping via SN1Ag-type processes; the latter being fa-
vored by more electrophilic silver salts such as perchlor-
I
I
Ag
BF4
BF4
O
+ AgI
OMe
+ HBF4
Me
ion-pair
SN2
OMe
mol complex
2
SN1
MeOH
BF4
OMe
OMe
BF4
Me
+ HBF4
O
O
Me
3a
dissociated ions
MeOH
OMe
+ HBF4
OMe
4
Overall reaction for formation of 3a, 4:
3a, 4 + 2 AgI + 2 HBF4
Cyclohexene + 2 AgBF4 + I2 + 2 MeOH
SYNTHESIS 2005, No. 8, pp 1333–1339
Advanced online publication: 21.04.2005
x
x
.
x
x
.2
0
0
5
Scheme 1
DOI: 10.1055/s-2005-865333; Art ID: M07104SS
© Georg Thieme Verlag Stuttgart · New York

1334
J. H. Schauble et al.
PAPER
In order to eliminate formation of the acetal 4, it was nec- rearrangement than the corresponding oxiranium–per-
essary to develop reaction conditions under which tet- chlorate complex.
rafluoroboric acid would be neutralized. Although
Results obtained for dietherification of cyclopentene and
dicollidine silver tetrafluoroborate (prepared in situ from
cyclohexene with silver perchlorate pentahydrate, colli-
collidine and silver tetrafluoroborate in a 2:1 molar ratio)5
dine, iodine (2:1:1) and 20 molar equivalents of various
saturated alcohols in CH2Cl2 at room temperature are
was essentially unreactive toward the iodoether 2; by us-
ing one, rather than two equivalents of collidine, the di-
shown in Table 1. Yields of diethers from cyclopentene
ether 3a was obtained in 90% relative yield, accompanied
were generally higher than those from cyclohexene. In
several reactions, particularly for cyclohexene, the di-
ethers were accompanied by small to moderate amounts
of the undesired trans-1,2-hydroxyethers. The hydroxy-
by acetal 4 (5%). This result is apparently due to the more
electrophilic mono-collidine silver salt, expected to be
formed under these conditions.9
The increased reactivity of silver tetrafluoroborate–colli- ether–diether ratios increased with steric bulk of the alco-
dine (1:1) in converting iodoether 2 to diether 3a suggest- hols, consistent with increased hindrance for rear-side
ed its potential for carrying out one-step dietherification displacement on oxiranium ion intermediates by alcohols
of alkenes. Thus, reaction of cyclohexene with silver tet- (Scheme 1) relative to water. As shown for the synthesis
rafluoroborate, collidine, iodine (1:2:2:1) and MeOH (20 of trans-1,2-di-tert-butoxycyclopentane (6d), hydroxy-
mol equiv) in CH2Cl2 netted the diether 3a in 73% yield, ether formation was eliminated by use of anhydrous silver
with only 2% of acetal 4. However, the iodofluoride 1 was perchlorate.
also obtained in 25% relative yield. To preclude forming
the iodofluoride, it was desired to replace silver tetrafluo-
roborate with the perchlorate. However, since silver per-
chlorate–collidine (1:1) was too unreactive to convert the
iodoether to the diether 3a, it was necessary to utilize the
uncomplexed silver salt for this step.
Dietherification of trans-bicyclo[4.4.0]dec-3-ene (8) with
anhydrous silver perchlorate collidine, and iodine (2:1:1)
and excess MeOH in CH2Cl2 gave only trans-(diaxial)-
3,4-dimethoxy-trans-bicyclo[4.4.0]decane (9), consistent
with axial mode nucleophilic displacement by MeOH on
the oxiranium species derived from the expected interme-
Thus, by using silver perchlorate–collidine–iodine in diate trans-(diaxial)-3-iodo-4-methoxy[4.4.0]decane.
2:1:1 molar ratio and MeOH (20 mol equiv), cyclohexene
was converted to 3a in 87% yield; no acetal 4 being de-
tected by GC.
Attempted dialkoxylation of cyclohexene using anhy-
drous silver perchlorate, collidine iodine (2:1:1) and
ethane-1,2-diol as solvent gave only 2-cyclopentyl-1,3-di-
The composition resulting from combination of silver per- oxolane (10) in 80% yield (Scheme 2). By analogy to the
chlorate, collidine, and iodine in 2:1:1 molar ratio is of im- formation of acetal 4, dioxolane 10 could form via 1-iodo-
portance here, since this mixture has proven effective for (2-hydroxyethoxy)cyclohexane (11) by Ag-assisted io-
conversion of cyclic alkenes to trans-diethers. Such a dide abstraction with anchimeric assistance by vicinal
mixture, prepared in CDCl3, resulted in precipitation of ether oxygen to give the oxiranium–perchlorate ion pair,
AgI (1 equiv). A 1H NMR study on the solution phase in- followed by dissociation and rearrangement to the oxocar-
dicated formation a 1:1 mixture of silver and mono-iodo- benium ion and ring closure (path b), which would be ex-
nium perchlorates,10,11 in which collidine is bonded pected to be favored by increased solvent polarity due to
principally to iodine (experimental section).
ethanediol. Alternately, dioxolane 10 could form simply
by Ag-assisted iodide abstraction with concerted intramo-
lecular hydroxyl attack and rearrangement (path a).
The decreased reactivity toward iodide abstraction result-
ing from substitution of silver perchlorate for tetrafluo-
roborate is consistent with other studies indicating that the
ability of silver salts to form n-type complexes with
amines or ethers decreases in the order: tetrafluoroborate
> perchlorate > nitrate.12 The same stability order has been
observed for silver salt–alkene p-complexes.13 Thus it
may be expected that silver perchlorate would be a weaker
Lewis acid (electrophile) than silver tetrafluoroborate.
The same would be expected for the congeneric pairs of
mono- and di-collidine silver salts.
O
O
a
OH
+ HClO4
+ AgI
ClO4
a
b
O
10
b
a
OH
HO
I
O
Ag
ClO4
11
O
ClO4
Scheme 2
The complete suppression of acetal formation observed
by substitution of silver perchlorate for the tetrafluorobo-
rate was surprising, since the amount of collidine em-
ployed was only half that required for neutralization of
perchloric acid formed in the overall reaction. However, it
is likely that the intermediate oxiranium–tetrafluoroborate
ion pair proposed for conversion of iodoether 2 to diether
3a (Scheme 1) would be more prone to dissociation and
Reaction of 1-methylcyclohexene with silver perchlorate
pentahydrate, collidine, iodine (2:2:1) and excess MeOH
gave trans-1,2-dimethoxy-1-methylcyclohexane (12),
methyl cyclopentyl ketone, and 2-methylcyclohexanone
in 28%, 24%, and 27% relative yields (Table 1).14 The
former ketone apparently derives from Ag-assisted rear-
rangement of 2-iodocyclohexanol (resulting from com-
petitive nucleophilic attack by water on the initial 1-
Synthesis 2005, No. 8, 1333–1339 © Thieme Stuttgart · New York

PAPER
Trans Dialkoxylation of Cyclic Alkenes
1335
Table l Dietherification of Cyclic Alkenes with Silver Perchlorate,a Iodine, Collidine and Alcohols
Alkene
Alcohol
Products, yield (%)b
6
7
a: MeOH
98 (99)
98 (99)
79 (80)
89 (96)a
0
b: n-BuOH
c: i-BuOH
d: t-BuOH
< 1
16
0
3
5
a: MeOH
b: i-PrOH
c: n-BuOH
d: i-BuOH
e: t-BuOH
87 (92)
91 (99)
60 (81)
70 (71)
49 (60)
(0)
0
10 (8)
22 (25)
(26)
MeOH
68
8
9
MeOH
MeOH
MeOH
28c,d
57 (66)e
12
47 (66)e
80 (51)
13
18
a Reactions of cyclopentene, cyclohexene, except for synthesis of 6d were run using AgClO4·5H2O; all others with anhyd. AgClO4, except for
synthesis of 12.
b Yields of isolated products; relative yields by GC.
c Reaction run using AgClO4·5H2O.
d Plus cyclopentyl methyl ketone (27%), 2-methylcyclohexanone (28%), and 12 minor products (1–5%) (GC–MS).
e Several side products (1–13%).
methylcyclohexene iodiranium ion); the latter, via Ag-as- clohexane, the configuration of 13 is (1R, 2R, 4R)-1,2-
sisted conversion of the iodohydrin to the epoxide, and re- dimethoxy-4-isopropyl-1-methylcyclohexane (diequato-
arrangement.15 By using anhydrous silver perchlorate, the rial methoxyls).
yield of 12 increased to ca 65%.
Reaction of bicyclo[2.2.1]heptene with anhydrous silver
Dimethoxylation of 1-methyl-4R-isopropylcyclohexene perchlorate, collidine, iodine (2:2:1) and excess MeOH
under anhydrous conditions gave the diether 13 in similar gave
7-syn-iodo-2-exo-methoxybicyclo[2.2.1]heptane
1
yield. The H NMR spectrum of 13 indicated the C-2 (14)16 in 76% yield (Scheme 3, path a). Failure of 14 to
methoxyl to be equatorial. Presuming rear side attack by undergo further methoxylation apparently derives from its
MeOH at C1 (electronic control) on the oxiranium ion de- stereochemistry precluding methoxyl assistance to iodide
rived from the likely trans-diaxial iodoether intermediate, abstraction by silver perchlorate. Likewise, reaction of
(1S, 2S, 4R)-2-iodo-4-isopropyl-1-methoxy-1-methylcy- norbornene using ethane-1,2-diol instead of MeOH gave
Synthesis 2005, No. 8, 1333–1339 © Thieme Stuttgart · New York

1336
J. H. Schauble et al.
PAPER
(1),5 cis- and trans-1,2-dimethoxycyclohexane,16 and trans-bicy-
7-syn-iodo-2-exo-(2-hydroxyethoxy)bicyclo[2.2.1]hep-
tane (15) in 61% yield and 3-exo-(2-hydroxyethoxy)tricy-
clo[4.4.0]dec-3-ene,22 were prepared by literature procedures.
clo[2.2.1.02,6]heptane (17) in 8.5% (20% relative) yield; Caution: Silver perchlorate per se is stable at temperatures below
ca 485 °C. Its solubility in organic solvents is due to formation of
the latter likely formed via 3-exo-iodotricy-
clo[2.2.1.02,6]heptane (16) by iodide abstraction to give
complexes, which may be isolated as crystalline materials. Such
perchlorate complexes are explosive, and may detonate, even upon
the relatively stable 3-nortricyclyl ion17 which is trapped
handling when cold.23,24
by ethylene glycol (path b).18 3-Iodonotricyclane 16 was
previously obtained as the sole product from reaction of
Synthesis of trans-1-Iodo-2-methoxycyclohexane (2)
norbornene with dicollidine iodonium tetrafluoroborate.5
To a magnetically stirred solution of dicollidine silver tetra-
fluoroborate5 (12.67 g, 29 mmol) in anhyd CH2Cl2 (85 mL) under
an inert atmosphere, iodine (3.68 g, 29 mmol) was added in one por-
tion, and the mixture stirred until all the iodine had reacted. AgI was
removed by vacuum filtration to give a clear amber solution of di-
collidine iodonium tetrafluoroborate,5 to which were added, cyclo-
hexene (2.30 g, 28 mmol) and MeOH (0.90 g, 28 mmol, in rapid
succession. The mixture was stirred for 2 h at 25 °C, filtered, and
the filtrate washed successively with 10% aq NaS2O3 (50 mL), 20%
cold HCl (50 mL), and water (50 mL), dried (anhyd MgSO4) and the
solvent stripped under reduced pressure. Short-path distillation
gave iodoether 2; yield: 4.37 g (65%); bp 47 °C (0.5 Torr); stable at
0 °C.
I
I
OR
a
a
I(col) ClO4
a
ROH
+ colH ClO4
b
H
ClO4
14 R = Me
15 R = CH2CH2OH
b
b
col
I
OR
AgClO4
ROH
+ colH ClO4
17 R = CH2CH2OH
+ AgI
1H NMR (200 MHz, CDCl3): d = 1.60–2.50 (m, 8 H, CH2), 3.24
(ddd, 1 H, H2), 3.40 (s, 3 H, OCH3), 4.07 (ddd, J1a,2a = 10.7 Hz,
J1a,6a = 8.74 Hz, J1a,6e = 4.28 Hz, 1 H, H1).
ClO4
16
col = collidine
The NMR data is consistent with literature25 1H NMR data.
Scheme 3
Anal. Calcd for C7H13IO: C, 35.02; H, 5.46; I, 52.86; O, 6.66.
Found: C, 35.34; H, 4.88; I, 53.10; O, 6.90.
Reaction of 3,4-dihydro-2H-pyran with anhydrous silver
perchlorate, collidine, iodine (2:1:1) and excess MeOH in
Synthesis of trans-1,2-Dimethoxycyclohexane (3a) from trans-1-
CH2Cl2 gave trans-(diaxial)-2,3-dimethoxytetrahydropy- Iodo-2-methoxycyclohexane
To a magnetically stirred solution of AgClO4⋅5H2O (2.97 g, ca 10
ran (18) (Table 1) as the only isolable product in 80%
mmol) in CH2Cl2 (25 mL) in a 50 mL round-bottomed flask at r.t.,
were added successively, trans-1-iodo-2-methoxycyclohexane
(2.40 g, 10 mmol) and MeOH (20 mmol). The mixture was stirred
for 2 h at r.t., then filtered to remove AgI. AgI was extracted with
CH2Cl2 (20 mL) and the combined filtrate washed successively with
water (75 mL), cold HCl (1.4 M, 75 mL), and Na2CO3 (0.1%, 75
mL). After drying (anhyd. MgSO4), the filtrate was evaporated un-
der reduced pressure, then purified by flash chromatography to give
3a; yield: 1.30 g (90%); GC and 1H NMR data are consistent with
those for a literature16 preparation.
yield. This result was consistent with the intermediacy of
trans-(diaxial)-3-iodo-2-methoxytetrahydropyran,
the
latter having previously been obtained by reaction of di-
hydropyran with silver acetate and iodine in MeOH.19 In
light of the facile acid-catalyzed isomerization of 2-alkox-
ytetrahydropyrans,20 the formation of solely the trans iso-
mer of dimethoxytetrahydropyran under the reaction
conditions employed was rather unexpected.
In summary, a one-step method for trans-1,2-dialkoxyla-
tion of cyclic alkenes has been developed based on a Pré- Composition of Reagent Mixture Used for Dialkoxylation
Sequential addition of AgClO4, sym-collidine, and iodine in 1:2:1
vost-type reaction using anhydrous silver perchlorate,
sym- collidine, and iodine (2:1:1 molar ratio) and an ex-
cess of a monohydric alcohol in CH2Cl2. Cyclic alkenes
mol ratio in CDCl3–TMS solution at r.t. resulted in instantaneous
1
quantitative precipitation of AgI. A H NMR spectrum for the re-
sulting solution of dicollidine iodonium perchlorate, Icol2ClO4,26
with unsubstituted carbon-carbon double bonds give di-
revealed one set of collidine resonances, including a ring proton sin-
ethers in high yields and purity. Paralleling the Prévost re-
action, alkenes with trisubstituted double bonds give
lower yields of diethers, accompanied by side products.
glet at d = 7.29 ppm (0.52 ppm downfield from neat collidine/
CDCl3). A similar solution prepared using 1 mol equiv of collidine
showed a slight upfield shift of the ring proton singlet to d = 7.19
ppm, consistent for formation of the mono-collidine iodonium salt.
Further addition of 1 equiv of AgClO4 to the latter solution had no
additional effect on the collidine shifts, as expected for a 1:1 mix-
ture of silver and mono-collidine iodonium perchlorates, with colli-
dine bonded principally to iodine.
Isolation of products was accomplished by flash liquid chromatog-
raphy on Kieselgel 60 using CH2Cl2 or MeOH–CH2Cl2 as eluent.
GC analyses were performed on a Hewlett-Packard 5890 instru-
ment; 15 m, 530 m macrocapillary silica column; 50% diphenylpol-
ysiloxane–50% dimethylpolysiloxane; injector 200 °C, detector
140 °C, oven temperature ramped from 50–200 °C at 3°C/min; de-
tection limit 0.1% rel. area. All NMR spectra were obtained on
Varian Associates XL-200 spectrometer in CDCl3, using TMS as
internal standard. 13C and 1H shift assignments were assisted by em-
pirical substituent effect additivity calculations,21 using ChemDraw
Ultra 7.01 (Cambridge Soft Corp., Cambridge, MA); 13C multiplic-
ities were determined by DEPT. trans-1-Fluoro-2-iodocyclohexane
Synthesis of trans-1,2-Diethers 6d, 9, 12, 13, 18 (Table 1) Using
Anhydrous Silver Perchlorate
Reactions of all alkenes except cyclopentene and cyclohexene were
carried out using anhyd AgClO4, prepared immediately prior to re-
action by heating AgClO4·5H2O (2.97g, ca 10.0 mmol) to 150 °C at
50 torr for 4 h24 in a 50 mL round-bottomed flask immersed in an
oil bath. Upon cooling to 25 °C, anhyd CH2Cl2 (25 mL), sym-colli-
dine (0.61 g, 5.0 mmol), alkene (5.0 mmol) and alcohol (80.0 mmol)
Synthesis 2005, No. 8, 1333–1339 © Thieme Stuttgart · New York

PAPER
Trans Dialkoxylation of Cyclic Alkenes
1337
were added successively with magnetic stirring, care being taken to
avoid unnecessary exposure to air. Stirring was continued for ca 5
min until the AgClO4 dissolved completely, then iodine (1.27 g, 5.0
mmol) was added and the mixture stirred for 2 h longer at 25 °C,
then filtered to remove AgI. The filtrate was washed successively
with distilled water (75 mL), 10% Na2S2O3 (75 mL), cold 1.4 M
HCl (75 mL) and 0.1% Na2CO3 (75 mL), dried (anhyd MgSO4) and
evaporated under reduced pressure to yield the crude products
which were assayed by GC and purified by flash liquid chromatog-
raphy.
trans-1,2-Di-tert-butoxycyclohexane (3e)
1H NMR (200 MHz, CDCl3): d = 1.18 (s, 18 H, 6 × CH3), 1.59 (m,
4 H, H4,5), 1.83 (m, 4 H, H3,6), 3.18 (m, 2 H, H1,2).
13C{1H} NMR (50.3 MHz, CDCl3): d = 24.08 (t, C4,5), 28.81 (q,
CH3), 34.01 (t, C3,6), 73.22 (d, C1,2), 73.27 [s, OC(CH3)2].
trans-2-n-Butoxycyclohexanol (5c)
1H NMR (200 MHz, CDCl3): d = 0.93 (t, J = 7.21 Hz, 3 H, CH3),
1.10–2.18 (m, 12 H, 6 × CH2), 2.27 (s, 1 H, OH), 2.90–3.10 (m, 1
H, H2), 3.37, 3.60 (m, 2 H, OCHaHb, diastereotopic), 3.50–3.70 (m,
1 H, H1).
Reactions of cyclohexene and bicyclo[2.2.1]heptene with silver
perchlorate, sym-collidine, iodine (2:1:1 mol ratio) and ethane-1,2-
diol were carried out analogously, except that ethanediol (25 mL)
was used as solvent; CH2Cl2 (2–3 mL) as co-solvent.
13C{1H} NMR (50.3 MHz, CDCl3): d = 13.78 (q, CH3), 19.26 (t,
CH2CH3), 23.89 (t, C5), 24.18 (t, C4), 29.04 (t, C3), 31.85 (t, C6),
32.12 (t, CH2CH2CH3), 68.39 (t, OCH2), 73.75 (d, C1), 83.56 (d,
C2).
Dietherification of Cyclopentene, Cyclohexene, and 1-Methyl-
cyclohexene Using Silver Perchlorate Pentahydrate (Table 1)
Reactions were carried out in the same manner as with anhyd silver
perchlorate, except that the perchlorate was not dried.
trans-2-Isobutoxycyclohexanol (5d)
1H NMR (200 MHz, CDCl3): d = 0.91 (d, J = 6.67 Hz, 3 H, CH3),
0.92 (d, J = 6.67 Hz, 3 H, CH3), 1.84 [m, J = 6.67 Hz, 1 H,
CH(CH3)2], 1.10–2.12 (m, 8 H, 4 × CH2), 2.58 (s, 1 H, OH), 3.00
(ddd, J1,2 = 10.41 Hz, J2,3e = 8.73 Hz, J2,3a = 4.21 Hz, 1 H, H2a), 3.12
(dd, Jvic = 8.95 Hz, Jgem = 6.64 Hz, 1 H, OCHa), 3.40 (dd, Jvic = 8.95
Hz, Jgem = 6.57 Hz, 1 H, OCHb), 3.40 (ddd, 1 H, H1ax); CH3 groups
and CHaHbO are diastereotopic; decoupling CH at d = 1.84 col-
lapsed CH2O double doublets to doublets, permitting assignment of
the overlapping H1 at d = 3.40.
Dimethoxylation of Cyclohexene Using Silver Tetrafluorobo-
rate
The procedure used was similar to that for synthesis of trans-1,2-di-
ethers using anhyd AgClO4, except that AgBF4 (1.95 g, 10.0 mmol)
and sym-collidine (1.21 g, 10.0 mmol) were employed.
Spectral and Analytical Data for Representative trans-1,2-Di-
ethers (3,6) and Alkoxyalcohols (5,7)
In most cases the ring methine (CHO) protons appeared as unre-
solved multiplets. Assignment of trans configurations to vic-di-
ethers was supported by half-height peak widths, w1/12. Only single
configurational isomers were observed in all cases.
13C{1H} NMR (50.3 MHz, CDCl3): d = 19.33 (q, CH3), 23.89, 24.18
(t, C4,5), 28.73 [d, CH(CH3)2], 28.98 (t, C3), 31.82 (t, C6), 73.83 (d,
C1), 75.50 (t, CH2O), 83.69 (d, C1).
trans-1,2-Dimethoxycyclopentane (6a)
1H NMR (200 MHz, CDCl3): d = 1.50–2.00 (m, 6 H, H3–5), 3.35 (s,
6 H, 2 × OCH3), 3.60–3.75 (m, 2 H, H1,2).
trans-1,2-Diisopropoxycyclohexane (3b)
1H NMR (200 MHz, CDCl3): d = 1.12 (d, J = 6.1 Hz, 6 H, 2 × CH3),
1.19 (d, J = 6.1 Hz, 6 H, 2 × CH3), 1.20–1.25 (m, 4 H), 1.55–1.70
(m, 2 H), 1.80–2.00 (m, 2 H), 3.05–3.15 (m, 2 H, 2 × CHOC), 3.82,
[h, 2 H, CH(CH3)2; the diastereotopic CH3 groups (d = 1.12, 1.19)
collapsed to doublets upon decoupling CH at 3.82].
13C{1H} NMR (50.3 MHz, CDCl3): d = 21.32 (t, C4), 29.72 (t, C3,5),
56.87 (q, OCH3), 86.37 (d, C1,2).
1H and 13C data for 6a are consistent with published28 data.
trans-1,2-Di-n-butoxycyclopentane (6b)
1H NMR shifts were consistent with literature27 data.
1H NMR (200 MHz, CDCl3): d = 0.92 (t, J = 7.2 Hz, 6 H, 2 × CH3),
1.24–2.00 (m, 14 H, 7 × CH2), 3.44 (t, Jvic = 6.4 Hz, 4 H, 2 ×
OCH2), 3.71 (m, w1/2 = 14 Hz, 2 H, H1,2).
13C{1H} NMR (50.3 MHz, CDCl3): d = 22.82 (q, CH3), 23.99 (t,
C4,5), 32.10 (t, C3,6), 70.91 [d, CH(CH3)2], 79.41 (s, C1,2).
13C{1H} NMR (50.3 MHz, CDCl3): d = 13.73 (q, CH3), 19.24, 21.30
(t, CH2CH3, C4), 30.11, 31.95 (t, C3,5, OCH2CH2), 68.80 (t, OCH2),
84.89 (d, C1,2).
Anal. Calcd for C12H24O2: C, 71.95; H, 12.08. Found: 71.94; H,
12.27.
trans-1,2-Di-n-butoxycyclohexane (3c)
1H NMR (200 MHz, CDCl3): d = 0.91 (t, J = 7.18 Hz, 6 H, 2 × CH3),
1.15–1.70 (m, 14 H), 1.90–2.15 (m, 2 H), 3.06–3.20 (m, w1/2 = 18
Hz, 2 H, H1,2, dieq alkoxyls), 3.55 (dt, Jvic = 6.49 Hz, 4 H, 2 ×
OCH2).
trans-1,2-Diisobutoxycyclopentane (6c)
1H NMR (200 MHz, CDCl3): d = 0.899 (d, J = 6.67 Hz, 6 H, 2 ×
CH3), 0.894 (d, J = 6.67 Hz, 6 H, 2 × CH3), 1.50–1.95 (m, 8 H,
H
3–5, 2 × CHCH3), 3.19 (d, 2 H, 2 × OCHa), 3.21 (d, J = 6.67 Hz, 2
H, 2 × OCHb), 3.65–3.75 (m, 2 H, H1,2); CH3 groups and OCHaHb
are diastereotopic.
13C{1H} NMR (50.3 MHz, CDCl3): d = 13.82 (q, CH3), 19.26 (t,
CH2CH3), 25.53 (t, C4,5), 30.19 (t, C3,6), 32.36 (t, OCH2CH2), 69.69
(t, OCH2), 81.23 (d, C1,2).
13C{1H} NMR (50.3 MHz, CDCl3): d = 19.45 (q, CH3), 21.42 [d,
CH(CH3)2], 28.63 (t, C4), 30.18 (t, C3,5), 76.18 (t, OCH2), 85.06 (d,
C1,2).
trans-1,2-Diisobutoxycyclohexane (3d)
1H NMR (200 MHz, CDCl3): d = 0.89 (d, J = 6.67 Hz, 6 H, 2 × CH3),
0.90 (d, J = 6.67 Hz, 6 H, 2 × CH3), 1.81 [m, 2 H, 2 × CH(CH3)2],
1.32–2.04 (m, 8 H, H3–6), 3.07–3.19 (m, w1/2 = 20 Hz, 2 H, H1,2; con-
sistent for dieq alkoxyls), 3.55 (d, J = 6.49 Hz, 4 H, 2 × OCH2); CH3
groups are diasterotopic.
trans-1,2-Di-tert-butoxycyclopentane (6d)
13C{1H} NMR (50.3 MHz, CDCl3): d = 20.55 (t, C4), 28.60 (q,
CH3), 31.86 (t, C3,5), 72.97 (s, C(CH3)2), 78.56 (C1,2).
Anal: Calcd for C13H26O2: C, 72.85; H, 12.24. Found: C, 72.59; H,
12.28.
13C{1H} NMR (50.3 MHz, CDCl3): d = 19.47 (q, CH3), 23.51 (t,
C4,5), 28.94 [d, CH(CH3)2], 30.01 (t, C3,6), 76.97 (t, CH2O), 81.26
(C1,2).
trans-2-Isobutoxycyclopentanol (7c)
1H NMR (200 MHz, CDCl3): d = 0.89 (d, J = 6.67 Hz, 6 H, 2 × CH3),
1.50–2.05 (m, 7 H, CH(CH3)2, H3–5), 3.21 (d, J = 6.67 Hz, 2 H,
Anal: Calcd for C14H28O2: C, 72.85; H, 12.34. Found: C, 73.10; H,
12.23.
Synthesis 2005, No. 8, 1333–1339 © Thieme Stuttgart · New York

1338
J. H. Schauble et al.
PAPER
OCH2), 3.52 (m, w1/2 = 18 Hz, 1 H, H2), 4.10 (m, w1/2 = 22 Hz, 1 H,
13C{1H} NMR (50.3 MHz, CDCl3): d = 25.63 (t, C5), 27.00 (t, C4),
53.84 (q, OCH3), 54.89 (q, OCH3), 69.50 (t, C6), 78.18 (d, C3),
105.82 (d, C2).
H1).
13C{1H} NMR (50.3 MHz, CDCl3): d = 19.31 (q, CH3), 20.33 (t,
C4), 29.17 (t, C5), 31.96; (t, C3), 76.32 (t, OCH2), 77.30 (d, C1),
86.82 (d, C2).
Acknowledgment
trans-2,3-Dimethoxy-trans-bicyclo[4.4.0]decane (9)29
1H NMR (200 MHz, CDCl3): d = 1.5–2.5 (m, 14 H), 3.35 (s, 6 H,
2 × OCH3), 3.42 (m, w1/2 = 6.4 Hz, 2 H, H2e,3e).
We wish to thank Dr. Robert Giuliano for advice in preparation of
the manuscript, and Drs. Janet Gagnon and Walter Boyko for pro-
viding assistance in obtaining and interpreting NMR data.
13C{1H} NMR (50.3 MHz, CDCl3): d = 26.49 (C6,7), 32.04, 33.45 (t,
C1,4;5,8), 36.19 (d, C9,10), 56.40 (OCH3), 76.83 (C2,3).
References
trans-1,2-Dimethoxy-1-methylcyclohexane (12)
1H NMR (200 MHz, CDCl3): d = 1.15 (s, 3 H, CH3), 1.25–2.0 (m, 8
H, H3–6), 3.11 (dd, J2a,3a = 7.0 Hz, J2a,3e = 3.5 Hz, 1 H, H2), 3.22, 3.38
(s, 6 H, 2 × OCH3).
13C{1H} NMR (50.3 MHz, CDCl3): d = 18.19, 21.51, 21.83 (CH3,
C4,5), 25.58 (C3), 32.26 (C6), 48.43, 57.01 (2 × OCH3), 76.48 (C1),
82.63 (C2).
(1) Professor Emeritus, Villanova University, Villanova, PA
19085, USA.
(2) Ph.D., Villanova University, 1992. Current address: Quaker
Chemical Corp., Conshohocken, PA 19428, USA.
(3) M.S., Villanova University, 1987. Current address: Bristol-
Myers Squibb Pharmaceutical Research Institute, Princeton,
NJ 08540, USA.
(4) M.S., Ph.D., Villanova University, 1983, 1986. Current
address: Quaker Chemical Corp., Conshohocken, PA 19428,
USA.
(5) Iodofluorination of alkenes using AgBF4, I2: Evans, R. D.;
Schauble, J. H. Synthesis 1987, 551.
(6) (a) Pocker, Y.; Kevill, D. N. J. Am. Chem. Soc. 1965, 87,
5060. (b) Kevill, D. N.; Suthoff, R. F. J. Chem. Soc., Perkin
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(7) Reviewed by: Kevill, D. N. In The Chemistry of Halides,
Pseudo-halides and Azides, Part 2; Patai, S.; Rappoport, Z.,
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(8) Vona, J. A.; Steigman, J. J. Am. Chem. Soc. 1959, 81, 1095.
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1593. (b) Bando, Y.; Nagakura, S. Theor. Chim. Acta 1968,
9, 210. (c) Molina, M.; Tabak, S. J. Inorg. Nucl. Chem.
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(10) Reviews on N-iodonium complexes: (a) Varvoglis, A. The
Organic Chemistry of Polycoordinated Iodine; VCH
Publishers, Inc.: New York, 1992, 355. (b) Moeller, T.
Inorganic Chemistry; John Wiley and Sons, Inc.: New York,
1952, 460.
1R,2R-Dimethoxy-1-methyl-4R-isopropylcyclohexane (13)
1H NMR (200 MHz, CDCl3): d = 0.86 [d, 6 H, (CH3)2C], 1.15 (s, 3
H, CH3), 1.20–2.11 [m, 8 H, H3–6, (CH3)2CH], 3.17 (dd, J2a,3a = 11.2
Hz, J2a,3e = 4.6 Hz, 1 H, H2), 3.2 (s, 3 H, OCH3), 3.4 (s, 3 H, OCH3).
13C{1H} NMR (50.3 MHz, CDCl3): d = 15.0, 19.7 (q, CH3), 25.9,
32.2, 34.4 (3 × t, C3,5,6), 48.9 (q, OCH3), 57.2 (q, OCH3), 77.80 (s,
C1), 84.3 (d, C2).
syn-7-Iodo-2-exo-methoxybicyclo[2.2.1]heptane (14)16
1H NMR (200 MHz, CDCl3): d = 0.91–1.05 (m, 1 H, H5n), 1.14–
1.28 (m, 1 H, H6n), 1.50–1.74 (m, 2 H, H5x, H6x), 1.76–1.90 (ddd,
J2n,3n = 7.4 Hz, J3n,4 = 1.3 Hz, J3n,3x = 13.2 Hz, 1 H, H3n), 2.02–2.17
(ddd, J3n,3x = 13.2 Hz, J2n,3x = 3.7 Hz, J3x,4 = 6.2 Hz, 1 H, H3x), 2.37–
2.50 (m, 1 H, H4), 2.57–2.65 (m, 1 H, H1), 3.30 (s, 3 H, OCH3),
3.40–3.46 (ddd, J2n,3n = 7.4 Hz, J1,2n = 1.3 Hz, J2n,3x = 3.7 Hz, 1 H,
H2n), 3.69–3.75 (dd. J = 1.4 Hz, 1 H, H7).
13C{1H} NMR (50.3 MHz, CDCl3): d = 25.41 (t, C5,6), 27.64 (d, C7),
38.67 (t, C3), 43.46 (d, C4), 45.39 (d, C1), 56.05 (q, OCH3), 84.45 (d,
C-2).
(11) Roberts, J. D. J. Org. Chem. 1979, 44, 2658.
(12) Crist, D. R.; Hsieh, Z.-H.; Jordan, G. J.; Schinco, F. P.;
Maciorowski, C. A. J. Am. Chem. Soc. 1974, 96, 4932.
(13) Crookes, J. V.; Woolf, A. A. J. Chem. Soc., Dalton Trans.
1973, 1241.
7-syn-Iodo-2-exo-(2-hydroxyethoxy)bicyclo[2.2.1]heptane (15)
1H NMR (200 MHz, CDCl3): d = 0.85–1.15 (m, 1 H, H5n), 1.15–
1.30 (m, 1 H, H6n), 1.60–1.75 (m, 2 H, H5x, H6n), 1.87 (ddd, J3n,3x
13.4 Hz, J2n,3n = 7.3 Hz, J3n,4 = 1.5 Hz, 1 H, H3n), 2.10 (ddd, J3n,3x
=
=
(14) Likewise, Prévost reactions of trisubstituted alkenes give
very low yields of diols, plus allylic alcohols and ketones:
Parrilli, M.; Dovinola, V.; Mangoni, L. Gazz. Chim. Ital.
1974, 104, 829.
(15) (a) Rickborn, B.; Gerkin, R. M. J. Am. Chem. Soc. 1968, 90,
4193. (b) Bhatia, K. A.; Eash, K. J.; Leonard, N. M.;
Oswald, M. C.; Mohan, R. S. Tetrahedron Lett. 2001, 42,
8129.
(16) (a) Davidson, R. I.; Kropp, P. J. J. Org. Chem. 1982, 47,
1904. (b) Iodoether 14 was previously obtained by reaction
of norbornene with silver oxide, I2 in MeOH.
(17) Jarret, R. M.; Veniero, J. C.; Byrne, T. P.; Saunders, M.;
Laidig, K. E. J. Am. Chem. Soc. 1988, 110, 8287.
(18) Analogous replacement of the 3-exo-iodo group by 3-exo-
acetoxyl has been reported: (a) Cambie, R. C.; Lindsay, B.
G.; Rutledge, P. S.; Woodgate, P. D. J. Chem. Soc., Perkin
Trans. 1 1976, 845. (b) Cambie, R. C.; Hayward, R. C.;
Lindsay, B. G.; Phan, A. I. T.; Rutledge, P. S.; Woodgate, P.
D. J. Chem. Soc., Perkin Trans. 1 1976, 1961.
(19) Lemieux, R. U.; Fraser-Reid, B. Can J. Chem. 1965, 43,
1460.
13.3 Hz, J3x,4 = 6.1 Hz, J2n,3x = 3.4 Hz, 1 H, H3x), 2.40, 2.50 (2 × s,
2 H, H1, H4), 3.25, 3.35 (2 × m, 4 H, OCH2CH2O), 3.60 (m, w1/2
20 Hz, 1 H, H2n), 3.73 (m, w1/2 = 10 Hz, 1 H, H7).
=
13C{1H} NMR (50.3 MHz, CDCl3): d = 25.06, 25.36 (2 × t, C5,6),
28.46 (d, C7), 38.86 (t, C3), 43.44 (d, C4), 45.95 (d, C1), 61.70 (t,
CH2OH), 69.19 (t, OCH2), 82.63 (d, C2).
3-exo-(2-Hydroxyethoxy)tricyclo[2.2.1.02,6]heptane (17)
1H NMR (200 MHz, CDCl3): d = 1.1–1.8 (m, 7 H, H1,2,5–7), 1.95 (m,
1 H, H4), 2.17 (s, 1 H, OH), 3.51 (dd, 2 H, OCH2), 3.58 (m, 1 H, H3),
3.73 (dd, 2 H, CH2OH).
13C{1H} NMR (50.3 MHz, CDCl3): d = 10.80, 12.75, 13.90 (3 × d,
C
1,2,6), 29.44, 30.25 (2 × t, CH2, C5,7), 32.30 (d, C4), 61.91 (t,
CH2OH), 69.78, (t, CH2O), 84.48 (d, C3).
trans-2,3-Dimethoxytetrahydropyran (18)20,30
1H NMR (200 MHz, CDCl3): d = 1.50–2.05 (m, 4 H, H4,5), 3.42 (s,
3 H, OCH3), 3.43 (s, 3 H, OCH3), 3.72–3.90 (m, 2 H, H6), 3.90–4.01
(m, 1 H, H3), 4.54 (d, J2,3 = 5.6 Hz, 1 H, H2).
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Trans Dialkoxylation of Cyclic Alkenes
1339
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Synthesis 2005, No. 8, 1333–1339 © Thieme Stuttgart · New York