Synthesis of substituted tetrahydrofuran by electrophile-induced cyclization of 4-pentene-1,2,3-triols - An example of 5-exo versus 5-endo cyclization governed by the electrophile

Article abstract of DOI:10.1002/1099-0690(200102)2001:3<507::AID-EJOC507>3.0.CO;2-R

Differently protected 4-pentene-1,2,3-triols 5-8 were obtained from glyceraldehyde and submitted to iodine-based electrophile-induced cyclization to give tetrahydrofuran derivatives 10 and 18, with high chemo-, regio-, and stereo-selectivity, through a 5-exo cyclization process. However, when an electrophilic selenium reagent was treated with similar alkene triols 5, 7, and 8, the product depended on the protecting group at the primary hydroxy moiety. Thus, while compounds 5a and 5b, unprotected at the primary hydroxy group, give compounds 26 and 27, and 32 and 33, respectively, through a 5-exo cyclization process, compounds 7 and 8, protected at the primary hydroxy group, give the 5-endo cyclization products 22-25 and 28-31 in good yields. The electrophile-induced cyclization of 4-pentene-1,2,3-triols to give tetrahydrofuran derivatives can be directed towards a 5-exo process by the use of iodine or, when the primary hydroxy group is unprotected, selenium. When the primary hydroxy group is protected, use of selenium results in 5-endo cyclization.

Full text of DOI:10.1002/1099-0690(200102)2001:3<507::AID-EJOC507>3.0.CO;2-R

FULL PAPER
Synthesis of Substituted Tetrahydrofuran by Electrophile-Induced Cyclization
of 4-Pentene-1,2,3-triols ؊ An Example of 5-exo versus 5-endo Cyclization
Governed by the Electrophile
[a]
[a]
´
Fernando Bravo and Sergio Castillon*
Keywords: Cyclizations / Iodine / Oxygen heterocycles / Selectivity / Selenium
Differently protected 4-pentene-1,2,3-triols 5−8 were ob-
tained from glyceraldehyde and submitted to iodine-based
electrophile-induced cyclization to give tetrahydrofuran de-
ively, through a 5-exo cyclization process, compounds 7 and
8, protected at the primary hydroxy group, give the 5-endo
cyclization products 22−25 and 28−31 in good yields. The
rivatives 10 and 18, with high chemo-, regio-, and stereo- electrophile-induced cyclization of 4-pentene-1,2,3-triols to
selectivity, through a 5-exo cyclization process. However,
when an electrophilic selenium reagent was treated with
similar alkene triols 5, 7, and 8, the product depended on the
protecting group at the primary hydroxy moiety. Thus, while
compounds 5a and 5b, unprotected at the primary hydroxy
group, give compounds 26 and 27, and 32 and 33, respect-
give tetrahydrofuran derivatives can be directed towards a
5-exo process by the use of iodine or, when the primary hy-
droxy group is unprotected, selenium. When the primary hy-
droxy group is protected, use of selenium results in 5-endo
cyclization.
Introduction
tiary[11] or quaternary[12]) or when the carbon atom of the
double bond closest to it is substituted.[12b,13] On the other
hand, 5-endo cyclizations take place when the double bond
is substituted at the carbon atom furthest from the nucleo-
phile.[11] In particular, 5-endo selenoetherification provides
good yields.[14] Iodine electrophiles can also produce a 5-
endo cyclization in these substrates, although reactions are
slow and yields are generally lower.[11,15] In the absence of
these structural factors it is not easy to predict the cycliza-
tion mode, and mixtures are usually obtained.[12b,16]
Cyclolactonization and cycloetherification induced by
electrophilic reagents are important tools in the synthesis
of complex organic molecules.[1] The conditions of cycliza-
tion are, in general, independent of the nucleophile (usually
O, N, S, and C), and electrophilic reagents commonly used
are, among others, mercury,[2] sulfur,[3] bromine,[4] selen-
ium,[5] and iodine.[6] The regioselectivity in alkenol cycliza-
tions can be explained by the Baldwin rules.[7] However, 5-
endo-trig electrophile-induced cyclizations, which are not
favored according to these rules, have been reported. The
fact that these cyclizations are electrophile- rather than nu-
cleophile-driven suggests that they are not true excep-
tions.[8]
In general, electrophilic cyclizations can be effected under
kinetic or thermodynamic conditions.[9] Under kinetic con-
ditions, a base is used to deprotonate the oxonium cation
in the cyclic intermediate, and this makes the reaction irre-
versible. Under these conditions, exo cyclizations are usu-
ally preferred.
Concerning the regioselectivity, cyclization of alkenols
has some general features. Firstly, 5-exo cyclization is gener-
ally preferred to 6-endo. The percentage of 6-endo products
increases as substitution increases at the terminal olefinic
carbon atom[10] (Scheme 1, a). Secondly, there is competi-
tion between 4-exo and 5-endo cyclization, dependent on
the double bond substitution pattern (Scheme 1, b). Thus,
4-exo cyclizations mainly occur when the carbon atom
bearing the internal nucleophile is highly substituted (ter-
[a]
´
´
´ `
i Quımica Organica,
Departament de Quımica Analıtica
Scheme 1
´
Facultat de Quımica, Universitat Rovira i Virgili,
Pc¸a. Imperial Tarraco 1, 43005 Tarragona, Spain
Fax: (internat.) 34-977/559-563
The situation is more complex for polyhydroxylated al-
kenes (Scheme 2), since several cyclization paths may be fol-
E-mail: castillon@quimica.urv.es
Eur. J. Org. Chem. 2001, 507Ϫ516
WILEY-VCH Verlag GmbH, 69451 Weinheim, 2001
1434Ϫ193X/01/0203Ϫ0507 $ 17.50ϩ.50/0
507

´
F. Bravo, S. Castillon
FULL PAPER
lowed. Cyclizations from tri- or tetrahydroxyhexenes with a
terminal double bond (usually derived from pentoses) have
been widely studied, and the preferred process is 5-exo
(Scheme 2, a).[17]
Scheme 2
However, reported electrophile-induced cyclizations in
polyhydroxypentenes mainly produce 5-endo cyclizations
(Scheme 2, b), probably because the substrates studied are
polysubstituted olefins (Scheme 2, b; R3 ϭ H, OR; R4 ϭ
furyl,[18] OR[19]).
Recently, we described an efficient procedure for synthes-
izing biologically active isonucleosides, based on the iodo-
cyclization of pentene diols (Scheme 2, b; R3 ϭ R4 ϭ H).[20]
Pursuing our interest in these reactions for use in the pre-
paration of biologically active products, we report in this
paper a general study of the electrophile-induced cyclization
of 4-pentene-1,2,3-triols (Scheme 2, b, R3 ϭ OR, R4 ϭ H),
and show that the regioselectivity of the process can be con-
trolled through 5-exo-trig-like or 5-endo-trig-like cyclization
depending on the electrophile used.
Scheme 3
Initially, we explored the role of protecting groups in the
iodine-induced cyclization of alkenetriols 5a؊8a. We
treated the alcohol 7a with iodine under basic conditions[8]
and obtained a mixture of tetrahydrofurans 10 and 12 in
an 86% yield (ratio 10/12 ϭ 77:23) (Table 1, Entry 1;
Scheme 4). These compounds were formed by 5-exo cycliza-
tion involving the oxygen atom bonded to C-1, with con-
comitant loss of the benzyl group. This consecutive cycliza-
tion/benzyl deprotection is
a
well-documented pro-
cess.[6c,18,23] It has also been observed that ethers do not
participate in the cyclization process when electrophiles
with a poorly nucleophilic counter-ion are used.[17d] Be-
cause of this, we used bis(syn-collidine)iodonium perchlor-
ate[24] and N-iodosuccinimide as electrophilic reagents, but
we obtained the same mixture of products (Entries 2 and
3). This shows that benzyl ethers also participate in cycliza-
tion when there is no nucleophilic counter-ion, probably by
formation of a benzyl cation.[25] When NIS was the elec-
Results and Discussion
To explore the role of protecting groups in the cycliza- trophile and benzene the solvent, the reaction was very slow
tion, we prepared the differently protected pentene triols and gave the compounds 10 and 12, together with their re-
5؊8 from glyceraldehyde,[21a] as shown in Scheme 3. Hy- spective derivatives 14 and 16, which are probably formed
droxyalkenes 2a and 2b were prepared as a diastereomeric by reaction with the benzyl cation liberated during the reac-
mixture, following reported procedures.[21b] The free hy- tion (Entry 4). Compounds 14 and 16 were inseparable and
1
droxy group in the mixture of 2a and 2b was protected by their structures were confirmed by comparing their H and
treatment with benzyl bromide in basic medium to give 13CNMR spectra with those of products obtained by treat-
compounds 3a and 3b, or with TBDPSCl to give com- ing 9a under conditions similar to those used for 7a; the
pounds 4a and 4b. The hydrolysis of the acetal groups in 3a spectra turned out to be identical (Scheme 4). Curiously,
and 3b, and 4a and 4b led to the diols 5a and 5b, and 6a when 7a was treated with KH[19b] to form the alkoxide and
and 6b, respectively. The primary alcohol moieties in com- then with I2, there was no further reaction even after 7 d.
pounds 5a and 5b were selectively protected by treatment
Since the benzyl group was easily removed under the re-
with Bu2SnO and BnBr,[22] or with TBDPSCl to afford the action conditions used, we next tried other protecting
partially protected trihydroxypentenols 7a and 7b, and 8a groups. When a pivaloyl group was present at the primary
and 8b, respectively. In the benzylation of 5a, compound 9a hydroxy group, iodine-induced cyclization resulted in a
was isolated as a minor product.
complex mixture of compounds, probably due to transes-
508
Eur. J. Org. Chem. 2001, 507Ϫ516

An Example of 5-exo versus 5-endo Cyclization Governed by the Electrophile
Table 1. Reaction of alkenols 5a؊8a with electrophilic iodine
FULL PAPER
Entry
Starting material
Iϩ
Conditions
Ratio of products (%)
Yield (%)
1
2
3
4
5
6
7
8
7a
7a
7a
7a
8a
5a
5a
6a
I2
NaHCO3, MeCN, 0 °C, 40 min
CH2Cl2, room temp., 3 h
10/12 (77:23)
10/12 (43:57)
10/12 (80:20)
10/12 (71:29)[a]
10/12 (73:27)[b]
10/12 (86:14)
10/12 (63:37)
11/13 (60:40)
86
57
64
62
65
91
38
46
I(syn-col)2ClO4
NIS
NIS
I2
CH2Cl2, Ϫ78°C to room temp., 8 d
benzene, room temp., 21 d
NaHCO3, MeCN, 0 °C, 18 h
NaHCO3, MeCN, 0 °C, 45 min
MeCN, 0 °C, 3 h
I2
I2
I2
NaHCO3, MeCN, 0 °C, 2 h
[a]
[b]
36% of compounds 14 and 16 was also obtained (ratio 73:27). Ϫ 21% of compounds 15 and 17 was also obtained (ratio 23:77).
(Scheme 5). Treatment of the diol 5b under the same condi-
tions increased the yield to 95%, with no loss in stereo-
selectivity (Entry 2). In this case, the absence of base de-
creased both the yield and the selectivity (Entry 3) and
necessitated longer reaction times. Treatment of 6b under
similar conditions provided compounds 19 and 21, in an
excellent yield, as an inseparable mixture. The presence of
a bulky group at the allylic position also slightly increased
the percentage of trans isomer (Entry 4), but did not invert
the diastereomer ratio.
Scheme 4
Table 2. Reaction of alkenols 5b, 6b, and 7b with electrophilic iod-
ine
terification processes. When silyl derivative 8a was treated
with iodine in basic medium, the reaction was very slow
and also afforded the 5-exo cyclization compounds 10 and
12 (Entry 5). An inseparable mixture of their derivatives 15
and 17 (Scheme 4), the result of the silylation of the free
secondary hydroxy group,[20] was also found. If 8a was pre-
viously treated with KH, or if bis(syn-collidine)iodonium
perchlorate was used, the starting material was unaltered.
In the absence of a nucleophilic counter-ion, the tert-butyl-
diphenylsilyl group is not liberated, and consequently there
is no reaction.
Entry[a]
Starting
material
Time
(min)
Ratio of products
(%)
Yield
(%)
1
7b
5b
5b
6b
30
30
120
20
18/20 (92:8)
18/20 (91:9)
18/20 (85:15)
19/21 (84:16)
81
95
61
99
2
3[b]
4
[a]
[b]
Conditions: I2, NaHCO3, MeCN, O°C. Ϫ
MeCN, 0°C.
Conditions: I2,
The yield of iodoetherification was increased by treating
the diol 5a with iodine in basic medium; a mixture of com-
pounds 10 and 12 (86:14) was obtained in a 91% yield,
through a 5-exo cyclization (Entry 6).
The observed stereoselectivity (Entries 1, 3Ϫ7) was con-
sistent with that reported for alkenols with an allylic alkoxy
group, which turned out to be cis to the iodoalkyl chain.[26]
It has been reported that bulky protecting groups in the
allylic alcohol can invert the stereoselectivity.[27] Thus, we
examined the iodine-induced cyclization of 6a, obtaining
compounds 11 and 13 as an inseparable mixture. The ratio
11/13 showed that the trans isomer had increased slightly,
but the stereoselectivity did not invert (Entry 8). However,
the yield decreased considerably.
Scheme 5
We tried to force the 4-exo, or possibly the 5-endo, pro-
cesses by treating the isopropylidene derivative[28] 3b with
bis(syn-collidine)iodonium perchlorate, but no reaction was
observed. Treating compound 3b with iodine in basic me-
dium, we recovered the 5-exo cyclization product 18 to-
gether with the diol 5b in low yields after 5 d (Scheme 6a).
In this case, the I2 seems to behave like a Lewis acid; first
it catalyses the deprotection of the acetal and then it in-
duces the cyclization. In fact, iodine has been used as a
catalyst in acetal formation.[29]
In the absence of base, treatment of 5a with iodine re-
sulted in a complex mixture of compounds from which
compounds 10 and 12 were isolated in a 38% yield and with
low stereoselectivity (Entry 7) (Scheme 4).
The diastereomer 7b behaved similarly to 7a when treated
with iodine. Thus, treatment of 7b with iodine in basic me-
dium gave the 5-exo cyclization products 18 and 20 in an
81% yield and a ratio of 18/20 ϭ 92:8 (Table 2, Entry 1) Scheme 6
Eur. J. Org. Chem. 2001, 507Ϫ516
509

´
F. Bravo, S. Castillon
FULL PAPER
Table 3. Reaction of alkenols 5a, 7a, and 8a with electrophilic selenium reagents
Entry
Starting material
Selenium reagent
Conditions
Ratio of products (%)
Yield (%)
1
2
3
4
5
5a
5a
7a
8a
8a
NPSP
CSA, CH2Cl2, room temp., 1 h
NEtiPr2, CH2Cl2, 0 °C,1 h
CSA, CH2Cl2, room temp., 1 h
CSA, CH2Cl2, reflux, 12 h
NEtiPr2, CH2Cl2, 0 °C, 30 min
26/27 (30:70)
26/27 (10:90)
22/24 (50:50)
23/25 (56:44)
23/25 (32:68)
99
55
55
87
42
PhSeOTf
NPSP
NPSP
PhSeOTf
The reaction of pentene-1,2,3-triols with iodine elec-
In contrast, treatment of compound 7a with NPSP/CSA
trophiles described above always results in a 5-exo cycliza- afforded the 5-endo cyclization products 22 and 24, in a
tion product, independently of the protecting groups on the 55% yield with zero stereoselectivity (Entry 3), through par-
different hydroxy moieties. The presence of a nucleophilic ticipation by the hydroxy group bonded to C-2. Small
counter-ion assists the process and increases the yield and amounts of 5-exo and 6-endo cyclization products were also
stereoselectivity.
detected, perhaps because of the lability of the benzyl group
It has been reported that PhSeCl gives the product of attached to the oxygen atom at C-1.
addition to terminal double bonds rather than cyclization
Since we know that TBDPS is stable in the absence of a
products.[30] This problem can be solved by using a reagent good nucleophile, we tried to make compound 8a react with
with a non-nucleophilic counter-ion, such as N-phenylseleno- NPSP, reducing the amount of CSA to prevent deprotec-
phthalimide (NPSP). However, this reagent is less elec- tion. Under these conditions (Entry 4), compounds 23 and
trophilic and usually requires the presence of acid to be 25 were obtained in an 87% yield and a ratio of 56:44.
active.[31] Thus, when the diol 5a was treated with NPSP in
the presence of camphorsulfonic acid (CSA), compounds
26 and 27 were obtained in a quantitative yield (ratio
Trying to improve the stereoselectivity, we examined 8a
in basic medium, treating it with PhSeOTf[32] and NEt2iPr,
but the yield was lower and the stereoselectivity towards the
cis isomer increased only slightly (Entry 5).
30:70), through
a 5-exo process (Table 3, Entry 1;
(Scheme 7). In order to determine how selenium reagents
behave in basic medium, 5a was treated with PhSeOTf[32]
in the presence of NEt2iPr to obtain the 5-exo products as
well. The yield was low, however (Entry 2).
Although examples of 5-endo cyclization of polysubsti-
tuted alkenes[14] induced by selenium reagents have been re-
ported, there are no examples of this cyclization in terminal
olefins and no cases of competition with a 5-exo cyclization
have been reported.
Treatment of the diastereomer 5b under acidic (Table 4,
Entry 1) or basic conditions (Entry 2) also resulted in the
5-exo cyclization products 32 and 33 (Scheme 8). However,
if 7b was treated with NPSP/CSA, the 5-endo cyclization
products 28 and 30 were obtained in moderate yields and
with low stereoselectivities (Entry 3). At low temperatures
the yield is much smaller. When 8b was treated with NPSP/
CSA, compounds 29 and 31 were obtained in a 96% yield
and with zero stereoselectivity (Entry 4). Under basic con-
ditions (Entry 5) the yield decreased to 61%. The selectivity
was inverted, although it still remained low. Compounds 28
and 30, and 29 and 31 were obtained as inseparable mix-
tures, and their 5-endo origin was confirmed by conversion
into the corresponding known glycals, through oxidation
and elimination of the selenoxide (Scheme 9).[33]
Finally, we attempted the cyclization reaction with the
isopropylidene derivative 3b. To prevent deprotection of the
isopropylidene group, we initially attempted the reaction in
Scheme 7
Table 4. Reaction of alkenols 5b, 7b, and 8b with electrophilic selenium reagents
Entry
Starting material
Selenium reagent
Conditions
Ratio of products (%)
Yield (%)
1
2
3
4
5
5b
5b
7b
8b
8b
NPSP
CSA, CH2Cl2, room temp., 1 h
NEtiPr2, CH2Cl2, 0 °C, 1 h
CSA, CH2Cl2, room temp., 20 min
CSA, CH2Cl2, reflux, 12 h
32/33 (43:57)
32/33 (34:66)
28/30 (36:64)
29/31 (50:50)
29/31 (64:36)
87
53
58
96
61
PhSeOTf
NPSP
NPSP
PhSeOTf
NEtiPr2, CH2Cl2, 0 °C, 1 h
510
Eur. J. Org. Chem. 2001, 507Ϫ516

An Example of 5-exo versus 5-endo Cyclization Governed by the Electrophile
FULL PAPER
stereochemistry of the stereocenter generated in the 5-exo
cyclization was determined on the basis of two factors: a)
the conversion of products 10 and 20, by treatment with
NaH in THF, into the same bicyclo compound 34 ([α]D25
ϭ
ϩ50.5) (Scheme 11), the enantiomer of which has been pre-
viously described[35] ([α]2D0 ϭ Ϫ48.1), whereas compounds
12 and 18 afforded a complex mixture under the same con-
ditions, and b) the fact that, in the 13C NMR spectra, the
signal of the carbon atom that bears the electrophile ap-
pears at higher fields, and the signals of the protons bonded
to it at lower fields, when it is cis with respect to the vicinal
group, as has previously been described.[12b,36]
Scheme 11
Scheme 8
Scheme 9
Conclusion
Pentenetriols 5؊8 are easily obtained from glyceral-
dehyde and react with iodine and selenium electrophilic re-
agents to give a set of differently substituted tetrahydrofur-
ans in high yields (Scheme 12). The most remarkable fea-
tures of this procedure are:
Ϫ Iodine electrophilic reagents always provide the 5-exo
cyclization products, independently of the protecting
groups. The best yield is obtained in the absence of pro-
tecting group at the primary hydroxy group.
Ϫ Selenium reagents can direct the cyclization reaction
towards either 5-endo or 5-exo cyclization, depending on
whether the primary hydroxy group is protected or not.
Ϫ When the primary alcohol is protected, cyclization can
be directed in either the 5-exo or the 5-endo direction, by
using iodine or selenium reagents, respectively.
the absence of CSA, but it did not take place. When a cata-
lytic amount of CSA was added, the reaction was complete
in 5 h, giving a mixture of compounds 32 and 33 in a 65%
yield and a ratio of 37:63, as a consequence of a 5-exo cyc-
lization process (Scheme 10). Also, in this case, the isoprop-
ylidene group was hydrolyzed before cyclization.
Scheme 10
Structural Elucidation
In the synthetic sequences discussed above, two new ste-
reocenters were generated. The first one was created by ad-
dition of vinylmagnesium chloride to 2,3-O-isopropylidene-
glyceraldehyde. The configuration of this stereocenter was
determined on the basis of two factors: a) comparison of
the NMR-spectroscopic data for the addition products (2a
and 2b) with those described in the literature,[34] and b) the
conversion of products of 5-endo selenoetherification into
glycals of known configuration (Scheme 9).
The second stereocenter is generated as the consequence
of the exo or endo cyclization. The mode of cyclization was
deduced by DEPT experiments, focusing on the carbon
atom bearing the iodine or selenium atom. The stereochem-
istry of the carbon atom bearing the electrophile in the 5-
endo selenoetherification products 22 and 24, and 28 and
30 was elucidated by NOE difference experiments. The ste-
reochemistry of the other 5-endo selenoetherification prod-
ucts (23 and 25, and 29 and 31) was assigned by comparing
Scheme 12
Experimental Section
General Remarks: Melting points are uncorrected. Optical rotations
their 13C NMR spectra to the previous ones. Finally, the were measured at 25°C in 10-cm cells. Ϫ H NMR and 13C NMR
1
Eur. J. Org. Chem. 2001, 507Ϫ516
511

´
F. Bravo, S. Castillon
FULL PAPER
spectra were recorded with a 300-MHz (300 and 75.4 MHz, re-
spectively) apparatus, with CDCl3 as solvent. Coupling constants
are given in Hz. Ϫ Elemental analyses were determined at the
(3b): Anhydrous THF (8 mL) was added to a 60% dispersion of
NaH in mineral oil (4.06 g, 101.51 mmol), previously washed with
anhydrous hexane. The flask was cooled in water/ice, and com-
Servei de Recursos Cientifics (Universitat Rovira i Virgili). Ϫ TLC pounds 2a/b (10.04 g, 63.44 mmol), dissolved in 20 mL of dried
was carried out on aluminium sheets precoated with silica gel 60
F254. Flash column chromatography was performed using Kieselgel
THF, were added dropwise and the mixture was stirred for 30 min.
Then, benzyl bromide (14 mL, 117.87 mmol) was added. The reac-
60 (particle size: 40Ϫ63 microns). Radial chromatography was per- tion mixture was stirred overnight and quenched by the careful
formed on 1-, 2-, or 4-mm plates of silica gel, depending on the
amount of product. Band separation was monitored by UV. Me-
dium pressure chromatography (MPLC) was performed using 60 A
CC silica gel (6Ϫ35 microns). All chromatographic solvents were
distilled at atmospheric pressure prior to use. Ϫ Dry solvents were
obtained according to conventional methods.[37] Bis(syn-collidine)-
iodonium perchlorate was prepared by Lemieux’s method.[24]
addition of a few mL of methanol. The solvent was then evaporated
under reduced pressure. The crude product was purified by flash
chromatography (ethyl acetate/hexane, 1:10) to recover 13.37 g of
diastereoisomers 3a (higher Rf) and 3b (86%) as a syrup. The mix-
ture 3a/3b was separated using MPLC, eluting with a linear gradi-
ent [from hexane to hexane/ethyl acetate (30:1), then to hexane/
ethyl acetate (20:1), and then to hexane/ethyl acetate (10:1)].
1
Compound 3a: [α]2D5 ϭ ϩ30.4 (CHCl3, c ϭ 0.68). Ϫ H NMR: δ ϭ
General Procedure for Iodoetherification under Basic Conditions:
Sodium hydrogen carbonate (9.00 mmol) was added to a solution
of the alkenol (3.00 mmol) in anhydrous acetonitrile (10 mL). The
mixture was cooled to 0 °C, stirred at this temperature for 5 min,
and then iodine (9.00 mmol) was added. The reaction was mon-
itored by TLC. After completion, the mixture was diluted with di-
ethyl ether and washed with aqueous sodium thiosulfate. The aque-
ous phase was extracted with more diethyl ether, and the organic
layers were combined and dried with magnesium sulfate. After fil-
tration, the solvent was removed under reduced pressure. The res-
idue thus obtained was purified by column chromatography.
1.38 (s, 3 H), 1.43 (s, 3 H), 3.74 (t, 1 H, J ϭ 6.9), 3.87 (dd, 1 H,
J ϭ 8.0, 5.4), 4.06 (dd, 1 H, J ϭ 8.0, 5.4), 4.13 (q, 1 H, J ϭ 6.0),
4.40 (d, 1 H, J ϭ 11.8), 4.65 (d, 1 H, J ϭ 11.8), 5.34 (ddd, 1 H,
J ϭ 17.2, 1.7, 0.8), 5.41 (dt, 1 H, J ϭ 10.4, 0.8), 5.83 (ddd, 1 H,
J ϭ 17.2, 10.4, 7.6), 7.20Ϫ7.40 (m, 5 H). Ϫ 13C NMR: δ ϭ 25.2,
26.5, 66.8, 70.4, 77.4, 80.9, 109.5, 119.9, 127.6, 127.8, 128.3, 135.0,
138.0. Ϫ C15H20O3 (248.32): calcd. C 72.55, H 8.12; found C 72.74,
H 8.23.
1
Compound 3b: [α]2D5 ϭ Ϫ18.7 (CHCl3, c ϭ 0.72). Ϫ H NMR: δ ϭ
1.38 (s, 3 H), 1.42 (s, 3 H), 3.74 (dd, 1 H, J ϭ 8.5, 6.4), 3.83 (t, 1
H, J ϭ 7.4), 3.95 (dd, 1 H, J ϭ 8.5, 6.6), 4.21 (q, 1 H, J ϭ 6.6),
4.69 (d, 1 H, J ϭ 12.3), 4.47 (d, 1 H, J ϭ 12.3), 5.34 (dt, 1 H, J ϭ
16.9, 1.0), 5.36 (dt, 1 H, J ϭ 10.7, 1.0), 5.72 (ddd, 1 H, J ϭ 16.9,
10.7, 7.3), 7.20Ϫ7.40 (m, 5 H). Ϫ 13C NMR: δ ϭ 25.3, 26.4, 65.7,
70.1, 77.3, 80.9, 109.6, 120.2, 127.5, 127.7, 128.2, 134.1, 138.2. Ϫ
C15H20O3 (248.32): calcd. C 72.55, H 8.12; found C 72.34, H 8.20.
General Procedure for Iodoetherification in the Absence of Base: The
method followed was exactly the same as the one described above,
but with the omission of sodium bicarbonate.
General Procedure for Selenoetherification under Basic Conditions:
A solution of phenylselenenyl chloride (0.39 mmol) in dry dichloro-
methane (4 mL) was cooled in a water/ice bath. Then, silver trifluo-
romethanesulfonate (0.39 mmol) was added, and the mixture was
stirred for 10 min. After this time, N-ethyldiisopropylamine
(0.33 mmol) and the alkenol (0.30 mmol), dissolved in dry di-
chloromethane (4 mL), were added sequentially. The progress of
the reaction was monitored by TLC, and when it had finished the
mixture was filtered through silica gel, and the solvent was removed
under vacuum. The crude product thus obtained was purified by
column chromatography.
(2R,3S)-3-O-tert-Butyldiphenylsilyl-1,2-O-isopropylidene-4-pentene-
1,2,3-triol (4a) and (2R,3R)-3-O-tert-Butyldiphenylsilyl-1,2-O-iso-
propylidene-4-pentene-1,2,3-triol (4b): The mixture 2a/b (2.03 g,
12.86 mmol) was treated using the general silylation procedure over
4 h at 55 °C. After the workup, the crude product was purified by
flash chromatography (hexane/ethyl acetate, 10:1) to furnish 4.51 g
of the diastereoisomeric mixture 4b (higher Rf) and 4a (88%) as a
syrup. Both isomers were isolated by MPLC, using linear gradient
[hexane to hexane/ethyl acetate (30:1), to hexane/ethyl acetate
(20:1)].
General Procedure for Selenoetherification under Acidic Conditions:
In a round-bottomed flask, the alkenol (1.00 mmol) was dissolved
in anhydrous dichloromethane (5 mL). Then, N-phenylseleno-
phthalimide (NPSP) (1.20 mmol) and camphorsulfonic acid (CSA)
(0.70 mmol) were added. The reaction was monitored by TLC, and
when it was complete the reaction mixture was filtered through
silica gel and concentrated under reduced pressure. The crude prod-
uct was purified by column chromatography.
1
Compound 4a: [α]2D5 ϭ Ϫ8.2 (CHCl3, c ϭ 1.66). Ϫ H NMR: δ ϭ
1.06 (s, 9 H), 1.32 (s, 6 H), 3.81 (dd, 1 H, J ϭ 7.9, 6.4), 3.97 (dd,
1 H, J ϭ 7.9, 6.3), 4.05 (q, 1 H, J ϭ 6.1), 4.15 (tt, 1 H, J ϭ 6.4,
1.2), 4.92 (dt, 1 H, J ϭ 17.2, 1.2), 4.99 (dt, 1 H, J ϭ 10.4, 1.2),
5.74 (ddd, 1 H, J ϭ 17.2, 10.4, 7.0), 7.30Ϫ7.80 (m, 10 H). Ϫ 13C
NMR: δ ϭ 19.3, 25.2, 26.3, 26.9, 66.3, 75.6, 78.8, 109.3, 117.5,
127.4, 127.6, 129.7, 129.8, 133.7, 133.9, 136.1, 136.2, 137.3. Ϫ
C24H32O3Si (396.60): calcd. C 72.68, H 8.13; found C 72.59, H
8.25.
General Method for Silylation: Imidazole (3.00 mmol) was added
to a stirred solution of the alcohol (1.43 mmol) in anhydrous DMF
(10 mL per gram of alcohol), and then tert-butyldiphenylsilyl chlor-
ide (1.57 mmol) was added under argon at 0°C. The reaction was
monitored by TLC and, when it had finished, the crude silyl ether
was recovered by evaporation of the solvent under vacuum. Then
it was diluted with dichloromethane, the organic phase was washed
with water, and the aqueous phase was extracted with more dichlo-
romethane. The combined of organic phases were dried with mag-
nesium sulfate, the solvent was removed in vacuo, and the product
purified by column chromatography.
1
Compound 4b: [α]2D5 ϭ ϩ30.7 (CHCl3, c ϭ 1.74). Ϫ H NMR: δ ϭ
1.08 (s, 9 H), 1.26 (s, 3 H), 1.32 (s, 3 H), 3.85 (dd, 1 H, J ϭ 8.5,
6.2), 3.93 (dd, 1 H, J ϭ 8.5, 6.6), 4.05 (q, 1 H, J ϭ 6.1), 4.30 (tt, 1
H, J ϭ 6.1, 1.5), 5.12 (dt, 1 H, J ϭ 10.5, 1.6), 5.16 (dt, 1 H, J ϭ
17.2, 1.5), 5.84 (ddd, 1 H, J ϭ 17.2, 10.5, 5.9), 7.20Ϫ7.70 (m, 10
H). Ϫ 13C NMR: δ ϭ 19.3, 24.9, 26.1, 26.9, 65.0, 74.6, 77.8, 109.4,
117.3, 127.5, 127.6, 129.7, 129.8, 133.7, 133.9, 135.7, 136.0. Ϫ
C24H32O3Si (396.60): calcd. C 72.68, H 8.13; found C 72.73, H
8.21.
(2R,3S)-3-O-Benzyl-1,2-O-isopropylidene-4-pentene-1,2,3-triol (3a) (2R,3S)-3-O-Benzyl-4-pentene-1,2,3-triol (5a): A solution of 3a
and (2R,3R)-3-O-Benzyl-1,2-O-isopropylidene-4-pentene-1,2,3-triol (7.01 g, 27.10 mmol) in dry methanol (45 mL) was prepared. Then,
512
Eur. J. Org. Chem. 2001, 507Ϫ516

An Example of 5-exo versus 5-endo Cyclization Governed by the Electrophile
Dowex 50 W/Hϩ acid resin (10.50 g) was added and the suspension (731 mg). This mixture was separated by radial chromatography
FULL PAPER
was stirred at room temperature for 2 h. The resin was filtered off,
and the filtrate was purified by column chromatography, to obtain
5.88 g of 5a (100%) as a syrup. Ϫ [α]2D5 ϭ ϩ46.6 (CHCl3, c ϭ 0.81).
(hexane with 1% of methanol). Finally, compounds 7a (625 mg,
71%) and 9a (106 mg, 12%) were isolated as syrups.
1
Compound 7a: [α]2D5 ϭ ϩ26.5 (CHCl3, c ϭ 1.60). Ϫ H NMR: δ ϭ
1
Ϫ H NMR: δ ϭ 2.50Ϫ3.10 (br. s, 2 H), 3.60Ϫ3.80 (m, 3 H), 3.89
2.41 (d, 1 H, J ϭ 4.5), 3.56 (dd, 1 H, J ϭ 9.8, 6.0), 3.62 (dd, 1 H,
J ϭ 9.8, 4.0), 3.86 (tt, 1 H, J ϭ 6.7, 0.8), 3.91 (br. s, 1 H), 4.37 (d,
1 H, J ϭ 11.7), 4.54 (s, 2 H), 4.62 (d, 1 H, J ϭ 11.7), 5.34 (ddd, 1
H, J ϭ 17.3, 1.8, 0.9), 5.40 (ddd, 1 H, J ϭ 10.4, 1.8, 0.7), 5.86
(ddd, 1 H, J ϭ 17.3, 10.4, 7.6), 7.20Ϫ7.40 (m, 10 H). Ϫ 13C NMR:
δ ϭ 70.2, 70.6, 72.2, 73.3, 80.7, 120.1, 127.6, 127.7, 127.8, 127.8,
128.4, 128.4, 135.0, 138.0, 138.1. Ϫ C19H22O3 (298.38): calcd. C
76.41, H 7.43; found C 76.37, H 7.51.
(dd, 1 H, J ϭ 7.7, 4.0), 4.36 (d, 1 H, J ϭ 11.7), 4.63 (d, 1 H, J ϭ
11.7), 5.36 (dt, 1 H, J ϭ 17.3, 0.9), 5.40 (dt, 1 H, J ϭ 10.4, 0.8),
5.82 (ddd, 1 H, J ϭ 17.3, 10.4, 7.7), 7.35 (m, 5 H). Ϫ 13C NMR:
δ ϭ 63.1, 70.6, 73.1, 82.0, 120.2, 127.8 (2 C), 128.4, 134.8, 137.7. Ϫ
C12H16O3 (208.26): calcd. C 69.21, H 7.74; found C 69.40, H 7.84.
(2R,3R)-3-O-Benzyl-4-pentene-1,2,3-triol (5b): This compound was
prepared according to the same procedure as for 5a, starting from
compound 3b (4.01 g, 16.14 mmol), dry methanol (25 mL), and
Dowex 50 W/Hϩ acid resin (6.40 g). After purification, 5b (3.36 g,
100%) was recovered. Ϫ [α]2D5 ϭ Ϫ40.6 (CHCl3, c ϭ 0.47). Ϫ 1H
NMR: δ ϭ 2.80 (br. s, 1 H), 3.00 (br. s, 1 H), 3.50Ϫ3.80 (m, 3 H),
3.84 (t, 1 H, J ϭ 7.7), 4.34 (d, 1 H, J ϭ 11.5), 4.65 (d, 1 H, J ϭ
11.5), 5.37 (ddd, 1 H, J ϭ 16.8, 1.6, 0.8), 5.39 (ddd, 1 H, J ϭ 11.0,
1.6, 0.6), 5.77 (ddd, 1 H, J ϭ 16.8, 11.0, 7.7), 7.20Ϫ7.40 (m, 5 H).
1
Compound 9a: [α]2D5 ϭ ϩ45.6 (CHCl3, c ϭ 1.72). Ϫ H NMR: δ ϭ
2.20Ϫ2.40 (br. s, 1 H), 3.55 (dd, 1 H, J ϭ 5.6, 10.0), 3.70Ϫ3.80 (br.
s, 2 H), 3.98 (dd, 1 H, J ϭ 7.5, 5.6), 4.40 (d, 1 H, J ϭ 11.8), 4.59
(d, 1 H, J ϭ 11.6), 4.66 (d, 1 H, J ϭ 11.8), 4.69 (d, 1 H, J ϭ 11.6),
5.37 (ddd, 1 H, J ϭ 17.0, 1.8, 0.8), 5.39 (ddd, 1 H, J ϭ 10.7, 1.8,
0.8), 5.87 (ddd, 1 H, J ϭ 17.0, 10.7, 7.5), 7.20Ϫ7.40 (m, 10 H). Ϫ
13C NMR: δ ϭ 61.8, 70.5, 72.6, 80.7, 81.0, 119.5, 127.7, 127.8,
128.0 (2 C), 128.5 (2 C), 135.6, 138.1, 138.1. Ϫ C19H22O3 (298.38):
calcd. C 76.41, H 7.43; found C 76.32, H 7.55.
Ϫ
13C NMR: δ ϭ 62.9, 70.4, 73.8, 81.3, 120.7, 127.9, 128.0, 128.5,
134.5, 137.5. Ϫ C12H16O3 (208.26): calcd. C 69.21, H 7.74; found
C 69.05, H 7.80.
(2R,3R)-1,3-Di-O-benzyl-4-pentene-1,2,3-triol (7b): The procedure
followed was the same as that for the synthesis of 7a, using diol 5b
(383 mg, 1.84 mmol), toluene (45 mL), 4-A molecular sieves
(2R,3S)-3-O-tert-Butyldiphenylsilyl-4-pentene-1,2,3-triol (6a): A so-
lution of dilute hydrochloric acid in ethanol (65 mL, 1 mL of con-
centrated HCl per 100 mL of ethanol) was added to compound 4a
(265 mg, 0.67 mmol). The reaction was complete after 3 h. The
excess of acid was neutralized by adding 1 mL of aqueous NH3,
and the solvent was removed in vacuo. The product was purified
by column chromatography (hexane/ethyl acetate, 2:1), and diol 6a
(216 mg, 91%) was obtained as a syrup. Ϫ [α]2D5 ϭ Ϫ4.84 (CHCl3,
˚
(4.00 g), dibutyltin oxide (595 mg, 2.39 mmol), benzyl bromide (370
µL, 3.12 mmol), and tetrabutylammonium bromide (664 mg,
1.84 mmol). Purification was carried out in an MPLC apparatus,
using a linear gradient [hexane to hexane/ethyl acetate (3:1)], to
obtain 368 mg of 7b (67%) as a syrup. Ϫ [α]2D5 ϭ Ϫ28.6 (CHCl3,
1
c ϭ 1.74). Ϫ H NMR: δ ϭ 2.64Ϫ2.92 (br. s, 1 H), 3.48 (dd, 1 H,
1
c ϭ 2.65). Ϫ H NMR: δ ϭ 1.08 (s, 9 H), 2.35 (br. s, 1 H), 2.53
J ϭ 10.0, 5.7), 3.58 (dd, 1 H, J ϭ 10.0, 3.9), 3.78 (td, 1 H, J ϭ 6.1,
3.8), 3.92 (t, 1 H, J ϭ 7.2), 4.36 (d, 1 H, J ϭ 11.4), 4.49 (d, 1 H,
J ϭ 12.0), 4.55 (d, 1 H, J ϭ 12.0), 4.63 (d, 1 H, J ϭ 11.4), 5.34
(ddd, 1 H, J ϭ 9.8, 1.5, 0.8), 5.34 (ddd, 1 H, J ϭ 17.9, 1.5, 0.8),
5.78 (ddd, 1 H, J ϭ 17.9, 9.8, 7.9), 7.30 (m, 10 H). Ϫ 13C NMR:
δ ϭ 70.3, 70.4, 72.8, 73.4, 80.7, 119.9, 127.7, 127.7, 127.8, 127.8,
127.9, 128.4, 128.4, 134.9, 138.0. Ϫ C19H22O3 (298.38): calcd. C
76.41, H 7.43; found C 76.19, H 7.52.
(br. s, 1 H), 3.60Ϫ3.70 (m, 3 H), 4.19 (ddt, 1 H, J ϭ 7.1, 3.9, 1.2),
4.94 (dt, 1 H, J ϭ 17.2, 1.2), 5.04 (dt, 1 H, J ϭ 10.4, 1.3), 5.79
(ddd, 1 H, J ϭ 17.2, 10.4, 7.1), 7.30Ϫ7.80 (m, 10 H). Ϫ 13C NMR:
δ ϭ 19.2, 26.9, 63.0, 74.5, 76.7, 118.0, 127.6, 127.8, 129.9, 130.1,
133.3, 133.2, 135.9, 136.1, 136.5. Ϫ C21H28O3Si (356.54): calcd. C
70.74, H 7.92; found C 70.84, H 8.06.
(2R,3R)-3-O-tert-Butyldiphenylsilyl-4-pentene-1,2,3-triol (6b): The
procedure used was identical to the one above, starting from com-
pound 4b (249 mg, 0.63 mmol) and a dilute solution of HCl in
ethanol (65 mL). After the workup and flash chromatography (hex-
ane/ethyl acetate, 2:1), diol 6b (202 mg, 90%) was recovered. Ϫ [α]
(2R,3S)-3-O-Benzyl-1-O-tert-butyldiphenylsilyl-4-pentene-1,2,3-triol
(8a): The diol 5a (264 mg, 1.27 mmol) was treated under the gen-
eral conditions for silylation. TLC monitoring showed that the
starting material was consumed in 50 min. The crude silyl ether
was recovered as usual and purified by column chromatography
(hexane/ethyl acetate, 10:1), to afford 537 mg of 8a (95%) as a
25 ϭ ϩ15.7 (CHCl3, c ϭ 2.64). Ϫ 1H NMR: δ ϭ 1.08 (s, 9 H), 2.04
D
(br. s, 1 H), 2.61 (br. s, 1 H), 3.50 (dd, 1 H, J ϭ 12.0, 6.9), 3.60Ϫ3.70
(m, 2 H), 4.19 (ddt, 1 H, J ϭ 7.3, 5.8, 1.3), 4.96 (dt, 1 H, J ϭ 17.3,
1.3), 5.02 (dt, 1 H, J ϭ 10.4, 1.3), 5.80 (ddd, 1 H, J ϭ 17.3, 10.4,
7.3), 7.30Ϫ7.80 (m, 10 H). Ϫ 13C NMR: δ ϭ 19.2, 26.9, 62.7, 74.7,
75.8, 117.8, 127.5, 127.7, 129.8, 129.9, 133.3, 135.8, 136.0, 136.6.
Ϫ C21H28O3Si (356.54): calcd. C 70.74, H 7.92; found C 70.86,
H 8.09.
1
syrup. Ϫ [α]2D5 ϭ ϩ4.9 (CHCl3, c ϭ 1.75). Ϫ H NMR: δ ϭ 1.01
(s, 9 H), 2.42 (d, 1 H, J ϭ 4.3 Hz), 3.06Ϫ3.80 (m, 3 H), 3.90 (dd,
1 H, J ϭ 7.7, 5.4), 4.33 (d, 1 H, J ϭ 11.8), 4.60 (d, 1 H, J ϭ 11.8),
5.32 (ddd, 1 H, J ϭ 17.2, 1.8, 0.9), 5.37 (ddd, 1 H, J ϭ 10.4, 1.8,
0.6), 5.85 (ddd, 1 H, J ϭ 17.2, 10.4, 7.7), 7.10Ϫ7.70 (m, 15 H). Ϫ
13C NMR: δ ϭ 19.1, 26.7, 64.3, 70.3, 73.4, 80.7, 119.8, 127.6, 127.8
(2 C), 128.4, 129.8 (2 C), 133.2, 135.2, 135.6 (2 C), 136.0, 138.2.
Ϫ C28H34O3Si (446.66): calcd. C 75.29, H 7.67; found C 75.42,
H 7.53.
(2R,3S)-1,3-Di-O-benzyl-4-pentene-1,2,3-triol (7a) and (2R,3S)-2,3-
Di-O-benzyl-4-pentene-1,2,3-triol (9a): To a solution of diol 5a
˚
(612 mg, 2.94 mmol) in toluene (75 mL) were added 4-A molecular
sieves (6.00 g) and dibutyltin oxide (951 mg, 3.82 mmol). The mix-
ture was heated at 110 °C for 2 d, removing water with a Dean-
Stark apparatus. Then, BnBr (600 µL, 5.05 mmol) and tetrabu-
(2R,3R)-3-O-Benzyl-1-O-tert-butyldiphenylsilyl-4-pentene-1,2,3-
triol (8b): Diol 5b (255 mg, 1.22 mmol) was treated under the gen-
eral conditions for silylation. After flash chromatography, 452 mg
tylammonium bromide (1.06 g, 2.94 mmol) were added, and the of the silyl ether 8b (83%) was obtained as a syrup. Ϫ [α]2D5 ϭ Ϫ19.6
1
mixture was stirred at 70°C for two more days. The solvent was
removed under vacuum, the molecular sieves were filtered off and
the residue was purified by MPLC using a linear gradient [hexane
to hexane/ethyl acetate (2:1)], to afford compounds 7a and 9a
(CHCl3, c ϭ 1.70). Ϫ H NMR: δ ϭ 1.04 (s, 9 H), 2.64 (d, 1 H,
J ϭ 4.5), 3.60Ϫ3.80 (m, 2 H), 3.77 (dd, 1 H, J ϭ 11.4, 6.3), 4.01
(ddt, 1 H, J ϭ 7.9, 5.1, 0.8), 4.37 (d, 1 H, J ϭ 11.6), 4.65 (d, 1 H,
J ϭ 11.6), 5.32 (ddd, 1 H, J ϭ 10.4, 1.8, 0.8), 5.33 (ddd, 1 H, J ϭ
Eur. J. Org. Chem. 2001, 507Ϫ516
513

´
F. Bravo, S. Castillon
FULL PAPER
1
17.3, 1.8, 0.8), 5.81 (ddd, 1 H, J ϭ 17.3, 10.4, 7.9), 7.20Ϫ7.70 (m, Compound 18: [α]2D5 ϭ ϩ81.5 (CHCl3, c ϭ 1.35). Ϫ H NMR: δ ϭ
15 H). Ϫ 13C NMR: δ ϭ 19.1, 26.7, 64.1, 70.4, 74.1, 80.3, 119.5,
127.8, 127.9 (2 C), 128.4, 129.8 (2 C), 133.3, 133.4, 135.2, 135.6,
2.10 (br. s, 1 H), 3.28 (dd, 1 H, J ϭ 9.3, 5.9), 3.35 (t, 1 H, J ϭ 9.0),
3.82 (d, 1 H, J ϭ 9.8), 4.00 (d, 1 H, J ϭ 3.5), 4.19 (dd, 1 H, J ϭ
135.7, 138.2. Ϫ C28H34O3Si (446.66): calcd. C 75.29, H 7.67; found 9.8, 3.8), 4.39 (br. s, 1 H), 4.42 (ddd, 1 H, J ϭ 9.0, 5.9, 3.5), 4.62
C 75.24, H 7.87.
(d, 1 H, J ϭ 11.4), 4.67 (d, 1 H, J ϭ 11.4), 7.20Ϫ7.40 (m, 5 H). Ϫ
13C NMR: δ ϭ 1.0, 72.9, 74.6, 74.6, 81.1, 83.7, 127.9, 128.1, 128.5,
137.5. Ϫ C12H15O3I (334.15): calcd. C 43.13, H 4.52; found C
43.25, H 4.58.
Reaction of 5a with Iodine under Basic Conditions. ؊ Synthesis of
(2S,3R,4R)-3-Benzyloxy-2-iodomethyltetrahydrofuran-4-ol (10) and
(2R,3R,4R)-3-Benzyloxy-2-iodomethyltetrahydrofuran-4-ol
(12):
Diol 5a (5.01 g, 24.04 mmol) was treated under the general basic
conditions for iodoetherification. The reaction was completed in
45 min. After the workup, the residue was purified by column chro-
matography (hexane/ethyl acetate, 2:1) to afford 7.34 g of diastereo-
Compound 20: Higher Rf value. Ϫ [α]2D5 ϭ ϩ7.8 (CHCl3, c ϭ 1.46).
1
Ϫ H NMR: δ ϭ 2.10 (br. s, 1 H), 3.30 (dd, 1 H, J ϭ 10.1, 5.4),
3.39 (dd, 1 H, J ϭ 10.1, 7.0), 3.84 (dt, 1 H, J ϭ 1.2, 3.0), 3.90Ϫ4.00
(m, 2 H), 4.02 (dd, 1 H, J ϭ 10.0, 3.4), 4.33 (br. s, 1 H), 4.64 (s, 2
isomers 10 and 12 (ratio 86:14, 91% yield) as a syrup. The two H), 7.20Ϫ7.40 (m, 5 H). Ϫ 13C NMR: δ ϭ 7.1, 71.9, 74.7, 76.1,
isomers were separated by MPLC (hexane/chloroform, 1:1).
83.6, 88.6, 127.9, 128.1, 128.6, 137.6. Ϫ C12H15O3I (334.15): calcd.
C 43.13, H 4.52; found C 43.26, H 4.62.
Compound 10: Higher Rf value. Ϫ m.p. ϭ 70Ϫ71°C. Ϫ [α]2D5
ϭ
Ϫ35.8 (CHCl3, c ϭ 0.56). Ϫ 1H NMR: δ ϭ 2.56 (d, 1 H, J ϭ 6.9),
Reaction of 6b with Iodine under Basic Conditions. ؊ Synthesis of
3.32 (dd, 1 H, J ϭ 9.9, 7.2), 3.38 (dd, 1 H, J ϭ 6.5, 9.9), 3.83 (dd, (2R,3S,4R)-3-tert-Butyldiphenylsilyloxy-2-iodomethyltetrahydro-
1 H, J ϭ 4.3), 3.89 (dd, 1 H, J ϭ 9.8, 5.3), 4.11 (t, 1 H, J ϭ 5.4), furan-4-ol (19) and (2S,3S,4R)-3-tert-Butyldiphenylsilyloxy-2-iodo-
4.19 (q, 1 H, J ϭ 6.0), 4.36 (ddt, 1 H, J ϭ 6.9, 4.1, 5.3), 4.70 (d, 1 methyltetrahydrofuran-4-ol (21): Diol 6b (220 mg, 0.62 mmol) was
H, J ϭ 11.2), 4.77 (d, 1 H, J ϭ 11.2), 7.20Ϫ7.40 (m, 5 H). Ϫ 13C
NMR: δ ϭ 3.0, 71.1, 72.9, 74.8, 79.2, 80.9, 128.0, 128.4, 128.7,
treated according to the general procedure for basic iodoether-
ification. The reaction mixture was stirred for 20 min. After the
136.9. Ϫ C12H15O3I (334.15): calcd. C 43.13, H 4.52; found C workup, the residue was purified by flash chromatography (hexane/
43.01, H 4.62.
ethyl acetate, 5:1), to afford 295 mg (99%) of diastereoisomers 19
and 21 in a ratio of 84:16 as an inseparable mixture. Spectroscopic
data obtained from the spectra of the mixture.
1
Compound 12: [α]2D5 ϭ Ϫ39.9 (CHCl3, c ϭ 1.80). Ϫ H NMR: δ ϭ
2.62 (d, 1 H, J ϭ 4.5), 3.22 (dd, 1 H, J ϭ 10.7, 3.9), 3.35 (dd, 1 H,
J ϭ 10.7, 4.6), 3.7Ϫ3.8 (m, 2 H), 3.84 (dd, 1 H, J ϭ 9.8, 3.3), 4.09
(dd, 1 H, J ϭ 9.8, 4.5), 4.24 (quint, 1 H, J ϭ 4.1), 4.66 (s, 2 H),
Compound 19: 1H NMR: δ ϭ 1.09 (s, 9 H), 1.60 (br. s, 1 H),
2.35Ϫ3.30 (m, 2 H), 3.61 (dd, 1 H, J ϭ 9.9, 1.6), 4.01 (dt, 1 H, J ϭ
7.3Ϫ7.5 (m, 5 H). Ϫ 13C NMR: δ ϭ 8.0, 69.9, 72.9, 73.5, 79.0, 4.5, 1.6), 4.19 (dd, 1 H, J ϭ 9.9, 4.5), 4.15Ϫ4.25 (m, 2 H),
83.1, 128.1, 128.5, 128.7, 137.0. Ϫ C12H15O3I (334.15): calcd. C 7.30Ϫ7.80 (m, 10 H). Ϫ 13C NMR: δ ϭ 1.9, 19.3, 26.8, 73.4, 77.4,
43.13, H 4.52; found C 43.22, H 4.63.
79.0, 82.0, 127.9, 128.0, 130.1, 130.3, 132.4, 133.7, 135.7, 135.9.
1
Reaction of 6a with Iodine under Basic Conditions. ؊ Synthesis of
(2S,3R,4R)-3-tert-butyldiphenylsilyloxy-2-iodomethyltetrahydro-
furan-4-ol (11) and (2R,3R,4R)-3-tert-butyldiphenylsilyloxy-2-iodo-
Compound 21: H NMR: δ ϭ 1.08 (s, 9 H), 1.74 (br. s, 1 H), 2.86
(dd, 1 H, J ϭ 10.5, 6.8), 2.97 (dd, 1 H, J ϭ 10.5, 5.4), 3.88 (br. s,
1 H), 3.97 (dt, 1 H, J ϭ 2.7, 1.2), 4.06 (dd, 1 H, J ϭ 9.9, 3.9),
methyltetrahydrofuran-4-ol (13): Diol 6a (173 mg, 0.48 mmol) was 4.15Ϫ4.25 (m, 2 H), 7.30Ϫ7.80 (m, 10 H). Ϫ 13C NMR: δ ϭ 6.5,
treated with iodine under the general basic conditions. The reaction
mixture was stirred for 2 h. After workup, the residue was purified
by flash chromatography (hexane/ethyl acetate, 5:1) to afford
108 mg (46%) of diastereoisomers 11 and 13 in a ratio of 60:40 as
an inseparable mixture.
18.9, 26.7, 74.0, 78.5, 82.4, 86.3, 128.0, 135.2, 135.7, 135.9.
Selenoetherification of 7a under Acidic Conditions. ؊ Synthesis of
(2R,3R,4R)-3-Benzyloxy-2-benzyloxymethyl-4-(phenylselenenyl)-
tetrahydrofuran (22) and (2R,3R,4S)-3-benzyloxy-2-benzyloxyme-
thyl-4-(phenylselenenyl)tetrahydrofuran (24): Alkenol 7a (216 mg,
1
Compound 11: H NMR: δ ϭ 1.14 (s, 9 H), 2.63 (br. s, 1 H), 3.30 0.72 mmol) was treated under the conditions described for seleno-
(dd, 1 H, J ϭ 10.8, 3.3), 3.41 (t, 1 H, J ϭ 10.8), 3.80Ϫ4.00 (m, 3
H), 4.00 (br. s, 1 H), 4.28 (dd, 1 H, J ϭ 6.9, 5.1), 7.30Ϫ7.80 (m,
etherification under acidic conditions. The reaction mixture was
stirred at room temperature for 1 h. After workup, the crude prod-
10 H). 13C NMR (aliphatic C): δ ϭ 6.2, 19.1, 26.9, 71.0, 71.7, uct was purified by MPLC, eluting with linear gradient [hexane to
74.5, 80.1.
hexane/ethyl acetate (1:3) to hexane/ethyl acetate (1:1)] to afford
181 mg of 5-endo products 22 and 24 (ratio 1:1, 55% yield). Prod-
ucts 22 and 24 were separated by MPLC, eluting with linear gradi-
ent [hexane to hexane/ethyl acetate (30:1) to hexane/ethyl acetate
(20:1) to hexane/ethyl acetate (10:1)].
Compound 13: 1H NMR: δ ϭ 1.12 (s, 9 H), 2.54 (dd, 1 H, J ϭ
11.0, 5.4), 2.64 (br. s, 1 H), 2.98 (dd, 1 H, J ϭ 11.0, 3.3), 3.64 (dt,
1 H, J ϭ 5.4, 3.0), 3.80Ϫ4.01 (m, 4 H), 4.06 (br. s, 1 H), 7.30Ϫ7.80
(m, 10 H). Ϫ 13C NMR (aliphatic C): δ ϭ 7.9, 19.1, 26.9, 71.5,
72.8, 77.2, 81.0.
Compound 22: Higher Rf value. Ϫ [α]2D5 ϭ ϩ2.0 (CHCl3, c ϭ 0.90).
1
Ϫ H NMR: δ ϭ 3.58 (dd, 1 H, J ϭ 10.3, 5.2), 3.62 (dd, 1 H, J ϭ
Reaction of 5b with Iodine under Basic Conditions. ؊ Synthesis of
(2R,3S,4R)-3-Benzyloxy-2-iodomethyltetrahydrofuran-4-ol (18) and
(2S,3S,4R)-3-Benzyloxy-2-iodomethyltetrahydrofuran-4-ol
Compound 5b (2.37 g, 11.37 mmol) was treated with iodine under
basic conditions. The reaction was stirred for 30 min. After flash
chromatography (hexane/ethyl acetate, 2:1), 3.61 g of diastereoiso-
mers 18 and 20 (ratio 91:9) were recovered (95%) as a syrup. The
two isomers were separated by MPLC, eluting with linear gradient
[hexane to hexane/ethyl acetate (10:1) to hexane/ethyl acetate (5:1)
to hexane/ethyl acetate (3:1)].
10.3, 5.7), 3.76 (ddd, 1 H, J ϭ 6.0, 3.8, 2.3), 3.98 (dd, 1 H, J ϭ
10.1, 3.8), 3.99 (dd, 1 H, J ϭ 3.8, 2.3), 4.06 (td, 1 H, J ϭ 5.6, 3.8),
4.25 (dd, 1 H, J ϭ 10.1, 6.0), 4.34 (d, 1 H, J ϭ 11.8), 4.45 (d, 1 H,
J ϭ 11.8), 4.56 (s, 2 H), 7.10Ϫ7.60 (m, 15 H). Ϫ 13C NMR: δ ϭ
45.6, 70.4, 71.7, 72.8, 73.3, 83.9, 85.8, 127.7, 127.8 (2 C), 127.9,
128.3, 128.4 (2 C), 129.0, 129.3, 134.5, 137.6, 138.1. Ϫ C25H26O3Se
(453.44): calcd. C 66.22, H 5.78; found C 66.43, H 5.85.
(20):
1
Compound 24: [α]2D5 ϭ ϩ2.1 (CHCl3, c ϭ 0.50). Ϫ H NMR: δ ϭ
3.46 (dd, 1 H, J ϭ 10.5, 4.8), 3.49 (dd, 1 H, J ϭ 10.5, 4.2), 3.76
514
Eur. J. Org. Chem. 2001, 507Ϫ516

An Example of 5-exo versus 5-endo Cyclization Governed by the Electrophile
FULL PAPER
1
(ddd, 1 H, J ϭ 9.2, 7.0, 6.0), 4.03 (t, 1 H, J ϭ 9.0), 4.13 (dd, 1 H, Compound 28: [α]2D5 ϭ Ϫ13.4 (CHCl3, c ϭ 1.16). Ϫ H NMR: δ ϭ
J ϭ 6.0, 3.1), 4.19 (td, 1 H, J ϭ 4.6, 3.1), 4.25 (dd, 1 H, J ϭ 9.2,
7.0), 4.49 (d, 1 H, J ϭ 12.0), 4.54 (d, 1 H, J ϭ 12.0), 4.58 (d, 1 H,
3.69 (dd, 1 H, J ϭ 9.8, 6.8), 3.72 (dd, 1 H, J ϭ 9.8, 5.8), 3.79 (ddd,
1 H, J ϭ 9.2, 7.8, 5.0), 4.05 (t, 1 H, J ϭ 8.8), 4.16 (q, 1 H, J ϭ
J ϭ 11.7), 4.64 (d, 1 H, J ϭ 11.7), 7.10Ϫ7.60 (m, 15 H). Ϫ 13C 5.6), 4.18 (dd, 1 H, J ϭ 8.8, 7.8), 4.26 (t, 1 H, J ϭ 4.5), 4.50 (d, 1
NMR: δ ϭ 45.1, 70.3, 72.0, 73.4, 73.9, 81.0, 82.8, 127.3, 127.7, H, J ϭ 11.7), 4.58 (d, 1 H, J ϭ 11.7), 4.61 (d, 1 H, J ϭ 11.4), 4.80
127.8, 127.9, 128.0, 128.4 (2 C), 129.2, 129.5, 133.6, 137.6, 138.0.
Ϫ C25H26O3Se (453.44): calcd. C 66.22, H 5.78; found C 66.41,
H 5.93.
(d, 1 H, J ϭ 11.4), 7.20Ϫ7.60 (m, 15 H). Ϫ 13C NMR: δ ϭ 46.5,
68.7, 72.9, 73.5, 74.5, 80.2, 80.7, 127.3, 127.7, 127.9, 127.9, 128.1,
128.4 (2 C), 129.2, 129.8, 133.5, 137.7, 138.0. Ϫ C25H26O3Se
(453.44): calcd. C 66.22, H 5.78; found C 66.32, H 5.69.
Selenoetherification of 8a under Acidic Conditions. ؊ Synthesis of
(2R,3R,4R)-3-Benzyloxy-2-(tert-butyldiphenylsilyloxy)-4-(phenyl-
selenenyl)tetrahydrofuran (23) and (2R,3R,4S)-3-Benzyloxy-2-(tert-
Compound 30: Higher Rf values. Ϫ [α]2D5 ϭ Ϫ42.3 (CHCl3, c ϭ
1
1.70). Ϫ H NMR: δ ϭ 3.69 (dd, 1 H, J ϭ 10.2, 5.2), 3.73 (dd, 1
H, J ϭ 10.2, 6.4), 3.78 (ddd, 1 H, J ϭ 8.0, 4.6, 1.5), 3.79 (dd, 1 H,
J ϭ 11.0, 4.6), 4.00 (dd, 1 H, J ϭ 4.1, 1.5), 4.15 (d, 1 H, J ϭ 12.3),
4.30 (td, 1 H, J ϭ 5.8, 4.1), 4.40 (d, 1 H, J ϭ 12.3), 4.44 (dd, 1 H,
J ϭ 11.0, 8.0), 4.50 (d, 1 H, J ϭ 11.8), 4.62 (d, 1 H, J ϭ 11.8),
7.00Ϫ7.70 (m, 15 H). Ϫ 13C NMR: δ ϭ 45.0, 68.8, 71.2, 72.0, 73.4,
79.7, 84.4, 127.6 (2 C), 127.8, 127.9, 128.2, 128.4 (2 C), 128.7, 129.4,
134.9, 137.7, 138.2. Ϫ C25H26O3Se (453.44): calcd. C 66.22, H 5.78;
found C 66.43, H 6.05.
butyldiphenylsilyloxy)-4-(phenylselenenyl)tetrahydrofuran
(25):
Compound 8a (330 mg, 0.74 mmol) was treated according to the
general procedure for selenoetherification under acidic conditions,
reducing the amount of CSA (35 mg, 0.15 mmol). The reaction
mixture was refluxed for 12 h. The residue was purified by MPLC,
eluting with linear gradient [hexane to hexane/ethyl acetate (5:10)
to hexane/ethyl acetate (3:1)], to obtain 388 mg of a mixture of 23
and 25 (87%, ratio 56:44) as an inseparable mixture. The spectral
data given are for this mixture. Ϫ 1H NMR: δ ϭ 1.02 (s, 9 H), 1.09
(s, 9 H), 3.61 (dd, 1 H, J ϭ 10.7, 5.4), 3.67 (dd, 1 H, J ϭ 10.7, 3.8),
3.70Ϫ3.80 (m, 4 H), 3.90Ϫ4.30 (m, 8 H), 4.37 (d, 1 H, J ϭ 11.8),
4.44 (d, 1 H, J ϭ 11.8), 4.62 (s, 2 H), 7.00Ϫ7.80 (m, 40 H). Ϫ 13C
NMR: δ ϭ 19.0, 26.7, 26.8, 29.6, 45.4, 45.6, 64.3, 64.5, 71.8, 71.9,
72.9, 73.9, 81.4, 84.0, 85.3, 85.7, 127.3, 127.7 (2 C), 127.8, 127.9 (2
C), 128.4, 128.5, 129.2, 129.3, 129.8, 129.9, 133.2, 133.3, 133.7,
134.4, 134.7, 135.6, 135.7, 135.8 (2 C), 137.8, 137.9.
Selenoetherification of 8b under Acidic Conditions. ؊ Synthesis of
(2R,3S,4R)-3-Benzyloxy-2-(tert-butyldiphenylsilyloxymethyl)-4-
(phenylselenenyl)tetrahydrofuran (29) and (2R,3S,4S)-3-Benzyloxy-
2-(tert-butyldiphenylsilyloxymethyl)-4-(phenylselenenyl)tetrahydro-
furan (31): Compound 8b (197 mg, 0.44 mmol) was treated accord-
ing to the general procedure for selenoetherification under acidic
conditions, reducing the amount of CSA to 20 mg (0.09 mmol).
The mixture was refluxed for 12 h. After workup, the mixture was
purified by flash chromatography (hexane/ethyl acetate, 10:1) to
afford 254 mg of compounds 29 and 31 (global yield: 96%, ratio
1:1) as an inseparable mixture. The spectral data given are for this
Selenoetherification of 5a under Acidic Conditions. ؊ Synthesis of
(2S,3R,4R)-3-Benzyloxy-2-(phenylselenenylmethyl)tetrahydrofuran-
4-ol (26) and (2R,3R,4R)-3-Benzyloxy-2-(phenylselenenylmethyl)-
tetrahydrofuran-4-ol (27): Compound 5a (75 mg, 0.36 mmol) was
treated under acidic conditions for selenoetherification. The reac-
tion mixture was stirred for 30 min. After the usual workup, the
crude product was purified by MPLC, eluting with a linear gradient
[hexane to hexane/ethyl acetate (1:4)], to afford 130 mg (99%) of
an inseparable mixture of 26 and 27 (ratio 70:30). Spectroscopic
data obtained from the spectra of the mixture.
1
mixture. Ϫ H NMR: δ ϭ 1.04 (s, 9 H), 1.07 (s, 9 H), 3.70Ϫ4.50
(m, 16 H), 4.78 (d, 1 H, J ϭ 11.1), 4.85 (d, 1 H, J ϭ 11.1),
7.00Ϫ7.80 (m, 40 H). Ϫ 13C NMR: δ ϭ 19.0 (2 C), 26.7, 26.8, 44.9,
46.5, 62.0, 62.1, 71.7, 72.0, 72.0, 73.1, 80.4, 81.0, 82.6, 84.2, 127.3,
127.6, 127.7 (2 C), 127.8, 128.0, 128.1, 128.4 (2 C), 128.5, 129.2,
129.4, 129.6, 129.7, 129.8, 130.0, 133.2, 133.5, 134.9, 135.7 (2 C),
137.0, 138.0.
Selenoetherification of 5b under Acidic Conditions. ؊ Synthesis of
(2R,3S,4R)-3-benzyloxy-2-(phenylselenenylmethyl)tetrahydrofuran-
4-ol (32) and (2S,3S,4R)-3-Benzyloxy-2-(phenylselenenylmethyl)-
tetrahydrofuran-4-ol (33): Compound 5b (63 mg, 0.30 mmol) was
treated with NPSP under acidic conditions. The reaction mixture
was stirred at room temperature for 1 h. After purification by
MPLC, eluting with linear gradient [hexane to hexane/ethyl acetate
(1:4)], 96 mg (87%) of 32 and 33 (ratio 43:57) were isolated as an
inseparable mixture. For analytical purposes, a pure sample of com-
pound 32 was obtained after successive purification by radial chro-
matography (hexane/ethyl acetate, 5:1).
Compound 26: 1H NMR: δ ϭ 2.92 (br. s, 1 H), 3.18 (m, 2 H),
3.70Ϫ3.80 (m, 1 H), 3.80Ϫ3.90 (m, 1 H), 4.10Ϫ4.20 (m, 2 H), 4.31
(br. s, 1 H), 4.64 (d, 1 H, J ϭ 11.2), 4.69 (d, 1 H, J ϭ 11.2),
7.30Ϫ7.80 (m, 10 H). Ϫ 13C NMR: δ ϭ 27.4, 70.8, 72.9, 74.1, 79.3,
79.4, 123.5, 128.2, 128.6, 129.0, 132.4, 134.2.
Compound 27: 1H NMR: δ 2.70 (br. s, 1 H), 3.04 (dd, 1 H, J ϭ 13,
5.2), 3.14 (dd, 1 H, J ϭ 13.0, 5.2), 3.78 (dd, 1 H, J ϭ 9.8, 3.9), 3.86
(t, 1 H, J ϭ 5.8), 4.06 (dd, 1 H, J ϭ 9.8, 5.1), 4.13 (q, 1 H, J ϭ 5.7),
4.31 (br. s, 1 H), 4.53 (s, 2 H), 4.65 (d, 1 H, J ϭ 11.7), 7.20Ϫ7.90 (m,
10 H). Ϫ 13C NMR: δ ϭ 30.7, 69.8, 72.6, 73.3, 79.5, 82.2, 127.0,
128.0, 128.3, 128.6, 129.1, 132.4, 137.0.
1
Compound 32: [α]2D5 ϭ Ϫ4.3 (CHCl3, c ϭ 1.36). Ϫ H NMR: δ ϭ
2.40 (br. s, 1 H), 3.12 (dd, 1 H, J ϭ 12.9, 4.8), 3.27 (dd, 1 H, J ϭ
12.9, 6.3), 3.70 (m, 2 H), 3.81 (d, 1 H, J ϭ 3.2), 4.11 (ddd, 1 H,
J ϭ 6.3, 4.8, 3.2), 4.27 (br. s, 1 H), 4.52 (d, 1 H, J ϭ 11.1), 4.59
(d, 1 H, J ϭ 11.8), 7.20Ϫ7.60 (m, 10 H). Ϫ 13C NMR: δ ϭ 31.1,
71.9, 74.5, 76.1, 83.4, 88.6, 127.3, 127.8, 128.0, 128.6, 129.3, 130.0,
132.8, 137.5. Ϫ C18H20O3Se (363.31): calcd. C 59.51, H 5.55; found
C 59.45, H 5.68.
Selenoetherification of 7b under Acidic Conditions. ؊ Synthesis of
(2R,3S,4R)-3-Benzyloxy-2-benzyloxymethyl-4-(phenyl-
selenenyl)tetrahydrofuran (28) and (2R,3S,4S)-3-Benzyloxy-2-
benzyloxymethyl-4-(phenylselenenyl)tetrahydrofuran (30): Com-
pound 7b (193 mg, 0.65 mmol) was treated with NPSP under acidic
conditions, and dichloromethane was replaced by dichloroethane.
The reaction mixture was heated to reflux. After 20 min, the mix-
ture was filtered and the solvent was removed. The crude product
was purified by MPLC, eluting with linear gradient [from hexane
to hexane/ethyl acetate (1:4) to hexane/ethyl acetate (1:2)] to afford,
Compound 33: Spectral data obtained from the spectra of the mix-
ture of diastereomers. Ϫ 1H NMR: δ ϭ 2.30 (br. s, 1 H), 3.10Ϫ3.20
(m, 2 H), 3.69 (dd, 1 H, J ϭ 10.0, 1.8), 3.93 (dd, 1 H, J ϭ 4.0, 1.0),
in order of elution, 108 mg (37%) of 28 and 62 mg (21%) of com- 4.15 (dd, 1 H, J ϭ 10.0, 4.4), 4.20Ϫ4.40 (m, 2 H), 4.50 (d, 1 H,
pound 30 as syrups.
J ϭ 11.8), 4.62 (d, 1 H, J ϭ 11.8), 7.10Ϫ7.60 (m, 10 H). Ϫ 13C
Eur. J. Org. Chem. 2001, 507Ϫ516
515

´
F. Bravo, S. Castillon
FULL PAPER
[10]
[11]
Y. Tamaru, M. Hojo, S. Kawamura, S. Sawada, Z. Yoshida, J.
Org. Chem. 1987, 52, 4062.[9]
NMR: δ ϭ 25.5, 72.3, 73.9, 74.7, 80.1, 84.1, 126.9, 127.7, 127.9,
128.5, 129.1, 130.2, 132.4, 137.8.
J. M. Barks, D. W. Knight, C. J. Seaman, G. G. Weingarten,
Tetrahedron Lett. 1994, 35, 7259.
Reaction of 10 with Sodium Hydride. ؊ Synthesis of (1R,4R)-7-
Benzyloxy-2,5-dioxabicyclo[2.2.1]heptane (34): In
[12] [12a]
B. Berthe, F. Outurquin, C. Paulmier, Tetrahedron Lett.
1997, 38, 1393. Ϫ [12b] R. D. Evans, J. W. Magee, J. H. Schauble,
Synthesis 1988, 862. Ϫ [12c] P. Galatsis, S. D. Millan, P. Nechala,
G. Ferguson, J. Org. Chem. 1994, 59, 6643.
a two-necked
flask, 60% sodium hydride (14 mg, 0.35 mmol) was washed with
anhydrous hexane. Then THF (8 mL) was added, and the flask
was cooled with ice/water/salt. Compound 10 (107 mg, 0.32 mmol),
dissolved in 8 mL of THF, was added dropwise. The reaction mix-
ture was stirred for 10 min, and TLC monitoring showed that the
starting material had been completely consumed and a that product
with nearly the same Rf had appeared. The reaction was quenched
by carefully adding a few drops of methanol and removing the
solvent in vacuo. The product was filtered through silica gel and
purified by radial chromatography to obtain 59 mg of 34 (89%). Ϫ
[13]
P. Galatsis, D. J. Parks, Tetrahedron Lett. 1994, 35, 6611.
[14] [14a]
O. Andrey, L. Ducry, Y. Landais, D. Planchenault, V.
[14b]
Weber, Tetrahedron 1997, 53, 4339. Ϫ
M. Tiecco, L.
Testaferri, F. Marini, L. Bagnoli, C. Santi, A. Temperini, Tetra-
hedron 1997, 53, 4441.[14c] Y. Landais, D. Planchenault, V.
Weber, Tetrahedron Lett. 1995, 36, 2987. Ϫ [14d] B. H. Lipshutz,
T. Gross, J. Org. Chem. 1995, 60, 3572.
[15] [15a]
E. D. Mihelich, G. A. Hite, J. Am. Chem. Soc. 1992, 114,
[15b]
7318. Ϫ
36, 8179. Ϫ
P. Galatsis, J. J. Manwell, Tetrahedron Lett. 1995,
[15c]
F. Bennett, S. B. Bedford, K. E. Bell, G. Fen-
1
[α]2D5 ϭ ϩ50.5 (CHCl3, c ϭ 1.35). Ϫ H NMR: δ ϭ 3.90 (d, 1 H,
ton, D. W. Knight, D. Shaw, Tetrahedron Lett. 1992, 33, 6507.
Ϫ [15d] S. B. Bedford, K. E. Bell, F. Bennett, C. J. Hayes, D. W.
Knight, D. Shaw, J. Chem. Soc., Perkin Trans. 1 1999, 2143.
J ϭ 8.4), 3.94 (d, 1 H, J ϭ 8.4), 3.99 (d, 1 H, J ϭ 8.1), 4.10 (dt, 1
H, J ϭ 8.1, 0.5), 4.12 (d, 1 H, J ϭ 2.4), 4.18 (dd, 1 H, J ϭ 1.0,
2.6), 4.29 (br. s, 1 H), 4.58 (d, 1 H, J ϭ 11.7), 4.68 (d, 1 H, J ϭ
11.7), 7.20Ϫ7.40 (m, 5 H). Ϫ 13C NMR: δ ϭ 72.1, 72.8, 73.8, 75.8,
75.8, 79.6, 127.9, 128.1, 128.6, 137.5. Ϫ C12H14O3 (206.24): calcd.
C 69.89, H 6.84; found C 70.03, H 6.95.
[16] [16a]
S. Murata, T. Suzuki, Tetrahedron Lett. 1987, 28, 4297.
Ϫ[16b] M. E. Jung, C. J. Nichols, Tetrahedron Lett. 1996, 37,
7667.
[17] [17a]
F. Freeman, K. D. Robarge, J. Org. Chem. 1989, 54, 346
[17b]
and references cited therein. Ϫ
F. Nicotra, L. Panza, F.
Ronchetti, G. Russo, L. Toma, Carbohydr. Res. 1987, 103, 49.
Ϫ
[17c] A. B. Reitz, S. O. Nortey, B. E. Maryanoff, J. Org. Chem.
1987, 52, 4191. Ϫ [17d] A. B. Reitz, S. O. Nortey, B. E. Maryan-
off, Tetrahedron lett. 1985, 26, 3915.
Acknowledgments
[18]
S. H. Kang, S. B. Lee, Tetrahedron Lett. 1993, 34, 7579.
[19] [19a]
Financial support by DGICYT PB95Ϫ521-A (Ministerio de Edu-
cacion y Cultura, Spain) is acknowledged. F. B. thanks CIRIT
(Generalitat de Catalunya) for a grant. Technical assistance by the
Servei de Recursos Cientifics (URV) is acknowledged.
I. R. Vlahov, P. I. Vlahova, R. R. Schmidt, Tetrahed-
ron:Asymmetry 1993, 4, 293. Ϫ [19b] B. H. Lipshutz, R. Tirado,
J. Org. Chem. 1994, 59, 8307.
[20]
´
´
Y. D ı az, F. Bravo, S. Castillon, J. Org. Chem. 1999, 64, 6508.
[21] [21a] C. R. Schmid, J. D. Bryant, M. Dowlatzedah, J. L. Phillips,
D. E. Prather, R. D. Schantz, N. L. Sear, C. S. Vianco, J. Org.
Chem. 1991, 56, 4056. Ϫ [21b] D. J. Walton, Can. J. Chem. 1967,
[1] [1a]
P. A. Bartlett, Asymmetric Synthesis (Ed. J. D. Morrison),
Academic Press, London, 1984, vol. 3, p. 411Ϫ454.[1b]T. L. B.
45, 2921.
[22]
[1c]
`
S. David, A. Thieffry, A. Veyrieres, J. Chem. Soc., Perkin Trans.
Boivin, Tetrahedron 1987, 43, 3309. Ϫ
G. Cardillo, M. Or-
ena, Tetrahedron 1990, 46, 3321. Ϫ [1d]M. Orena, Houben-Weyl
(Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schum-
ann), Georg Thieme Verlag, Stuttgart, New York, 1995, vol.
21e, p. 4760؊4817.
1 1979, 1568.
[23]
S. D. Rychnovsky, P. A. Bartlett, J. Am. Chem. Soc. 1981,
103, 3963.
[24]
[25]
[26]
[27]
[28]
[29]
[30]
R. U. Lemieux, A. R. Morgan, Can. J. Chem. 1965, 43, 2190.
M. E. Jung, C. J. Nichols, J. Org. Chem. 1998, 63, 347.
M. Labelle, Y. Guindon, J. Am. Chem. Soc. 1989, 111, 2204.
Y. Landais, D. Planchenault, Synlett 1995, 1191.
H. Zhang, D. R. Mootoo, J. Org. Chem. 1995, 60, 8134.
K. P. R. Kartha, Tetrahedron Lett. 1986, 27, 3415.
S. D. Rychnovsky, P. A. Bartlett, J. Am. Chem. Soc. 1981,
103, 3963.
[2] [2a]
P. A. Bartlett, D. P. Richardson, J. Myerson, Tetrahedron
[2b]
1984, 40, 2317. Ϫ
K. E. Harding, T. H. Marman, J. Org.
[2c]
Chem. 1984, 49, 2838. Ϫ
J. R. Pougny, M. A. M. Nassr, P.
[2d]
Sinay, J. Chem. Soc., Chem. Commun. 1981, 375. Ϫ
P.
Bravo, G. Resnati, F. Viani, A. Arnone, J. Chem. Soc., Perkin
Trans. 1 1989, 839.
[3] [3a]
´
P. L. Lopez-Tudanca, K. Jones, P. Brownbridge, Tetrahedron
[3b]
Lett. 1991, 32, 2261. Ϫ
J. Eames, S. Warren, Tetrahedron
[31]
K. C. Nicolaou, D. A. Claremon, W. E. Barnette, S. P. Seitz,
Lett. 1996, 37, 3525.
J. Am. Chem. Soc. 1979, 101, 3704.
[4] [4a]
[32] [32a]
[32b]
Y. Ohfune, K. Hori, M. Sakaitani, Tetrahedron Lett. 1986,
S. Murata, T. Suzuki, Tetrahedron Lett. 1987, 28, 4415. Ϫ
S. Murata, T. Suzuki, Chem. Lett. 1987, 849.
F. Bravo, M. Kassou, S. Castillon, Tetrahedron Lett. 1999, 40,
[4b]
27, 6079. Ϫ
P. C. Ting, P. A. Bartlett, J. Am. Chem. Soc.
1984, 106, 2668.
[33]
´
[5]
[5a] K. C. Nicolaou, R. L. Magolda, W. J. Sipio, W. E. Barnette,
1187.
Z. Lysenko, M. M. Joullie, J. Am. Chem. Soc. 1980, 102, 3784.
Ϫ
[34]
[35]
V. Jäger, B. Häfele, Synthesis 1987, 801.
P. Crotti, V. Di Bussolo, L. Favero, C. Gozzi, M. Pineschi, Tet-
rahedron: Asymmetry 1997, 8, 1611.
[5b]
R. R. Webb II, S. Danishefsky, Tetrahedron Lett. 1983,
[5c]
´
24, 1357. Ϫ
R. Deziel, E. Malenfant, J. Org. Chem. 1995,
60, 4660.
[36] [36a]
W. Shan, P. Wilson, W. Liang, D. R. Mootoo, J. Org.
[6] [6a]
[6b]
L. Do Amaral, S. C. Melo, J. Org. Chem. 1973, 38, 800. Ϫ
Chem. 1994, 59, 7986. Ϫ [36b] D. R. Williams, J. Grote, Y. Hari-
S. P. Elvey, D. R. Mootoo, J. Am. Chem. Soc. 1992, 114,
[36c]
gaya, Tetrahedron Lett. 1984, 25, 5231. Ϫ
Y. Tamaru, M.
[6c]
9685. Ϫ
52, 5067.
D. R. Williams, F. H. White, J. Org. Chem. 1987,
Hojo, S. Kawamura, S. Sawada, Z. Yoshida, J. Org. Chem.
1987, 52, 4062.
[7]
[8]
[37]
J. E. Baldwin, J. Chem. Soc., Chem. Commun. 1976, 734.
A. D. Jones, D.W. Knight, A. L. Redfern, J. Gilmore, Tetrahed-
ron Lett. 1999, 40, 3267 and references cited therein.
D. D. Perrin, W. L. F. Armarego, Purification of Laboratory
Chemicals, 3rd ed., Pergamon Press, Oxford, 1989.
Received July 3, 2000
[9]
P. A. Bartlett, J. Myerson, J. Am. Chem. Soc. 1978, 100, 3950.
[O00329]
516
Eur. J. Org. Chem. 2001, 507Ϫ516