New trimethylenemethane dianion synthons: Application to the preparation of substituted perhydrofuro[2,3-b]furans

Article abstract of DOI:10.1016/S0040-4020(00)00060-0

The reaction of 3-chloro-2-(chloromethyl)prop-1-ene (1) with lithium powder and a catalytic amount of naphthalene in the presence of different electrophiles in THF at -78°C yields products 2. When carbonylic compounds are used as electrophiles the corresponding methylenic diols are obtained, which by tandem hydroboration-oxidation with alkaline hydrogen peroxide and treatment with PCC (for ketone derivatives) or (Ph₃P)₃RuCl₂ (for aldehyde derivatives) furnish the expected perhydrofurofurans 3. Using 2-chloromethyl- 3-(2-methoxyethoxy)prop-1-ene (4) as starting material and under the above conditions, the selective chloro/lithium exchange versus the allylic carbon- oxygen bond cleavage allows the introduction of a first electrophile at -78 to -30°C, and a second electrophile at -30°C to room temperature to give products 5. The same oxidation protocol mentioned above, when applied to diols 5, lead to the differently substituted perhydrofurofurans 7. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00060-0

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1745–1757
New Trimethylenemethane Dianion Synthons: Application to the
Preparation of Substituted Perhydrofuro[2,3-b]furans
*
Emilio Lorenzo, Francisco Alonso and Miguel Yus
´
´
Departamento de Quımica Organica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, E-03080 Alicante, Spain
Received 29 October 1999; revised 21 December 1999; accepted 13 January 2000
Abstract—The reaction of 3-chloro-2-(chloromethyl)prop-1-ene (1) with lithium powder and a catalytic amount of naphthalene in the
presence of different electrophiles in THF at Ϫ78ЊC yields products 2. When carbonylic compounds are used as electrophiles the corre-
sponding methylenic diols are obtained, which by tandem hydroboration–oxidation with alkaline hydrogen peroxide and treatment with PCC
(for ketone derivatives) or (Ph3P)3RuCl2 (for aldehyde derivatives) furnish the expected perhydrofurofurans 3. Using 2-chloromethyl-3-(2-
methoxyethoxy)prop-1-ene (4) as starting material and under the above conditions, the selective chloro/lithium exchange versus the allylic
carbon–oxygen bond cleavage allows the introduction of a first electrophile at Ϫ78 to Ϫ30ЊC, and a second electrophile at Ϫ30ЊC to room
temperature to give products 5. The same oxidation protocol mentioned above, when applied to diols 5, lead to the differently substituted
perhydrofurofurans 7. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
methane synthon III and a carbonyl compound IV to
build the carbon skeleton corresponding to the bicycle II.
Dianion III, which has interest not only from a theoretical19
but also from a synthetic point of view (two electrophilic
fragments can be introduced in only one step), can be
prepared by double deprotonation using n-butyllithium in
the presence of tetramethylethylenediamine (TMEDA),20 or
potassium tert-butoxide.21,22 However, the use of a chloro/
lithium exchange reaction for the preparation of III failed
due to the intermolecular coupling of the monolithium
derivative initially formed. This problem was overcome
recently23 using an arene-catalysed lithiation20–26 in the
presence of several carbonyl compounds (Barbier type
conditions).27 In this paper we apply this methodology28 to
generate dianions28c of the type III as the key step in the
synthesis of the perhydrofurofuran core of compounds of
the type shown in Fig. 1.29
The perhydrofurofuran unit is present in many biologically
active natural products. One important family of molecules
having this fragment belong to the clerodan-type diterpenes,
which show potential insect antifeedant activity1 as well as
antibacterial activity.2 Some representative examples are
lupulin A, scuterepenin A1 or scupolin B (Fig. 1).4 In
3
some cases, the mentioned heterocyclic core is attached to
a steroid structure, such as in the case of vernionioside D1.5
However, aflatoxin B2 and asteltoxin8 are, probably, the
6,7
most famous members of the perhydrofurofuran core-
containing molecules because they are important myco-
toxins with very potent toxicity and carcinogenecity,9 and
they have been detected in several foods, therefore intense
interest from toxicologists and government regulators has
been shown.10
Most of the methodologies to synthesise the 1,7-dioxa-
bicyclo[3.3.0]octane moiety use an inter- or intramolecular
cylisation on a preformed tetrahydrofuran ring through
dehydration,11 radical cyclisation,12 iodocycloetherifica-
tion,13 dipolar cycloaddition,14 intramolecular carbozinca-
tion,15 intramolecular carbenoid insertion16 or metal-
promoted cyclisation,17 among others. Ten years ago, de
Groot et al.18a reported the synthesis of perhydrofurofuran
II starting from the di-O-silylated dihydroxyaldehyde I by
acid-catalysed cyclisation in 20% yield (Scheme 1). This
double cyclisation prompted us to use a different strategy
from an analogue of compound I using a trimethylene-
Results and Discussion
The reaction of 3-chloro-2-(chloromethyl)prop-1-ene (1)30
with lithium and a catalytic amount of naphthalene
(5 mol%) in the presence of different electrophiles
[PriCHO, ButCHO, Me2CO, Et2CO, Cy2CO, (CH2)5CO,
Y(CH2CH2)2CO (YˆO, S, PrnN), ButCOMe, PhCOMe,
EtCOMe, Me3SiCl, (MeS)2] in THF at temperatures ranging
from Ϫ78 to 20ЊC led, after hydrolysis with water, to the
expected compounds 2 (Scheme 2 and Table 1), some of
them (compounds 2a, 2c, 2d, and 2f, Table 1, entries 1, 3, 4,
and 6, respectively) having been already described by us
using the same methodology.23
Keywords: lithium; arene-catalysis; dianion synthons; perhydrofurofurans.
* Corresponding author. Fax: ϩ34-96-5903549; e-mail: yus@ua.es
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00060-0

1746
E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
Figure 1.
Scheme 1.
Concerning the mechanism of this reaction, we think that
the reaction involves a double tandem process of lithiation–
SE reaction with the electrophile present in the reaction
medium. In the absence of the electrophile, an intramolecu-
lar coupling of the monolithium intermediate initially
formed takes place, giving 1,4-dimethylenecyclohexane as
the only reaction product.25 For these reactions, we think
that a dilithiated species, corresponding to the dianion III, is
probably not generated.
furans 3, was carried out in a three-step process involving
first a hydroboration with borane in THF at 0ЊC, followed by
in situ oxidation with 33% hydrogen peroxide in 3 M
sodium hydroxide at 0ЊC. The resulting triol intermediates
were not purified and were further oxidised using two
different methods depending on the nature of the triol:
dichlorotris(triphenylphosphine)ruthenium(II) in benzene
at 0ЊC (Method A, for R2ˆH) or pyridinium chlorochromate
(PCC) in CH2Cl2 at 0ЊC (Method B, for R2±H) (Scheme 3
and Table 2).
The transformation of the unsaturated diols 2 derived from
carbonyl compounds into the corresponding perhydrofuro-
In the transformation 2!3, non-isolated compounds of the
type V–VII are probably involved, the last one undergoing
spontaneous cyclisation to give directly the expected
products 3 (Fig. 2).
In the case of aldehyde (3a, b) or unsymmetrically substi-
tuted ketone (3j, k) derivatives (Table 2, entries 1, 2, 8, and
9, respectively), the expected mixture of diastereoisomers
(transϩa-cisϩb-cis) was obtained (Fig. 3), which could
be separated by column chromatography (except for
Scheme 2. Reagents and conditions: (i) Li, C10H8 cat. (5%), EˆPriCHO,
ButCHO, Me2CO, Et2CO, Cy2CO, (CH2)5CO, Y(CH2CH2)2CO (YˆO, S,
PrnN), ButCOMe, PhCOMe, EtCOMe, Me3SiCl, (MeS)2, THF, Ϫ78 to
20ЊC; (ii) H2O.

E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
1747
Table 1. Preparation of compounds 2
compound 3k) and their structures unequivocally
assigned by 300 or 500 MHz 1H NMR analysis (see
Experimental).
Entry Electrophile
No.
Producta
X
Yield (%)b
In the second part of this study we have introduced the
1
2
3
4
5
6
7
8
PriCHO
2a
2b
2c
2d
2e
2f
PriCHOH
ButCHOH
Me2COH
Et2COH
Cy2COH
(CH2)5COH
64c
61c
74
72
50
67
56
43
reagent
2-chloromethyl-3-(2-methoxyethoxy)prop-1-ene
ButCHO
(4) in order to be able to prepare perhydrofurofurans result-
ing from the introduction of two different carbonyl
compounds. Thus, using different reaction temperatures it
was possible to perform the chloro/lithium exchange at
Ϫ78ЊC, introducing the first electrophile (Barbier condi-
tions), whereas after warming up to Ϫ30ЊC the allylic
carbon–oxygen bond reductive cleavage took place
allowing the introduction of the second electrophile. After
hydrolysis with water, compounds 5 were isolated (Scheme
4 and Table 3).
Me2CO
Et2CO
Cy2COd
(CH2)5CO
O(CH2CH2)2CO
S(CH2CH2)2CO
2g
2h
O(CH2CH2)2
S(CH2CH2)2COH
9
PrnN(CH2CH2)2CO 2i
PrnN(CH2CH2)2COH 34
10
11
12
13
14
ButCOMe
PhCOMe
EtCOMe
Me3SiCl
(MeS)2
2j
2k
2l
ButC(OH)Me
PhC(OH)Me
EtC(OH)Me
66c
41c
52c
73e
82e
2m Me3Si
2n MeS
As Table 3 shows, a variety of electrophiles (E1 and E2) can
be used in both steps, making the reaction very versatile
compared to other similar processes working under Barbier-
type conditions. It is noteworthy that halogenated materials
can be used as electrophiles under the mentioned conditions,
this reaction being rare using reactive functionalised
organolithium intermediates.25,27,28
a All products 2 were Ͼ95% pure (GLC and 300 MHz 1H NMR) and
were fully characterised by spectroscopic means (IR, 1H and 13C NMR,
and mass spectrometry).
b Isolated yield after column chromatography (silica gel, hexane/diethyl
ether) based on the starting material 1, unless otherwise is stated.
c Product 2 was obtained as a ca. 1:1 mixture of diastereoisomers.
d Cyˆcyclohexyl.
e Crude reaction yield.
Concerning a mechanism for the transformation 4!5, we
have proven that at low temperature only the carbon–
chlorine bond is cleaved. Thus, performing the first step
of the reaction with 3-pentanone or cyclopentanone as
electrophiles, compounds 6a and 6b were isolated in
97 and 65% yield, respectively. These experiments
demonstrated the participation of intermediates VIII
for the first step and probably IX for the second one
(Fig. 4).
Scheme 3. Reagents and conditions: (i) BH3·THF, 0ЊC; (ii) 33% H2O2, 3 M
NaOH, 0ЊC; (iii) (Ph3P)3RuCl2, PhH, 0ЊC (for R2ˆH) or PCC, CH2Cl2, 0ЊC.
Table 2. Preparation of compounds 3
Entry
Diol 2
Oxidation methoda
Productb
No.
R1
R2
Yield (%)c
trans/a-cis/b-cisd
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2j
2k
A
A
B
B
B
B
B
B
B
3a
3b
3c
3d
3e
3f
3g
3j
3k
Pri
H
H
Me
Et
Cy
41
57
51
75
60
58
56
68
53
71:–:29
53:21:26
–
–
–
–
–
But
Me
Et
Cy
(CH2)5
(CH2)2O(CH2)2
But
Ph
Me
Me
47:47:6
36e:47:17e
a Corresponding to the last step (reaction (iii) in Scheme 3); Method A: (Ph3P)3RuCl2; Method B: PCC.
1
1
b All products 3 were Ͼ95% pure (GLC and 300 MHz H NMR) and were fully characterised by spectroscopic means (IR, H and 13C NMR, and mass
spectrometry).
c Isolated yield after column chromatography (silica gel, hexane/diethyl ether) based on the corresponding starting diol 2.
d Diastereomeric ratio determined by GLC; the corresponding assignments were made on the basis of NMR experiments on the isolated diastereoisomers
(see text).
e These diastereoisomers could not be separated by column chromatography; assignments were carried out on the corresponding mixture.
Figure 2.

1748
E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
Figure 3.
As a conclusion, we have reported herein the use of a new
trimethylenemethane dianion synthon of type III for the
introduction of two equal or different electrophiles in the
isobutylene skeleton. For carbonyl compound derivatives,
simple transformation (hydroboration–oxidation) of the
unsaturated diols led to the expected perhydrofurofurans,
which are structural units of important biologically active
natural compounds.
Scheme 4. Reagents and conditions: (i) Li, C10H8 cat. (2.5%), E1ˆButCHO,
Et2CO, (CH2)5CO, O(CH2CH2)2CO, PhCOMe, Me3SiCl, THF, Ϫ78 to Ϫ30
(or 0) ЊC; (ii) E2ˆButCHO, Me2CO, Et2CO, But2CO, (CH2)4CO, (CH2)5CO,
ButCOMe, PhCHvNPh, Me3SiCl, MeI, BunHal (HalˆCl, Br, I), D2O,
THF, Ϫ30 (or 0) to 20ЊC; (iii) H2O.
Table 3. Preparation of compounds 5
Entry
Electrophile E1
Electrophile E2
Producta
No.
X1
X2
Yield (%)b
1
2
3
4
5
6
7
8
ButCHO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
Et2CO
(CH2)5CO
(CH2)5CO
O(CH2CH2)2CO
PhCOMe
Me3SiCl
Et2CO
5a
5a
5b
5c
5d
5e
5f
5g
5h
5i
5i
5i
5j
5k
5l
ButCHOH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
Et2COH
(CH2)5COH
(CH2)5COH
O(CH2CH2)2COH
PhC(OH)Me
Me3Si
Et2COH
ButCHOH
Me2COH
ButC(OH)Me
But2COH
PhCHNHPh
Me3Si
43
34
47
44
61
34
12
77
42
40
45
38
57
25
47
38
75
ButCHO
Me2CO
ButCOMe
But2CO
PhCHvNPh
Me3SiCl
D2O
D
9
MeI
Me
10
11
12
13
14
15
16
17
BunCl
Bun
BunBr
Bun
BunI
Bun
(CH2)4CO
PhCHvNPh
(CH2)5CO
(CH2)5CO
Et2CO
(CH2)4COH
PhCHNHPh
(CH2)5COH
(CH2)5COH
Et2COH
5m
5f
1
1
a All products 5 were Ͼ95% pure (GLC and 300 MHz H NMR) and were fully characterised by spectroscopic means (IR, H and 13C NMR, and mass
spectrometry).
b Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the starting chloroether 4.
Figure 4.
Finally, we carried out the transformation of some of the
Experimental
compounds 5 into the corresponding differently substituted
perhydrofurofurans 7 using the same methodologies used
for compounds 3 (Scheme 5 and Table 4). Also here,
when possible, the expected mixture of diastereoisomers
(ca. 1:1) was obtained (Table 4, entries 1, 3, and 7, and
footnote d).
General
Melting points were obtained with a Reichert Thermovar
apparatus. NMR spectra were recorded on a Bruker AC-
300 (300 MHz for H NMR and 75 MHz for 13C NMR)
1

E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
1749
2. Compounds 2a, 2c, 2d, and 2f were fully characterised by
comparison of their chromatographic and spectral data with
those reported in the literature.23 For new compounds,
physical and spectroscopic data follow:
dl and meso-2,2,8,8-Tetramethyl-5-methylidenenonane-
3,7-diol (2b). Colourless crystals; tr 11.760 and 11.757; Rf
0.73 (hexane/ethyl acetate 1:1); mp 50–52ЊC; n((KBr) 3394
Scheme 5. Reagents and conditions: (i) BH3·THF, 0ЊC; (ii) 33% H2O2, 3 M
NaOH, 0ЊC; (iii) (Ph3P)3RuCl2, PhH, 0ЊC (for R2ˆH) or PCC, CH2Cl2, 0ЊC.
Table 4. Preparation of compounds 7
Entry
Diol 5
Oxidation methoda
Productb
No.
R1
R2
R3
R4
Yield (%)c
1
2
3
4
5
6
7
5a
5b
5c
5d
5j
A
B
B
B
B
B
B
7a
7b
7c
7d
7j
But
Et
Et
Et
H
Et
Et
36d
58
Et
Et
Et
Me
Me
Me
But
But
53d
72
But
(CH2)5
(CH2)2O(CH2)2
Ph
(CH2)4
(CH2)5
(CH2)5
56
5l
5m
7l
7m
47
Me
47d
a Corresponding to the last step (reaction (iii) in Scheme 5); Method A: (Ph3P)3RuCl2; Method B: PCC.
1
1
b All products 7 were Ͼ95% pure (GLC and 300 MHz H NMR) and were fully characterised by spectroscopic means (IR, H and 13C NMR, and mass
spectrometry).
c Isolated yield after column chromatography (silica gel, hexane/ethyl acetate) based on the corresponding starting diol 5.
d Obtained as a ca. 1:1 diastereomeric mixture (300 MHz 1H NMR).
using CDCl3 as solvent and TMS as internal standard;
chemical shifts are given in d (ppm) and coupling constants
(J) in Hz. Mass spectra (EI) were obtained at 70 eV on a
Shimadzu QP-5000 spectrometer, fragment ions in m/z with
relative intensities (%) in parenthesis. HRMS analyses were
carried out on a Finnigan MAT95S spectrometer. Elemental
analyses were performed on a Carlo Erba CHNS-O EA1108
elemental analyzer. The purity of volatile and the chromato-
graphic analyses (GLC) were determined with a Hewlett
Packard HP-5890 instrument equipped with a flame
ionisation detector and a 12 m capillary column (0.2 mm
diametre, 0.33 mm film thickness), using nitrogen (2 ml/
min) as carrier gas, Tinjectorˆ275ЊC, Tcolumnˆ60ЊC (3 min)
and 60–270ЊC (15ЊC/min); retention times (tr) are given
under these conditions. Column chromatography was
performed using silica gel 60 of 40–60 mm. Thin layer
chromatography was carried out on TLC plastic sheets
with silica gel 60 F254 (Merck). All starting compounds
were of the best available grade (Acros, Aldrich, Fluka)
and were used without further purification. THF was dried
over benzophenone ketyl under an argon atmosphere and
distilled before use.
(OH), 3072, 1645 (CvCH), and 1032 cmϪ1 (CO); dH 0.93
(36H, s, 12×CH3), 2.00 (4H, dd, Jˆ14.0, 11.0 Hz,
4×HCHCOH), 2.35 (4H, d, Jˆ14.0 Hz, 4×HCHCOH),
3.32 (4H, dd, Jˆ11.0, 1.8 Hz, 4×CH), and 5.01 (4H, s,
4×H2CvC); dC 25.7 (12×CH3), 34.55 (4×CCH3),
37.8(4×CH2CO), 76.3 (4×CHOH), 115.55 (2×H2CvC),
and 145.3 (2×CvCH2); m/z 174 (MϩϪ54, 1%), 57 (78),
55 (16), and 43 (100); HRMS calcd for C14H28O2
228.2089, (MϩϪCH5O) 195.1749, found 195.1743.
1,1,5,5-Tetracyclohexyl-3-methylidenepentane-1,5-diol
(2e). Colourless crystals; mp 126–128ЊC; tr 16.34; n (KBr)
3250 (OH), 3062, 1633 (CvCH), and 1120 cmϪ1 (CO); dH
(C6D6) 1.11–1.68, 1.78–1.91 [44H, 2m, 4×(CH2)5, 4×CH],
2.65 (4H, br s, 2×CH2CO), and 4.94 (2H, s, H2CvC); dC
(C6D6) 27.15, 27.65, 27.8, 28.05 [4×(CH2)5], 42.05
(2×CH2CO), 46.7 (2×CH), 77.75 (2×CO), 117.25
(H2CvC), and 149.3 (CvCH2); m/z 444 (Mϩ, Ͻ1%), 83
(100), and 55 (53); HRMS calcd for C30H52O2 444.3967,
found 444.3984.
4-[2-(4-Hydroxytetrahydro-2H-pyran-4-ylmethyl)allyl]-
tetrahydro-2H-pyran-4-ol (2g). Colourless oil; tr 16.45; Rf
0.53 (methanol); n (film) 3342 (OH), 3096, 1635 (CvCH),
1109, 1061, and 1026 cmϪ1 (CO); dH 1.66, 1.85 (8H, 2br s,
4×CH2CH2O), 1.91, 1.95, 2.31, 2.83 (4H, 4d, Jˆ6.1,
13.4 Hz, 2×CH2CvC), 3.39–3.93 (8H, m, 4×CH2O) 4.78,
4.98 (2H, 2s, H2CvC); dC 37.2, 37.85, 39.4 (2×CH2CH2O),
49.2, 51.35 (2×CH2vC), 72.35, 73.9 (2×CO), 116.05
(H2CvC), and 141.95 (CvCH2); m/z 238 (MϩϪ18,
Ͻ1%), 101 (77), 93 (20), 91 (13), 83 (100), 71 (58), and
55 (31); HRMS calcd for C14H24O4 256.1675, (MϩϪH2O)
238.1568, found 238.1553.
Preparation of diols 2. General procedure
A solution of 3-chloro-2-chloromethylprop-1-ene (0.16 ml,
2 mmol) and the corresponding electrophile (3.96 mmol) in
THF (6 ml) was added to a green suspension of lithium
powder (100 mg, 14 mmol) and naphthalene (25 mg,
0.2 mmol) in THF (6 ml) at Ϫ78ЊC. The mixture was
allowed to reach room temperature continuing the stirring
for 8 h. Then it was hydrolysed with water (10 ml),
extracted with ethyl acetate (3×15 ml), and the organic
phase was dried over anhydrous sodium sulfate. After
removal of the solvent under reduced pressure (15 Torr),
the resulting residue was purified by column chromato-
graphy (silica gel, hexane/ethyl acetate) to yield compounds
4-[2-(4-Hydroxytetrahydro-2H-4-thiopyranylmethyl)-
allyl]tetrahydro-2H-thiopyran-4-ol (2h). Colourless oil; tr
17.86; Rf 0.80 (methanol); n (film) 3391 (OH), 3095, 1638

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E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
(CvCH), and 1073 cmϪ1 (CO); dH 1.68–1.87 (8H, m,
4×CH2CH2S), 1.97 (2H, br s, 2×OH), 2.35 (4H, s,
2×CH2CvC), 2.35–2.47, 2.63–2.94 (8H, 2m, 4×CH2S),
and 4.97 (2H, s, H2CvC); dC 24.45 (4×CH2CH2S), 39.0
(2×CH2CvC), 49.6 (4×CH2S), 70.1 (2×CO), 119.35
(CH2vC), and 141.3 (CvCH2); m/z 290 (Mϩϩ2, Ͻ1%),
288 (Mϩ, Ͻ1%), 117 (70), 99 (100), 67 (10), and 55 (81);
HRMS calcd for C14H24O2S2 288.1217, found 288.1228.
4×CH3CH2), 1.13, 1.14 (12H, 2s, 4×CH3CO), 1.49 (8H, q,
Jˆ7.6 Hz, 4×CH2CH3), 2.04–2.54 (4H, 2m, 4×CH2CvC),
and 4.91 (4H, d, Jˆ2.1 Hz, 2×H2CvC); dC 8.35
(4×CH3CH2), 26.35, 26.6 (4×CH3CO), 35.15, 35.6
(4×CH2CH3), 47.5, 47.6 (4×CH2CvC), 73.0 (4×CO),
117.75, 117.8 (2×H2CvC), and 144.25 (2×CvCH2); m/z
153 (MϩϪ47, Ͻ1%), 73 (36), and 43 (100); HRMS calcd
for C12H24O2 200.1766, (MϩϪCH5O) 167.1436, found
167.1452.
4-[2-(4-Hydroxy-1-propyl-4-piperidylmethyl)allyl]-1-
propylpiperidin-4-ol (2i). Colourless oil; tr 20.21; Rf 0.18
(methanol); n (film) 3369 (OH), 3066, 1629 (CvCH),
1139, 1065, and 1105 (CO, CN) cmϪ1; dH 0.86 (6H, t,
Jˆ7.4 Hz, 2×CH3), 1.41–1.80 (12H, m, 2×CH2CH3,
4×CH2CH2CO), 2.24–2.32 (8H, m, 4×CH2CH2CO), 2.36
(4H, s, 2×CH2CvC), 2.53–2.65 (4H, m, 2×CH2CH2CH3),
and 4.91 (2H, s, H2CvC); dC 12.05 (2×CH3), 20.25
(2×CH2CH3), 37.65 (4×CH2CH2CO), 49.6, 60.8 (6×CN),
49.7 (2×CH2CvC), 70.35 (2×CO), 118.45 (H2CvC), and
142.35 (CvCH2); m/z 320 (MϩϪ18, Ͻ1%), 114 (100), and
43 (93). HRMS calcd for C20H38N2O2 338.2933,
(MϩϪH2O) 320.2828, found 320.2835.
3-Trimethylsilyl-2-(trimethylsilylmethyl)prop-1-ene (2m).
Colourless oil; tr 7.26; Rf 0.91 (hexane/ethyl acetate 5:1);
n (film) 3073, 1629 (CvCH), and 1252 (CSi) cmϪ1; dH 0.05
(18H, s, 6×CH3), 1.49 (4H, s, 2×CH2Si), and 4.39 (2H, s,
H2CvC); dC Ϫ1.3 (6×CH3), 29.3 (2×CH2Si), 105.5
(H2CvC), and 145.1 (CvCH2); m/z 202 (Mϩϩ2, Ͻ1%),
200 (Mϩ, 8%), 185 (11), 112 (45), 97 (21), and 73 (100);
HRMS calcd for C10H24Si2 200.1417, found 200.1420.
3-Methylsulfanyl-2-methylsulfanylmethylprop-1-ene (2n).
Colourless oil; tr 9.15; Rf 0.56 (hexane/ethyl acetate 5:1); n
(film) 3078, 1653 (CvCH) cmϪ1; dH 1.95 (6H, s, 2×CH3),
3.24 (4H, s, 2×CH2S), and 4.96 (2H,s, H2CvC); dC 14.75
(2×CH3), 37.5 (2×CH2S), 115.25 (H2CvC), and 139.9
(CvCH2); m/z 150 (Mϩϩ2, Ͻ1%), 148 (Mϩ, 8%), 101
(54), 85 (100), and 47 (14); HRMS calcd for C6H12S2
148.0380, found 148.0386.
dl and meso-2,2,3,7,8,8-Hexamethyl-5-methylidene-
nonane-3,7-diol (2j) ( first diastereomer). Colourless crys-
tals; mp 50–52ЊC; tr 13.82; Rf 0.62 (hexane/ethyl acetate
2:1); n (film) 3404 (OH), 3060, 1637 (CvCH), and
1049 cmϪ1 (CO); dH 0.94 [18H, s, 2×(CH3)3C], 1.08 (6H,
s, 2×CH3CO), 2.08–2.32 (4H, m, 2×CH2CO), and 4.83 (2H,
s, H2CvC); dC 21.2 (2×CH3CO), 25.30 [2×(CH3)3C], 38.45
[2×C(CH3)3], 42.05 (2×CH2CO), 76.0 (2×CO), 117.95
(H2CvC), and 147.7 (CvCH2); m/z 181 (MϩϪ75, 1%),
123 (11), 57 (44), and 44 (100); HRMS calcd for
C16H32O2 256.2402, (MϩϪH3O2) 221.2269, found
221.2298. (second diastereomer): colourless crystals; mp
50–52ЊC; tr 13.91; Rf 0.62 (hexane/ethyl acetate 2:1); n
(film) 3404 (OH), 3060, 1637 (CvCH), and 1049 cmϪ1
(CO); dH 0.96 [18H, s, 2×(CH3)3C], 1.15 (6H, s,
2×CH3CO), 2.37–2.49 (4H, m, 2×CH2CO), and 4.98 (2H,
s, H2CvC); dC 22.5 (2×CH3CO), 25.40 [2×(CH3)3C], 38.15
[C(CH3)3], 43.55 (2×CH2CO), 76.6 (2×CO), 118.4
(H2CvC), and 146.1 (CvCH2); m/z 163 (MϩϪ93, 1%),
123 (11), 101 (14), 83 (13), 57 (48), 44 (100), and 43
(58). HRMS calcd for C16H32O2 256.2402, (MϩϪH3O2)
221.2269, found 221.2298.
Hydroboration–oxidation of diols 2. General procedure
1 M BH3·THF (5 mmol) was added to the corresponding
alkene (1 mmol) and the mixture was stirred for 6 h at
room temperature. Then, water (5 ml) was added at 0ЊC
and after 5 min, 3 M NaOH (10 ml) and H2O2 (33% vol.)
(10 ml) were added successively, maintaining the stirring
for 8 h. The reaction mixture was extracted with ethyl
acetate (3×15 ml), and the organic phase was dried over
anhydrous sodium sulfate. After removal of the solvent
under reduced pressure (15 Torr), the corresponding triols
were obtained and used in the next step without further
purification.
Preparation of the perhydrofuro[2,3-b]furans 3a and 3b.
General procedure
The complex RuCl2(Ph3P)3 (767 mg, 0.8 mmol) was added
to a solution of the corresponding triol (1 mmol) derived
from 2 in benzene (10 ml). The reaction mixture was stirred
for 24 h at room temperature and then passed through a pad
containing neutral alumina. The solvent was evaporated
under reduced pressure (15 Torr), and the resulting residue
purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield the expected products 3a and 3b.
Their physical and spectroscopic data follow:
4-Methylidene-2,6-diphenylheptane-2,6-diol (2k). Colour-
less oil; tr 15.81; Rf 0.75 (hexane/ethyl acetate 1:1); n (film)
3402 (OH), 3060, 3023, 1637 (CvCH), and 1051 cmϪ1
(CO); dH 1.46, 1.50 (6H, 2s, 2×CH3), 2.28–2.57 (2H, m,
CH2CO), 4.76, 4.85 (2H, 2s, H2CvC), and 7.18–7.38 (10H,
m, ArH); dC 29.9, 30.55 (2×CH3), 50.35, 50.45
(2×CH2CO), 74.0, 74.3 (2×CO), 119.55, 119.65
(2×H2CvC), 124.75, 124.8, 126.45, 126.55, 128.0,
142.75, 143.05, 147.9, and 148.1 (12×ArC and CvCH2);
m/z 260 (MϩϪ36, 1%), 143 (69), 105 (54), 91 (15), 77 (51),
and 43 (100); HRMS calcd for C20H24O2 296.1776,
(MϩϪ2H2O) 260.1565, found 260.1564.
(2Rء,3aSء,5Rء,6aRء)-2,5-Diisopropylperhydrofuro[2,3-
b]furan (trans-3a). Colourless oil; tr 10.82; Rf 0.12 (hexane/
ethyl acetate 5:1); n (film) 1031 cmϪ1 (CO); dH 0.86, 0.88
(6H, 2d, Jˆ6.4, 6.7 Hz, 2×CH3), 0.99 (6H, d, Jˆ6.7 Hz,
2×CH3), 1.18–1.28 (2H, m, 2×CHCH3), 1.51–1.86 (4H,
m, 2×CH2), 2.72–2.89 (1H, m, CH2CHCH2), 3.41–3.49,
3.65–3.89 (2H, 2m, 2×CH2CHO), and 5.30 (1H, d,
Jˆ5.5 Hz, OCHO); dC 18.35, 18.4, 19.65, 19.75 (4×CH3),
dl and meso-3,7-Dimethyl-5-methylidenenonane-3,7-
diol (2l). Colourless oil; tr 11.29; Rf 0.23 (hexane/diethyl
ether 2:1); n (film) 3425 (OH), 3068, 1633 (CvCH), and
1059 cmϪ1 (CO); dH 0.90, 0.91 (12H, 2t, Jˆ7.6 Hz,

E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
1751
32.55, 32.95 (2×CHCH3), 35.0, 35.95 (2×CH2), 43.2
C14H26O2 226.1933, (Mϩϩ1) 227.2011, found 227.2020.
(CH2CHCH2), 82.75, 84.4 (2×COCH2), and 108.5 (OCO);
m/z 156 (MϩϪ42, 5%), 155 (48), 137 (13), 109 (14), 69
(52), 55 (36), 44 (100), and 43 (71); HRMS calcd for
C12H22O2 198.1620, found 198.1592.
(2R, 3aS, 5S, 6aR)-2,5-Diisopropylperhydrofuro[2,3-
b]furan (b-cis-3a). Colourless oil; tr 10.97; Rf 0.12 (hex-
ane/ethyl acetate 5:1); n (film) 1031 cmϪ1 (CO); dH 0.84,
0.99 (12×H, 2d, Jˆ6.4 Hz, 4×CH3), 1.18–1.23 (2H, m,
2×CHCH3), 1.54–1.67, 1.71–1.80 (4H, 2m, 2×CH2),
2.85–2.98 (1H, m, CH2CHCH2), 3.74–3.90 (2H, 2m,
2×CH2CHO), and 5.70 (1H, d, Jˆ5.2 Hz, OCHO); dC
18.3, 18.4, 19.45, 19.5 (4×CH3), 32.55, 32.95
(2×CHCH3), 35.0, 36.0 (2×CH2), 43.15 (CH2CHCH2),
85.35, 86.65 (2×COCH2), and 108.75 (OCO); m/z 156
(MϩϪ42, 7%), 155 (64), 137 (14), 109 (17), 69 (62), 55
(43), 44 (100), and 43 (82); HRMS calcd for C12H22O2
198.1620, found 198.1592.
Preparation of the perhydrofuro[2,3-b]furans 3c–g, 3j,
and 3k. General procedure
Pyridinium chlorochromate (2.4 mmol, 254 mg) was added
to a solution of the corresponding triol (1 mmol) derived
from 2 in CH2Cl2 (5 ml) and the mixture was stirred for
6 h at room temperature. Then it was passed through a
pad containing neutral alumina, the solvent was evaporated
under reduced pressure (15 Torr), and the resulting residue
purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield the expected products. Their physical
and spectroscopic data follow:
2,2,5,5-Tetramethylperhydrofuro[2,3-b]furan (3c). Colour-
less oil; tr 6.44; Rf 0.27 (hexane/ethyl acetate 7:3); n (film)
1090 and 1024 cmϪ1 (CO); dH 1.20, 1.41 (12H, 2s, 4×CH3),
1.69, 2.00 (4H, 2dd, Jˆ12.8, 5.5 and 12.8, 9.8 Hz, 2×CH2),
3.0 (1H, ddd, Jˆ12.8, 9.8, 5.5 Hz, CHCH2), and 5.66 (1H, d,
Jˆ5.5 Hz, OCHO); dC 29.2, 29.3 (4×CH3), 44.5 (CHCH2),
44.95 (2×CH2), 83.25 (2×COCH2), and 109.35 (OCO); m/z
170 (Mϩ, Ͻ1%), 155 (36), 109 (20), 55 (20), and 43 (100);
HRMS calcd for C10H18O2 170.1307, (MϩϪCH3) 155.1072,
found 155.1049.
(2Rء, 3aSء, 5Rء, 6aRء)-2,5-Di(tert-butyl)perhydrofuro-
[2,3-b]furan (trans-3b). Colourless oil; tr 11.75; Rf 0.77
(hexane/diethyl ether 3:2); n (film) 1128 cmϪ1 (CO); dH
0.89, 0.92 [18H, 2s, 2×(CH3)3C], 1.33–1.45, 1.63–1.76
(4H, 2m, 2×CH2), 2.73–2.82 (1H, m, CH2CHCH2), 3.50–
3.55, 3.74–3.80 (2H, 2m, 2×CH2CHO), and 5.57 (1H, d,
Jˆ5.5 Hz, OCHO); dC 25.6, 25.95 (6×CH3), 32.15, 33.0
(2×CH2), 43.1 (CH2CHCH2), 85.2, 86.9 (2×COCH2), and
108.5 (OCO); m/z 193 (MϩϪ33, Ͻ1%), 169 (100), 109 (26),
107 (73), 57 (71), 55 (61), and 43 (83). HRMS calcd for
C14H26O2 226.1933, (Mϩϩ1) 227.2011, found 227.1990.
2,2,5,5-Tetraethylperhydrofuro[2,3-b]furan (3d). Colour-
less oil; tr 12.51; Rf 0.10 (hexane/ethyl acetate 5:1); n
(film) 1034 cmϪ1 (CO); dH 0.83–0.91 (12H, m, 4×CH3),
1.18–1.23, 1.34–1.81, 1.89–1.97 (12H, 3m, 6×CH2),
2.83–2.92 (1H, m, CHCH2), and 5.61 (1H, d, Jˆ5.5 Hz,
OCHO); dC 8.2, 8.85 (4×CH3), 30.85, 31.6 (4×CH2CH3),
41.0 (2×CH2CH), 43.7 (CHCH2), 88.7 (2×COCH2), and
108.95 (OCO); m/z 199 (MϩϪ27, Ͻ1%), 197 (40), 107
(79), 57 (100), and 55 (55); HRMS calcd for C14H26O2
226.1933, (MϩϪC2H5) 197.1542, found 197.1549.
(2R, 3aR, 5S, 6aS)-2,5-Di(tert-butyl)perhydrofuro[2,3-
b]furan (a-cis-3b). Colourless oil; tr 12.00; Rf 0.77 (hexane/
diethyl ether 3:2); n (film) 1050 cmϪ1 (CO); dH 0.92 [18H,
s, 2×(CH3)3C], 1.22–1.47 (4H, m, 2×CH2), 2.65–2.71 (1H,
m, CH2CHCH2), 3.50–3.56 (2H, m, 2×CH2CHO), and 5.40
(1H, d, Jˆ5.2 Hz, OCHO); dC 25.55 (6×CH3), 33.15
(2×CH2), 42.75 (CH2CHCH2), 89.0 (2×COCH2), and
108.3 (OCHO); m/z 211 (MϩϪ15, Ͻ1%), 169 (69), 151
(15), 123 (14), 109 (23), 107 (62), 57 (61), 55 (53), 44
(100), and 43 (82); HRMS calcd for C14H26O2 226.1933,
(MϩϪC2H5) 197.1541, found 197.1554.
2,2,5,5-Tetracyclohexylperhydrofuro[2,3-b]furan (3e).
Colourless crystals; mp 158–160ЊC; Rf 0.81 (hexane/ethyl
acetate 5:1); n (KBr) 1110 cmϪ1 (CO); dH 0.83–2.89 (48H,
m, 22×CH2, 4×cyclohexyl CH), 2.66–2.89 (1H, m,
CHCHO), and 5.61 (1H, d, Jˆ6.1 Hz, OCHO); dC 22.7,
26.65, 26.8, 27.0, 27.1, 27.6, 28.25, 28.55, 28.95, 29.35,
29.7, 31.95, 37.55 (22×CH2), 44.55, 45.05, 45.55 (4×cyclo-
hexyl CH, CHCHO), 94.65 (2×COCH2), and 110.8 (OCO);
Anal. calcd for C30H50O2: C, 81.39; H, 11.38; found C,
81.19; H, 11.58.
(2R, 3aS, 5S, 6aR)-2,5-Di(tert-butyl)perhydrofuro[2,3-
b]furan (b-cis-3b). Colourless oil; tr 11.85; Rf 0.77 (hexane/
diethyl ether 3:2); n (film) 1074 cmϪ1 (CO); dH 0.87 [18H,
s, 2×(CH3)3C], 1.57–1.62, 1.79–1.86 (4H, 2m, 2×CH2),
2.69–2.87 (1H, m, CH2CHCH2), 3.83–3.96 (2H, m,
2×CH2CHO), and 5.67 (1H, d, Jˆ5.0 Hz, OCHO); dC
25.7 (6×CH3), 33.45, 33.6 (2×CH2), 42.95 (CH2CHCH2),
87.45 (2×COCH2), and 109.15 (OCO); m/z 193 (MϩϪ33,
Ͻ1%), 169 (100), 151 (13), 123 (17), 109 (27), 107 (73), 57
(76), 55 (67), 44 (73), and 43 (89). HRMS calcd for
Dispiro[cyclohexane-1,20-perhydrofuro[2,3-b]furan-
50,100-cyclohexane] (3f). Colourless oil; tr 15.78; Rf 0.68
(hexane/diethyl ether 2:1); n (film) 1018 cmϪ1 (CO); dH
1.20–1.81 [20H, m, 2×(CH2)5], 1.98 (4H, dd, Jˆ12.8,
9.5 Hz, 2×CH2CH), 2.90 (1H, m, CHCH2), and 5.64 (1H,
d, Jˆ5.2 Hz, OCHO); dC 23.35, 23.75, 25.50, 38.2
[2×(CH2)5)], 43.05 (CHCH2), 85.3 (2×COCH2), and

1752
E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
108.15 (OCO); m/z 251 (Mϩϩ1, 3%), 250 (Mϩ, 21%), 232
(15), 83 (10), 55 (100), and 54 (14); HRMS calcd for
C16H26O2 250.1932, found 250.2014.
Dispiro[1-oxacyclohexane-4,20-perhydrofuro[2,3-b]furan-
50,400-100-oxacyclohexane] (3g). Colourless oil; tr 14.39; Rf
0.13 (hexane/ethyl acetate 4:1); n (film) 1101 and
1019 cmϪ1 (CO); dH 1.52–1.85 (12H, m, 4×CH2CH2CO,
2×CH2CH), 2.87–3.04 (1H, m, CHCH2), 3.61–3.69,
3.77–3.89 (8H, 2m, 4×CH2O), and 5.70 (1H, d, Jˆ5.5 Hz,
OCHO); dC 38.15, 38.8, 43.85 (4×CH2CH2O, 2×CH2CH),
42.55 (CHCH2), 64.85, 65.15 (4×CH2O), 82.15
(2×COCH2CH), and 108.55 (OCO); m/z 254 (Mϩ, 21%),
109 (25), 96 (88), 83 (65), 55 (78), 54 (12), and 41
(100); HRMS calcd for C14H22O4 254.1518, found
254.1544.
(2Rء, 3aSء, 5Rء, 6aRء) and (2R, 3aS, 5S, 6aR)-2,5-
Dimethyl-2,5-diphenylperhydrofuro[2,3-b]furan (trans-
3k and b-cis-3k). Colourless oil; tr 17.36, 17.89; Rf 0.65
(hexane/diethyl ether 3:2); n (film) 1047 cmϪ1 (CO); dH
1.23, 1.52, 1.73 (12H, s, 4×CH3), 2.11–2.25, 2.51–2.61
(8H, 2m, 4×CH2), 2.66–2.81 (2H, m, 2×CHCH2), 5.79,
5.95 (2H, 2d, Jˆ5.5, 5.8 Hz, 2×OCHO), and 7.18–7.61
(20H, m, ArH); dC 29.85, 31.55, 32.7 (4×CH3), 43.6,
43.8, 43.95 (4×CH2), 44.1 (2×CHCH2), 87.1, 87.3
(4×CCH3), 109.15, 109.6 (2×OCO), 124.35, 124.4,
125.45, 126.4, 127.8, 128.1, 128.2, 128.05, and 148.1
(24×ArC); m/z (tr 17.36) 281 (MϩϪ13, Ͻ2%), 105 (13),
91 (10), and 44 (100); m/z (tr 17.89) 281 (MϩϪ13, Ͻ1%),
105 (12), and 44 (100); HRMS calcd for C20H22O2
294.1620, (Mϩϩ1) 295.1698, found 295.1674.
(2Rء, 3aSء, 5Rء, 6aRء)-2,5-Di(tert-butyl)-2,5-dimethylper-
hydrofuro[2,3-b]furan (trans-3j). Colourless oil; tr 13.25;
Rf 0.33 (hexane/diethyl ether 3:2); n (film) 1100 cmϪ1 (CO);
dH 0.88, 0.99 [18H, 2s, 2×(CH3)3C], 1.13, 1.37 (6H, 2s,
2×CH3CO), 1.72–1.88 (4H, m, 2×CH2), 2.81–3.05 (1H,
m, CHCH2), and 5.64 (1H, d, Jˆ5.5 Hz, OCHO); dC
21.85, 25.2 (2×CH3CO), 25.35, 25.75 [2×(CH3)3C], 36.45
[2×C(CH3)3], 39.25, 39.75 (2×CH2), 49.05 (CHCH2), 89.9,
91.9 (2×COCH2), and 109.95 (OCO); m/z 253 (MϩϪ1,
Ͻ1%), 197 (32), 57 (81), 55 (27), and 43 (100). HRMS
calcd for C16H30O2 254.2245, (MϩϪC4H9) 197.1542,
found 197.1546.
Preparation of 2-chloromethyl-3-(2-methoxyethoxy)-
prop-1-ene (4)
(2R, 3aR, 5S, 6aS)-2,5-Di(tert-butyl)-2,5-dimethylperhy-
drofuro[2,3-b]furan (a-cis-3j). Colourless oil; tr 13.15; Rf
0.33 (hexane/diethyl ether 3:2); n (film) 1082 and
1028 cmϪ1 (CO); dH 0.97 [18H, s, 2×(CH3)3C], 1.14 (6H,
s, 2×CH3CO), 1.66–1.84 (4H, m, 2×CH2), 2.93–3.07 (1H,
m, CHCH2), and 5.60 (1H, d, Jˆ6.1 Hz, OCHO); dC 22.3
(2×CH3CO), 25.7 [2×(CH3)3C], 36.3 [2×C(CH3)3], 38.6
(2×CH2), 42.05 (CHCH2), 91.3 (2×COCH2), and 107.9
(OCO); m/z 240 (MϩϪ14, Ͻ1%), 197 (55), 57 (66), 55
(26), and 43 (100); HRMS calcd for C16H30O2 254.2245,
found 254.2233.
Dry THF (14 ml) was added to NaH (60% dispersion in
mineral oil) (890 mg, 22 mmol), previously washed with
dry toluene, the resulting suspension was cooled to 0ЊC
and then a solution of 2-methoxyethan-1-ol (1.6 ml,
20 mmol) in THF (14 ml) was added. After stirring for
30 min, 3-chloro-2-(chloromethyl)prop-1-ene (2.43 ml,
21 mmol) was added and the stirring continued for 8 h.
The mixture was hydrolysed with water (50 ml), extracted
with ethyl acetate (3×40 ml), the organic phase was dried
over anhydrous sodium sulfate, and the solvent removed by
distillation under reduced pressure (15 Torr). The residue
obtained was purified by column chromatography (silica
gel, hexane/ethyl acetate) to furnish compound 4 in 40%
yield. Its physical and spectroscopic data follow:
2-Chloromethyl-3-(2-methoxyethoxy)prop-1-ene (4). Colour-
less oil; tr 7.40; Rf 0.83 (hexane/ethyl acetate 4:1); n (film)
3067, 1656 (CvCH), 1199, and 1045 cmϪ1 (CO); dH 3.34
(3H, s, CH3), 3.53 (4H, m, OCH2CH2O), 4.06 (4H, s, CH2Cl
and CvCCH2O), 5.20, and 5.25 (2H, 2s, H2CvC); dC
45.05 (CH2Cl), 59.0 (CH3), 69.5, 71.25, 71.8 (3×CH2O),
116.8 (H2CvC), and 141.9 (CvCH2); m/z 129
(MϩϪ35.5, 35%), 59 (100), and 45 (99); HRMS calcd for
C7H13ClO2 164.0604, found 164.0620.
(2R, 3aR, 5S, 6aS)-2,5-Dimethyl-2,5-diphenylperhydro-
furo[2,3-b]furan (a-cis-3k). Colourless oil; tr 16.81; Rf
0.65 (hexane/diethyl ether 3:2); n (film) 1047 cmϪ1 (CO);
dH 1.44 (6H, s, 2×CH3), 1.88–1.94, 2.13–2.21 (4H, 2m,
2×CH2), 3.13–3.22 (1H, m, CHCH2), 6.05 (1H, d,
Jˆ5.5 Hz, OCHO), 7.04–7.11, and 7.20–7.54 (10H, 2m,
ArH); dC 31.4 (2×CH3), 43.5 (2×CH2), 44.45 (CHCH2),
86.85 (2×CCH3), 109.6 (OCHO), and 124.75, 127.6,
126.05, 147.6 (12×ArC); m/z 281 (MϩϪ13, Ͻ1%), 280
(10), 279 (49), 105 (100), 91 (29), 77 (34), and 44 (91).
HRMS calcd for C20H22O2 294.1620, (MϩϪCH3)
279.1385, found 279.1363.
Preparation of compounds 5. General procedure
A solution of chloroether 4 (329 mg, 2 mmol) and the corre-
sponding first electrophile (1.98 mmol) in THF (6 ml) was
added dropwise for 1.5 h, to a green suspension of lithium
powder (100 mg, 14 mmol) and naphthalene (25 mg,
0.2 mmol) in THF (6 ml) at Ϫ78ЊC. After finishing the

E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
1753
addition the mixture was warmed up to Ϫ30ЊC (0ЊC for
compounds 5e–i and 5k) then a solution of the correspond-
ing second electrophile (4 mmol) in THF (6 ml) was added
dropwise for 1.5 h (only 0.5 min for compounds 5f and 5g).
The stirring was maintained for 8 h allowing the mixture to
reach room temperature. Then it was hydrolysed with water
(10 ml), extracted with ethyl acetate (3×15 ml), and the
organic phase was dried over anhydrous sodium sulfate.
After removal of the solvent under reduced pressure
(15 Torr) the resulting residue was purified by column
chromatography (silica gel, hexane/ethyl acetate) to yield
compounds 5. 3-Ethyl-5-trimethylsilylmethylhex-5-en-3-ol
(5f) has been previously reported.31 For the rest of
compounds 5 physical and spectroscopic data follow:
(4H, 2m, 2×CH2CH3), 2.51, 2.66 (4H, 2s, 2×CH2CvC),
4.82, and 4.96 (2H, 2s, H2CvC); dC 8.05 (2×CH3CH2),
29.45 [2×(CH3)C], 31.4 (2×CH2CH3), 39.95 [2×C(CH3)3],
42.45, 45.75 (2×CH2CvC), 75.1 (COCH2CH3), 82.2
[CO(CH3)3], 117.3 (H2CvC), and 147.75 (CvCH2); m/z
209 (MϩϪ75, 3%), 57 (100), and 43 (11); HRMS calcd
for C18H36O2 284.2715, (MϩϪC4H11O) 209.1905, found
209.1917.
5-(2-Anilino-2-phenylethyl)-3-ethylhex-5-en-3-ol
(5e).
Brown oil; tr 19.46; Rf 0.20 (hexane/ethyl acetate 7:3); n
(film) 3564 (OH), 3406 (NH), 3060, 3026, 1601, 1495
(CvCH), and 917 cmϪ1 (CO); dH 0.85, 0.87 (6H, 2t,
Jˆ7.3 Hz, 2×CH3CH2), 1.47 (4H, q, Jˆ7.3 Hz,
2×CH2CH3), 2.20, 2.13 (2H, AB system, JABˆ10.1 Hz,
CvCCH2CO), 2.47, 2.78 (2H, 2dd, Jˆ14.3, 10.1 and
14.3, 3.8 Hz, CH2CN), 4.45 (1H, dd, Jˆ10.1, 3.8 Hz,
CHN), 4.96, 5.06 (2H, 2s, H2CvC), 6.46–6.60, 6.62–
6.64, and 7.04–7.40 (10H, 3m, ArH); dC 8.0, 8.05
(2×CH3), 30.6, 31.5 (2×CH2CH3), 43.4 (CH2CN), 47.55
(CvCCH2CO), 56.35 (CN), 75.05 (CO), 113.4 (H2CvC),
117.15, 117.25, 126.15, 126.8, 128.55, 128.95, 143.95,
147.6 (12×ArC), and 144.45 (CvCH2); m/z 267 (MϩϪ56,
22%), 266 (100), 77 (12), and 55 (11); HRMS calcd for
C22H29NO 323.2249, found 323.2239.
7-Ethyl-2,2-dimethyl-5-methylidenenonane-3,7-diol (5a).
Colourless oil; tr 12.42; Rf 0.22 (hexane/ ethyl acetate
7:3); n (film) 3384 (OH), 3070, 1629 (CvCH), and
925 cmϪ1 (CO); dH 0.87 (6H, t, Jˆ7.3 Hz, 2×CH3CH2),
0.92 (9H, s, (CH3)3C), 1.42–1.54 (4H, m, 2×CH2CH3),
2.19–2.32, 2.41–2.49 (4H, 2m, 2×CH2CvC), 3.36 (1H,
dd, Jˆ10.4, 1.8 Hz, CH), 4.92, 5.01 (2H, 2s, H2CvC); dC
7.9, 8.00 (2×CH3CH2), 25.65 [(CH3)3C], 30.7, 31.1
(2×CH2CH3), 34.7 [C(CH3)3], 39.75, 44.15 (2×CH2CvC),
65.8 (CH), 74.95 (COCH2CH3), 116.3 (H2CvC), and
145.35 (CvCH2); m/z 199 (MϩϪ29, Ͻ1%), 87 (100), 57
(92), 55 (25), and 45 (71); HRMS calcd for C14H28O2
228.2089, (MϩϪC2H5) 199.1714, found 199.1698.
6-Deuterio-3-ethyl-5-methylidenehexan-3-ol (5g). Colour-
less oil; tr 6.42; Rf 0.27 (hexane/ethyl acetate 5:1); n (film)
3375 (OH), 3033, 1596 (CvCH), and 1031 cmϪ1 (CO); dH
0.79 (6H, t, Jˆ7.3 Hz, 2×CH3CH2), 1.39 (4H, d, Jˆ7.3 Hz,
2×CH2CH3), 1.74 (2H, br s, CH2D), 2.08 (2H, s,
CvCCH2CO), 4.67, and 4.83 (2H, 2s, H2CvC); dC 7.95
(2×CH3), 24.7 (t, Jˆ19.5 Hz, CH2D), 31.25 (2×CH2CH3),
46.15, (CvCCH2CO), 114.6 (H2CvC), and 142.75
(CvCH2); m/z 114 (MϩϪ30, 3%), 87 (71), 69 (20), and
57 (100); HRMS calcd for C9H17DO 143.1436, (MϩϪOH)
126.1406, found 126.1408.
6-Ethyl-2-methyl-4-methylidenoctane-2,6-diol (5b). Colour-
less oil; tr 10.86; Rf 0.125 (hexane/ethyl acetate 5:1); n
(film) 3371 (OH), 3072, 1637 (CvCH), and 1138 cmϪ1
(CO); dH 0.86 (6H, t, Jˆ7.5 Hz, 2×CH3CH2), 1.22 (6H, s,
2×CH3CO), 1.47 (4H, q, Jˆ7.5 Hz, 2×CH2CH3), 2.20–2.60
(2H, br s, 2×OH), 2.38, 2.42 (4H, 2s, 2×CH2CvC), and
5.26 (2H, s, H2CvC); dC 8.0 (2×CH3CH2), 30.1
(2×CH3CO),
31.25
(2×CH2CH3),
44.95,
49.85
(2×CH2CvC), 70.95 (COCH3), 75.05 (COCH2CH3),
117.85 (H2CvC), and 144.25 (CvCH2); m/z 164
(MϩϪ36, 3%), 135 (17), 107 (12), 57 (100), 55 (29), 44
(100), and 43 (88); HRMS calcd for C12H24O2 200.1776,
(MϩϪH3O) 181.1592, found 181.1617.
3,5-Diethylhex-5-en-3-ol (5h). Colourless oil; tr 7.81; Rf
0.14 (hexane/ethyl acetate 5:1); n (film) 3425 (OH), 3080,
3024, 1634 (CvCH), and 1017 cmϪ1 (CO); dH 0.89 (6H, t,
Jˆ8.7 Hz, 2×CH3CH2CO), 1.04 (3H, t, Jˆ7.3 Hz,
CH3CH2CvC), 1.47 (4H, t, Jˆ8.7 Hz, 2×CH3CH2CO),
2.13 (2H, t, Jˆ7.3 Hz, CH3CH2CvC), 2.19 (2H, s,
CvCCH2CO), and 4.81, 4.92 (2H, 2s, H2CvC); dC 8.05
7-Ethyl-2,2,3-trimethyl-5-methylidenenonane-3,7-diol (5c).
Colourless crystals; mp 85–87ЊC; tr 13.23; Rf 0.38 (hexane/
ethyl acetate 5:1); n (KBr) 3320 (OH), 3068, 1628
(CvCH), and 1113 cmϪ1 (CO); dH 0.84, 0.88 (6H, 2t,
Jˆ7.2, 7.6 Hz, 2×CH3CH2), 0.95 [9H, s, (CH3)3C], 1.09
(3H, s, CH3CO), 1.45, 1.46 (4H, 2q, Jˆ7.2, 7.6 Hz,
2×CH2CH3), 2.18, 2.74 (4H, 2m, 2×CH2CvC), 4.86, 4.90
(2H, 2s, H2CvC); dC 7.65, 8.35 (2×CH3CH2), 21.4
(CH3CO), 25.35 [(CH3)3C], 30.55, 32.3 (2×CH2CH3),
42.2, 44.8 (2×CH2CvC), 75.2, 76.5 (2×CO), 117.9
(H2CvC), and 145.2 (CvCH2); m/z 177 (MϩϪ65, 2%),
149 (17), 57 (98), 55 (28), 45 (20), 44 (100), and 43
(88); HRMS calcd for C15H30O2 242.2245, found
242.2173.
(2×CH3CH2CO),
12.55
(CH3CH2CvC),
30.96
(CH3CH2CvC, 2×CH3CH2CO), 44.7 (CvCCH2O), 74.35
(CO), 112.35 (H2CvC), and 148.5 (CvCH2); m/z 141
(MϩϪ15, Ͻ1%), 57 (81), 55 (23), and 43 (100); HRMS
calcd for C10H20O 156.1514, (MϩϪCH3) 141.1279, found
141.1290.
3-Ethyl-5-pentylhex-5-en-3-ol (5i). Colourless oil; tr
10.89; Rf 0.42 (hexane/ethyl acetate 5:1); n (film) 3493
(OH), 3074, 1637 (CvCH), and 975 cmϪ1 (CO); dH 0.88
(9H, m, Jˆ7.3 Hz, 3×CH3), 1.26–1.40 [6H, m, (CH2)3CH3],
1.47 (4H, q, Jˆ7.3 Hz, 2×CH3CH2CO), 2.10 [2H, t,
Jˆ6.9 Hz, CH2(CH2)3CH3], 2.17 (2H, s, CvCCH2CO)
4.81, and 4.92 (2H, 2s, H2CvC); dC 8.10 (2×CH3CH2CO),
14.05 [CH3(CH2)4], 22.6, 23.4, 29.7, 30.95 [2×CH3CH2CO,
(CH2)3CH3], 38.00, 44.35 [CvCCH2CO, CH2(CH2)3CH3],
74.35 (CO), 113.35 (H2CvC), and 147.1 (CvCH2); m/z
169 (MϩϪ29, Ͻ5%), 112 (10), 87 (100), 57 (86), 55 (21),
3-(tert-Butyl)-7-ethyl-2,2-dimethyl-5-methylidenenonane-
3,7-diol (5d). Colourless crystals; mp 63–65ЊC; tr 14.91; Rf
0.49 (hexane/ethyl acetate 5:1); n (KBr) 3425 (OH), 3068,
1628 (CvCH), and 1105 cmϪ1 (CO); dH 0.86 (6H, t,
Jˆ7.5 Hz, 2×CH3CH2), 1.10 [18H, s, 2×(CH3)3C], 1.46

1754
E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
and 43 (25); HRMS calcd for C13H26O 198.1984, (Mϩϩ1)
199.2062, found 199.2084.
(329 mg, 2 mmol) and the corresponding electrophile
(1.98 mmol) in THF (6 ml) was added dropwise for 1.5 h.
The mixture was stirred for 30 min at that temperature and
then it was hydrolysed with water (10 ml), extracted with
ethyl acetate (3×15 ml), and the organic phase was dried
over anhydrous sodium sulfate. After removal of the solvent
under reduced pressure (15 Torr), the resulting residue was
purified by column chromatography (silica gel, hexane/
ethyl acetate) to yield compounds 6a and 6b. Their physical
and spectroscopic data follow:
1-[2-(1-Hydroxycyclopentylmethyl)allyl]cyclohexan-1-ol
(5j). Colourless crystals; mp 57–59ЊC; tr 15.05; Rf 0.10
(hexane/ethyl acetate 5:1); n (KBr) 3332 (OH), 3071,
1632 (CvCH), and 1055 cmϪ1 (CO); dH 1.23–1.33,
1.38–1.64, 1.68–1.85 [18H, 3m, (CH2)5, (CH2)4], 2.37,
2.49 (4H, 2s, 2×CH2CvC), 4.92, 4.96 (2H, 2s, H2CvC);
dC 22.35, 23.4, 25.7, 38.1, 38.15, 39.95 (11×CH2), 71.55,
81.7 (2×CO), 117.35 (H2CvC), and 144.1 (CvCH2); m/z
203 (MϩϪ35, Ͻ1%), 99 (55), 85 (19), 55 (88), and 44
(100); HRMS calcd for C15H26O2 238.1933, (MϩϪH2O)
220.1827, found 220.1824.
3-Ethyl-5-(2-methoxyethoxymethyl)hex-5-en-3-ol (6a).
Yellow oil; tr 12.15; Rf 0.24 (hexane/ethyl acetate 5:1); n
(film) 3460 (OH), 3073, 1649 (CvCH), and 910 cmϪ1
(CO); dH 0.82 (6H, t, Jˆ7.3 Hz, 2×CH3CH2), 1.44 (4H, q,
Jˆ7.3 Hz, 2×CH2CH3), 2.28 (2H, s, CvCCH2CO), 3.29
(1H, br s, OH), 3.35 (3H, s, CH3O), 3.50–3.59 (4H, m,
OCH2CH2O), 4.01 (2H, s, CvCCH2O), 5.20, and 5.25
(2H, 2s, H2CvC); dC 8.05 (2×CH3CH2), 30.85
(2×CH2CH3), 43.95 (CvCCH2CO), 59.0 (CH3O), 69.5,
71.7 (OCH2CH2O), 73.75 (COH), 75.8 (CvCCH2O),
117.8 (H2CvC), and 142.45 (CvCH2); m/z 198 (MϩϪ18,
1%), 111 (64), 87 (63), 59 (100), 57 (93), 55 (40), 54 (38),
and 45 (91); HRMS calcd for C12H24O3 216.1725,
(MϩϪH2O) 198.1620, found 198.1653.
1-[2-(2-Anilino-2-phenylethyl)allyl]cyclohexan-1-ol (5k).
Brown oil; tr 22.67; Rf 0.28 (hexane/ethyl acetate 5:1); n
(film) 3521 (OH), 3420 (NH), 3055, 3026, 1603, 1504
(CvCH), and 1045 cmϪ1 (CO); dH 1.22–1.64 [10H, m,
(CH2)5], 2.11, 2.20 (2H, AB system, JABˆ14.0 Hz,
CvCCH2CO), 2.44, 2.74 (2H, 2dd, Jˆ14.3, 10.1 and
14.3, 3.9 Hz, CH2CN), 4.44 (1H, dd, Jˆ10.1, 3.9 Hz,
HCN), 6.17, 6.18 (2H, 2s, H2CvC), and 6.45–6.62, 7.00–
7.38 (10H, m, ArH); dC 22.15, 22.2, 25.5, 37.25, 38.4
[(CH2)5], 47.5 (CH2CH), 56.2 (CvCCH2CO), 71.45 (CN),
73.25 (CO), 117.3 (H2CvC), 116.95, 117.0, 125.1, 126.0,
126.65, 128.4, 128.45, 128.8, 130.95, 136.75, 143.4, 144.35,
147.5 (12×ArC, CvCH2); m/z 317 (MϩϪ18, 1%), 182
(100), 77 (37), 55 (12); HRMS calcd for C23H29NO
335.2249, found 335.2279.
1-[2-(Methoxyethoxymethyl)allyl]cyclopentan-1-ol (6b).
Yellow oil; tr 12.15; Rf 0.23 (hexane/ethyl acetate 5:1); n
(film) 3469 (OH), 3073, 1649 (CvCH), 1112, and
1058 cmϪ1 (CO); dH 1.58–2.10 [8H, m, (CH2)4], 2.42
(2H, s, CvCCH2CO), 3.26 (1H, br s, OH), 3.38 (3H, s,
CH3O), 3.54–3.62 (4H, m, OCH2CH2O), 4.04 (2H, s,
CvCCH2O), 5.15 and 5.16 (2H, 2s, H2CvC); dC 23.65,
39.8 [(CH2)4], 46.35 (CvCCH2CO), 69.3 (CH3O), 69.3,
71.6 (OCH2CH2O), 75.55 (CvCCH2O), 80.88 (COH),
117.75 (H2CvC), and 142.9 (CvCH2); m/z 196 (MϩϪ18,
3%), 59 (100), 55 (39), and 54 (14); HRMS calcd for
C12H22O3 214.1569, (MϩϪH2O) 196.1463, found
196.1469.
4-[2-(1-Hydroxycyclohexylmethyl)allyl]tetrahydro-2H-
pyran-4-ol (5l). Colourless oil; tr 16.16; Rf 0.57 (ethyl ace-
tate); n (film) 3449 (OH), 3048, 1637 (CvCH),1117, 1026,
996 cmϪ1 (CO); dH 1.17–1.68 (14H, m, (CH2)5,
2×CH2CH2O), 2.33, 2.61 (4H, 2s, 2×CH2CvC), 3.61–
3.75 (4H, m, 2×CH2O), 4.87, 4.88 (2H, 2s, H2CvC); dC
22.3, 25.45, 38.0, 38.3 [(CH2)5, 2×CH2CH2O], 37.85, 49.3
(2×CH2CvC), 63.9 (2×CH2O), 68.4, 71.95 (2×CO),
118.25 (H2CvC), and 142.2 (CvCH2); m/z 255 (Mϩϩ1,
Ͻ1%), 101 (100), 83 (18), 71 (87), and 55 (36); HRMS
calcd for C15H26O3 254.1882, found 254.1908.
Preparation of the perhydrofuro[2,3-b]furans 7
The diols 5 were subjected to tandem hydroboration–oxida-
tion as reported for diols 2. Compound 7a was obtained by
oxidation of the triol derived from 5a with RuCl2(Ph3P)3
following the same procedure as described for compounds
3a and 3b. The rest of the triols were oxidised with PCC, as
described for compounds 3c–g, 3j, and 3k, to yield the
expected products 7b–d, 7j, 7l, and 7m. The physical and
spectroscopic data of compounds 7 follow:
1-[2-(2-Hydroxy-2-phenylpropyl)allyl]cyclohexan-1-ol
(5m). Colourless oil; tr 15.06; Rf 0.17 (hexane/ethyl acetate
5:1); n (film): 3360 (OH), 3093, 3070, 3020, 1625, 1601
(CvCH), and 1070 cmϪ1 (CO); dH 1.23–1.62 [10H, m,
(CH2)5], 1.55 (3H, s, CH3), 2.09, 2.10 (4H, 2s,
2×CH2CvC), 4.87, 4.88 (2H, s, H2CvC), 7.19–7.35, and
7.43–7.45 (5H, 2m, ArH); dC 22.3, 22.35, 25.6, 38.0, 38.4
(7×CH2), 30.3 (CH3), 71.75, 74.05 (2×CO), 118.75
(H2CvC) and 124.85, 126.4, 128.0, 143.1, 144.1 (6×ArC,
CvCH2); m/z 241 (MϩϪ33, 4%), 143 (98), 105 (46), 91
(34), 77 (44), 55 (50), 44 (84), and 43 (100); HRMS calcd
for C18H26O 274.1933, (MϩϪH2O–CH3) 241.1592, found
241.1576.
(3aRء,5Rء,6aSء) and (3aRء,5Sء,6aSء)-5-(tert-Butyl)-2,2-
diethylperhydrofuro[2,3-b]furan (7a, mixture of diaster-
eoisomers): colourless oil; tr 11.75, 11.89; Rf 0.31 (hexane/
ethyl acetate 5:1); n (film) 1100 and 1031 cmϪ1 (CO); dH
0.85, 0.86 (12H, 2t, Jˆ7.7, 7.6 Hz, 4×CH3CH2), 0.89, 0.93
[18H, 2s, 2×(CH3)3C], 1.57–2.00 (16H, m, 4×CH2CH3,
4×CH2CH), 2.78, 2.87 (2H, 2m, 2×CH2CHCH2); 3.59,
3.80 (2H, 2dd, Jˆ11.0, 5.0 and 10.4 Hz, 6.0,
2×CH2CHO); 5.51, and 5.61 (2H, 2d, Jˆ5.5, 5.2 Hz,
2×OCHO); dC 8.35, 8.8, 8.85 (4×CH3CH2); 25.75, 25.85
[2×(CH3)3C], 30.5, 31.05, 31.4, 31.95 (4×CH2CH3), 32.8,
33.0, 33.2, 33.35 (4×CH2CH), 39.95, 40.2 (2×CH2CHCH2),
Preparation of compounds 6a and 6b
General procedure
A green suspension composed of lithium powder (100 mg,
14 mmol), naphthalene (25 mg, 0.2 mmol), and THF (6 ml)
was cooled to Ϫ78ЊC. Then, a solution of chloroether 4

E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
1755
43.3 [2×C(CH3)3], 76.95 (2×COCH2CH3), 85.0, 87.35
[2×CHC(CH3)3], 108.7, and 108.85 (2×OCO); m/z (tr
11.75) 197 (MϩϪ29, 22%), 169 (29), 107 (57), and 57
(100); m/z (tr 11.89) 197 (MϩϪ29, 22%), 169 (26), 107
(60), and 57 (100); HRMS calcd for C14H26O2 226.1933,
found 226.1950.
(3aRء,6aSء)-2,2-Diethyl-5,5-dimethylperhydrofuro[2,3-
b]furan (7b). Colourless oil; tr 10.27; Rf 0.38 (hexane/ethyl
acetate 4:1); n (film) 1094 and 1024 cmϪ1 (CO); dH 0.84,
0.89 (6H, 2t, Jˆ7.6 Hz, 2×CH3CH2), 1.20, 1.41 (6H, 2s,
2×CH3CO), 1.44, 1.75 (4H, 2q, Jˆ7.6 Hz, 2×CH2CH3),
1.64, 1.98 (4H, 2m, 2×CH2CH), 2.93 (1H, m, CHCH2),
and 5.63 (1H, d, Jˆ5.7 Hz, OCHO); dC 8.2, 8.9
(2×CH3CH2), 29.5, 29.55 (2×CH3CO), 30.45, 31.4
(2×CH2CH3), 41.9 (H2CCCH2CH3), 44.1 (CHCH2), 44.95
(CH2CCH3), 83.15 (COCH2), 88.7 (COCH3), and 109.1
(OCO); m/z 183 (MϩϪ15, Ͻ1%), 169 (35), 151 (10), 123
(10), 57 (100); HRMS calcd for C12H22O2 198.1620,
(MϩϪC2H5) 169.1229, found 169.1231.
(3aRء,6aSء)-Dispiro[cyclohexane-1,20-perhydrofuro[2,3-
b]furan-50,100-cyclopentane] (7j). Colourless oil; tr 14.56;
Rf 0.81 (hexane/ethyl acetate 4:1); n (film) 1018 cmϪ1 (CO);
dH 1.20–1.80, 1.95–2.14 (22H, m, 11×CH2), 2.94 (1H, m,
CHCH2), and 5.63 (1H, d, Jˆ5.2 Hz, OCHO); dC 23.3, 23.5,
23.75, 24.35, 25.55, 37.4, 38.5, 39.1, 39.9, 42.65 (11×CH2),
43.4 (2×CHCH2), 73.35, 85.05 (2×COCH2), and 108.15
(OCO); m/z 236 (Mϩ, 20%), 207 (20), 55 (66), and 41
(100); HRMS calcd for C15H24O2 236.1776, found
236.1770.
(3aRء,6aSء)-Dispiro[cyclohexane-1,20-perhydrofuro[2,3-
b]furan-50,400-100-oxacyclohexane] (7l). Colourless oil; tr
14.32; Rf 0.17 (hexane/ethyl acetate 5:1); n (film)1105
and 1031 cmϪ1 (CO); dH 1.23–2.05 [18H, m, (CH2)5,
2×CH2CH, 2×CH2CH2O], 2.90–2.99 (1H, m, CHCH2),
3.60–3.67, 3.74–3.89 (4H, 2m, 2×CH2O), and 5.66 (1H,
d, Jˆ5.5 Hz, OCHO); dC 23.25, 23.65, 25.4, 37.85, 38.3,
38.75, 38.8 [(CH2)5, 2×CH2CH2O], 42.75 (CHCH2), 43.0,
43.9 (2×CH2CH), 64.9, 65.15 (2×CH2O), 81.95, 85.4
(2×COCH2CH), and 108.35 (OCO); m/z 254 (Mϩϩ2,
Ͻ1%), 253 (Mϩϩ1, 7%), 252 (Mϩ, 39%), 223 (20), 110
(12), 55 (86), and 41 (100); HRMS calcd for C15H24O3
252.1725, found 252.1725.
(2Rء,3aSء,6aRء) and (2Sء,3aSء,6aRء)-2-(tert-Butyl)-5,5-
diethyl-2-methylperhydrofuro[2,3-b]furan (7c, mixture
of diasteroisomers): colourless crystals; mp 154ЊC; tr
12.73, 12.83; Rf 0.21 (hexane/ethyl acetate 5:1); n (film)
1091 and 1019 cmϪ1 (CO); dH 0.83, 0.94 (12H, m,
4×CH3CH2), 0.85, 0.97 [18H, 2s, 2×(CH3)3C], 1.12, 1.25
(6H, 2s, 2×CH3CO), 1.40–1.79 (16H, m, 4×CH2CH3,
4×CH2CH), 2.74–2.92 (2H, m, 2×CHCH2); 5.60, and 5.62
(2H, 2d, Jˆ5.5 Hz, 2×OCHO); dC 8.15, 8.3, 8.85, 8.95
(4×CH3CH2),
22.25
(2×COCH3),
25.44,
25.8
[2×(CH3)3C], 30.6, 31.4, 31.6, 32.0 (4×CH2CH3), 36.4,
38.1[2×C(CH3)3], 38.05, 39.4, 39.9, 40.0 (4×CH2CH),
43.1, 44.65 (2×CHCH2), 87.85, 88.9, 91.05, 91.5
(2×COCH2CH3, 2×COCH3), 108.5, 110.2 (2×OCO); m/z
(tr 12.73) 225 (MϩϪ15, 2%), 211 (21), 183 (27), 57
(100), and 43 (76); m/z (tr 12.83) 225 (MϩϪ15, 1%), 211
(20), 183 (36), 165 (11), 57 (100), and 43 (91); HRMS
calcd for C15H28O2 240.2089, (Mϩϩ1) 241.2168, found
241.2158.
(2Rء,3aRء,6aSء) and (2Sء,3aRء,6aSء)-2-Phenyl-2-methyl-
perhydrofuro[2,3-b]furan-5-spiro-10-cyclohexane (7m,
mixture of diastereoisomers): colourless oil; tr 16.18,
16.72; Rf 0.72 (hexane/ethyl acetate 4:1); n (film)
1010 cmϪ1 (CO); dH 1.12–2.00 [20H, m, 2×(CH2)5], 1.63
(6H, 2s, 2×CH3), 1.77, 2.04, 2.26, 2.61 (8H, 4br s,
4×CH2CH), 2.73, 3.03 (2H, 2m, 2×CHCH2), 5.71, 5.86
(2H, 2d, Jˆ5.2, 5.5 Hz, 2×OCHO), and 7.19–7.51 (10H,
m, ArH); dC 23.35, 23.4, 23.55, 23.7, 25.45 [2×(CH2)5],
25.4 (2×CH3), 38.5, 38.75, 44.95, 46.1 (4×CH2CH),
43.35, 43.75 (2×CHCH2), 85.65, 86.3 (4×COCH2),
108.65, 108.95 (2×OCO), 124.35, 125.15, 126.2, 126.35,
127.65, 128.1, 148.1, 148.15 (12×ArC); m/z (tr 16.18) 273
(Mϩϩ1, 5%), 272 (Mϩ, 27%), 257 (53), 91 (45), 77 (36),
and 43 (100); m/z (tr 16.72) 273 (Mϩϩ1, 5%), 272 (Mϩ,
22%), 257 (64), 105 (71), 91 (45), 77 (36), and 43 (100);
HRMS calcd for C18H24O2 272.1776, found 272.1794 and
272.1793.
(3aRء,6aSء)-2,2-Di(tert-butyl)-5,5-diethylperhydro-
furo[2,3-b]furan (7d). Colourless oil; tr 15.14; Rf 0.29
(hexane/diethyl ether 5:1); n (film) 1109 and 1033 cmϪ1
(CO); dH 0.86 (6H, t, Jˆ7.5 Hz, 2×CH3CH2), 1.10 [18H,
s, 2×(CH3)3C], 1.18–1.84, 1.93–2.25 (8H, 2m, 2×CH2CH3,
2×CH2CH), 2.90 (1H, m, CHCH2), and 5.71 (1H, d,
Jˆ8.1 Hz, OCHO); dC 7.95 (2×CH3CH2), 28.95
[2×(CH3)3C], 29.15, 29.4, 40.4, 42.0 (4×CH2), 38.6 [2×
C(CH3)3], 43.4 (CHCH2), 73.1, 82.15 (2×CH2CO), and
111.15 (OCO); m/z 264 (MϩϪ18, Ͻ1%), 107 (16), 57
(100), and 55 (15); HRMS calcd for C18H34O2 282.2559,
(MϩϪC4H9) 225.1854, found 225.1853.

1756
E. Lorenzo et al. / Tetrahedron 56 (2000) 1745–1757
8352. (b) Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61, 5743–
Acknowledgements
5753.
16. Yong, K.; Salim, M.; Capretta, A. J. Org. Chem. 1998, 63,
9828–9833.
This work was generously supported by the DGICYT (no.
PB94-1514 and PB97-0133) from the Spanish Ministerio de
´
Educacion y Cultura (MEC). E. L. thanks the MEC for a
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predoctoral grant.
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