Efficiency of acid- and mercury-catalyzed cyclization reactions in the synthesis of tetrahydrofurans from allylsilyl alcohols

Article abstract of DOI:10.1002/ejoc.201200666

The scope of the acid-catalyzed and mercury-catalyzed cyclization reactions of allylsilyl alcohols is described. This methodology has been found to be an efficient approach to the synthesis of highly substituted tetrahydrofurans. The stereoselectivity of the cyclization is dependent both on the substitution of the starting alcohol and on the catalyst. A plausible mechanism has been proposed that is consistent with the results. Copyright

Full text of DOI:10.1002/ejoc.201200666

Job/Unit: O20666
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Date: 02-08-12 12:03:14
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FULL PAPER
DOI: 10.1002/ejoc.201200666
Efficiency of Acid- and Mercury-Catalyzed Cyclization Reactions in the
Synthesis of Tetrahydrofurans from Allylsilyl Alcohols
Francisco J. Pulido,*[a] Asunción Barbero,*[a] Patricia Val,[a] Alberto Diez,[a] and
Alfonso González-Ortega[a]
Keywords: Synthetic methods / Cyclization / Allenes / Allylic compounds / Oxygen heterocycles / Mercury
The scope of the acid-catalyzed and mercury-catalyzed cycli-
zation reactions of allylsilyl alcohols is described. This meth-
odology has been found to be an efficient approach to the
synthesis of highly substituted tetrahydrofurans. The stereo-
selectivity of the cyclization is dependent both on the substi-
tution of the starting alcohol and on the catalyst. A plausible
mechanism has been proposed that is consistent with the re-
sults.
Introduction
Substituted tetrahydrofurans are structural motifs pres-
ent in a great number of natural products, such as macrodi-
olides,[1] lignans,[2] amphidinolides,[3] or antibiotic poly-
ethers.[4] As a result of their important biological activities,
considerable effort has been directed towards developing
new stereoselective routes to these oxacycles.[5]
An efficient and widely used methodology for the synthe-
sis of tetrahydrofurans is the electrophilic cyclization of γ,δ-
unsaturated alcohols.[6]
Among others,[7] a commonly employed approach is the
mercury-catalyzed cyclization reaction. It has been reported
that the stereoselectivity of mercury-catalyzed cyclization
reactions depends on several factors, such as the nature of
the mercury salt,[8] the structure of the unsaturated
alcohol,[9] and the presence or not of additives, such as
water,[10] in the reaction media (Scheme 1).
Scheme 1. Mercury-catalyzed cyclization of unsaturated alcohols.
An alternative strategy to the synthesis of tetra-
hydrofurans is the acid-catalyzed cyclization of unsaturated
alcohols, although this route has shown major limitations.
However, Hosomi and co-workers[11] reported that the cy-
clization of vinylsilyl alcohols in the presence of a Lewis
acid proceeds with high trans selectivity. A plausible mecha-
nism for this reaction involves electrophilic addition to the
vinylsilane to give a β-silyl carbocation, which is then
trapped by the internal hydroxy group to give the tetra-
hydrofuran derivative (Scheme 2).
Scheme 2. Acid-catalyzed cyclization of vinylsilyl alcohols.
formations,[12] especially in the area of stereoselective allyl-
ation processes.[10] Thus, these organosilicon compounds
are nucleophilic units that are stable towards most reagents
and reaction conditions and are thus able to react with a
wide range of electrophiles.
For many years our research group has been involved in
the study of the synthetic applications of allylsilanes con-
taining an electrophilic moiety within the same molecule.[13]
The so-called allylsilane-terminated cyclization of these
substrates has allowed the synthesis of different-sized
Moreover, allylsilanes have been widely recognized as
valuable synthons in controlling, in a very effective way, the
regio- and stereochemical outcome of many chemical trans-
[a] Department of Organic Chemistry, University of Valladolid,
Po Belén 7, 47011 Valladolid, Spain
Fax: +34-983423013
E-mail: barbero@qo.uva.es
pulido@qo.uva.es
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200666.
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F. J. Pulido, A. Barbero, P. Val, A. Diez, A. González-Ortega
FULL PAPER
carbocycles, such us methylenecyclopentanols,[14] methyl-
First, we studied the scope of this methodology in the
enecyclohexanols,[15] methylenecycloheptanols,[16] or spiro- synthesis of substituted tetrahydrofurans, comparing the
cyclopropylcyclopentanols[17] (Scheme 3).
efficiency of the acid-catalyzed and mercury-catalyzed cycli-
zation reactions of allylsilyl alcohol 2e. The results are
shown in Table 2.
Table 2. Cyclization of allylsilyl alcohol 2e.
Scheme 3. Synthesis of different-sized carbocycles from allylsilyl
ketones.
Entry Reagent
Molar Temp. Time Ratio[a] Yield [%]
equiv.
[°C]
[h]
4e/5e
1
2
3
4
5
6
Hg(OCOCF3)2
1
1
1
1
0.2
1
–40Ǟ0
–40Ǟ0
–60Ǟ0
r.t.
0
–78
2
4
16
4
1
2
50:50
50:50
50:50
79
70[b]
65[c]
–
75
62
Hg(OAc)2
Hg(OAc)2
HgCl2
TsOH
AlCl3
Results and Discussion
In this paper we describe an interesting approach
towards the synthesis of tetrahydrofurans from allylsilyl
alcohols by mercury-catalyzed cyclization and acid-cata-
lyzed reactions.
Thus, following our methodology for the silylcupration
of allene and the capture of the intermediate cuprate with
50:50
55:45
1
[a] The ratios of isomers 4e and 5e were determined by H NMR
analysis. [b] A 1:1 mixture of the corresponding 1-hydroxymethyl-
THF derivatives were also obtained in a yield of 9%. [c] A 1:1
mixture of the corresponding 1-hydroxymethyl THF derivatives
α,β-unsaturated carbonylic compounds we were able to pre- were also obtained in a yield of 7%.
pare allylsilyl aldehydes and ketones 1a–i in high yields. The
corresponding allylsilyl alcohols needed for this study were
readily obtained by reduction with LiAlH4 in a quantitative
manner (Table 1).
As shown in Table 2, the mercury-catalyzed cyclization
reaction of 2e with Hg(OCOCF3)2 afforded a 1:1 mixture
of tetrahydrofurans 4e and 5e in good yield. Similar results
were obtained by using Hg(OAc)2, although the yield was
slightly decreased due to the formation of minor amounts
of the 1-hydroxymethyl-THF derivatives.[18] However, with
HgCl2, no cyclization products were obtained. In contrast
to the results reported by Landais and co-workers, the
stereoselectivity of this kinetically controlled mercury-cata-
lyzed cyclization reaction is not affected by the nature of
the mercury salt, nor by the temperature of the reaction.[8]
The acid-catalyzed cyclization also yielded an equimolar
mixture of diastereoisomers 4e and 5e. The use of a Lewis
acid (AlCl3) provided similar results to the Brønsted acid
(pTsOH) with regard to stereoselectivities, although the
yield was lower.
Table 1. Synthesis of allylsilyl alcohols 2 and 3.
With these results in hand we decided to study the influ-
ence of the substituents of the allylsilyl alcohol on the
stereoselectivity of the cyclization. The results are shown in
Table 3. The cyclization of allylsilanes 2b–2g with mercuric
salts provided the substituted tetrahydrofurans 4b–g and
5b–g in good yields as nearly 1:1 mixtures of diastereoiso-
mers (Table 3, entries 2, 4, 5, 8, 10 and 12). On the other
hand, the stereoselectivity of the acid-catalyzed cyclization
of allylsilyl alcohols depends on their substitution patterns.
Thus, allylsilanes 2b and 2d bearing an allylic substituent
gave 2,2,3-trisubstituted tetrahydrofurans in high yields and
with moderate selectivity towards the stereoisomers 4b and
Entry
Compound[a]
Ratio
2/3
Yield
[%]
R1
R2
R3
1
2
3
4
5
6
7
8
9
H
H
H
H
Me
Et
Me
Me
Ph
H
Me
Pr
Ph
H
H
H
H
H
H
2a
2b
90
91
92
90
89
92
90
90
88
2c
2d
2e
H
H
Me
H
2f
Me
Ph
Ph
2g
2h/3h
2i/3i
50:50
50:50
H
[a] All the alcohols are obtained as racemic mixtures.
2
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Synthesis of Tetrahydrofurans from Allylsilyl Alcohols
Table 3. Scope of the cyclization of allylsilyl alcohols 2a–g.
Entry
Compound
R2 R3
Reagent
Molar
equiv.
Temperature
[°C]
Time
[h]
Ratio[a]
4/5
Yield
[%]
R1
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
Me
Me
Et
Et
Me
H
Me
Me
Pr
Ph
Ph
Ph
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
Me
2a
2b
2b
2c
2d
2d
2d
2e
2e
2f
Hg(OAc)2
Hg(OAc)2
pTsOH
Hg(OAc)2
Hg(OAc)2
pTsOH
AlCl3
Hg(OCOCF3)2
pTsOH
1
1
0.3
1
–40Ǟ0
–40Ǟ0
0
–40Ǟ0
–40Ǟ0
0
–78
–40Ǟ0
0
2
4
1.5
2
4
1.5
2
2
1
2.5
1.5
2
70
68
78
85
68
50:50
66:34
66:34
50:50
73:27
72:28
50:50
50:50
50:50
50:50
66:34
1
0.3
0.5
1
0.2
1
0.2
1
79
67[b]
79
9
75
70
72
74
10
11
12
Hg(OAc)2
pTsOH
Hg(OAc)2
–40Ǟ0
0
–40Ǟ0
2f
2g
1
[a] The ratios of isomers 4 and 5 were determined by H NMR analysis. [b] Yield calculated from the recovered starting material.
4d with a trans arrangement between the R2 and the sil-
We next decided to study the influence of both substitu-
ylmethyl substituent (up to 3:1 dr; Table 3, entries 3 and ents R1 ϶ H and R2 ϶ H. Allylsilanes 2h,i and 3h,i under-
6), whereas substrates 2e,f with an alkyl substituent as R1 went cyclization to provide mixtures of two diastereoiso-
provided substituted tetrahydrofurans as equimolar mix- mers in high yields, the major isomers (4 or 6) being those
tures of diastereoisomers 4 and 5 (Table 3, entries 9, 11).
with a 2,3-trans relationship between the R2 and the sil-
Table 4. Scope of the cyclization of allylsilyl alcohols 2h,i.
Entry
Compound
R3
Reagent
Molar
equiv.
Temperature
[°C]
Time
[h]
Ratio[a]
4/5
Yield
[%]
R1
R2
1
2
3
4
5
6
7
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
2h
2h
2h
2h
2i
Hg(OCOCF3)2
pTsOH
1
0.2
1
–
0.2
1
–40Ǟ0
0
–78
62
0
–78
62
6
1
2
1
1
2
1
60:40
83:17
71:29
72:28
81:19
70:30
60:40
75
87
AlCl3
CHCl3
65[b]
35
[c]
pTsOH
82
2i
AlCl3
CHCl3
69[b]
34
[c]
2i
–
1
[a] The ratios of isomers 4 and 5 were determined by H NMR analysis. [b] Yield calculated from the recovered starting material. [c]
CHCl3 was used as solvent.
Table 5. Scope of the cyclization of allylsilyl alcohols 3h,i.
Entry
Compound
Reagent
Molar
equiv.
Temperature
[°C]
Time
[h]
Ratio[a]
6/7
Yield
[%]
R1
R2
R3
1
2
3
4
5
6
7
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
H
H
H
3h
3h
3h
3h
3i
Hg(OCOCF3)2
pTsOH
1
0.2
1
–
0.2
1
–40Ǟ0
0
–78
62
0
–78
62
5
1
2
2
1
2
2
63:37
78:22
74:26
76:24
77:23
78:22
78:22
80
86
AlCl3
CHCl3
65[b]
33
[c]
pTsOH
79
3i
AlCl3
CHCl3
69[b]
37
[c]
3i
–
1
[a] The ratios of isomers 6 and 7 were determined by H NMR analysis. [b] Yield calculated from the recovered starting material. [c]
CHCl3 was used as solvent.
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F. J. Pulido, A. Barbero, P. Val, A. Diez, A. González-Ortega
FULL PAPER
ylmethyl group. As shown in Tables 4 and 5, in general, the
acid-catalyzed cyclization provided higher stereoselectivities
than the corresponding mercury-catalyzed cyclization reac-
tion.[19] Note that a solution of these allylsilyl alcohols in
chloroform at reflux also underwent cyclization. In this
case, HCl generated in situ would be the catalyst.[20]
On the other hand, the acid-mediated cyclizations
showed the best stereoselectivities and yields when pTsOH
was used as the catalyst (Table 4, entries 2 and 5; Table 5,
entry 2). However, the cyclization of stereoisomers 2h and
2i proceeded with better stereoselectivity (up to 5:1 dr;
Table 4, entries 2 and 5) than the corresponding cyclization
of 3h and 3i (up to 3.5:1 dr; Table 5, entries 2 and 5).
A plausible mechanism for this acid-catalyzed cyclization
involves the electrophilic addition of the proton to the allyl-
silane moiety to give a stabilized carbocation β to the sili-
con, which, in turn, is trapped by the internal hydroxy
group. In the reactive conformation, the C–Si bond is ori-
ented parallel to the empty p orbital of the intermediate
carbocation to allow the corresponding σ-p hyperconjuga-
tive stabilization and therefore intramolecular attack of the
nucleophile will occur anti to the hindered silyl group.
Hosomi and co-workers[11b] reported that the proton-
ation step in the acid-catalyzed cyclization of vinylsilyl
alcohols occurs through the attachment of a proton or
AlCl3 to the hydroxy group to form an oxonium ion, which
will then deliver the proton to the double bond.[21] More-
over, they reported that the addition of the hydroxy group
and the proton proceeds stereospecifically on the same side
of the π bond. Based on these observations, we will assume
the same syn addition for our allylsilanes (Scheme 4).
Scheme 5. Stereochemical outcome of the cyclization.
Conclusions
We have shown that allylsilyl alcohols undergo both mer-
cury and acid-catalyzed cyclization reactions to give substi-
tuted tetrahydrofurans in high yields. The stereoselectivity
of the ring-forming process depends both on the nature of
the catalyst and on the substitution pattern of the allyl-
silane. A mechanism for the reaction has been proposed
that is consistent with the stereochemical outcome of the
cyclization process.
Experimental Section
General: All the reactions were carried out under argon or nitrogen
in dried glassware unless otherwise indicated. Materials were ob-
tained from commercial suppliers and used without further purifi-
cation unless otherwise noted. Solvents were dried and distilled ac-
cording to the standard protocols. Flash column chromatography
was performed on silica gel by using the indicated solvent. The
syntheses and spectroscopic data of allylsilyl aldehydes and ketones
1a–i have been described previously.[14a,15]
Synthesis of Allylsilyl Alcohols 2 and 3: A solution of the allylsilyl
aldehydes or ketones 1a–i (2 mmol) in dry ether (2 mL) was added
to a suspension of LiAlH4 (1.7 mmol) in dry diethyl ether (8 mL)
at 0 °C. The mixture was stirred for 1 h at 0 °C and then quenched
with NaHCO3 (10%, 4 mL) and NaOH (20%, 4 mL). The organic
layer was dried, the solvent evaporated, and the mixture was puri-
fied by flash chromatography (EtOAc/hexane) to give alcohols 2
and 3.
Scheme 4. Mechanism of the acid-catalyzed cyclization.
With regard to the stereochemical outcome of the cycli-
zation reaction, two different reactive conformations can be
drawn, namely I and II (Scheme 5).
In conformer II, an unfavorable steric interaction be-
tween the 1,3-diaxial substituents (Ph and H) would ac-
count for the major product proceeding from conformer I.
This hypothesis is consistent with the fact that cyclization
of allylsilyl alcohols 2h and 2i proceeded with higher stereo-
selectivity than the corresponding cyclization of 3h and 3i,
namely because the diaxial steric strain between Ph and R1
is greater.
(2SR,4SR)-5-[Dimethyl(phenyl)silylmethyl]-4-phenyl-5-hexen-2-ol
(2h): Chromatography gave complete separation of the diastereo-
isomeric alcohols. Colorless oil (45%). IR (film): νmax = 3385, 1633,
˜
1599, 1249, 1113 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.75–7.71
(m, 2 H), 7.55–7.51 (m, 3 H), 7.46–7.41 (m, 2 H), 7.37–7.29 (m, 3
H), 5.08 (s, 1 H), 4.93 (s, 1 H), 3.61–3.48 (m, 1 H), 3.35 (dd, J =
10.1, 4.4 Hz, 1 H), 1.99–1.74 (m, 3 H), 1.92 (d, J = 14.0 Hz, 1 H),
4
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Synthesis of Tetrahydrofurans from Allylsilyl Alcohols
1.76 (d, J = 14.0 Hz, 1 H), 1.21 (d, J = 6.6 Hz, 3 H), 0.52 (s, 3 H,
Synthesis of Tetrahydrofurans 4–7 by Acid Catalysis: The acid cata-
CH3Si), 0.47 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ lyst in CH2Cl2 (0.5 mL) was added to a solution of the alcohol
= 149.8 (C), 143.4 (C), 139.3 (C), 133.9 (CH), 129.2 (CH), 128.5 (1 mmol) in CH2Cl2 (5 mL). The mixture was stirred under the
(CH), 128.0 (CH), 126.5 (CH), 107.8 (CH2), 65.4 (CH), 48.9 (CH), conditions shown in Tables 2–5) and then quenched with a satu-
44.0 (CH2), 26.0 (CH2), 24.5 (CH3), –2.5 (CH3), –2.9 (CH3) ppm. rated solution of NaHCO3 (5 mL). The organic layer was washed
MS (EI): m/z = 324 [M]+, 309 [M – Me]+, 247 [M – Ph]+, 135
[SiMe2Ph]+. C21H28OSi (324.54): calcd. C 77.72, H 8.70; found C
78.04, H 8.98.
three times with NaHCO3, dried with MgSO4, evaporated in vacuo,
and purified by flash chromatography (EtOAc/hexane). The relative
stereochemistries of the tetrahydrofurans were assigned on the ba-
sis of NOE experiments.
(2RS,4SR)-5-[Dimethyl(phenyl)silylmethyl]-4-phenyl-5-hexen-2-ol
2-Methyl-2-[dimethyl(phenyl)silylmethyl]tetrahydrofuran (4a): Col-
(3h): White solid (45%), m.p. 91–92 °C. IR (film): ν
= 3460,
˜
max
1
1629, 1548, 1249, 1113 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.61–7.57 (m, 2 H), 7.46–7.43 (m, 3 H), 7.34–7.24 (m, 3 H), 7.15–
7.12 (m, 2 H), 4.91 (s, 1 H), 4.81 (s, 1 H), 3.61–3.51 (m, 1 H), 2.99
(t, J = 7.5 Hz, 1 H), 1.86–1.81 (m, 2 H), 1.76 (d, J = 14.1 Hz, 1
H), 1.58 (d, J = 14.1 Hz, 1 H), 1.32 (s, 1 H), 1.07 (d, J = 6.1 Hz, 3
H), 0.38 (s, 3 H, CH3Si), 0.33 (s, 3 H, CH3Si) ppm. 13C NMR
(75 MHz, CDCl3): δ = 148.6 (C), 143.5 (C), 139.1 (C), 133.7 (CH),
129.2 (CH), 128.4 (CH), 128.1 (CH), 127.9 (CH), 126.5 (CH), 107.7
(CH2), 66.2 (CH), 49.2 (CH), 43.9 (CH2), 25.6 (CH2), 23.2 (CH3),
–2.6 (CH3), –3.3 (CH3) ppm. MS (EI): m/z = 324 [M]+, 309 [M –
Me]+, 247 [M – Ph]+, 135 [SiMe2Ph]+. C21H28OSi (324.54): calcd.
C 77.72, H 8.70; found C 78.06, H 9.02.
orless oil (70%). H NMR (300 MHz, CDCl3): δ = 7.59–7.52 (m,
2 H), 7.41–7.33 (m, 3 H), 3.81–3.76 (m, 2 H), 1.98–1.85 (m, 2 H),
1.71–1.62 (m, 2 H), 1.39 (d, J = 14.7 Hz, 1 H), 1.28 (d, J = 14.7 Hz,
1 H), 1.21 (s, 3 H), 0.39 [s, 6 H, (CH3)2Si] ppm. 13C NMR
(75 MHz, CDCl3): δ = 140.1 (C), 133.6 (CH), 128.7 (CH), 127.7
(CH), 82.9 (C), 66.3 (CH2), 39.4 (CH2), 30.5 (CH2), 28.5 (CH3),
26.0 (CH2), –1.2 (CH3), –1.3 (CH3) ppm. MS (EI): m/z = 233 [M –
1]+, 219 [M – Me]+, 157 [M – Ph]+, 135 [SiMe2Ph]+. C14H22OSi
(234.41): calcd. C 71.73, H 9.46; found C 72.04, H 9.75.
(2RS,3RS)-2,3-Dimethyl-2-[dimethyl(phenyl)silylmethyl]tetrahydro-
furan (4b): Chromatography gave complete separation of the diaste-
reoisomeric tetrahydrofurans. Colorless oil (52 %). 1H NMR
(300 MHz, CDCl3): δ = 7.57–7.51 (m, 2 H), 7.37–7.31 (m, 3 H),
3.80–3.73 (m, 1 H), 3.71–3.63 (m, 1 H), 2.02–1.94 (m, 1 H), 1.92–
1.85 (m, 1 H), 1.63–1.50 (m, 1 H), 1.37 (d, J = 14.9 Hz, 1 H), 1.20
(d, J = 14.9 Hz, 1 H), 1.00 (s, 3 H), 0.89 (d, J = 6.6 Hz, 3 H), 0.37
[s, 6 H, (CH3)2Si] ppm. 13C NMR (75 MHz, CDCl3): δ = 140.9 (C),
133.7 (CH), 128.7 (CH), 127.7 (CH), 84.6 (C), 64.7 (CH2), 44.0
(CH), 33.7 (CH2), 29.7 (CH2), 23.6 (CH3), 14.8 (CH3), –0.8 (CH3),
–1.0 (CH3) ppm. MS (EI): m/z = 247 [M – 1]+, 233 [M – Me]+, 171
[M – Ph]+, 135 [SiMe2Ph]+. C15H24OSi (248.44): calcd. C 72.52, H
9.74; found C 72.84, H 10.05.
(1RS,3SR)-4-[Dimethyl(phenyl)silylmethyl]-1,3-diphenyl-4-penten-1-
ol (2i): Chromatography gave complete separation of the diastereo-
isomeric alcohols. Colorless oil (44%). IR (film): νmax = 3375, 1633,
˜
1
1249, 1112 cm–1. H NMR (300 MHz, [D6]acetone): δ = 7.55–7.49
(m, 2 H), 7.36–7.14 (m, 13 H), 4.83 (s, 1 H), 4.68 (s, 1 H), 4.29–
4.23 (m, 1 H), 4.13 (d, J = 4.7 Hz, 1 H, OH), 3.62 (dd, J = 11.0,
3.8 Hz, 1 H), 2.15 (ddd, J = 13.9, 10.2, 3.8 Hz, 1 H), 2.04–1.96 (m,
1 H), 1.77 (d, J = 13.9 Hz, 1 H), 1.62 (d, J = 13.9 Hz, 1 H), 0.33
(s, 3 H, CH3Si), 0.30 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz,
[D6]acetone): δ = 150.9 (C), 147.5 (C), 144.0 (C), 139.7 (C), 134.3
(CH), 129.6 (CH), 129.3 (CH), 129.0 (CH), 128.8 (CH), 128.5 (2SR,3RS)-2,3-Dimethyl-2-[dimethyl(phenyl)silylmethyl]tetra-
(CH), 127.4 (CH), 127.0 (CH), 126.3 (CH), 108.0 (CH2), 71.4 (CH), hydrofuran (5b): Colorless oil (26%). 1H NMR (300 MHz, CDCl3):
49.6 (CH), 45.5 (CH2), 26.1 (CH2), –2.4 (CH3), –2.5 (CH3) ppm. δ = 7.58–7.51 (m, 2 H), 7.39–7.31 (m, 3 H), 3.71–3.62 (m, 1 H),
MS (EI): m/z = 368 [M – H2O]+, 309 [M – Ph]+, 135 [SiMe2Ph]+. 3.59–3.49 (m, 1 H), 2.00–1.93 (m, 1 H), 1.86–1.78 (m, 1 H), 1.61–
C26H30OSi (386.61): calcd. C 80.78, H 7.82; found C 81.12, H 8.12.
1.51 (m, 1 H), 1.21 (s, 3 H), 1.09 (d, J = 14.9 Hz, 1 H), 0.94 (d, J
= 6.6 Hz, 3 H), 0.78 (d, J = 14.9 Hz, 1 H), 0.39 (s, 3 H, CH3Si),
0.38 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.1
(C), 133.7 (CH), 128.7 (CH), 127.7 (CH), 84.5 (C), 64.7 (CH2), 45.3
(CH), 33.3 (CH2), 27.6 (CH3), 23.1 (CH2), 14.5 (CH3), –0.8 (CH3),
–1.1 (CH3) ppm. MS (EI): m/z = 247 [M – 1]+, 233 [M – Me]+, 171
[M – Ph]+, 135 [SiMe2Ph]+.
(1SR,3SR)-4-[Dimethyl(phenyl)silylmethyl]-1,3-diphenyl-4-penten-1-
ol (3i): Colorless oil (44%). IR (film): ν
= 3395, 1633, 1245,
˜
max
1109 cm–1. 1H NMR (300 MHz, [D6]acetone): δ = 7.43–7.09 (m, 15
H), 4.92 (s, 1 H), 4.72 (s, 1 H), 4.49 (td, J = 6.9, 4.2 Hz, 1 H), 4.16
(d, J = 4.2 Hz, 1 H, OH), 3.18 (t, J = 7.4 Hz, 1 H), 2.27–2.10 (m,
2 H), 1.69 (d, J = 13.9 Hz, 1 H), 1.52 (d, J = 13.9 Hz, 1 H), 0.18
(s, 3 H, CH3Si), 0.15 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz,
[D6]acetone): δ = 149.7 (C), 146.5 (C), 144.5 (C), 139.6 (C), 134.2
(CH), 129.6 (CH), 129.0 (CH), 128.9 (CH), 128.4 (CH), 128.4
(CH), 127.8 (CH), 127.0 (CH), 126.9 (CH), 108.2 (CH2), 72.4 (CH),
49.4 (CH), 44.9 (CH2), 25.9 (CH2), –2.6 (CH3), –2.6 (CH3) ppm.
MS (EI): m/z = 368 [M – H2O]+, 309 [M – Ph]+, 135 [SiMe2Ph]+.
2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3-propyltetrahydrofuran
[(2RS,3SR)-4c and (2SR,3SR)-5c]: Chromatography gave tetra-
hydrofurans 4c and 5c as a mixture. Colorless oil (85%).
4c: 1H NMR (300 MHz, CDCl3): δ = 7.61–7.53 (m, 2 H), 7.39–
7.32 (m, 3 H), 3.84–3.73 (m, 1 H), 3.72–3.66 (m, 1 H), 2.02–1.96
(m, 1 H), 1.78–1.69 (m, 1 H), 1.61–1.49 (m, 1 H), 1.39–1.25 (m, 4
H), 1.32 (d, J = 14.9 Hz, 1 H), 1.25 (d, J = 14.9 Hz, 1 H), 1.01 (s,
3 H), 0.88 (t, J = 6.6 Hz, 3 H), 0.40 [s, 6 H, (CH3)2Si] ppm. 13C
NMR (75 MHz, CDCl3): δ = 140.8 (C), 133.5 (CH), 128.5 (CH),
127.6 (CH), 84.2 (C), 64.7 (CH2), 49.4 (CH), 32.4 (CH2), 31.6
(CH2), 29.7 (CH2), 23.9 (CH3), 22.1 (CH2), 14.4 (CH3), –0.9 (CH3),
–1.2 (CH3) ppm. MS (EI): m/z = 275 [M]+, 261 [M – Me]+, 199
[M – Ph]+, 135 [SiMe2Ph]+.
Synthesis of Tetrahydrofurans 4–7 by the Use of Mercury Salts: A
solution of the corresponding alcohol (1 mmol) in dry THF (1 mL)
was added to a suspension of the mercury salt (1.09 mmol) and
CaCO3 (2.17 mmol) in dry THF (9 mL) at –40 °C. The stirred mix-
ture was warmed to 0 °C and then NaBH4 (0.72 mmol) in a 2.5 m
solution of NaOH (4 mL) was added dropwise at 0 °C. The reac-
tion mixture was vigorously stirred at 0 °C for l h and then a satu-
rated NaCl solution was added (4 mL). The aqueous layer was ex-
tracted with diethyl ether and the combined extracts were washed
with brine, dried with MgSO4, and the solvents evaporated in
vacuo to give an oil that was purified by chromatography (EtOAc/
hexane).
1
5c: Recognisable signals: H NMR (300 MHz, CDCl3): δ = 3.72–
3.66 (m, 1 H), 3.62–3.54 (m, 1 H), 2.02–1.96 (m, 1 H), 1.78–1.69
(m, 1 H), 1.61–1.49 (m, 1 H), 1.39–1.25 (m, 4 H), 0.95 (t, J =
6.8 Hz, 3 H), 0.79 (d, J = 14.5 Hz, 1 H), 0.42 (s, 3 H, CH3Si), 0.41
(s, 3 H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.0 (C),
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20666
/KAP1
Date: 02-08-12 12:03:14
Pages: 8
F. J. Pulido, A. Barbero, P. Val, A. Diez, A. González-Ortega
FULL PAPER
133.5 (CH), 128.5 (CH), 127.6 (CH), 84.1 (C), 64.7 (CH2), 51.3 4g: 1H NMR (300 MHz, CDCl3): δ = 7.69–7.59 (m, 2 H), 7.43–
(CH), 32.4 (CH2), 31.2 (CH2), 27.8 (CH3), 23.4 (CH2), 22.1 (CH2), 7.35 (m, 3 H), 4.21–4.09 (m, 1 H), 1.89 (dd, J = 12.1, 7.2 Hz, 1 H),
14.5 (CH3), –0.9 (CH3), –1.2 (CH3) ppm.
1.58 (dd, J = 12.1, 7.8 Hz, 1 H), 1.26 (d, J = 13.5 Hz, 1 H), 1.24
(d, J = 6.3 Hz, 3 H), 1.14 (s, 3 H), 1.02 (s, 3 H), 1.01 (d, J =
13.5 Hz, 1 H), 1.00 (s, 3 H), 0.47 (s, 3 H, CH3Si), 0.42 (s, 3 H,
CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.4 (C), 133.7
(CH), 128.6 (CH), 127.7 (CH), 86.5 (C), 71.1 (CH), 47.8 (CH2),
45.0 (C), 26.2 (CH2), 25.3 (CH3), 24.6 (CH3), 23.1 (CH3), –0.3
(CH3), –0.4 (CH3) ppm. MS (EI): m/z = 275 [M – 1]+, 261 [M –
Me]+, 199 [M – Ph]+, 135 [SiMe2Ph]+.
(2RS,3SR)-2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3-phenyl-
tetrahydrofuran (4d): Chromatography gave complete separation of
the diastereoisomeric tetrahydrofurans. Colorless oil (58 %). H
1
NMR (300 MHz, CDCl3): δ = 7.66–7.59 (m, 2 H), 7.42–7.39 (m, 3
H), 7.36–7.26 (m, 3 H), 7.25–7.18 (m, 2 H), 4.10–4.03 (m, 1 H),
3.92–3.87 (m, 1 H), 3.08 (t, J = 8.5 Hz, 1 H), 2.35–2.27 (m, 2 H),
1.42 (d, J = 14.9 Hz, 1 H), 1.32 (d, J = 14.9 Hz, 1 H), 0.91 (s, 3
H), 0.48 (s, 3 H, CH3Si), 0.45 (s, 3 H, CH3Si) ppm. 13C NMR
(75 MHz, CDCl3): δ = 141.0 (C), 140.5 (C), 133.7 (CH), 128.7
(CH), 128.3 (CH), 128.1 (CH), 127.7 (CH), 126.5 (CH), 85.2 (C),
64.9 (CH2), 55.7 (CH), 31.7 (CH2), 29.9 (CH2), 24.8 (CH3), –0.94
(CH3) ppm. MS (EI): m/z = 310 [M]+, 295 [M – Me]+, 233 [M –
Ph]+, 135 [SiMe2Ph]+. C20H26OSi (310.51): calcd. C 77.36, H 8.44;
found C 77.68, H 8.75.
1
5g: Recognisable signals: H NMR (300 MHz, CDCl3): δ = 4.01–
3.89 (m, 1 H), 1.99 (dd, J = 12.6, 8.4 Hz, 1 H), 1.44 (dd, J = 12.6,
6.2 Hz, 1 H), 1.29 (d, J = 14.0 Hz, 1 H), 1.23 (d, J = 6.2 Hz, 3 H),
1.16 (s, 3 H), 1.01 (s, 3 H), 0.99 (s, 3 H), 0.82 (d, J = 14.0 Hz, 1
H), 0.48 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ =
141.2 (C), 86.4 (C), 70.3 (CH), 47.4 (CH2), 45.2 (C), 25.6 (CH3),
24.4 (CH3) ppm.
(2RS,3SR,5SR)-2,5-Dimethyl-2-[dimethyl(phenyl)silylmethyl]-3-
phenyltetrahydrofuran (4h): Chromatography gave complete separa-
tion of the diastereoisomeric tetrahydrofurans. Colorless oil (72%).
1H NMR (300 MHz, CDCl3): δ = 7.63–7.60 (m, 2 H), 7.40–7.38
(m, 3 H), 7.33–7.24 (m, 3 H), 7.20–7.17 (m, 2 H), 4.17–4.06 (m, 1
H), 3.24 (dd, J = 11.2, 6.8 Hz, 1 H), 2.31–2.21 (m, 1 H), 2.03–1.92
(m, 1 H), 1.46 (d, J = 14.9 Hz, 1 H), 1.35 (d, J = 6.1 Hz, 3 H), 1.33
(d, J = 14.9 Hz, 1 H), 0.88 (s, 3 H), 0.48 (s, 3 H, CH3Si), 0.43 (s, 3
H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.7 (C), 140.6
(C), 133.7 (CH), 128.6 (CH), 128.0 (CH), 127.7 (CH), 126.4 (CH),
85.0 (C), 72.4 (CH), 57.0 (CH), 39.6 (CH2), 30.9 (CH2), 27.4 (CH3),
22.1 (CH3), –0.9 (CH3), –1.0 (CH3) ppm. MS (EI): m/z = 323 [M –
1]+, 309 [M – Me]+, 247 [M – Ph]+. C21H28OSi (324.54): calcd. C
77.72, H 8.70; found C 78.04, H 9.03.
(2SR,3SR)-2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3-phenyl-
tetrahydrofuran (5d): Colorless oil (21 %). 1H NMR (300 MHz,
CDCl3): δ = 7.53–7.47 (m, 2 H), 7.39–7.31 (m, 5 H), 7.29–7.21 (m,
3 H), 3.91–3.76 (m, 2 H), 3.06 (dd, J = 11.2, 7.2 Hz, 1 H), 2.46–2.31
(m, 1 H), 2.28–2.15 (m, 1 H), 1.34 (s, 3 H), 1.15 (d, J = 14.9 Hz, 1
H), 0.42 (d, J = 14.9 Hz, 1 H), 0.36 (s, 3 H, CH3Si), 0.33 (s, 3 H,
CH3Si) ppm. 13C NMR (75 MHz, CDCl3): δ = 140.7 (C), 139.8
(C), 133.5 (CH), 128.4 (CH), 128.1 (CH), 127.5 (CH), 126.6 (CH),
84.8 (C), 64.6 (CH2), 56.7 (CH), 30.5 (CH2), 28.1 (CH3), 24.2
(CH2), –0.9 (CH3), –1.2 (CH3) ppm. MS (EI): m/z = 310 [M]+, 295
[M – Me]+, 233 [M – Ph]+, 135 [SiMe2Ph]+.
2,5-Dimethyl-2-[dimethyl(phenyl)silylmethyl]tetrahydrofuran
[(2RS,5SR)-4e and (2SR,5SR)-5e]: Chromatography gave tetra-
hydrofurans 4e and 5e as a mixture. Colorless oil (79%). 1H NMR
(300 MHz, CDCl3): δ = 7.62–7.52 (m, 2 H), 7.43–7.35 (m, 3 H),
4.12–3.97 (m, 1 H), 2.08–1.94 (m, 1 H), 1.82–1.62 (m, 2 H), 1.60–
1.43 (m, 1 H), 1.45 (d, J = 14.5 Hz, 1 H), 1.33 (d, J = 14.5 Hz, 1
H), 1.27 (s, 3 H, CH3), 1.24 (d, J = 6.2 Hz, 3 H), 0.42 [s, 6 H,
(CH3)2Si] ppm. Isomer A. 13C NMR (75 MHz, CDCl3): δ = 140.2
(C), 133.6 (CH), 128.7 (CH), 127.7 (CH), 83.0 (C), 73.5 (CH), 39.6
(CH2), 33.6 (CH2), 32.0 (CH2), 28.8 (CH3), 21.8 (CH3), –1.1
(CH3) ppm. Isomer B: 13C NMR (75 MHz, CDCl3): δ = 140.1 (C),
133.6 (CH), 128.7 (CH), 127.7 (CH), 83.0 (C), 73.9 (CH), 40.3
(CH2), 34.0 (CH2), 31.0 (CH2), 30.4 (CH3), 22.0 (CH3), –1.2
(CH3) ppm. MS (EI): m/z = 248 [M]+, 233 [M – Me]+, 171 [M –
Ph]+, 135 [SiMe2Ph]+.
(2SR,3SR,5SR)-2,5-Dimethyl-2-[dimethyl(phenyl)silylmethyl]-3-
phenyltetrahydrofuran (5h): Colorless oil (15 %). 1H NMR
(300 MHz, CDCl3): δ = 7.47–7.44 (m, 2 H), 7.32–7.27 (m, 5 H),
7.25–7.22 (m, 3 H), 4.22–4.11 (m, 1 H), 3.23 (dd, J = 12.3, 6.1 Hz,
1 H), 2.22–2.14 (m, 1 H), 2.09–1.98 (m, 1 H), 1.35 (s, 3 H), 1.26
(d, J = 5.7 Hz, 3 H), 1.04 (d, J = 14.5 Hz, 1 H), 0.36 (d, J =
14.5 Hz, 1 H), 0.34 [s, 6 H, (CH3)2Si] ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.0 (C), 139.9 (C), 133.6 (CH), 128.4 (CH), 128.3
(CH), 127.5 (CH), 126.5 (CH), 84.9 (C), 73.0 (CH), 57.9 (CH), 38.7
(CH2), 29.1 (CH3), 26.8 (CH2), 21.7 (CH3), –0.5 (CH3) ppm. MS
(EI): m/z = 323 [M – 1]+, 309 [M – Me]+, 247 [M – Ph]+.
(2RS,3SR,5RS)-2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3,5-di-
phenyltetrahydrofuran (4i): Chromatography gave complete separa-
tion of the diastereoisomeric tetrahydrofurans. Colorless oil (67%).
1H NMR (300 MHz, CDCl3): δ = 7.62–7.53 (m, 2 H), 7.40–7.30
(m, 7 H), 7.27–7.15 (m, 6 H), 5.01 (dd, J = 10.3, 5.8 Hz, 1 H), 3.35
(dd, J = 12.4, 6.2 Hz, 1 H), 2.47 (ddd, J = 12.4, 6.2, 5.8 Hz, 1 H),
2.29 (td, J = 12.4, 10.3 Hz, 1 H), 1.51 (d, J = 14.6 Hz, 1 H), 1.37
(d, J = 14.6 Hz, 1 H), 0.92 (s, 3 H), 0.44 (s, 3 H), 0.40 (s, 3 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 144.3 (C), 140.8 (C), 139.4 (C),
133.9 (CH), 128.8 (CH), 128.4 (CH), 128.4 (CH), 128.2 (CH), 127.8
(CH), 127.1 (CH), 126.8 (CH), 125.6 (CH), 85.7 (C), 78.2 (CH),
57.7 (CH), 40.2 (CH2), 31.2 (CH2), 27.1 (CH3), –0.6 (CH3), –0.7
(CH) ppm. C26H30OSi (386.61): calcd. C 80.78, H 7.82; found C
81.17, H 8.16.
5-Ethyl-2-methyl-2-[dimethyl(phenyl)silylmethyl]tetrahydrofuran
[(2RS,5SR)-4f and (2SR,5SR)-5f]: Chromatography gave tetra-
1
hydrofurans 4f and 5f as a mixture. Colorless oil (72%). H NMR
(300 MHz, CDCl3): δ = 7.61–7.53 (m, 2 H), 7.42–7.31 (m, 3 H),
3.83–3.75 (m, 1 H), 2.05–1.95 (m, 1 H), 1.73–1.43 (m, 5 H), 1.39–
1.22 (m, 2 H), 1.19 (s, 3 H, isomer A), 1.17 (s, 3 H, isomer B),
0.99–0.91 (m, 3 H), 0.36 [s, 6 H, (CH3)2Si] ppm. Isomer A: 13C
NMR (75 MHz, CDCl3): δ = 140.2 (C), 133.6 (CH), 128.7 (CH),
127.6 (CH), 82.8 (C), 79.1 (CH), 39.4 (CH2), 31.8 (CH2), 31.3
(CH2), 29.3 (CH2), 28.5 (CH3), 10.5 (CH3), –1.0 (CH3), –1.1
(CH3) ppm. Isomer B: 13C NMR (75 MHz, CDCl3): δ = 140.1 (C),
133.6 (CH), 128.7 (CH), 127.6 (CH), 82.7 (C), 79.5 (CH), 40.1
(CH2), 31.5 (CH2), 30.9 (CH2), 30.2 (CH2), 29.4 (CH3), 10.3 (CH3),
–1.2 (CH3), –1.3 (CH3) ppm. MS (EI): m/z = 261 [M – 1]+, 247
[M – Me]+, 185 [M – Ph]+, 135 [SiMe2Ph]+.
(2SR,3SR,5RS)-2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3,5-di-
phenyltetrahydrofuran (5i): Colorless oil (15 %). 1H NMR
(300 MHz, CDCl3): δ = 7.40–7.17 (m, 15 H), 5.04 (dd, J = 10.4,
2,3,3,5-Tetramethyl-2-[dimethyl(phenyl)silylmethyl]tetrahydrofuran 5.2 Hz, 1 H), 3.37 (dd, J = 12.1, 6.2 Hz, 1 H), 2.45 (ddd, J = 12.1,
[(2RS,5SR)-4g and (2SR,5SR)-5g]: Chromatography gave tetra-
hydrofurans 4g and 5g as a mixture. Colorless oil (87%).
6.2, 5.2 Hz, 1 H), 2.31 (td, J = 12.1, 10.4 Hz, 1 H), 1.44 (s, 3 H),
1.10 (d, J = 14.7 Hz, 1 H), 0.46 (d, J = 14.7 Hz, 1 H), 0.28 (s, 3
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20666
/KAP1
Date: 02-08-12 12:03:14
Pages: 8
Synthesis of Tetrahydrofurans from Allylsilyl Alcohols
H), 0.27 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 142.6 (C),
141.0 (C), 140.2 (C), 133.7 (CH), 128.7 (CH), 128.7 (CH), 128.4
(CH), 128.3 (CH), 127.8 (CH), 127.3 (CH), 126.8 (CH), 126.3
(CH), 85.7 (C), 78.8 (CH), 58.3 (CH), 40.2 (CH2), 29.4 (CH3), 26.9
(CH2), –0.3 (CH3), –0.4 (CH3) ppm.
Acknowledgments
We thank the Ministry of Science and Technology (MCYT) of
Spain (CTQ2009-09302) and the “Junta de Castilla y León”
(GR170 and VA074A08) for financial support.
(2RS,3SR,5RS)-2,5-Dimethyl-2-[dimethyl(phenyl)silylmethyl]-3-
phenyltetrahydrofuran (6h): Chromatography gave complete separa-
tion of the diastereoisomeric tetrahydrofurans. Colorless oil (67%).
1H NMR (300 MHz, CDCl3): δ = 7.62–7.59 (m, 2 H), 7.42–7.36
(m, 3 H), 7.33–7.20 (m, 5 H), 4.39–4.29 (m, 1 H), 3.17 (dd, J =
10.1, 8.8 Hz, 1 H), 2.51 (ddd, J = 12.7, 10.1, 8.3 Hz, 1 H), 1.86
(ddd, J = 12.7, 8.8, 4.6 Hz, 1 H), 1.39 (d, J = 14.9 Hz, 1 H), 1.29
(d, J = 6.1 Hz, 3 H), 1.23 (d, J = 14.9 Hz, 1 H), 0.91 (s, 3 H), 0.47
(s, 3 H, CH3Si), 0.42 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz,
CDCl3): δ = 140.8 (C), 140.0 (C), 133.7 (CH), 128.6 (CH), 128.4
(CH), 128.0 (CH), 127.6 (CH), 126.5 (CH), 85.7 (C), 71.5 (CH),
55.3 (CH), 38.0 (CH2), 30.3 (CH2), 23.9 (CH3), 23.1 (CH3), –0.7
(CH3) ppm. MS (EI): m/z = 323 [M – 1]+, 309 [M – Me]+, 247 [M –
Ph]+. C21H28OSi (324.54): calcd. C 77.72, H 8.70; found C 78.01,
H 8.98.
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phenyltetrahydrofuran (7h): Colorless oil (19 %). 1H NMR
(300 MHz, CDCl3): δ = 7.52–7.45 (m, 2 H), 7.39–7.19 (m, 8 H),
4.10–4.00 (m, 1 H), 3.15 (dd, J = 11.0, 8.3 Hz, 1 H), 2.61–2.50 (m,
1 H), 1.83 (ddd, J = 12.8, 8.3, 3.9 Hz, 1 H), 1.35 (s, 3 H), 1.25 (d,
J = 14.9 Hz, 1 H), 1.23 (d, J = 6.1 Hz, 3 H), 0.41 (d, J = 14.9 Hz,
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(CH), 128.0 (CH), 127.5 (CH), 126.5 (CH), 85.5 (C), 70.9 (CH),
56.3 (CH), 37.0 (CH2), 28.5 (CH3), 23.1 (CH3), 22.9 (CH2), –0.9
(CH3), –1.1 (CH3) ppm. MS (EI): m/z = 323 [M – 1]+, 309 [M –
Me]+, 247 [M – Ph]+.
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[12] I. Fleming, A. Barbero, D. Walter, Chem. Rev. 1997, 97, 2063–
2192.
[13] a) A. Barbero, F. J. Pulido, Acc. Chem. Res. 2004, 37, 817–825;
b) A. Barbero, F. J. Pulido, Synthesis 2004, 779–785.
[14] a) A. Barbero, C. García, F. J. Pulido, Tetrahedron 2000, 56,
2739–2751; b) A. Barbero, Y. Blanco, F. J. Pulido, Chem. Com-
mun. 2001, 66, 7723–7728; c) A. Barbero, Y. Blanco, F. J. Pul-
ido, J. Org. Chem. 2005, 70, 6876–6883.
2-Methyl-2-[dimethyl(phenyl)silylmethyl]-3,5-diphenyltetrahydro-
furan (6i and 7i): Chromatography gave tetrahydrofurans 6i and 7i
as a mixture. Colorless oil (79%).
[15] a) A. Barbero, P. Castreño, F. J. Pulido, Org. Lett. 2003, 5,
4045–4048; b) F. J. Pulido, A. Barbero, P. Castreño, Eur. J. Org.
Chem. 2010, 1307–1313.
6i: 1H NMR (300 MHz, CDCl3): δ = 7.52–7.45 (m, 2 H), 7.28–7.13
(m, 13 H), 5. 18 (dd, J = 8.9, 4.2 Hz, 1 H), 3.15 (dd, J = 10.9,
8.4 Hz, 1 H), 2.88–2.80 (m, 1 H), 2.20–2.13 (m, 1 H), 1.42 (d, J =
14.6 Hz, 1 H), 1.29 (d, J = 14.6 Hz, 1 H), 0.96 (s, 3 H), 0.38 (s, 3
H, CH3Si), 0.37 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz, CDCl3):
δ = 145.1 (C), 140.8 (C), 139.4 (C), 133.8 (CH), 128.8 (CH), 128.7
(CH), 128.5 (CH), 128.3 (CH), 127.8 (CH), 126.9 (CH), 126.8
(CH), 125.8 (CH), 86.6 (C), 76.8 (CH), 56.5 (CH), 39.3 (CH2), 30.4
(CH2), 23.0 (CH3), –0.4 (CH3), –0.5 (CH3) ppm.
[16] F. J. Pulido, A. Barbero, P. Castreño, J. Org. Chem. 2011, 76,
5850–5855.
[17] A. Barbero, P. Castreño, F. J. Pulido, J. Am. Chem. Soc. 2005,
127, 8022–8023.
[18] Small amounts of the oxidation products (2-hydroxymethyl-5-
methyl-2-dimethyl(phenyl)silylmethyltetrahydrofurans)
also obtained.
were
[19] The mercuri-cyclization would proceed through a mechanism
involving a bridged mercurium ion that will attack the alcohol
to give a protonated tetrahydrofuran. The irreversible depro-
tonation step under basic conditions would lead to the corre-
sponding mercuri-tetrahydrofuran intermediate.
7i: Recognisable signals: 1H NMR (300 MHz, CDCl3): δ = 4.81
(dd, J = 9.0, 3.3 Hz, 1 H), 3.13–3.08 (m, 1 H), 2.88–2.80 (m, 1 H),
2.20–2.13 (m, 1 H), 0.27 (s, 3 H, CH3Si) ppm. 13C NMR (75 MHz,
CDCl3): δ = 145.3 (C), 140.9 (C), 139.2 (C), 133.8 (CH), 128.7
(CH), 128.6 (CH), 128.4 (CH), 127.8 (CH), 127.0 (CH), 126.9
(CH), 125.8 (CH), 86.3 (C), 76.8 (CH), 55.9 (CH), 38.6 (CH2), 28.5
(CH2), 23.9 (CH3), –0.7 (CH3), –0.9 (CH3) ppm.
[20] No protodesilylation was observed, in contrast to the results
reported by other authors: a) S. R. Wilson, M. F. Price, J. Am.
Chem. Soc. 1982, 104, 1124–1126; b) P. Mohr, Tetrahedron Lett.
1995, 36, 7221–7224.
[21] Hosomi[11] has proposed that the acid-catalyzed cyclization is
not reversible because the recovered deuterium-labeled vinylsi-
lane maintains both the configuration and the deuterium.
Received: May 17, 2012
Supporting Information (see footnote on the first page of this arti-
1
cle): Full characterization data for compounds 2a–2g and H and
13C NMR spectra for all new compounds.
Published Online: ᭿
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7

Job/Unit: O20666
/KAP1
Date: 02-08-12 12:03:14
Pages: 8
F. J. Pulido, A. Barbero, P. Val, A. Diez, A. González-Ortega
FULL PAPER
Tetrahydrofuran Synthesis
F. J. Pulido,* A. Barbero,* P. Val, A. Diez,
A. González-Ortega .......................... 1–8
Efficiency of Acid- and Mercury-Catalyzed
Cyclization Reactions in the Synthesis of
Tetrahydrofurans from Allylsilyl Alcohols
The synthesis of highly substituted tetra-
hydrofurans from allylsilyl alcohols is de-
scribed, comparing the efficiency of the
mercury- versus the acid-catalyzed cycli-
zation.
Keywords: Synthetic methods
/ Cycli-
zation / Allenes / Allylic compounds / Oxy-
gen heterocycles / Mercury
8
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Eur. J. Org. Chem. 0000, 0–0