Synthesis of 2-(phenylselanyl)tetrahydrofurans from γ-lactones and of γ-hydroxydiselenoacetals from γ-lactols

Article abstract of DOI:10.1055/s-2001-13408

A known one-pot procedure for the synthesis of 2-(phenylselanyl)tetrahydrofurans could be applied to the transformation of γ-lactones 3a-c into 2-(phenylselanyl)tetrahydrofurans 1a-c. Surprisingly, formation of γ-hydroxydiselenoacetals 5b and 5c was observed when γ-lactols 4b and 4c were treated with selenophenol and boron trifluoride etherate.

Full text of DOI:10.1055/s-2001-13408

PAPER
867
Synthesis of 2-(Phenylselanyl)tetrahydrofurans from γ-Lactones and of
γ-Hydroxydiselenoacetals from γ-Lactols
Andreas Schmitt, Hans-Ulrich Reissig*
Freie Universität Berlin, Institut für Chemie – Organische Chemie, Takustr. 3, 14195 Berlin, Germany
Fax +49(30)83855367; E-mail: Hans.Reissig@Chemie.FU-Berlin.DE
Received 12 December 2000; revised 1 February 2001
Abstract: A known one-pot procedure for the synthesis of 2-(phe-
nylselanyl)tetrahydrofurans could be applied to the transformation
of γ-lactones 3a-c into 2-(phenylselanyl)tetrahydrofurans 1a-c. Sur-
prisingly, formation of γ-hydroxydiselenoacetals 5b and 5c was ob-
served when γ-lactols 4b and 4c were treated with selenophenol and
boron trifluoride etherate.
Key words: furans, lactones, reductions, selenium, selenoacetal
In a series of publications, we reported that γ-lactols are
converted into 2-substituted tetrahydrofuran derivatives
by treatment with silylated nucleophiles1 or organometal-
lic compounds2 in the presence of a suitable Lewis acid.
The stereoselectivity of this transformation was systemat-
ically studied and found to be particularly high for 4-sub-
stituted γ-lactols. In these investigations, we also wanted
to vary the leaving group at the tetrahydrofuran core and
therefore became interested in the synthesis of 2-(phenyl-
selanyl)tetrahydrofurans 1. These cyclic selenoacetals
should not only be of importance for the nucleophilic sub-
stitution given in Scheme 1, but they might also be
precursors for the generation of tetrahydrofuryl radicals3
or 2-lithiotetrahydrofurans.4
Scheme 2
control. Goldsmith, Liotta et al.5 also obtained a diastere-
omeric mixture (3:1) of 1c and assigned trans-configura-
tion to the major isomer. Contrarily, we assume that this
major component should have a cis-configuration.6
Scheme 1
We here report that the required 2-(phenylselanyl)tetrahy-
drofurans 1a−c can be easily prepared in a one-pot proce-
dure using the γ-lactones 3a−c as starting material. This
method has been described by Goldsmith, Liotta et al.5 for
γ-lactone 3c and two δ-lactones and consists of the subse-
quent treatment of lactones with diisobutylaluminium hy-
dride, selenophenol, and boron trifluoride followed by
aqueous workup. When applied to γ-lactones 3a−c, this
procedure furnished the desired (phenylselanyl)tetrahy-
drofurans 1a−c in high yields and good purity (Scheme 2).
We were rather surprised that our first attempt to prepare
1 the γ-lactols 4 did not provide the desired cyclic O,Se-
acetals but the acyclic γ-hydroxydiselenoacetals 5
(Scheme 3). Treatment of γ-lactols 4b and 4c with sele-
nophenol and boron trifluoride afforded compounds 5b
and 5c as crude products in high yield and reasonable pu-
rity, containing only diphenyldiselenide as side product.
Column chromatography furnished pure 5b and 5c in
good yield.7
The formation of the cyclic selenoacetals 1 in the one-pot
procedure must occur by nucleophilic attack of sele-
nophenol to the cyclic oxocarbenium ion 7 derived from
the intermediate reduction product 6 and boron trifluoride
(Scheme 4). In contrast, γ-lactols 4 apparently react with
selenophenol via the γ-hydroxyaldehydes 8, thus giving
the acyclic products 5. The Lewis acid added to the mix-
The trans:cis ratios range from 85:15 to 26:74 and are
probably the result of thermodynamic rather than kinetic
Synthesis 2001, No. 6, 04 05 2001. Article Identifier:
1437-210X,E;2001,0,06,0867,0870,ftx,en;T04400SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

868
A. Schmitt, H.-U. Reissig
PAPER
BF3•OEt2 and, after 15 min, 2 equivalents of selenophenol were
added. The mixture was warmed to –30 ºC within 2 h, then hydrol-
ysed with 10 mL of H2O and warmed to r.t. After precipitation of
the aluminium hydroxides the mixture was filtered through a Celite
pad and the filtrate was extracted with tert-butyl methyl ether. The
combined organic layers were dried (MgSO4) and concentrated.
The residue was purified by Kugelrohr distillation.
3-Methyl-2-(phenylselanyl)tetrahydrofuran (1a)
According to the general procedure, a solution of γ-lactone 3a
(2.00 g, 20.0 mmol) in toluene was treated with diisobutylalumini-
um hydride, then with BF3•OEt2 and finally with selenophenol. Af-
ter workup the residue was purified by distillation (110 °C/0.01
torr). Yield: 4.41 g (91%) as a trans:cis-mixture of 1a (85:15). The
NMR data are given in Tables 1 and 2.
Scheme 3
IR (neat): ν = 3080–3020 (=CH), 2980–2840 (CH), 1570 (C=C),
1070–1000 cm−1 (O-C-Se).
Anal. Calcd for C11H14OSe (241.2): C, 54.78; H, 5.85. Found: C,
54.98; H, 6.08.
ture of γ-lactol and selenophenol may only be involved af-
ter formation of semiacetal 9, which, after dissociation
and reaction with the second equivalent of selenophenol,
gives the isolated diselenoacetals 5 (Scheme 4). A similar
dichotomy of γ-lactols has been reported by Paquette et
al.8 for reactions with thiols which strongly depend on the
Lewis acid used.
4-Methyl-2-(phenylselanyl)tetrahydrofuran (1b)
According to the general procedure, a solution of γ-lactone 3b
(1.50 g, 15.0 mmol) in toluene was treated with diisobutylalumini-
um hydride, then with BF3•OEt2 and finally with selenophenol. Af-
ter workup the residue was purified by distillation (110 °C/0.01
torr). Yield: 3.00 g (83%) as a trans:cis-mixture of 1b (54:46). The
NMR data are given in Tables 1 and 2.
IR (neat): ν = 3090–3030 (=CH), 2980–2830 (CH), 1580 (C=C),
1100–990 cm−1 (O-C-Se).
Anal. Calcd for C11H14OSe (241.2): C, 54.78; H, 5.85. Found: C,
55.16; H, 6.03.
5-Methyl-2-(phenylselanyl)tetrahydrofuran (1c)
According to the general procedure, a solution of γ-lactone 3c (1.50
g, 15.0 mmol) in toluene was treated with diisobutylaluminium hy-
dride, then with BF3•OEt2 and finally with selenophenol. After
workup the residue was purified by distillation (110 °C/0.01 torr).
Yield: 3.04 g (84%) as a trans:cis-mixture of 1c (26:74). The NMR
data are given in Tables 1 and 2.
IR (neat): ν = 3090–3040 (=CH), 3000–2840 (CH), 1575 (C=C),
1090–1030 cm−1 (O-C-Se).
Anal. Calcd for C11H14OSe (241.2): C, 54.78; H, 5.85. Found: C,
54.91; H, 5.80.
2-Methyl-4,4-bis(phenylselanyl)-1-butanol (5b)
A solution of γ-lactol 4b (500 mg, 4.90 mmol) and selenophenol
(1.15 g, 7.37 mmol) in diethyl ether (20 mL) was slowly treated
with BF3•OEt2 (0.8 mL). The mixture was stirred at room tempera-
ture for 3 h, quenched with water (7.5 mL) and extracted with dieth-
yl ether (3 × 10 mL). The combined organic layers were dried
(Na2SO4) and evaporated to dryness. Yield: 1.30 g (89%) of 5b con-
taining traces of diphenyldiselenide. Analytically pure 5b (872 mg,
59%) was obtained by thin layer chromatography (silicagel, pen-
tane–diethyl ether, 1:1).
Scheme 4
All reactions were performed under argon atmosphere in flame-
dried flasks and the components were added by means of syringes.
All solvents were dried by standard methods. For other general in-
formation and synthesis of γ-lactols 4b and 4c see ref. 2. Starting
material γ-lactones 3b,9 3c,10 and selenophenol11 were prepared ac-
cording to literature procedures. Compound 3a was purchased from
Lancaster.
IR (film): ν = 3600–3100 (O-H), 3040, 3030 (=C-H), 2980–2800
(C-H), 1570 (C=C), 1470, 1430 (C-H), 1100–1000 cm−1
[C(SePh)2].
1H NMR (CDCl3, 300 MHz): δ = 7.54–7.02 (m, 10 H, Ph), 4.55 (dd,
J = 8.5 Hz, J = 6.5 Hz, 1 H, 4-H), 3.36 (d, J = 5.5 Hz, 2 H, 1-H),
2.15–1.95 (m, 2 H, 3-H), 1.80–1.68 (m, 1 H, 2-H), 1.70–1.50 (br s,
1 H, OH), 0.83 (d, J = 6.5 Hz, 3 H, 2-Me).
13C NMR (CDCl3, 75.5 MHz): δ = 134.8, 129.0, 128.1 (3 d, Ph),
130.2 (s, Ph), 67.5 (t, C-1), 41.5 (d, J 13C-77Se = 75 Hz C-4), 41.1 (t,
C-3) 34.8 (d, C-2), 16.3 (q, 2-Me).
Synthesis of 2-(Phenylselanyl)tetrahydrofurans 1 Starting from
γ-Lactones 3; General One-pot Procedure
γ-Lactone 3 was dissolved in toluene (2 mL/mmol of 3) and cooled
to –80 °C to –90 ºC. Then, 1.2 equivalents of diisobutylaluminium
hydride (1 M solution in toluene) were added within 30 min. The re-
sulting solution was stirred for 30 min at –78 ºC, 3 equivalents of
Synthesis 2001, No. 6, 867–870 ISSN 0039-7881 © Thieme Stuttgart · New York

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Synthesis of 2-(Phenylselanyl)tetrahydrofurans from -Lactones
869
Table 1 1H NMR (300 MHz, CDCl3), Data of Compounds 1a−ca; δ, J (Hz)
Product 2-H
3-H
3-H
-
4-H
4-H
5-H
5-H
3/4/5-Me
1.13 (d,
2-SePh
trans-1a 5.41
2.39 (sext.
d, J = 7, 5)
2.12 (ddt, 1.52 (dtd, 3.98 (dd,
J = 12,
7, 5)
3.98 (dd,
J = 8.5, 5) J = 7)
7.70−7.58,
7.30−7.20
(2 m)
(d, J = 5)
J = 12,
8.5, 7)
J = 8.5, 5)
cis-1a
5.93
(d, J = 5.5)
2.58–2.44
(m)
-
2.18–2.00 1.72 (dtd, 4.15 (td, J = 9, 3.89
1.18
7.70−7.58,
(m)
J = 12,
4.5)
(q, J = 9)
(d, J = 7) 7.30−7.20
9, 8)
(2 m)
trans-1b 5.94
2.22 (ddd,
1.95 (dt,
J = 13.5,
7)
2.25–2.15
(m)
-
4.11 (dd,
J = 8.5, 7)
3.43 (dd,
J = 8.5, 5) J = 7)
0.99 (d,
7.70−7.45,
7.32−7.10
(2 m)
(dd, J = 7, 3) J = 13.5,
7.5, 3)
cis-1b
5.85
2.58 (ddd,
1.57 (ddd,
J = 13.5,
8.5, 6)
2.42
(br sext.,
J = 8)
-
3.93 (dd, J = 8, 3.50 (dd,
1.02
7.70−7.45,
(dd, J = 7, 6) J = 13.5,
7)
J = 9, 8)
(d, J = 6.5) 7.32−7.10
9, 7)
(2 m)
trans-1c 5.87
2.45−
2.45−
1.65−
1.65−
4.22
-
1.18
7.55−7.45,
(dd, J = 7, 3) 1.85 (m)
1.85 (m)
1.48 (m)
1.48 (m) (br sext.,
(d, J = 6) 7.20−7.10
J = 6.5)
(2 m)
cis-1c
5.67
2.45−
2.45−
1.65−
1.65−
4.09
-
1.24
7.55−7.45,
(dd, J = 6.5,
1.85 (m)
1.85 (m)
1.48 (m)
1.48 (m) (br sext.,
(d, J = 6) 7.20−7.10
3)
J = 6.5)
(2 m)
a The integrals have the expected intensities.
Table 2 13C NMR (75.5 MHz, CDCl3), Data of Compounds 1a–c; δ
Product
trans-1a
cis-1a
C-2a
C-3
C-4
C-5
3/4/5-Me
18.6 (q)
16.2 (q)
16.5 (q)
16.4 (q)
19.8 (q)
21.7 (q)
2-SePh
91.2 (d)
92.3 (d)
84.3 (d)
84.6 (d)
84.3 (d)
83.4 (d)
41.5 (d)
39.9 (d)
42.1 (t)
41.7 (t)
33.8 (t)c
34.8 (t)c
33.4 (t)
32.6 (t)
33.2 (d)
32.5 (d)
31.7 (t)c
32.3 (t)c
67.7 (t)
67.1 (t)
74.3 (d)
73.5 (t)
74.6 (d)
77.9 (d)
133.7, 128.9, 127.2 (3 d), 130.6 (s)
134.3 (d)b
trans-1b
cis-1b
133.3, 128.6, 127.0 (3 d), 130.7 (s)
133.7 (d)b
trans-1c
cis-1c
133.3, 128.9, 127.0 (3 d), 130.7 (s)
134.4, 127.1 (2 d)b
a J = 75 Hz.
b The other signals of SePh are overlapping with signals of the major diastereomer and cannot be assigned unambiguously.
c Assignment interchangeable.
Anal. Calcd for C17H20OSe2 (398.3): C, 51.27; H, 5.06. Found: C,
51.42; H, 5.17.
13C NMR (CDCl3, 75.5 MHz): δ = 134.6, 129.2, 128.0 (3 d, Ph),
130.2 (s, Ph), 67.2 (d, J 13C-77Se = 75 Hz, C-5), 43.8 (d, C-2), 37.7,
33.3 (2 t, C-4, C-3), 23.5 (q, C-1).
5,5-Bis(phenylselanyl)-2-pentanol (5c)
MS (70 eV, EI): m/z = 405, 404, 403, 402, 401, 400, 399, 398, 397,
Analogously to the synthesis of 5b, γ-lactol 4c (450 mg, 4.41 mmol)
and selenophenol (942 mg, 6.03 mmol) in diethyl ether (10 mL)
were treated with BF3•OEt2 (0.7 mL). Yield: 1.37 g of crude 5c con-
taining traces of diphenyldiselenide. Analytically pure 5c (580 mg,
48%) was obtained by thin layer chromatography (silicagel, pen-
tane–diethyl ether, 1:1).
1H NMR (CDCl3, 300 MHz): δ = 7.59–7.31 (m, 10 H, Ph), 4.50 (t,
J = 6.5 Hz, 1 H, 5-H), 3.82 (sext., J = 6.0 Hz, 1 H, 2-H), 2.12–1.89,
1.75–1.65 (2 m, 5 H, 4-H, 3-H, OH), 1.10 (d, J = 6.0 Hz, 3 H, 1-H).
396, 395, 394, 393, 392, 390 (M+), 159, 157, 155, 153 (SePh+), 85
+
[M+-(2 SePh + H)], 77 (C6H5 ).
Acknowlegdement
Generous support by the Deutsche Forschungsgemeinschaft and the
Fonds der Chemischen Industrie is most gratefully acknowledged.
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A. Schmitt, H.-U. Reissig
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(5) Goldsmith, D. J.; Liotta, D. C.; Volmer, M.; Hoekstra, W.;
Waykole, L. Tetrahedron 1985, 41, 4873.
References
(6) In ref. 7 only a 90 MHz 1H NMR spectrum of 1c was
reported. We present data resulting from a 300 MHz
spectrum and a 13C NMR spectrum. Comparing our data
with many other 1,5-disubstituted tetrahydrofuran
derivatives, a cis-configuration of the major isomer is very
likely.
(1) (a) Schmitt, A.; Reissig, H.-U. Eur. J. Org. Chem. 2000,
3893. (b) Schmitt, A.; Reissig, H.-U. Eur. J. Org. Chem.
2001, 1169. (c) For a preliminary communication of our
results see: Schmitt, A.; Reissig, H.-U. Synlett 1990, 40. (d)
For earlier work with highly substituted γ-lactols see:
Brückner, C.; Lorey, H.; Reissig, H.-U. Angew. Chem., Int.
Ed. Engl. 1986, 25, 556. (e) Brückner, C.; Holzinger, H.;
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(4) Review: Ponthieux, S.; Paulmier, C. Top. Curr. Chem. 2000,
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(7) Reviews about synthesis and reactions of selenoacetals see:
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Synthesis 2001, No. 6, 867–870 ISSN 0039-7881 © Thieme Stuttgart · New York