Palladium-catalyzed cyclization of silyl-substituted bis(homo)propargylic alcohols to 2,3-dihydrofurans

Article abstract of DOI:10.1002/(SICI)1099-0690(199809)1998:9<1873::AID-EJOC1873>3.0.CO;2-7

Ring-opening of oxiranes 1 by the silicon- and sulfur-functionalized propargyl anions 2 yields the corresponding alk-4-yn-1-ols 3. Cyclization of 3 to 2,3-dihydro-4-phenylthiofurans 5 is achieved by reaction with palladium(II) acetate. The corresponding f

Full text of DOI:10.1002/(SICI)1099-0690(199809)1998:9<1873::AID-EJOC1873>3.0.CO;2-7

FULL PAPER
Palladium-Catalyzed Cyclization of Silyl-Substituted Bis(homo)propargylic
Alcohols to 2,3-Dihydrofurans
Silke Schabbert and Ernst Schaumann*
Institut für Organische Chemie, Technische Universität Clausthal,
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany
Fax: (internat.) ϩ 49(0)5323/722858
E-mail: ernst.schaumann@tu-clausthal.de
Received March 18, 1998
Keywords: Oxiranes / Alkynols / 2,3-Dihydrofurans / Furans / Palladium catalysis
Ring-opening of oxiranes 1 by the silicon- and sulfur-
phenylthiofurans 5 is achieved by reaction with palladium(II)
functionalized propargyl anions 2 yields the corresponding acetate. The corresponding furans 7 are obtained when
alk-4-yn-1-ols 3. Cyclization of
3
to 2,3-dihydro-4-
copper(II) chloride is added to the reaction mixtures.
Dihydrofuran derivatives are of interest as synthetic in- by 2b at Ϫ10°C. In this case, a migration of the phenyldi-
termediates and are also a structural feature in a number methylsilyl group of the starting oxirane to the neighbour-
of natural products, e.g. aflatoxins.[1] Here, we report an ing alkoxide oxygen atom results in elimination of the phen-
efficient and selective approach to sulfur-substituted 2,3-di- ylthio group (Scheme 2). The silyl ether is cleaved during
hydrofurans 5 by palladium-catalyzed cyclization of 3-thio- chromatographic purification on silica gel to give the corre-
5-silyl-substituted alk-4-yn-1-ols 3. These functionalized sponding alcohol 4, which is isolated as a mixture of E/Z
bis(homo)propargylic alcohols are synthesized starting isomers in 47% yield. However, the formation of the desired
from epoxides 1 by reaction with the ω-silyl-substituted sul- silyl-substituted bis(homo)propargylic alcohol 3j can be ac-
fur-stabilized alkynyl anions 2. In this way, products 3 are complished in the presence of boron trifluorideϪdiethyl
obtained as diastereomeric mixtures in good yields (Scheme ether, which allows the reaction of epoxysilane 1e with alky-
1, Table 1). Previously, we have used alkynyl anions 2 for nyl anion 2b to be performed at Ϫ78°C.
the successful preparation of ethynylcyclopropanes from
epoxides.[2] However, the anion building block 2 should also
Table 1. Preparation of bis(homo)propargylic alcohols 3
be a convenient precursor for the synthesis of five-mem-
bered unsaturated oxacycles. In particular, because of their
spearhead-type anion structure, the silylalkynes 2 are steri-
cally less hindered than the corresponding allyl anions, and
thus react more readily with epoxides, especially with bulky
1,2-disubstituted oxiranes.
The reaction of 2 with monosubstituted epoxides occurs
at Ϫ78°C; for the complete conversion of disubstituted oxi-
ranes the temperature is allowed to rise to Ϫ10°C. An ex-
ception is the ring-opening of the disubstituted epoxide 1e
Products R1
R2
Yield (%)[a]
R3 ϭ Me R3 ϭ Ph
3a, 3b
3c, 3d
3e, 3f
3g, 3h
3i, 3j
Me
H
68
70
51
60
78
71
57
70
64
BnOCH2
sec-C5H11
H
Me
Ϫ[CH2]4Ϫ
Me
SiMe2Ph 41
[a]
Isolated yields of pure products.
Scheme 1
Eur. J. Org. Chem. 1998, 1873Ϫ1878
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
1434Ϫ193X/98/0909Ϫ1873 $ 17.50ϩ.50/0
1873

S. Schabbert, E. Schaumann
FULL PAPER
Scheme 2
Table 2. Formation of 2,3-dihydrofurans 5 and ketones 6 from alky-
nols 3
Substrate Products R1
R2 R3
Yield (%)[a]
Dihydrofuran 5 Ketone 6
3a
3d
3f
5a, 6a
5b, 6b
5c, 6c
5d, 6d
Me
H
H
Me 56
Ph 51
18
BnOCH2
21
sec-C5H11 Me Ph 54
15
3g
Ϫ[CH2]4Ϫ
Me 1[b]
26[b]
[a]
[b]
Isolated yields of pure products. Ϫ 40% of 3g recovered.
ditions does not yield the corresponding 3-silyl-substituted
2,3-dihydrofuran, but rather furan 7 in 18% yield, because
the additional silyl substituent is eliminated (Scheme 4).
However, the major product is the alkenyne 8, which is
formed in 48% yield as a result of Peterson olefination. By
the addition of a copper(II) salt, the isolated yield of furan
7 can be increased to 44%.
Scheme 4
The cyclization of the ω-silyl-substituted γ-alkynols 3 can
be achieved in acetonitrile at room temperature using hy-
drochloric acid and palladium(II) acetate as catalysts. Un-
der these conditions, the intramolecular addition of the
hydroxy group to the CϪC triple bond gives exclusively 2,3-
dihydrofurans 5 with the sulfur substituent at C-4 in a 5-
exo-dig ring closure. Moreover, the terminal silyl group is
removed in this process. Some γ-hydroxy ketone 6 is ob-
tained as by-product in 15Ϫ26% yield, which is the result
of hydration of the γ-alkynol 3 (Scheme 3, Table 2).
Scheme 3
Upon treatment of bis(homo)propargylic alcohol 3a with
palladium(II) acetate and additional copper(II) chloride,
the cyclization to 2,3-dihydrofuran 5a and the in situ oxi-
dation to furan 7 are also observed (Scheme 5). The yield
of furan can be increased by extending the reaction time,
which is in accord with the dihydrofuran being the precur-
sor of the furan. In fact, the oxidation of dihydrofuran 5a
to the furan 7 can be accomplished merely by the addition
of copper(II) chloride (Scheme 6). This method represents
a general and simple means of converting substituted 2,3-
dihydrofurans into the corresponding furans under mild
conditions. Usually, the direct oxidation of dihydrofurans
When chiral alcohols are used, e.g. those generated by requires high reaction temperatures.[3]
employing optically pure epoxides, the ring closure pro-
There are a few reports in the literature[4][5][6][7][8][9] on
ceeds with complete retention of configuration. Thus, (Ϫ)- the PdII-catalyzed cyclization of alkynols. Thus, it is known
(S)-propene oxide furnishes chiral (S)-2,5-dimethyl-4-phen- that dihydrofurans may be formed by palladium-catalyzed
ylthio-2,3-dihydrofuran (5a) with excellent optical purity cyclization of 4-alkyl-substituted alk-3-yn-1-ols by 5-endo-
(99% ee), as determined by GLC analysis on a chiral cyclo- dig ring closure.[4] In contrast, bis(homo)propargylic al-
dextrin phase.
cohols with a terminal alkyl substituent on the CϪC triple
The reaction of the phenyldimethylsilyl-substituted alky- bond cyclize to dihydropyrans in a 6-endo-dig manner.[4] In
nol 3i with palladium(II) acetate under analogous con- addition, the corresponding hydroxy ketones analogous to
1874
Eur. J. Org. Chem. 1998, 1873Ϫ1878

Palladium-Catalyzed Cyclization of Silyl-Substituted Bis(homopropargylic) Alcohols
FULL PAPER
(70Ϫ230 mesh), petroleum ether (PE) of boiling range 60Ϫ70°C
Scheme 5
and ethyl acetate (EA) were used.
Silyl-Substituted Bis(homopropargylic) Alcohols 3aϪj. Ϫ General
Procedure: A solution of 1 equiv. of 3-silyl-substituted phenyl pro-
pargyl sulfide 2 in dry THF (7 ml/mmol) was cooled to Ϫ78°C.
Then, 1 equiv. of n-BuLi (1.6  solution in n-hexane) was slowly
added and the mixture was stirred for 2 h. At Ϫ78°C, 1 equiv. of
epoxide 1 was added and stirring was continued at this temperature
for 2 h to complete the reaction. When starting from disubstituted
epoxides, the mixture was warmed to Ϫ10°C after the complete
addition and then stirred for about 12 h. The cold solution was
hydrolyzed by the addition of aqueous NH4Cl and diethyl ether.
After separation of the phases, the organic layer was washed with
brine, dried (Na2SO4), and concentrated in vacuo. The resulting
crude product was purified by column chromatography on silica
gel.
4-Phenylthio-6-(trimethylsilyl)hex-5-yn-2-ol (3a): Reaction of
propene oxide (1a) and 2a at Ϫ78°C. Column chromatography
(PE/EA, 10:1) gave 2 diastereomers (1:1*) as a clear oil (68%). Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 0.11 (s, each 9 H, SiMe3,
SiMe3*), 1.22, 1.23 (each d, J ϭ 6.2 Hz, 3 H, CH3, CH3*), 1.86
(m, 5 H, 3-H, 3-H*, OH), 2.15 (br. s, 1 H, OH*), 3.93 (t, J ϭ 7.4
Hz, 1 H, 4-H), 4.03 (dd, J ϭ 9.0 Hz, 5.6 Hz, 1 H, 4-H*), 4.12 (m,
each 1 H, 2-H, 2-H*), 7.3 (m, each 3 H, arom. H, arom. H*), 7.5
(m, each 2 H, arom. H, arom. H*). Ϫ 13C NMR (50 MHz, CDCl3):
δ ϭ Ϫ0.2, Ϫ0.1 (SiMe3), 23.3, 23.7 (CH3), 36.6, 36.9 (CHSPh),
43.7, 43.9 (CH2), 66.0, 66.1 (CHOH), 89.9, 90.0, 104.8, 105.3 (ace-
tylenic C), 128.0, 128.2, 128.7, 128.7, 133.7, 134.0 (arom. CH),
132.8, 133.1 (arom. C). Ϫ IR (film): ν˜ ϭ 3356, 3060, 2963, 2169,
1250, 843, 759, 692 cmϪ1. Ϫ C15H22OSSi (278.5): calcd. C 64.69,
H 7.96, S 11.51; found C 64.69, H 7.96, S 11.47.
Scheme 6
6 are obtained, and particularly in acetonitrile they become
the major products.
6-(Dimethylphenylsilyl)-4-phenylthiohex-5-yn-2-ol (3b): Reaction
of propene oxide (1a) and 2b at Ϫ78°C. Column chromatography
(PE/EA, 10:1) gave 2 diastereomers (1:1*) as a clear oil (78%). Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 0.30 (s, each 6 H, SiMe2,
SiMe2*), 1.15, 1.16 (each d, J ϭ 6.2 Hz, 3 H, CH3, CH3*), 1.82
(m, 4 H, 3-H, 3-H*), 2.00 (br. s, each 1 H, OH, OH*), 3.97Ϫ4.16
(m, each 2 H, 2-H, 4-H, 2-H*, 4-H*), 7.2Ϫ7.5 (m, each 10 H, arom.
H, arom. H*). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ Ϫ1.02, Ϫ0.99,
Ϫ0.96, Ϫ0.03 (SiMe2), 23.3, 23.7 (CH3), 36.5, 36.7 (CHSPh), 43.5,
43.8 (CH2), 65.8, 65.9 (CHOH), 87.5, 87.6, 106.7, 107.1 (acetylenic
C), 128.7, 128.9, 129.0, 129.6, 130.3, 134.5, 134.8 (arom. CH),
133.6, 133.9, 137.6, 137.7 (arom. C). Ϫ IR (film): ν˜ ϭ 3356, 3069,
2964, 2925, 2169, 1430, 1250, 1116, 816, 733, 701 cmϪ1. Ϫ
C20H24OSSi (340.5): calcd. C 70.54, H 7.10, S 9.41; found C 69.96,
H 6.95, S 9.30.
In our case, the silyl group at the acetylenic terminus di-
rects the nucleophilic attack of the hydroxy group to the
carbon atom in the β-position to the silicon atom, leading
to regioselective formation of the five-membered oxacycle.
The application of this method allows the introduction of
the sulfur substituent at C-4, in contrast to the situation
using alkyl-substituted β-alkynols.
Similarly, γ-lactones have been obtained by the cycliza-
tion of 4-(trimethylsilyl)-substituted homopropargylic al-
cohols with palladium(II) acetate and copper(II) chloride
in acetonitrile in a method related to the Wacker pro-
cess.[10][11] In our case, an analogous process would yield a
δ-lactone, but the possibility of the required 6-endo-dig ring
closure is overruled by the directing effect of silicon.
In summary, the reaction system with palladium(II) ace-
tate described here allows the conversion of silyl-substituted
bis(homo)propargylic alcohols into the corresponding sub-
stituted 2,3-dihydrofurans in good yields. By the addition
1-Benzyloxy-4-phenylthio-6-(trimethylsilyl)hex-5-yn-2-ol
(3c):
Reaction of benzylglycidol (1b) and 2a at Ϫ78°C. Column chroma-
tography (PE/EA, 30:1) gave 2 diastereomers (1:1*) as a clear oil
(70%). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.11 (s, each 9 H,
SiMe3, SiMe3*), 1.73 (ddd, J ϭ 13.4 Hz, 10.8 Hz, 2.8 Hz, 1 H,
CH2*), 1.84Ϫ2.04 (m, 3 H, CH2, CH2*), 2.48, 2.54 (each br. s, 1
of copper(II) chloride to the reaction mixture, the corre- H, OH, OH*), 3.36 (dd, J ϭ 10.0 Hz, 7.2 Hz, 1 H, CH2O), 3.41
(dd, J ϭ 10.0 Hz, 6.8 Hz, 1 H, CH2O*), 3.50, 3.55 (each t, J ϭ 2.8
Hz, each 1 H, CH2O, CH2O*), 3.97 (dd, J ϭ 8.0 Hz, 6.4 Hz, 1 H,
CHSPh), 4.09 (dd, J ϭ 10.8 Hz, 4.6 Hz, 1 H, CHSPh*), 4.16 (m,
each 1 H, CHOH, CHOH*), 4.56 (s, each 2 H, PhCH2, PhCH2*),
7.1Ϫ7.4 (m, each 10 H, arom. H, arom. H*). Ϫ 13C NMR (50
MHz, CDCl3): δ ϭ Ϫ0.21, Ϫ0.15 (SiMe3), 36.0, 36.1 (CHSPh),
sponding substituted furans are obtained.
Support by the Fonds der Chemischen Industrie is gratefully
acknowledged.
Experimental Section
General: NMR: Bruker AMX Ϫ IR: Pye Unicam SP3-200. Ϫ 38.4, 38.8 (CH2), 68.0, 68.4 (CHOH), 73.3, 73.3, 73.7, 74.1 (PhCH2,
Elemental analyses: Institut für Pharmazeutische Chemie, TU
Braunschweig. Column chromatography: Merck silica gel
CH2O), 89.3, 89.7, 104.5, 105.4 (acetylenic C), 127.8, 127.9, 128.1,
128.4, 128.6, 133.6, 134.0 (arom. CH), 132.7, 133.0, 137.7, 137.8
Ϫ
Eur. J. Org. Chem. 1998, 1873Ϫ1878
1875

S. Schabbert, E. Schaumann
FULL PAPER
(arom. C). Ϫ IR (film): ν˜ ϭ 3440, 3062, 2957, 2860, 2169, 1583, 733, 701 cmϪ1. Ϫ C25H34OSSi (410.7): calcd. C 73.11, H 8.34, S
1477, 1453, 1250, 1094, 844, 745, 696 cmϪ1. Ϫ C22H28O2SSi 7.80; found C 73.13, H 8.35, S 8.30.
(384.6): calcd. C 68.70, H 7.34, S 8.33; found C 68.70, H 7.36,
2-(1-Phenylthio-3-trimethylsilyl-2-propynyl)cyclohexanol
(3g):
S 8.24.
Reaction of cyclohexene oxide (1d) and 2a at Ϫ78°C to Ϫ10°C.
Column chromatography (PE/EA, 30:1) gave 2 diastereomers
(2.5:1*) as a yellow oil (60%). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ
0.08*, 0.09 (each s, 9 H, SiMe3, SiMe3*), 1.1Ϫ1.3, 1.6Ϫ1.75,
1.9Ϫ2.05 (m, each 10 H, CH2, CH2*, CH, CH*, OH, OH*), 3.54
(td, J ϭ 9.6 Hz, 4.8 Hz, 1 H, CHOH), 3.75 (td, J ϭ 10.0 Hz, 4.4
Hz, 1 H, CHOH*), 4.17 (d, J ϭ 3.6 Hz, 1 H, CHSPh*), 4.46 (d,
J ϭ 3.2 Hz, 1 H, CHSPh), 7.2Ϫ7.5 (m, each 5 H, arom. H, arom.
H*). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ Ϫ0.06, Ϫ0.14* (SiMe3),
24.2*, 24.7, 25.1, 25.5*, 26.0, 28.1*, 35.1*, 35.7 (CH2), 41.5,
43.0*, 48.7, 49.0* (CH, CHSPh), 71.4*, 72.0 (CHOH), 90.2*, 90.6,
103.2, 104.9* (acetylenic C), 127.2, 127.5*, 128.7, 128.8*, 132.1,
132.7* (arom. CH), 134.5*, 134.7 (arom. C). Ϫ IR (film): ν˜ ϭ 3383,
3059, 2932, 2858, 2167, 1583, 1479, 1449, 1250, 1048, 845, 757, 692
cmϪ1. Ϫ C18H26OSSi (318.5): calcd. C 67.87, H 8.22, S 10.06;
found C 67.82, H 8.31, S 10.67.
1-Benzyloxy-6-(dimethylphenylsilyl)-4-phenylthiohex-5-yn-2-ol
(3d): Reaction of benzylglycidol (1b) and 2b at Ϫ78°C. Column
chromatography (PE/EA, 10:1) gave 2 diastereomers (1:1*) as a
1
clear oil (71%). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.36 (s, each
6 H, SiMe2, SiMe2*), 1.70Ϫ2.08 (m, each 2 H, CH2, CH2*), 2.47
(br. s, each 1 H, OH, OH*), 3.32Ϫ3.56 (m, each 2 H, CH2O,
CH2O*), 4.05 (dd, J ϭ 8.5 Hz, 6.2 Hz, 1 H, CHSPh), 4.15 (dd,
J ϭ 10.7 Hz, 4.5 Hz, 1 H, CHSPh*), 4.16 (m, each 1 H, CHOH,
CHOH*), 4.54 (s, each 2 H, PhCH2, PhCH2*), 7.25Ϫ7.4 and
7.5Ϫ7.55 (m, each 15 H, arom. H, arom. H*). Ϫ 13C NMR (50
MHz, CDCl3): δ ϭ Ϫ0.97, Ϫ0.92 (SiMe2), 36.0, 36.1 (CHSPh),
38.3, 38.8 (CH2), 67.8, 68.4 (CHOH), 73.3, 73.3, 73.7, 74.1 (PhCH2,
CH2O), 87.1, 87.5, 106.5, 107.3 (acetylenic C), 127.7, 127.8, 127.9,
128.1, 128.4, 128.5, 128.7, 129.3, 133.6, 134.0 (arom. CH), 132.7,
133.0, 136.7, 136.8, 137.7, 137.8 (arom. C). Ϫ IR (film): ν˜ ϭ 3447,
3065, 2956, 2861, 2170, 1250, 1116, 1096, 838, 817, 735, 698 cmϪ1
.
2-(3-Dimethylphenylsilyl-1-phenylthio-2-propynyl)cyclohexanol
(3h): Reaction of cyclohexene oxide (1d) and 2b at Ϫ78°C to
Ϫ10°C. Column chromatography (PE/EA, 15:1) gave 2 dia-
Ϫ C27H30O2SSi (446.7): calcd. C 72.60, H 6.77, S 7.18; found C
72.32, H 7.01, S 7.27.
1
stereomers (4.4:1*) as a yellow oil (70%). Ϫ H NMR (200 MHz,
4,6-Dimethyl-3-phenylthio-1-(trimethylsilyl)non-1-yn-5-ol
(3e):
CDCl3): δ ϭ 0.37 (s, each 6 H, SiMe2, SiMe2*), 1.2Ϫ1.35,
1.65Ϫ1.80, 1.95Ϫ2.10 (m, each 10 H, CH2, CH2*, CH, CH*, OH,
OH*), 3.60, 3.82* (each dt, J ϭ 10.0 Hz, 4.8 Hz, 1 H, CHOH,
CHOH*), 4.31*, 4.57 (each d, J ϭ 3.2 Hz, 1 H, CHSPh,
CHSPh*), 7.2Ϫ7.5 (m, each 10 H, arom. H, arom. H*). Ϫ 13C
NMR (50 MHz, CDCl3): δ ϭ Ϫ0.77, Ϫ0.87* (SiMe2), 24.3*,
24.6*, 24.7, 25.2, 25.5*, 26.2, 35.2*, 35.8 (CH2), 41.5, 42.9*, 48.8,
49.2* (CH, CHSPh), 72.0*, 72.1 (CHOH), 87.9*, 88.5, 105.2,
106.8* (acetylenic C), 127.3, 127.5*, 127.8, 127.9*, 128.8, 128.9*,
129.3, 129.6*, 132.1, 132.6*, 133.6, 133.8* (arom. CH), 134.6*,
134.7, 137.0*, 137.1 (arom. C). Ϫ IR (film): ν˜ ϭ 3386, 3068, 2932,
Reaction of 2,3-epoxy-4-methylheptane (1c) (2 diastereomers, 3:1)
and 2a at Ϫ78°C to Ϫ10°C. Column chromatography (PE/EA,
20:1) gave 4 diastereomers (2.9:2.3:1.3:1) as an oil (51%). Ϫ 1H
NMR (200 MHz, CDCl3): δ ϭ 0.13, 0.14 (each s, 18 H, SiMe3),
0.77Ϫ0.95 (m, each 6 H, 9-H, 6-CH3), 1.01Ϫ1.13 (m, each 3 H, 4-
CH3), 1.21Ϫ1.48 (m, each 4 H, CH2), 1.53Ϫ1.74 (m, each 2 H, 6-
H, OH), 1.85Ϫ2.15 (m, each 1 H, 4-H), 3.30, 3.37, 3.50, 3.59 (each
m, 1 H, CHOH), 4.31, 4.34, 4.43, 4.48 (each d, J ϭ 3.2 Hz, 1 H,
CHSPh), 7.25Ϫ7.35 (m, each 5 H, arom. H). Ϫ 13C NMR (50
MHz, CDCl3): δ ϭ Ϫ0.24, Ϫ0.21, Ϫ0.08, Ϫ0.06 (SiMe3), 11.8,
11.9, 12.3, 12.3, 14.2, 14.3 (C-9, 6-CH3, 4-CH3), 20.3, 20.4 (C-7),
34.1, 34.6 (C-6), 36.6, 36.6 (C-8), 39.9, 40.4 (C-4), 42.1, 42.3
(CHSPh), 76.1, 77.2, 77.9, 78.8 (CHOH), 82.2, 82.8, 83.2, 84.5,
102.4, 102.4, 103.2, 103.4 (acetylenic C), 127.1, 127.2, 127.4, 128.7,
128.8, 128.9, 129.0, 132.0, 132.2, 132.6, 132.7 (arom. CH), 134.7,
134.7, 134.8, 134.8 (arom. C). Ϫ IR (film): ν˜ ϭ 3449, 3060, 2960,
2858, 2166, 1481, 1430, 1250, 1115, 1046, 837, 816, 733, 700 cmϪ1
.
Ϫ C23H28OSSi (380.6): calcd. C 72.58, H 7.41, S 8.42; found C
72.07, H 7.50, S 8.81.
3-(Dimethylphenylsilyl)-4-phenylthio-6-(trimethylsilyl)hex-5-yn-
2-ol (3i): Reaction of 1-(dimethylphenylsilyl)-1,2-epoxypropane (1e)
(2 diastereomers, 3:1) and 2a at Ϫ78°C in the presence of
BF3 ·OEt2. Column chromatography (PE/EA, 15:1) gave 2 dia-
stereomers (1:1*) as an oil (41%). Ϫ 1H NMR (200 MHz, CDCl3):
δ ϭ 0.09, 0.16 (each s, 9 H, SiMe3, SiMe3*), 0.43, 0.44, 0.54, 0.57
(each s, 3 H, SiMe2, SiMe2*), 1.21, 1.36 (each d, J ϭ 6.4 Hz, 3 H,
CH3, CH3*), 1.56 (dd, J ϭ 7.2 Hz, 1.8 Hz, 1 H, CHSi), 1.70 (dd,
J ϭ 7.2 Hz, 3.6 Hz, 1 H, CHSi*), 2.6, 2.9 (each br. s, 1 H, OH,
OH*), 4.13 (d, J ϭ 1.8 Hz, 1 H, CHSPh), 4.26 (d, J ϭ 3.6 Hz, 1
H, CHSPh*), 4.22, 4.37 (each m, 1 H, CHOH, CHOH*), 7.1Ϫ7.5
(m, each 10 H, arom. H, arom. H*). Ϫ 13C NMR (50 MHz,
CDCl3): δ ϭ Ϫ2.9, Ϫ2.0, Ϫ1.6, Ϫ0.9 (SiMe2), Ϫ0.4, Ϫ0.3 (SiMe3),
23.8, 24.1 (CH3), 39.2, 39.9, 40.4, 40.9 (CHSi, CHSPh), 68.5, 68.6
(CHOH), 90.8, 91.8, 104.8, 107.1 (acetylenic C), 127.6, 127.7,
127.8, 127.9, 128.7, 128.9, 129.0, 129.2, 132.7, 132.8, 133.8, 134.1
(arom. CH); 134.6, 134.7, 137.8, 138.7 (arom. C). Ϫ IR (film): ν˜ ϭ
3448, 3069, 2961, 2169, 1583, 1479, 1438, 1250, 1113, 843, 737, 701
cmϪ1. Ϫ C23H32OSSi2 (412.7): calcd. C 66.93, H 7.81, S 7.77; found
C 66.92, H 7.85, S 7.77.
2930, 2170, 1583, 1478, 1439, 1250, 844, 750, 691 cmϪ1
.
4,6-Dimethyl-1-(dimethylphenylsilyl)-3-phenylthionon-1-yn-5-ol
(3f): Reaction of 2,3-epoxy-4-methylheptane (1c) (2 diastereomers,
3:1) and 2b at Ϫ78°C to Ϫ10°C. Column chromatography (PE/
1
EA, 20:1) gave 4 diastereomers (3:2.6:1.1:1) as an oil (57%). Ϫ H
NMR (200 MHz, CDCl3): δ ϭ 0.37, 0.38 (each s, each 12 H,
SiMe2), 0.78Ϫ0.97 (m, each 6 H, 9-H, 6-CH3), 1.00Ϫ1.17 (m, each
3 H, 4-CH3), 1.20Ϫ1.43 (m, each 4 H, CH2), 1.55Ϫ1.79 (m, each
2 H, 6-H, OH), 1.97, 2.02, 2.15, 2.20 (each br. dq, J ϭ 6.8 Hz, 3.2
Hz, 1 H, 4-H), 3.42 (dd, J ϭ 8.8 Hz, 2.8 Hz, 1 H, CHOH), 3.54
(dd, J ϭ 9.6 Hz, 1.6 Hz, 1 H, CHOH), 3.65 (dd, J ϭ 9.2 Hz, 2.0
Hz, 1 H, CHOH), 3.76 (dd, J ϭ 9.6 Hz, 1.6 Hz, 1 H, CHOH),
4.42, 4.45, 4.52, 4.58 (each d, J ϭ 3.2 Hz, 1 H, CHSPh), 7.1Ϫ7.6
(m, each 10 H, arom. H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ
Ϫ0.8 (SiMe2), 11.8, 11.8, 12.0, 12.3, 13.1, 13.3, 13.7, 14.2, 14.2,
14.3, 14.3, 14.4 (C-9, 6-CH3, 4-CH3), 20.3, 20.4, 20.5, 20.5 (C-7),
34.0, 34.1, 34.4, 34.5 (C-6), 36.1, 36.6, 36.6, 36.8 (C-8), 40.1, 40.5,
41.2, 41.5 (C-4), 42.1, 42.3, 43.7, 43.8 (CHSPh), 74.7, 75.9, 77.4,
78.7 (CHOH), 87.1, 87.1, 88.6, 88.9, 105.2, 105.4, 107.8, 107.9 (ace-
tylenic C), 127.2, 127.3, 127.4, 127.8, 128.8, 129.2, 129.3, 131.9,
3,6-Bis(dimethylphenylsilyl)-4-phenylthiohex-5-yn-2-ol (3j): Reac-
tion of 1-(dimethylphenylsilyl)-1,2-epoxypropane (1e) (2 dia-
132.1, 132.4, 132.5, 133.5, 133.6 (arom. CH), 134.6, 134.6, 134.7, stereomers, 3:1) and 2b at Ϫ78°C in the presence of BF3 ·OEt2.
134.7, 136.9, 137.0, 137.0, 137.0 (arom. C). Ϫ IR (film): ν˜ ϭ 3483, Column chromatography (PE/EA, 15:1) gave 2 diastereomers
1
3069, 2960, 2931, 2168, 1584, 1480, 1430, 1250, 1115, 838, 816,
1876
(1:1*) as an oil (64%). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 0.35,
Eur. J. Org. Chem. 1998, 1873Ϫ1878

Palladium-Catalyzed Cyclization of Silyl-Substituted Bis(homopropargylic) Alcohols
FULL PAPER
0.41 (each s, 6 H, SiMe2, SiMe2*), 0.44, 0.45, 0.51, 0.54 (each s, 3
H, SiMe2, SiMe2*), 1.22, 1.35 (each d, J ϭ 6.4 Hz, 3 H, CH3,
CH3*), 1.61 (dd, J ϭ 7.2 Hz, 2.0 Hz, 1 H, CHSi), 1.74* (dd, J ϭ
H, 3-H), 3.48 (dd, J ϭ 10.4 Hz, 4.0 Hz, 1 H, CH2O), 3.55 (dd, J ϭ
10.4 Hz, 6.0 Hz, 1 H, CH2O), 4.53 (s, 2 H, PhCH2), 4.73 (m, 1 H,
CHO), 7.0Ϫ7.3 (m, 10 H, arom. H). Ϫ 13C NMR (50 MHz,
7.2 Hz, 3.6 Hz, 1 H, CHSi*), 2.50, 2.90 (each br. s, 1 H, OH, OH*), CDCl3): δ ϭ 12.3 (CH3), 35.7 (CH2-ring), 72.2, 73.4 (CH2O,
4.21 (d, J ϭ 2.0 Hz, 1 H, CHSPh), 4.35* (d, J ϭ 3.6 Hz, 1 H, PhCH2), 79.4 (CHO), 95.7 (ϭCSPh), 125.0, 126.2, 127.7, 127.7,
CHSPh*), 4.24, 4.40 (each m, 1 H, CHOH, CHOH*), 7.1Ϫ7.4 (m, 128.4, 128.8 (arom. CH), 137.1, 137.9 (arom. C), 161.7 (ϭCO). Ϫ
each 15 H, arom. H, arom. H*). Ϫ 13C NMR (50 MHz, CDCl3): IR (film): ν˜ ϭ 3061, 3030, 2920, 2859, 1652, 1582, 1477, 1380, 1222,
δ ϭ Ϫ2.8, Ϫ1.9, Ϫ1.7, Ϫ1.2, Ϫ1.1, Ϫ1.09, Ϫ1.06, Ϫ0.8 (SiMe2), 1119, 740, 695 cmϪ1. Ϫ C19H20O2S (312.4): calcd. C 73.04, H 6.45,
23.8, 24.1 (CH3), 39.1, 40.0, 40.5, 40.8 (CHSi, CHSPh), 68.4, 68.5
(CHOH), 88.6, 89.7, 106.7, 108.9 (acetylenic C), 127.6, 127.7,
127.8, 127.8, 127.8, 127.9, 128.7, 128.8, 129.0, 129.2, 129.4, 129.5,
132.5, 132.7, 133.6, 133.7, 134.1 (arom. CH); 134.5, 134.7, 136.3,
136.4, 137.7, 138.5 (arom. C). Ϫ IR (film): ν˜ ϭ 3406, 3069, 2960,
2166, 1583, 1251, 1116, 820, 736, 700 cmϪ1. Ϫ C28H34OSSi2
(474.8): calcd. C 70.83, H 7.22, S 6.75; found C 69.82, H 7.31,
S 7.72.
S 10.26; found C 72.47, H 6.49, S 10.02.
3,5-Dimethyl-2-sec-pentyl-4-phenylthio-2,3-dihydrofuran
(5c):
Column chromatography (PE) gave 2 diastereomers (2.4:1*) as a
colorless oil (54%). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 0.87 (each
t, J ϭ 6.8 Hz, 3 H, CH3-chain), 0.89 (d, J ϭ 6.8 Hz, each 3 H,
CH3-chain), 1.01 (d, J ϭ 7.0 Hz, each 3 H, 3-CH3), 1.1Ϫ1.5 (m,
each 4 H, CH2), 1.7 (m, each 1 H, CH-chain), 1.91 (d, J ϭ 1.6 Hz,
each 3 H, 5-CH3), 2.68 (br. q, J ϭ 7.0 Hz, 1 H, 3-H), 3.97 (dd, J ϭ
7.0 Hz, 5.2 Hz, each 1 H, CHO), 7.1Ϫ7.2 (m, each 5 H, arom. H).
6-(Dimethylphenylsilyl)hex-3-en-5-yn-2-ol (4): Reaction of 1-(di-
methylphenylsilyl)-1,2-epoxypropane (1e) (2 diastereomers, 3:1)
Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 12.5, 12.5* (5-CH3), 14.2,
and 2b at Ϫ78°C to Ϫ10°C. Column chromatography (PE/EA, 9:1) 14.2*, 14.3, 14.3* (CH3-chain), 20.1, 20.2* (CH2), 20.2, 20.3* (3-
gave 2 diastereomers (E/Z*, 3:1*) as an oil (47%). Ϫ 1H NMR (200 CH3), 34.0*, 34.3 (CH2), 37.3, 37.3* (CH-chain), 41.5*, 42.1 (C-3),
MHz, CDCl3): δ ϭ 0.31, 0.32* (each s, 6 H, SiMe2, SiMe2*), 1.14, 92.7, 92.8* (CHO), 101.2, 101.2* (ϭCSPh), 124.9, 124.9*, 126.3,
1.17* (each d, J ϭ 6.4 Hz, 3 H, CH3, CH3*), 1.70 (br. s, each 1 H,
OH, OH*), 4.20 (dq, J ϭ 6.4 Hz, 1.6 Hz, 1 H, CHOH), 4.73 (m,
126.3*, 128.7, 128.7* (arom. CH), 137.8, 137.8* (arom. C), 162.1,
162.1* (ϭCO). Ϫ IR (film): ν ϭ 3069, 2960, 2925, 2872, 1650,
˜
1 H, CHOH*), 5.42 (dd, J ϭ 11.0 Hz, 1.0 Hz, 1 H, 4-H*), 5.62 1582, 1476, 1380, 1226, 999, 739, 692 cmϪ1. Ϫ C17H24OS (276.4):
(dd, J ϭ 16.0 Hz, 1.6 Hz, 1 H, 4-H), 5.86 (dd, J ϭ 11.0 Hz, 8.0 calcd. C 73.86, H 8.75, S 11.59; found C 74.24, H 8.79, S 11.37.
Hz, 1 H, 3-H*), 6.14 (dd, J ϭ 16.0 Hz, 6.4 Hz, 1 H, 3-H), 7.2Ϫ7.55
2-Methyl-3-phenylthio-3a,4,5,6,7,7a-hexahydrobenzofuran (5d):
Column chromatography (PE) gave an oil (1%). Ϫ H NMR (200
(m, each 5 H, arom. H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ
1
Ϫ0.99*, Ϫ0.96 (SiMe2), 22.3*, 22.8 (CH3), 66.4*, 68.0 (CHOH),
MHz, CDCl3): δ ϭ 1.1Ϫ1.3, 1.4Ϫ1.8 (m, 8 H, CH2), 2.12 (s, 3 H,
93.0, 98.6*, 102.2*, 104.6 (acetylenic C), 108.9, 133.0*, 148.1*,
CH3), 2.75 (m, 1 H, CH), 4.01 (m, 1 H, CHO), 7.2 (m, 5 H, arom.
148.2 (CϭC), 127.8, 127.9*, 129.4, 129.5*, 133.5*, 133.6 (arom.
CH), 136.6*, 136.8 (arom. C). Ϫ IR (film): ν˜ ϭ 3356, 3069, 2964,
2145, 1428, 1250, 1116, 1062, 817, 780, 731, 700 cmϪ1; no elemental
analyses of 4 could be obtained because of its tendency to decom-
pose.
H). Ϫ IR (film): ν ϭ 1655 cmϪ1
.
˜
5-Hydroxy-3-phenylthiohexan-2-one (6a): Column chromatogra-
phy (PE/EA, 10:1) gave 2 diastereomers (1:1*) as a colorless oil
(18%). Ϫ 1H NMR (200 MHz, CDCl3): δ ϭ 1.22, 1.26 (each d,
J ϭ 6.2 Hz, 3 H, CH3, CH3*), 1.80 (m, each 3 H, CH2, CH2*, OH,
OH*), 2.24, 2.25 (each s, 3 H, 1-H, 1-H*), 3.80 (dd, J ϭ 7.6 Hz,
6.6 Hz, 1 H, CHSPh), 3.87* (dd, J ϭ 9.6 Hz, 4.8 Hz, 1 H,
CHSPh*), 4.06 (m, each 1 H, CHOH, CHOH*), 7.2Ϫ7.4 (m, each
5 H, arom. H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 23.9, 24.1,
25.8, 26.1 (CH3), 39.5, 39.6 (CH2), 53.7, 54.6 (CHSPh), 65.6, 65.9
(CHOH), 128.1, 128.2, 128.9, 129.0, 131.3, 131.4 (arom. CH),
132.8, 132.9 (arom. C), 205.2, 205.3 (CϭO). Ϫ IR (film): ν˜ ϭ 3406,
3059, 2970, 2928, 1707, 1584, 1480, 1439, 1377, 1090, 742, 692
Cyclization of γ-Hydroxyalkynes 3. Ϫ General Procedure: To a
solution of alkynol 3 (1 mmol) in CH3CN (3 ml/mmol) were added
0.05Ϫ0.1 equiv. of Pd(OAc)2 and one drop of conc. HCl. The mix-
ture was stirred at room temperature under air for 2Ϫ10 h, de-
pending on the substrate. For the preparation of furans, an ad-
ditional 0.25 equiv. of CuCl2 was added. When the reaction was
complete, the mixture was diluted with CHCl3, washed with water,
and dried (Na2SO4). Then the solvent was evaporated under re-
duced pressure. The residue was purified by chromatography on a
silica gel column.
cmϪ1
.
6-Benzyloxy-5-hydroxy-3-phenylthiohexan-2-one (6b): Column
2,5-Dimethyl-4-phenylthio-2,3-dihydrofuran (5a): Column chro-
matography (PE) gave a colorless liquid (56%). Ϫ H NMR (200
chromatography (PE/EA, 20:1) gave 2 diastereomers (1:1*) as a yel-
1
1
low oil (21%). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 1.95 (m, each
MHz, CDCl3): δ ϭ 1.32 (d, J ϭ 6.2 Hz, 3 H, 2-CH3), 1.88 (t, J ϭ
2.0 Hz, 3 H, 5-CH3), 2.25 (ddq, J ϭ 14.0 Hz, 7.6 Hz, 2.0 Hz, 1 H,
3-H), 2.79 (ddq, J ϭ 14.0 Hz, 9.8 Hz, 2.0 Hz, 1 H, 3-H), 4.68 (ddq,
J ϭ 9.8 Hz, 7.6 Hz, 6.2 Hz, 1 H, CHO), 7.1Ϫ7.3 (m, 5 H, arom.
H). Ϫ 13C NMR (50 MHz, CDCl3): δ ϭ 12.3 (5-CH3), 22.0 (2-
CH3), 40.7 (CH2), 77.3 (CHO), 95.3 (ϭCSPh), 125.0, 126.1, 128.8
(arom. CH), 137.4 (arom. C), 161.5 (ϭCO). Ϫ IR (film): ν˜ ϭ 3070,
2972, 2922, 2858, 1649, 1583, 1477, 1439, 1377, 1224, 1024, 956,
2 H, CH2, CH2*), 2.29, 2.30* (each s, 3 H, CH3, CH3*), 2.45 (br.
s, each 1 H, OH, OH*), 3.3Ϫ3.5 (m, each 2 H, CH2O, CH2O*),
3.95 (m, each 1 H, CHSPh, CHSPh*), 4.30 (m, each 1 H, CHOH,
CHOH*), 4.52, 4.55 (each br. d, J ϭ 12.0 Hz, each 1 H, PhCH2,
˜
PhCH2*), 7.2Ϫ7.5 (m, each 10 H, arom. H). Ϫ IR (film): ν ϭ 3425,
3061, 3031, 2924, 2861, 1707, 1583, 1478, 1440, 1358, 1100, 742,
697 cmϪ1
.
739, 691 cmϪ1. Ϫ MS; m/z (%): 206 (100) [Mϩ], 129 (46) [Mϩ
Ϫ
5-Hydroxy-4,6-dimethyl-3-phenylthiononan-2-one (6c): Column
chromatography (PE/EA, 10:1) gave 4 diastereomers as an oil
(15%). Ϫ IR (film): ν˜ ϭ 3400, 3061, 2961, 2930, 2873, 1719, 1445,
Ph], 109 (15) [SPh], 77 (20) [Ph]. Ϫ C12H14OS (206.3): calcd. C
69.86, H 6.84, S 15.54; found C 69.57, H 6.84, S 15.03. (S)-5a:
1383, 1085, 747, 695 cmϪ1
.
24
[α]D ϭ Ϫ56.4 (c ϭ 0.7 in CHCl3).
2-Benzyloxymethyl-5-methyl-4-phenylthio-2,3-dihydrofuran (5b):
1-(2-Hydroxycyclohexyl)-1-phenylthiopropan-2-one (6d): Column
Column chromatography (PE/EA, 40:1) gave a colorless oil (51%). chromatography (PE/EA, 8:1) gave 2 diastereomers (2.5:1*) as an
1
1
Ϫ H NMR (200 MHz, CDCl3): δ ϭ 1.90 (s, 3 H, CH3), 2.45 (dd,
oil (26%). Ϫ H NMR (200 MHz, CDCl3): δ ϭ 1.1Ϫ1.3, 1.6Ϫ1.8,
J ϭ 14.4 Hz, 8.0 Hz, 1 H, 3-H), 2.70 (dd, J ϭ 14.4 Hz, 10.8 Hz, 1 1.9Ϫ2.1 (m, each 10 H, CH2, CH2*, CH, CH*, OH, OH*), 2.24,
Eur. J. Org. Chem. 1998, 1873Ϫ1878
1877

S. Schabbert, E. Schaumann
FULL PAPER
2.27* (each s, 3 H, CH3, CH3*), 3.55 (m, each 1 H, CHOH, (CHSPh), 90.9, 102.9 (acetylenic C), 128.1, 134.4 (CϭC), 127.7,
CHOH*), 4.01* (d, J ϭ 4.0 Hz, 1 H, CHSPh*), 4.03 (d, J ϭ 6.4 129.2, 132.9 (arom. CH), 139.8 (arom. C). Ϫ IR (film): ν˜ ϭ 3023,
Hz, 1 H, CHSPh), 7.3 (m, each 5 H, arom. H). Ϫ IR (film): ν˜ ϭ 2959, 2168, 1428, 1252, 1119, 1066, 843, 793, 700 cmϪ1; no elemen-
3422, 3058, 2931, 2858, 1702, 1582, 1442, 1353, 1045, 741, 696
tal analysis of 8 could be obtained because of its tendency to de-
compose.
cmϪ1
.
2,5-Dimethyl-3-phenylthiofuran (7): Column chromatography
(PE) gave a colorless liquid, which was kept in the cold. Ϫ 1H
NMR (200 MHz, CDCl3): δ ϭ 2.27 (s, 3 H, CH3), 2.31 (s, 3 H,
CH3), 5.94 (s, 1 H, 4-H), 7.1Ϫ7.3 (m, 5 H, arom. H). Ϫ 13C NMR
(50 MHz, CDCl3): δ ϭ 11.7 (CH3), 13.5 (CH3), 107.7 (ϭCSPh),
110.9 (C-4), 124.9, 126.0, 128.8 (arom. CH), 138.3 (arom. C), 150.7,
155.0 (ϭCO). Ϫ IR (film): ν˜ ϭ 3059, 2920, 1583, 1478, 1439, 1224,
1068, 738, 689 cmϪ1. Ϫ MS; m/z (%): 204 (100) [Mϩ], 109 (6) [SPh],
77 (10) [Ph]. Ϫ C12H12OS (204.3): calcd. C 70.55, H 5.92, S 15.69;
found C 70.54, H 5.73, S 15.36.
[1]
P. F. Schuda, Top. Curr. Chem. 1980, 91, 75Ϫ111.
[2]
F. Narjes, E. Schaumann, Synthesis 1991, 1168Ϫ1170.
[3]
W. Eberbach in Methods Org. Chem. (Houben-Weyl), 1994, vol.
E 6a, p. 70.
[4]
K. Utimoto, Pure Appl. Chem. 1983, 55, 1845Ϫ1852.
[5]
N. G. Kundu, M. Pal, J. S. Mahanty, S. K. Dasgupta, J. Chem.
Soc., Chem. Commun. 1992, 41Ϫ42.
[6]
T. Hosokawa, S. J. Murahashi, Heterocycles 1992, 33,
1079Ϫ1100.
[7]
B. Gabriele, G. Salerno, J. Chem. Soc., Chem. Commun. 1997,
1083Ϫ1084.
[8]
Y. Fukuda, H. Shiragami, K. Utimoto, H. Nozaki, J. Org.
3-Phenylthio-1-(trimethylsilyl)hex-4-en-1-yne (8): Column chro-
matography (PE) gave 1 diastereomer (trans) as a colorless oil. Ϫ
1H NMR (200 MHz, CDCl3): δ ϭ 0.13 (s, 9 H, SiMe3), 1.67 (dt,
J ϭ 6.2 Hz, 1.0 Hz, 3 H, CH3), 4.36 (dq, J ϭ 6.2 Hz, 1.0 Hz, 1 H,
CHSPh), 5.49 (ddq, J ϭ 14.8 Hz, 6.2 Hz, 1.0 Hz, 1 H, 4-H), 5.67
(dq, J ϭ 14.8 Hz, 6.2 Hz, 1 H, 5-H), 7.3Ϫ7.5 (m, 5 H, arom. H).
Chem. 1991, 56, 5816Ϫ5819.
[9]
Y. Wakabayashi, Y. Fukuda, H. Shiragami, K. Utimoto, H. No-
zaki, Tetrahedron 1985, 41, 3655Ϫ3661.
[10] [10a]
´
´
P. Compain, J. Gore, J. M. Vatele, Tetrahedron 1996, 52,
[10b]
´ ´
P. Compain, J. M. Vatele, J. Gore, Synlett
10405Ϫ10416.
1994, 943Ϫ945.
[11]
J. Tsuji, Top. Curr. Chem. 1980, 91, 29Ϫ74.
Ϫ
13C NMR (50 MHz, CDCl3): δ ϭ 0.8 (SiMe3), 17.5 (CH3), 41.7
[98109]
1878
Eur. J. Org. Chem. 1998, 1873Ϫ1878