Chiral diselenides in the total synthesis of (+)-samin

Article abstract of DOI:10.1021/jo952093m

Chiral selenium compounds are applied to stoichiometric as well as to catalytic reactions in the synthesis of substituted tetrahydrofuran derivatives: The selenium compound 1 was used in catalytic amounts for a rapid access to chiral diselenide 3. The efficient stereoselective addition to alkene 5 yields product 8 with a selenium functionality as a precursor for an intramolecular radical cyclization. In this way a short total synthesis of (+)-samin (11), a naturally occurring furofuran lignan, was achieved.

Full text of DOI:10.1021/jo952093m

2686
J . Org. Chem. 1996, 61, 2686-2689
Ch ir a l Diselen id es in th e Tota l Syn th esis of (+)-Sa m in
Thomas Wirth,* Klaus J . Kulicke, and Gianfranco Fragale
Institut fu¨r Organische Chemie der Universita¨t Basel, St. J ohanns-Ring 19, CH-4056 Basel, Switzerland
Received November 28, 1995X
Chiral selenium compounds are applied to stoichiometric as well as to catalytic reactions in the
synthesis of substituted tetrahydrofuran derivatives: The selenium compound 1 was used in
catalytic amounts for a rapid access to chiral diselenide 3. The efficient stereoselective addition to
alkene 5 yields product 8 with a selenium functionality as a precursor for an intramolecular radical
cyclization. In this way a short total synthesis of (+)-samin (11), a naturally occurring furofuran
lignan, was achieved.
Sch em e 1
Lignans are widely distributed in the plant kingdom.
Within this general class many compounds have been
identified and because of the broad range of structures
as well as biological activities they have attracted con-
siderable attention.1 The furofuran lignans are one of
the largest groups of naturally occurring lignans and
their synthesis is a challenge to organic chemists. Samin
is a component of sesame oil2 and a known precursor for
the synthesis of a variety of furofuran lignans.3 Many
efforts have been made to construct the furofuran (3,7-
dioxabicyclo[3.3.0]octane) skeleton.4 To our knowledge
only two synthetic strategies to nonracemic samin have
been reported to date5 beside various routes to racemic
samin.6
pyrrolidine11 in 83% yield by ortho-deprotonation with
tert-butyllithium,12 treatment with elemental selenium,
and air oxidation. Addition of diethylzinc to benzalde-
hyde is catalyzed by 1 mol % 1, and (S)-1-phenylpropanol
(2) is obtained in 97% yield and 98% ee. The ortho-
lithiation of 2 required a slightly modified procedure.13
Compound 2 must be refluxed with n-BuLi in the
presence of TMEDA for 12 h. After addition of selenium
and oxidative workup diselenide 3 is obtained in 61%
yield.
An elegant method for the creation of a heteroatom-
substituted asymmetric benzylic carbon atom is the
reaction of an arylalkene with a chiral selenium reagent.
In the total synthesis of samin we planned to use this
stereoselective reaction by reacting alkene 5 with the
electrophilic selenium compound 6 derived from di-
selenide 3. The newly generated asymmetric carbon
could then be used to control the other stereocenters of
samin. Facial selectivity in addition reactions of various
chiral selenium electrophiles to substituted alkenes has
also been observed by other research groups,14 however,
the reasons for this are not yet fully understood and are
Recently we found that simple chiral diselenides are
versatile reagents for an asymmetric functionalization
of arylalkenes.7 We now report an optimized and shorter
access to the diselenide 3 and its application in the total
synthesis of (+)-samin (11).
The chiral diselenide 3 is obtained by a two-step
synthesis. For the stereoselective addition of diethylzinc
to benzaldehyde many powerful catalysts have been
reported.8 We found that nitrogen-based chiral di-
selenides are suitable procatalysts9 for this reaction.10
Diselenide 1 is prepared from (R)-1-(1-phenylethyl)-
X Abstract published in Advance ACS Abstracts, March 15, 1996.
(1) Reviews: (a) MacRae, W. D.; Towers, G. H. N Phytochemistry,
1984, 23, 1207-1220. (b) Ayres, D. C.; Loike, J . D. Lignans: Chemical,
biological and clinical properties; Cambridge University Press: Cam-
bridge, 1990. (c) Ward, R. S. Nat. Prod. Rep. 1995, 12, 183-205.
(2) (a) Adriani, W. Z. Unters. Lebensm. 1928, 56, 187-194. (b)
Budowski, P. J . Am. Oil Chem. Soc. 1964, 41, 280-285.
(3) Fukuda, Y.; Isobe, M.; Nagata, M.; Osawa, T.; Namiki, M.
Heterocycles 1986, 24, 923-926.
(4) (a) Ward, R. S. Tetrahedron 1990, 46, 5029-5041. (b) Feringa,
B. L.; de Lange, B.; J ansen, J . F. G. A.; de J ong, J . C.; Lubben, M.;
Faber, W.; Schudde, E. P. Pure Appl. Chem. 1992, 64, 1865-1871. (c)
van Oeveren, A.; J ansen, J . F. G. A.; Feringa, B. L. J . Org. Chem. 1994,
59, 5999-6007. (d) Ogiku, T.; Yoshida, S.; Ohmizu, H.; Iwasaki, T. J .
Org. Chem. 1995, 60, 1148-1153. (e) Yoshida, S.; Yamanaka, T.;
Miyake, T.; Moritani, Y.; Ohmizu, H.; Iwasaki, T. Tetrahedron Lett.
1995, 36, 7271-7274. (f) Suginome, H.; Orito, K.; Yorita, K.; Ishikawa,
M.; Shimoyama, N.; Sasaki, T. J . Org. Chem. 1995, 60, 3052-3064.
(g) Pelter, A.; Ward, R. S. Heterocycles 1994, 137-147. (h) Mikami,
K.; Matsueda, H.; Nakai, T. Synlett 1993, 235-236.
(8) (a) Dervant, R. M.; Radunz, H. E. In Houben-Weyl, Helmchen,
G., Hoffmann, R. W., Mulzer, J ., Schaumann, E., Eds.; Thieme:
Stuttgart, 1995; Vol. E 21 b; p 1314. (b) Soai, K.; Niwa, S. Chem. Rev.
1992, 92, 833-856.
(9) Wirth, T.; Kulicke, K. J . Unpublished results. Recent NMR
investigations have shown, that the Se-Se bond is cleaved rapidly and
the active catalyst is a selenolate coordinated to zinc. Similar sulfur
systems have been reported: (a) Rijnberg, E.; J astrzebski, J . T. B. H.;
J anssen, M. D.; Boersma, J .; van Koten, G. Tetrahedron Lett. 1994,
35, 6521-6524. (b) Hof, R. P.; Poelert, M. A.; Peper, N. C. M. W.;
Kellogg, R. M. Tetrahedron: Asymmetry 1994, 5, 31-34. (c) Fitzpatrick,
K.; Hulst, R.; Kellogg, R. M. Tetrahedron: Asymmetry 1995, 6, 1861-
1864.
(5) (a) Takano, S.; Ohkawa, T.; Tamori, S.; Satoh, S.; Ogasawara,
K. J . Chem. Soc., Chem. Commun. 1988, 189-191. (b) Samizu, K.;
Ogasawara, K. Chem. Lett. 1995, 543-544.
(6) (a) Bradley, H. M.; Knight, D. W. J . Chem. Soc., Chem. Commun.
1991, 1641-1643. (b) Bradley, H. M.; J ones, R. G.; Knight, D. W.
Synlett 1992, 479-480. (c) Takano, S.; Samizu, K.; Ogasawara, K. J .
Chem. Soc., Chem. Commun. 1993, 1032-1033. (d) Takano, S.; Samizu,
K.; Ogasawara, K. Synlett 1993, 785-787. (e) Maiti, G.; Adhikari, S.;
Roy, S. C. Tetrahedron Lett. 1994, 35, 6731-6732. (f) Maiti, G.;
Adhikari, S.; Roy, S. C. Tetrahedron 1995, 51, 8389-8396.
(7) Wirth, T. Angew. Chem., Int. Ed. Engl. 1995, 34, 1726-1728.
Angew. Chem. 1995, 107, 1872-1873.
(10) Wirth, T. Tetrahedron Lett. 1995, 36, 7849-7852.
(11) Baba, N.; Nishiyama, K.; Oda, J .; Inouye, Y. Agric. Biol. Chem.
1976, 40, 1441-1443.
(12) van Koten, G.; J astrzebski, J . T. B. H. Tetrahedron 1989, 45,
569-578.
(13) Meyer, N.; Seebach, D. Chem. Ber. 1980, 113, 1304-1319.
0022-3263/96/1961-2686$12.00/0 © 1996 American Chemical Society

Chiral Diselenides in the Total Synthesis of (+)-Samin
Sch em e 2
J . Org. Chem., Vol. 61, No. 8, 1996 2687
currently under investigation. To take advantage of the
selenium functionality as a radical precursor, we planned
to introduce a nucleophile bearing a double bond that can
be used for a radical cyclization. Because the double bond
of the nucleophile can also be attacked by the selenium
reagent, the formation of the selenonium ion by reaction
of the selenium cation with the alkene must be performed
before adding the nucleophile.
analogy to results obtained in a synthesis of racemic
samin.6e,f This can be explained by a transition state in
which the aromatic and hydroxymethyl substituents are
arranged in pseudoequatorial positions. The stereo-
chemical outcome of the reaction at C-4 is dependent on
whether the reaction proceeds via the boatlike transition
state 8A or the chairlike transition state 8B. Treatment
of 8 with triphenyltin hydride and AIBN in toluene at
110 °C yields a 1:1 mixture of 9a and 9b in 56% yield.
Lowering the reaction temperature to 90 °C gives 9 in a
1:2 (9a :9b) mixture in 64% yield. This shows that the
boatlike transition state 8A (leading to 9a ) is similar in
energy to 8B (leading to 9b). Experiments21 and calcula-
tions22 have shown that boatlike and chairlike transition
states of comparable systems are only slightly different
in energy.20b The stereochemistry at C-4 was determined
after cleavage of the double bond to the aldehyde 10 with
osmium tetroxide followed by sodium periodate (57%
yield). The mixture of 10a and 10b shows two distinct
Readily available allylic alcohol 415 was first protected
with a TBDMS-group. Cleavage of the diselenide 3 with
bromine and then treatment with silver triflate afforded
electrophilic selenium species 6. Reaction with alkene
5 for 15 min, followed by addition of 2,3-butadien-1-ol
(7)16 (-100 °C, 3 h) afforded the addition product 8 in
56% yield with a diastereomeric ratio of 16:1.17 Com-
pound 8 was then subjected to a radical cyclization
reaction by treatment with triphenyltin hydride and
AIBN. Although intramolecular radical cyclizations of
allenes via the 6-endo pathway have been reported,18 the
normally favored 5-exo pathway was observed in the
cyclization leading to the tetrahydrofuran derivative 9
in 64% yield. Only a few stereochemical investigations
have been performed using 1,2-disubstituted radicals in
intramolecular 5-exo radical cyclizations leading to furan
or pyrrolidine derivatives.19 Also, intramolecular 5-exo
cyclizations to cyclopentane derivatives show generally
a preference for anti stereochemistry with regard to the
1,2-substituents.20 The stereochemistry of the substitu-
ents at C-2 and C-3 in 9 was found to be anti also in
1
signals in the H NMR for the aldehyde protons. Com-
pound 10 is a known intermediate in the synthesis of
samin.6e,f By treatment with sodium methoxide it can
be isomerized to the thermodynamically more stable
stereoisomer which was shown to be the 3,4-trans-isomer
10b after performing a series of NOE experiments.23
After the final cleavage of the TBDMS-group with tet-
rabutylammonium fluoride, cyclization to the hemiacetal
occurs spontaneously with either the mixture of isomers
10a /10b or only 10b affording (+)-samin (11) in 67%
yield. This shows that under the conditions of deprotec-
tion, isomerization to the 3,4-cis-isomer occurred leading
to (+)-samin (11) as the only product. The existence of
samin as a single stereoisomer was confirmed by NOE
experiments.5b By comparison of the optical rotation of
11 {[R]25D ) +74.5 (c 0.49, CHCl3)} with literature data5a
(14) (a) De´ziel, R.; Malenfant, E. J . Org. Chem. 1995, 60, 4660-
4662. (b) Fukuzawa, S.; Kasugahara, Y. Tetrahedron Lett. 1994, 35,
9403-9406. (c) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S.
Tetrahedron Lett. 1995, 36, 5219-5222.
(15) Kanematsu, K.; Tsuruoka, M.; Takaoka, Y.; Sasaki, T. Hetero-
cycles 1991, 32, 859-862.
(16) Adegoke, E. A.; Emokpae, T. A.; Ephraim-Bassey, H. J . Het-
erocycl. Chem. 1986, 23, 1195-1198.
(17) Propargylic alcohol can be used as nucleophile as well, but the
yield of the addition reaction is lower (20%) and the subsequent radical
cyclization to the already known tetrahydrofuran intermediate [lit. 6e,f]
less efficient (29%).
(18) (a) Apparu, M.; Crandall, J . K. J . Org. Chem. 1984, 49, 2125-
2130. (b) Burnett, D. A.; Choi, J .; Hart, D. J .; Tsai, Y. J . Am. Chem.
Soc. 1984, 106, 8201-8209.
(19) (a) Lu¨bbers, T.; Scha¨fer, H. J . Synlett 1990, 44-46. (b) Lu¨bbers,
T.; Scha¨fer, H. J . Synlett 1991, 861-862. (c) Baldwin, J . E.; Li, C. J .
Chem. Soc., Chem. Commun. 1987, 166-168.
(20) (a) Giese, B.; Kopping, B.; Go¨bel, T.; Dickhaut, J .; Thoma, G.;
Kulicke, K. J .; Trach, F. in Organic Reactions; Paquette, L. A., Ed.;
Wiley: New York, 1996; Vol. 48, p 301. (b) Curran, D. P.; Porter, N.A.;
Giese, B. Stereochemistry of Radical Reactions; Verlag Chemie: Wein-
heim, 1996.
(21) RajanBabu, T. V. Acc. Chem. Res. 1991, 24, 139-145.
(22) Spellmeyer, D. C.; Houk, K. N. J . Org. Chem. 1987, 52, 959-
974.
(23) The treatment with sodium methoxide was wrongly reported
to yield the 3,4-cis-isomer. [lit. 6d-f].

2688 J . Org. Chem., Vol. 61, No. 8, 1996
Wirth et al.
{[R]24 ) -88.2 (c 1.1, CHCl3) for the (-)-enantiomer},
the enantiomeric excess of 11 is 85% consistent with the
diastereomeric ratio of 8 that was measured by 1H NMR
to be 1:16 (88% de).
In conclusion, we have accomplished a short total
synthesis of (+)-samin (11) in 12% overall yield from
allylic alcohol 4. Moreover, we have provided further
evidence of the value of easily accessible chiral selenium
reagents for stereoselective addition reactions to double
bonds. Further investigations of the scope and mecha-
nisms of stoichiometric and catalytic reactions of chiral
selenium compounds are in progress.
(q) (2C), 31.3 (t) (2C), 74.7 (d) (2C), 126.4 (d) (2C), 128.3 (d)
(2C), 129.1 (d) (2C), 130.0 (s) (2C), 135.3 (d) (2C), 146.5 (s) (2C);
77Se NMR δ 456.1; MS (EI) m/z (relative intensity) 430(M+,
39), 213(43), 197(100), 185(83), 183(79), 157(32), 116(93),
105(24), 91(45), 77(79), 57(33) 51(37); IR (CHCl3) ν 3601, 3413,
3018, 2967, 1462, 1434, 1210, 1096, 973 cm-1. Anal. Calcd
for C18H22O2Se2: C, 50.49; H, 5.18. Found: C, 50.35; H, 5.43.
(E )-[3-(1,3-Be n zod ioxol-5-yl)-2-p r op e n yloxy](1,1-d i-
m eth yleth yl)d im eth ylsila n e (5). To a solution of 415 (248
mg, 1.39 mmol), TBDMSCl (486 mg, 3.22 mmol), and 4-(di-
methylamino)pyridine (17 mg, 0.14 mmol) in CH2Cl2 (10 mL)
was added triethylamine (0.9 mL, 12.3 mmol) and stirred for
24 h. The reaction mixture was diluted with CH2Cl2 and
washed with 1 N HCl. The organic phase was concentrated
leaving a residue which was purified by flash-chromatography
(silica gel, pentane:tert-butyl methyl ether 10:1) affording 5
(360 mg, 89% yield): colorless oil; 1H NMR δ 0.11 (s, 6H), 0.94
(s, 9H), 4.33 (dd, J ) 5.2, 1.7 Hz, 2H), 5.95 (s, 2H), 6.12 (dt, J
) 15.8, 5.2 Hz, 1H), 6.50 (dt, J ) 15.8, 1.7 Hz, 1H), 6.75 (d, J
) 8.0 Hz, 1H), 6.81 (dd, J ) 8.0, 1.6 Hz, 1H), 6.93 (d, J ) 1.6
Hz, 1H); 13C NMR δ -5.2 (q) (2C), 18.4 (s), 26.0 (q) (3C), 63.9
(t), 101.0 (t), 105.7 (d), 108.2 (d), 120.9 (d), 127.4 (d), 129.2
(d), 131.6 (s), 147.0 (s), 147.9 (s); MS (EI) m/z (relative
intensity) 292(M+, 14), 235(26), 179(6), 161(100), 131(83),
103(43), 77(19), 59(6); IR (CHCl3) ν 3007, 2956, 2857, 1607,
D
Exp er im en ta l Section
Gen er a l. All reactions were carried out under a dry argon
1
atmosphere. The H and 13C NMR spectra were measured in
CDCl3 using TMS as an internal standard at 300 and 75 MHz,
respectively. 77Se NMR spectra were recorded in CDCl3 at 76
MHz using (PhSe)2 (δ ) 475 ppm) as an external standard.
Diethyl ether and tetrahydrofuran were distilled from sodium-
benzophenone prior to use. Melting points are uncorrected.
(R,R)-Bis[2-[1-p yr r olid in -1-yl-eth yl]p h en yl] Diselen id e
(1). To a solution of (R)-1-(1-phenylethyl)pyrrolidine11 (1.75
g, 10 mmol) in dry pentane (10 mL) was added 1.6 M tert-
butyllithium solution in pentane (6.25 mL, 10 mmol). After
stirring for 40 h the solution was cooled to -78 °C and dry
THF (10 mL) was added. The reaction mixture was allowed
to warm up to room temperature and was again cooled to -78
°C. After addition of selenium (0.79 g, 10 mmol) the solution
was warmed up to room temperature and quenched after all
selenium was dissolved by adding aqueous saturated NH4Cl.
The solution was extracted five times with tert-butyl methyl
ether. The combined organic phases were dried and concen-
trated to leave a residue which was purified by flash-chroma-
tography (silica gel, acetone:pentane 1:3) affording 1 (2.11 g,
83% yield): yellow oil; [R]25D ) -42.1 (c 0.82, CHCl3); 1H NMR
δ 1.44 (d, J ) 6.6 Hz, 6H), 1.80 (m, 8H), 2.58 (m, 8H), 3.74 (q,
J ) 6.6 Hz, 2H), 7.06 (td, J ) 7.5, 1.7 Hz, 2H), 7.13 (td, J )
7.2, 1.4 Hz, 2H), 7.23 (dd, J ) 7.5, 1.6 Hz, 2H), 7.79 (dd, J )
7.8, 1.4 Hz, 2H); 13C NMR δ 19.0 (q) (2C), 23.7 (t) (4C), 51.1 (t)
(4C), 63.7 (d) (2C), 126.0 (d) (2C), 126.5 (d) (2C), 127.4 (d) (2C),
131.3 (d) (2C), 131.3 (s) (2C), 144.9 (s) (2C); 77Se NMR δ 439.9;
MS (EI) m/z (relative intensity) 508(M+, 0.5), 254(100), 183(27),
174(28), 104(23), 91(11), 70(62); IR (CHCl3) ν 2973, 2805, 1584,
1462, 1434, 1371, 1219, 1143 cm-1. Anal. Calcd for C24H32N2-
Se2: C, 56.92; H, 6.37; N, 5.53. Found: C, 56.85; H, 6.12; N,
5.58.
(S)-1-P h en ylp r op a n ol (2). To a cold (0 °C) solution of 1
in toluene (100 mL) was added diethylzinc (6.15 mL, 60 mmol),
and after 10 min benzaldehyde (5.31 g, 50 mmol) was added.
After stirring for 20 h at 0 °C 1 N HCl (100 mL) was added
and the solution extracted twice with tert-butyl methyl ether.
The combined organic phases were dried, concentrated, and
subjected to a kugelrohr distillation affording 2 (6.61 g, 97%
yield). The enantiomeric excess of 98% was determined by GC
(Chrompack, â-CD-permethylated, 25 m).
(S,S)-Bis[2-[1-h yd r oxyp r op yl]p h en yl] Diselen id e (3).
To a cold (0 °C) solution of (S)-1-phenylpropanol (4.49 g, 33
mmol) and tetramethylethylenediamine (7.67 g, 66 mmol) in
dry pentane (50 mL) was added dropwise 2.0 M n-butyllithium
solution in pentane (33 mL, 66 mmol). The bright yellow
solution was refluxed for 12 h. The solution was cooled to 0
°C, and dry THF (30 mL) was added followed by selenium (2.61
g, 33 mmol). After stirring for 5 h at room temperature 1 N
HCl (250 mL) was added and the solution extracted five times
with tert-butyl methyl ether. The combined organic phases
were dried and concentrated to leave a residue which was
purified by flash-chromatography (silica gel, pentane:tert-butyl
methyl ether 4:1) affording 3 (3.91 g, 61% yield): yellow oil;
[R]25D ) +262.0 (c 1.00, CHCl3); 1H NMR δ 0.82 (t, J ) 7.0 Hz,
6H), 1.65 (quint, J ) 7.0 Hz, 4H), 2.28 (s, 2H), 4.76 (t, J ) 7.0
Hz, 2H), 7.19 (t, J ) 7.5 Hz, 2H), 7.33 (t, J ) 7.5 Hz, 2H), 7.45
(d, J ) 7.5 Hz, 2H), 7.75 (d, J ) 7.5 Hz, 2H); 13C NMR δ 10.3
1503, 1490, 1446, 1254, 1126, 1112, 1041, 838 cm-1
. Anal.
Calcd for C16H24O3Si: C, 65.71; H, 8.27. Found: C, 65.83; H,
8.38.
(2S,3R)-[3-(1,3-Ben zodioxol-5-yl)-3-(bu ta-2,3-dien yloxy)-
2-[[2-[(S)-1-h yd r oxyp r op yl]p h en yl]selen yl]p r op oxy](1,1-
d im eth yleth yl)d im eth ylsila n e (8). To a stirred solution of
diselenide 3 (254 mg, 0.59 mmol) in dry diethyl ether (24 mL)
at -78 °C was added a 1 M solution of bromine in CCl4 (0.65
mL, 0.65 mmol). After 15 min a solution of silver trifluo-
romethane sulfonate (360 mg, 1.4 mmol) in dry THF (0.7 mL)
was added dropwise. The resulting yellowish heterogenous
solution was stirred for 10 min and cooled to -100 °C. Alkene
5 was added (230 mg, 0.78 mmol) followed after 15 min by
2,3-butadien-1-ol (7)16 (105 mg, 1.5 mmol). After stirring for
3 h at -100 °C the reaction mixture was quenched by adding
2,4,6-collidine (0.2 mL, 1.8 mmol) and a 7% aqueous solution
of citric acid (10 mL). After warming up to room temperature
the aqueous phase was extracted three times with tert-butyl
methyl ether, and the combined organic phases were dried and
concentrated. The crude material was then purified by flash-
chromatography (silica gel, pentane:tert-butyl methyl ether
5:1) to afford 8 (250 mg, 56% yield): colorless oil; [R]25D ) -36.5
(c 0.53, CHCl3); 1H NMR δ 0.00 (s, 6H), 0.89 (s, 9H), 0.95 (t, J
) 7.4 Hz, 3H), 1.74 (m, 2H), 2.32 (d, J ) 4.4 Hz, 1H), 3.49 (dt,
J ) 6.4, 4.5 Hz, 1H), 3.70 (dd, J ) 10.5, 6.4 Hz, 1H), 3.82 (ddt,
J ) 11.5, 7.6, 2.2 Hz, 1H), 4.00 (m, 2H), 4.74 (m, 3H), 5.00 (q,
J ) 5.9 Hz, 1H), 5.21 (dq, J ) 7.6, 6.5 Hz, 1H), 5.94 (dd, J )
6.5, 1.5 Hz, 2H), 6.74 (d, J ) 7.9 Hz, 1H), 6.80 (dd, J ) 7.9,
1.6 Hz, 1H), 6.83 (d, J ) 1.6 Hz, 1H), 7.08 (td, J ) 7.7, 1.5 Hz,
1H), 7.25 (td, J ) 7.7, 1.5 Hz, 1H), 7.39 (dd, J ) 7.7, 1.5 Hz,
1H), 7.43 (dd, J ) 7.7, 1.5 Hz, 1H); 13C NMR δ -5.5 (q) (2C),
10.4 (q), 18.2 (s), 25.8 (q) (3C), 30.9 (t), 54.8 (d), 62.9 (t), 66.4
(t), 74.5 (d), 75.5 (t), 79.2 (d), 87.6 (d), 100.8 (t), 107.6 (d), 107.7
(d), 121.4 (d), 126.1 (d), 127.4 (d), 127.8 (d), 129.2 (s), 132.7
(s), 135.7 (d), 146.7 (s), 147.2 (s), 147.5 (s), 209.2 (s); 77Se NMR
δ 266.5; MS (EI) m/z (relative intensity) 576(M+, 2), 449(1),
361(4), 292(6), 251(6), 203(93), 151(100), 73(30), 55(43); IR
(CHCl3) ν 2930, 2857, 1956, 1487, 1442, 1249, 1091, 1042, 838
cm-1
. Anal. Calcd for C29H40O5SeSi: C, 60.51; H, 7.00.
Found: C, 60.62; H, 7.07.
[(2S,3S,4RS)-[2-(1,3-Ben zod ioxol-5-yl)-4-vin yltetr a h y-
d r ofu r a n -3-yl]m et h oxy](1,1-d im et h ylet h yl)d im et h ylsi-
la n e (9). A solution of triphenyltin hydride (118 mg, 0.37
mmol), AIBN (20 mg, 0.12 mmol), and 8 (160 mg, 0.28 mmol)
in toluene (60 mL) was degassed and then heated for 1 h to
90 °C. After cooling, the reaction mixture was concentrated
and the residue purified by flash-chromatography (silica gel,
pentane:tert-butyl methyl ether 20:1) affording a mixture of
9a and 9b (65 mg, 64% yield): colorless oil; 1H NMR δ 0.05 (s,
6H), 0.89 (s, 9H), 2.28 (dq, J ) 8.2, 6.2 Hz, 1H), 3.06 (m, 1H),
3.65 (m, 2H), 3.79 (dd, J ) 8.3, 7.2 Hz, 1H), 4.17 (dd, J ) 8.4,

Chiral Diselenides in the Total Synthesis of (+)-Samin
J . Org. Chem., Vol. 61, No. 8, 1996 2689
1724, 1504, 1490, 1446, 1252, 1098, 1041, 838 cm-1
. Anal.
Calcd for C19H28O5Si: C, 62.61; H, 7.74. Found: C, 62.60; H,
7.83.
(1S,3a R,4S,6a R)-4-(1,3-Ben zod ioxol-5-yl)-t et r a h yd r o-
1H,3H-fu r o[3,4-c]fu r a n -1-ol, (+)-Sa m in (11). 10b (22 mg,
0.06 mmol) was dissolved in dry THF (1 mL) at 0 °C, and a 1
M solution of tetrabutylammonium fluoride in THF (0.2 mL,
0.2 mmol) was added. After stirring for 4 h the solvent was
removed and after addition of water, the residue was extracted
three times with tert-butyl methyl ether. The combined
organic phases were dried and concentrated. Purification by
flash-chromatography (silica gel, pentane:tert-butyl methyl
6.9 Hz, 1H), 4.80 (d, J ) 6.3 Hz, 1H), 5.09 (m, 2H), 5.86 (m,
1H), 5.94 (s, 2H), 6.74-6.88 (m, 3H); 13C NMR δ -5.4 (q) (2C),
18.2 (s), 25.9 (q) (3C), 46.1 (d), 53.7 (d), 61.1 (t), 72.8 (t), 82.6
(d), 100.9 (t), 106.5 (d), 108.0 (d), 117.1 (t), 119.2 (d), 135.4
(d), 137.2 (s), 146.7 (s), 147.7 (s); MS (EI) m/z (relative
intensity) 362(M+, 13), 305(9), 275(8), 230(12), 213(18), 176(70),
161(66), 149(100), 135(68), 89(28), 75(69), 73(68), 59(44); IR
(CHCl3) ν 2955, 2858, 1504, 1489, 1445, 1251, 1096, 1041, 839
cm-1. Anal. Calcd for C20H30O4Si: C, 66.26; H, 8.34. Found:
C, 66.10; H, 8.25.
(3S,4R,5S)-5-(1,3-Ben zod ioxol-5-yl)-4-[[[(1,1-d im eth yl-
eth yl)d im eth ylsilyl]oxy]m eth yl]tetr a h yd r ofu r a n -3-ca r -
boxa ld eh yd e (10b). To a cold (0 °C) solution of 9 (90 mg,
0.25 mmol) and N-methylmorpholine N-oxide (0.35 mmol, 47
mg) in acetone (5 mL), tert-butyl alcohol (1 mL), and water
(0.5 mL) was added OsO4 (4 mg, 0.016 mmol). The reaction
was complete after stirring for 4 h (TLC-monitored). The
solvent was removed and after dissolving the residue in THF
(3 mL) and water (2 mL), NaIO4 (64 mg, 0.3 mmol) was added.
After stirring for 8 h the reaction mixture was diluted with
water and extracted three times with tert-butyl methyl ether.
The combined organic phases were dried and concentrated.
Purification of the residue by flash-chromatography (silica gel,
pentane:tert-butyl methyl ether 3:1) yields 10a /b (52 mg, 57%
ether 1:2) yields 11 (10 mg, 67% yield): colorless crystals; mp
1
83-85 °C; [R]25 ) +74.5 (c 0.49, CHCl3); H NMR δ 2.43 (s,
D
1H), 2.87 (dtd, J ) 7.6, 7.2, 1.2 Hz, 1H), 3.08 (q, J ) 8.4 Hz,
1H), 3.57 (1/2 ABX, J AB ) 9.1, J ) 7.4 Hz, 1H), 3.91 (1/2 ABX,
J AB ) 9.1, J ) 1.0 Hz, 1H), 4.17 (1/2 ABX, J AB ) 9.1, J ) 6.0
Hz, 1H), 4.35 (d, J ) 7.1 Hz, 1H), 4.38 (1/2 ABX, J AB ) 9.1, J
) 9.1 Hz, 1H), 5.38 (s, 1H), 5.95 (s, 2H), 6.75-6.86 (m, 3H);
13C NMR δ 52.8 (d), 53.6 (d), 69.4 (t), 71.2 (t), 86. 9 (d), 101.1
(t), 102.2 (d), 106.5 (d), 108.2 (d), 119.6 (d), 134.6 (s), 147.3 (s),
148.0 (s); MS (EI) m/z (relative intensity) 250(M+, 42), 194(10),
176(17), 150(99), 149(100), 135(22), 121(18), 115(17), 103(15),
93(15),77(25), 65(33); IR (KBr) ν 3390, 2860, 1608, 1504, 1454,
1242, 1100, 1018 cm-1. Anal. Calcd for C13H14O5: C, 62.39;
H, 5.64; O, 31.97; Found: C, 62.47; H, 5.61; O, 31.73.
1
yield). The ratio of 10a :10b was determined by H NMR. For
isomerization to 10b the mixture of 10a /10b was then dis-
solved in a 0.2 M NaOMe/MeOH solution (3 mL) and stirred
for 2 h at 0 °C. The solvent was removed and after addition
of water extracted three times with tert-butyl methyl ether.
The combined organic phases were dried and concentrated
leaving 10b as the only product (50 mg, 55% yield): colorless
oil; [R]25D ) +14.3 (c 1.29, CHCl3); 1H NMR δ 0.05 (s, 3H), 0.06
(s, 3H), 0.90 (s, 9H), 2.49 (m, 1H), 3.13 (m, 1H), 3.65 (1/2 ABX,
J AB ) 10.3, J ) 5.1 Hz, 1H), 3.73 (1/2 ABX, J AB ) 10.3, J ) 4.4
Hz, 1H), 4.00 (dd, J ) 9.3, 8.2 Hz, 1H), 4.38 (dd, J ) 9.3, 4.5
Hz, 1H), 4.58 (d, J ) 8.2 Hz, 1H), 5.95 (s, 2H), 6.76 (m, 2H),
6.84 (s, 1H), 9.73 (d, J ) 2.3 Hz, 1H); 13C NMR δ -5.5 (q) (2C),
18.2 (s), 25.8 (q) (3C), 51.4 (d), 55.3 (d), 61.6 (t), 67.2 (t), 83.1
(d), 101.0 (t), 106.7 (d), 108.1 (d), 119.9 (d), 134.2 (s), 147.4 (s),
147.9 (s), 200.7 (d); MS (EI) m/z (relative intensity) 364(M+,
3), 307(17), 277(14), 185(14), 161(24), 157(23), 149(38), 135(100),
131(23), 105(14), 75(33), 59(8); IR (CHCl3) ν 2955, 2859,
Ack n ow led gm en t. Support of this work by the
Fonds der Chemischen Industrie with a Liebig-Stipen-
dium to T.W. is gratefully acknowledged. The authors
would like to thank Prof. B. Giese for his generous
support.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 1, 3, 5, 8, 9, 10b, and 11 (7 pages). This material
is contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
J O952093M