An Improved Photosensitizer for the Photoinduced Electron-Transfer Deoxygenation of Benzoates and m-(Trifluoromethyl)benzoates

Full text of DOI:10.1021/jo971332y

J . Org. Chem. 1997, 62, 8257-8260
8257
Sch em e 1
An Im p r oved P h otosen sitizer for th e
P h otoin d u ced Electr on -Tr a n sfer
Deoxygen a tion of Ben zoa tes a n d
m -(Tr iflu or om eth yl)ben zoa tes
Daniel R. Prudhomme, Zhiwei Wang, and
Carmelo J . Rizzo*
Department of Chemistry, Box 1822, Station B, Vanderbilt
University, Nashville, Tennessee 37235
Received J uly 22, 1997
In 1975 Barton and McCombie introduced the deoxy-
genation of secondary alcohols via a free radical chain
mechanism.1,2 This procedure involved the tin hydride
reduction of thionocarbonyl derivatives of the alcohol
such as xanthates, thionobenzoates, and thionocarbon-
ylimidazolides. Since this time, other derivatives have
been developed for this process.3
Sch em e 2
Saito and co-workers reported the deoxygenation of
benzoates and m-(trifluoromethyl)benzoates via a photo-
induced electron-transfer mechanism in which 9-methyl-
carbazole (MCZ, 2) was used as the photosensitizer.4 We
have recently used this reaction as the key step in a
stereocontrolled, de novo synthesis of â-2′-deoxyribo-
nucleosides.5 The mechanism is shown in Scheme 1.4
Photoinduced electron transfer from MCZ (D) to the
benzoyl group gives a radical ion pair. Solvent cage
escape, which is promoted by salts such as Mg(ClO4)2,
and protonation of the radical anion gives radical 1 which
undergoes â-scission to give the deoxygenated radical.
Hydrogen atom abstraction from solvent (SH, i.e., 2-pro-
panol) gives the deoxygenated product. The solvent
radical is then oxidized by the donor radical cation. In
principle, the photosensitizer (D) could be used in subs-
toichiometric amounts since it is regenerated; however,
in practice at least 1 equiv is generally used.6 We report
here the development of a new photosensitizer which
shows turnover in its function and can be used in
substoichiometric amounts.
Sch em e 3
The radical cation chemistry of carbazoles (D+• in
Scheme 1) has been studied electrochemically by Am-
brose.7 Cyclic voltammetric analysis showed that 9-
methylcarbazole (2) is irreversibly oxidized, indicating
that the radical cation undergoes further reaction or
degradation. After bulk electrolysis, a bicarbazole as a
result of radical coupling at the 3-positions was isolated;
the mechanism of this process is shown in Scheme 2.7
The electrochemical oxidation of many 9-alkylcarbazoles
substituted at the 3- and 6-positions showed improved
reversibility, indicating that their radical cations were
longer lived and did not undergo degradation on the CV
time scale.
(1) Barton, D. H. R; McCombie, S. W. J . Chem. Soc. Perkin Trans 1
1975, 1574.
(2) (a) Hartwig, W. Tetrahedron 1983, 39, 2609. (b) McCombie, S.
W. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; pp 811-833.
(3) (a) Barton, D. H. R; Subramanian, R. J . Chem. Soc., Perkin
Trans. 1 1977, 1718. (b) Rasmussen, J . R.; Slinger, C. J .; Kordish, R.
J .; Newman-Evans, D. D. J . Org. Chem. 1981, 46, 4843. (c) Robins, M.
J .; Wilson, J . S. J . Am. Chem. Soc. 1981, 103, 932. (d) Dolan, S. C.;
MacMillan, J . J . Chem. Soc. Chem. Commun. 1985, 1588. (e) Barton,
D. H. R.; Blundell, P.; Dorchak, J .; J ang, D. O.; J aszberenyi, J . C.
Tetrahedron 1991, 43, 8969. (f) Oba, M.; Nishiyama, K. Tetrahedron
1994, 50, 10193.
(4) Saito, I.; Ikehira, H.; Kasatani, R.; Watanabe, M.; Matsuura, T.
J . Am. Chem. Soc. 1986, 108, 3115.
We reasoned that the turnover properties of the
carbazole photosensitizer in the deoxygenation of benzoyl
derivatives could be improved by blocking the 3- and
6-positions. Importantly, we needed to choose groups
that would not significantly change the redox potential
or chromophore of the photosensitizer so as not to alter
its excited-state electron-transfer properties. We chose
to study 3,6-dimethyl-9-ethylcarbazole (3, DMECZ), which
was synthesized according to a known procedure from
commercially available 9-ethylcarbazole-3-carboxalde-
(5) (a) Park, M.; Rizzo, C. J . J . Org. Chem. 1996, 61, 6092. (b) Huang,
Z.; Schneider, K. C.; Benner, S. A. J . Org. Chem. 1991, 56, 3869.
(6) (a) Barvian, M. R.; Barkley, R. M.; Greenberg, M. M. J . Am.
Chem. Soc. 1995, 117, 4894. (b) Myers, A. G.; Condroski, K. R. J . Am.
Chem. Soc. 1995, 117, 3057. (c) Matray, T. J .; Greenberg, M. M. J .
Am. Chem. Soc. 1994. 116, 6931. (d) Barvian, M. R.; Greenberg, M.
M. J . Org. Chem. 1993, 58, 6151. (e) Ireland, R. E.; Armstrong, J . D.;
Lebreton, J .; Meissner, R. S.; Rizzacasa, M. A. J . Am. Chem. Soc. 1993,
115, 7152. (f) Barvian, M. R.; Greenberg, M. M. Tetrahedron Lett. 1992,
33, 6057. (g) Myers, A. G.; Condroski, K. R. J . Am. Chem. Soc. 1993,
115, 7926. (h) Clive, D. L. J .; Daigneault, S. J . Org. Chem. 1991, 56,
3801. (i) Almond, M. R.; Collins, J . L.; Reitter, B. E.; Rideout, J . L.;
Freeman, G. A.; St Clar, M. H. Tetrahedron Lett. 1991, 32, 5745. (j)
Suzuki, M.; Koyano, H.; Noyori, R. J . Org. Chem. 1987, 52, 5583. (k)
Clive, D. L. J .; Daigneault, S. J . Chem. Soc. Chem. Commun. 1989,
332.
(7) (a) Ambrose, J . F.; Nelson, R. F. J . Electrochem. Soc. 1968, 115,
1159. (b) Ambrose, J . F.; Carpenter, L. L.; Nelson, R. F. J . Electrochem.
Soc. 1975, 122, 876.
S0022-3263(97)01332-7 CCC: $14.00 © 1997 American Chemical Society

8258 J . Org. Chem., Vol. 62, No. 23, 1997
Notes
Ta ble 1
which there is a competition between the 3′-benzoate and
2′-[m-(trifluoromethyl)benzoate], we obtained the pro-
tected thymidine (12) in 51% yield along the correspond-
ing 2′,3′-dideoxy derivative in 16% yield; no 3′-deoxy-5-
methyluridine was observed. Optimal conditions for
selective 2′-deoxygenation required Mg(ClO4)2, 15 mol %
photosensitizer, and a reaction temperature of 0 °C
maintained by a circulating temperature bath. We
previously found that the m-(trifluoromethyl)benzoate of
5 could be selectively deoxygenated using N-methylcar-
bazole (MCZ) as the photosensitizer.5a It would appear
that DMECZ shows both turnover and improved reactiv-
ity as a photosensitizer.
To examine the reactivity of DMECZ, we also synthe-
sized the corresponding benzoates of the secondary
alcohols shown in Table 1 (4b, 7b-9b) and found they
are easily deoxygenated in the presence of Mg(ClO4)2
using 10 mol % photosensitizer. In previous work by us
and others,5,6 the photodeoxygenation of m-(trifluoro-
methyl)benzoates with MCZ required reaction times from
5 to 16 h and benzoates are still slower. With DMECZ
(3), the deoxygenation of m-(trifluoromethyl)benzoates
and benzoates are usually complete within 2 h at room
temperature. The only exception were cholesterol de-
rivatives 7, which required 9 h. In the case of long
photolysis times, a second portion of photosensitizer is
added after about 3-4 h.
We have developed 3,6-dimethyl-9-ethylcarbazole (3)
as a new photosensitizer for the photoinduced electron-
transfer deoxygenation of m-(trifluoromethyl)benzoates
and benzoates. By examining the radical cation chem-
istry of carbazoles, a substitution pattern was chosen to
slow the rates of potential degradation pathways. The
increased lifetime of the radical cation of carbazole 3
allows for the photosensitizer to be regenerated (Scheme
1) and thus it can be used in substoichiometric amounts.
Importantly, it appears that 3 is a more reactive photo-
sensitizer. An advantage of the photodeoxygenation over
the Barton and related deoxygenation reactions is that
toxic tin species are avoided. In addition, the deoxygen-
ation is carried at at room temperature or below, and
benzoyl derivatives are attractive due their easy synthetic
access under mild and neutral conditions.
hyde.8 Ambrose showed that DMECZ (3) undergoes
quasi-reversible oxidation, indicating that the stability
of the radical cation was improved over MCZ but still
undergoes slow reaction on the time scale of the cyclic
voltammetry experiment. After bulk electrolysis, a dimer
of DMECZ arising from radical coupling at the C3 methyl
group was isolated (Scheme 3).
The results of our deoxygenation study using DMECZ
as the photosensitizer is summarized in Table 1. Deoxy-
genations were carried out with a Hanovia 450 W
medium-pressure Hg lamp in a Pyrex reaction vessel and
the temperature of the reaction was maintained by a
coldfinger. The substrate concentration was approxi-
mately 1.5 mM in degassed 10% water in 2-propanol with
3.0 mM Mg(ClO4)2. The m-(trifluoromethyl)benzoate
derived from diacetone glucose (1a ) was smoothly deoxy-
genated with DMECZ within 2 h using 10 mol % of
DMECZ. We found that the deoxygenation of m-
(trifluoromethyl)benzoates did not require Mg(ClO4)2,
although its inclusion increased the rate of deoxygen-
ation. For protected 5-methyluridine derivative 5, in
Exp er im en ta l Section
All commercially obtained chemicals were used as received.
HPLC grade 2-propanol (99.5%) was purchased from Aldrich in
a Sure-seal bottle and used as received. m-(Trifluoromethyl)-
benzoates and benzoates 4, 7a , and 9 were prepared from the
corresponding commercially available alcohol by standard meth-
ods. Cholesterol benzoate (7b) was purchased from Aldrich.
m-(Trifluoromethyl)benzoate 10 was prepared from the corre-
sponding alcohol, which is available from quinic acid.9 Benzoyl
derivatives 8a and 8b were prepared from commercially avail-
able methyl 4,6-O-benzylidene-R-D-glucopyranose (Aldrich) by
formation of the 2,3-O-dibutylstannylene (Bu2SnO, toluene,
-H2O) followed by regioselective esterification with 1.1 equiv
of the appropriate benzoyl chloride in the presence of 1 equiv of
Bu4NF (1.0 M in THF) in CH2Cl2 to give the corresponding 2-O-
benzoyl derivative;10 esterification with acetyl chloride gave 8a
and 8b. Protected nucleoside derivatives 5 and 6 were prepared
by Vorbruggen glycosylation of the corresponding protected
ribose 1-O-benzoate5a and arabinose 1-O-acetate, respectively,
with bis(trimethylsilyl)thymine and SnCl4 in acetonitrile. 3,6-
(9) Elliot J . D.; Kelson, A. B.; Purcell, N.; Stoodley, R. J .; Palfreyman,
M. N. J . Chem. Soc., Perkin Trans I 1983, 2441.
(10) (a) David, S.; Hanessian, S. Tetrahedron 1985, 41, 643. (b)
Holzapfel, C. W.; Koekemoer, J . M.; Marais, C. F. S. Afr. J . Chem.
1984, 37, 19.
(8) Buu-Hoi, N. P.; Hoan, N. J . Org. Chem. 1951, 16, 1327.

Notes
J . Org. Chem., Vol. 62, No. 23, 1997 8259
Dimethyl-9-ethylcarbazole (3) was prepared as previously de-
scribed starting from commercially available 9-ethlcarbazole-3-
carboxaldehyde (Aldrich).8 All reactions were performed under
an argon atmosphere. Proton and carbon-13 NMR data were
recorded at 300 and 75 MHz, respectively, in CDCl3 unless
otherwise noted. Chemical shifts are reported in ppm downfield
from TMS (δ ) 0); coupling constants are given in hertz.
1,2:5,6-Di-O-isop r op ylid en e-3-O-[3-(tr iflu or om eth yl)ben -
zoyl]-r-D-glu cofu r a n ose (4a ): 1H NMR (CDCl3) δ 8.26 (s, 1H),
8.20 (d, J ) 7.8 Hz, 1H), 7.85 (d, J ) 7.8 Hz, 1H), 7.61 (t, J )
7.8 Hz, 1H), 5.97 (d, J ) 3.7 Hz, 1H), 5.52 (d, J ) 2.1 Hz, 1H),
4.64 (d, J ) 3.7 Hz, 1H), 4.37-4.29 (m, 2H), 4.16-4.05 (m, 2H),
1.56 (s, 3H), 1.41 (s, 3H), 1.33 (s, 3H), 1.26 (s, 3H); 13C NMR
(CDCl3) δ 164.0, 132.8, 131.2 (q, J C-F ) 33 Hz), 130.4, 130.0,
129.3, 126.5, 123.5 (q, J C-F ) 275 Hz), 112.4, 109.5, 105.1, 83.3,
79.9, 77.2, 72.5, 67.4, 26.8, 26.6, 26.1, 25.1.
3-O-Ben zoyl-1,2:5,6-d i-O-isop r op ylid en e-r-D-glu cofu r a -
n ose (4b):11 1H NMR (CDCl3) δ 8.02 (d, J ) 7.2 Hz, 2H), 7.57-
7.62 (m, 2H), 7.46 (t, J ) 7.5 Hz, 2H), 5.95 (d, J ) 3.6 Hz, 1H),
5.50 (d, J ) 2.5 Hz, 1H), 4.63 (d, J ) 3.6 Hz, 1H), 4.39-4.31 (m,
2H), 4.17-4.06 (m, 2H), 1.56 (s, 3H), 1.41 (s, 3H), 1.32 (s, 3H),
1.27 (s, 3H); 13C NMR (CDCl3) δ 165.1, 133.5, 129.7, 129.5, 128.5,
112.3, 109.4, 105.1, 83.4, 79.9, 76.6, 72.6, 67.2, 26.8., 26.7, 26.2,
25.2.
4.72 (d, J ) 3.7 Hz, 1H), 4.65-4.62 (m, 2H), 1.58 (s, 3H), 1.36
(s, 3H); 13C NMR δ 164.8, 164.0, 132.9, 132.3 (q, J C-F ) 33 Hz),
131.0, (q, J C-F ) 33 Hz), 130.2, 129.7, 129.4, 129.1, 126.6, 123.6
(q, J C-F ) 273 Hz), 123.4 (q, J C-F ) 273 Hz), 112.6, 105.1, 83.4,
77.2, 76.9, 62.2, 26.6, 26.1.
4,5-Di-O-b e n zoyl-1,2-O-isop r op ylid e n e -r-D-xylofu r a -
n ose (9b):12 1H NMR (CDCl3) δ 8.02 (d, J ) 8.0 Hz, 4H), 7.61-
7.51 (m, 2H), 7.46-7.37 (m, 4H), 6.07 (d, J ) 3.7 Hz, 1H), 5.62
(d, J ) 3.0 Hz, 1H), 4.81-4.75 (m, 1H), 4.69 (d, J ) 3.7 Hz, 1H),
4.61 (dd, J ) 6.2, 2.2 Hz, 2H), 1.56 (s, 3H), 1.31 (s, 3H); 13C NMR
δ 166.2, 165.3, 133.1, 132.8, 129.8, 129.5, 129.0, 128.6, 128.4,
112.4, 105.1, 83.5, 77.1, 76.8, 62.0, 26.8, 26.2.
[3-(Tr iflu or om eth yl)ben zoyl]la cton e 10: 1H NMR (CDCl3)
δ 8.29 (s, 1H), 8.23 (d, J ) 7.8 Hz, 1H), 7.85 (d, J ) 7.8 Hz, 1H),
7.61 (t, J ) 7.8 Hz, 1H), 4.88 (dd, J ) 6.4, 2.5 Hz, 1H), 4.62-
4.57 (m, 1H), 4.40-4.36 (m, 1H), 3.20-3.14 (m, 1H), 2.71 (d, J
) 11.4 Hz, 1H), 2.63 (ddd, J ) 14.5, 7.4, 2.1 Hz, 1H), 2.54 (dd,
J ) 14.5, 4.4 Hz, 1H), 1.80-1.55 (m, 8H), 1.50-1.25 (m, 2H);
13C NMR δ 173.1, 163.3, 133.1, 131.1 (q, J C-F ) 33 Hz), 130.1,
129.9, 129.2, 126.8, 123.0 (q, J C-F ) 273 Hz), 110.9, 77.2, 75.6,
72.1, 70.7, 36.9, 35.7, 33.7, 30.6, 25.0, 24.0, 23.5.
Gen er a l P r oced u r e for th e P h otosen sitized Deoxygen -
a t ion R ea ct ion . 3-Deoxy-1,2:5,6-d i-O-isop r op ylid en e-r-D-
glu cofu r a n ose (11).13 In a custom-made Pyrex reaction vessel
equipped with a coldfinger, a solution of 4a (61 mg, 0.14 mM),
magnesium perchlorate hydrate (46 mg, 0.14 mM), and 3,6-
dimethyl-9-ethylcarbazole (3 mg, 0.014 mM) in 100 mL of 10%
deionized water/2-propanol was degassed by bubbling UHP
argon through the solution for 30 min. The reaction was
photolyzed with a Hanovia 450W medium-pressure Hg lamp
while the temperature was maintained at 23 °C with a circulat-
ing temperature bath. After 2 h, the reaction was evaporated
to remove the 2-propanol and the aqueous residue extracted
three times with ethyl acetate. The organic phases were washed
with saturated brine, dried over magnesium sulfate, filtered, and
evaporated. Purification by flash chromatography on silica gave
11 as a clear oil (29 mg, 84% yield). 1H NMR (CDCl3) δ 5.80 (d,
J ) 3.6 Hz, 1H), 4.74 (t, J ) 4.2 Hz, 1H), 4.19-4.06 (m, 3H),
3.84-3.77 (m, 1H), 2.17 (dd, J ) 4.0, 13.3 Hz, 1H), 1.80-1.70
2′-O-[3-(Tr iflu or om eth yl)ben zoyl]-3′,5′-d i-O-ben zoyl-â-D-
5-m eth ylu r id in e (5):5a mp 92-95 °C; [R]21 -78.0° (c, 0.1,
D
1
CHCl3); H NMR (CDCl3) δ 8.78 (br s, 1H), 8.17-7.99 (m, 4H),
7.93 (d, J ) 7.3 Hz, 2H), 7.63-7.33 (m, 8H), 6.33 (d, J ) 6.1 Hz,
1H), 5.84 (dd, J ) 3.8, 6.0 Hz, 1H), 5.75 (t, J ) 6.1 Hz, 1H), 4.70
(ABX, J AB ) 12.3, J AX ) 2.6, J BX ) 3.5, ∆νAB ) 69.5 Hz, 2H),
4.65 (m, 1H), 1.54 (s, 3H); 13C NMR δ 166.2, 165.7, 164.4, 163.7,
150.6, 135.1, 134.0, 133.4, 132.0 (q, J C-F ) 30 Hz), 130.6, 130.0,
129.9, 129.6, 129.4, 129.1, 128.9, 128.7, 127.0, 124.2 (q, J C-F
270 Hz) 112.5, 87.3, 80.8, 74.0, 71.6, 64.2, 12.4; IR (KBr) 3373,
3276, 3074, 1725, 1619, 1452, 1267, 1128, 1095, 713 cm-1
)
.
2′-O-Acetyl-2′,5′-O-d iben zoyl-r-D-a r a bin oth ym id in e (6):
1H NMR (CDCl3) δ 8.52 (br s, 1H), 8.10-7.99 (m, 4H), 7.63-
7.53 (m, 2H), 7.47-7.38 (m, 4H), 7.20 (d, J ) 1.5 Hz, 1H), 6.18
(d, J ) 3.6 Hz, 1H), 5.77 (t, J ) 3.6 Hz, 1H), 5.54 (t, J ) 3.6 Hz,
1H), 4.82-4.77 (m, 1H), 4.68-4.56 (m, 2H), 2.14 (s, 3H), 1.96
(d, J ) 1.5 Hz, 3H); 13C NMR δ 169.7, 166.1, 165.4, 163.3, 150.0,
135.9, 133.9, 133.4, 130.0, 129.8, 129.4, 128.7, 128.5, 128.3, 111.4,
90.8, 82.8, 80.3, 63.8, 20.7, 12.6.
(m, 1H), 1.50 (s, 3H), 1.41 (s, 3H), 1.34 (s, 3H), 1.30 (s, 3H); 13
C
NMR δ 111.3, 109.6, 105.6, 80.4, 78.6, 76.7, 67.2, 35.3, 26.7, 26.5,
26.1, 25.1.
3′,5′-Di-O-b en zoyl-â-D-t h ym id in e (12):5a mp 193-195 °C
(lit.14 mp 194-195 °C); 1H NMR (CDCl3) δ 8.50 (br s, 1H), 8.09-
8.03 (m, 4H), 7.65-7.60 (m, 2H), 7.51-7.46 (m, 5H), 6.47 (dd, J
[3-(Tr iflu or om eth yl)ben zoyl]ch olester ol (7a ): 1H NMR
(CDCl3) δ 8.29 (s, 1H), 8.22 (d, J ) 7.8 Hz, 1H), 7.80 (d, J ) 7.8
Hz, 1H), 7.56 (t, J ) 7.8 Hz, 1H), 5.42 (d, J ) 4.5 Hz, 1H), 4.95-
4.85 (m 1H), 2.47 (m, 2H), 2.05-0.95 (m, 26H), 1.08 (s, 3H), 0.92
(d, J ) 6.5 Hz, 3H), 0.86 (d, J ) 6.6 Hz, 6H), 0.69 (s, 3H); 13C
NMR δ 164.6, 139.4, 132.8, 131.7, 130.9 (q, J C-F ) 33 Hz), 129.3,
128.9, 126.5, 123.7 (q, J C-F ) 273 Hz), 123.0, 75.3, 56.7, 56.1,
50.0, 42.3, 39.7, 39.5, 38.1, 37.0, 36.6, 36.2, 35.8, 31.9, 31.8, 28.2,
28.0, 27.8, 24.3, 23.8, 22.8, 22.6, 21.0, 19.4, 18.7, 11.9.
Meth yl 3-O-a cetyl-4,6-O-ben zylid en e-2-O-[3-(tr iflu or om -
eth yl)ben zoyl]-r-D-glu cop yr a n osid e (8a ): 1H NMR (CDCl3)
δ 8.32 (s, 1H), 8.22 (d, J ) 7.8 Hz, 1H), 7.84 (d, J ) 7.8 Hz, 1H),
7.61 (t, J ) 7.8 Hz, 1H), 7.44-7.49 (m, 2H), 7.35-7.39 (m, 3H),
5.80 (t, J ) 9.8 Hz, 1H), 5.55 (s, 1H), 5.14 (d, J ) 3.7 Hz, 1H),
5.06 (dd, J ) 9.8, 3.8 Hz, 1H), 4.34 (dd, J ) 10.2, 4.7 Hz, 1H),
3.96-4.04 (m, 1H), 3.72-3.86 (m, 2H), 3.41 (s, 3H), 2.00 (s, 3H);
13C NMR δ 169.9, 164.7, 136.9, 133.1, 131.2 (q, J C-F ) 33 Hz),
130.0, 129.4, 129.2, 128.3, 126.9, 126.2, 123.1 (q, J C-F ) 273 Hz),
101.7, 97.5, 79.0, 73.1, 68.9, 62.5, 55.5, 20.8.
Met h yl 3-O-a cet yl-2-O-b en zoyl-4,6-O-b en zylid en e-r-D-
glu cop yr a n osid e (8b): 1H NMR (CDCl3) δ 8.03 (d, J ) 7.2 Hz,
2H). 7.59 (t, J ) 7.2 Hz, 1H), 7.50-7.43 (m, 4H), 7.39-7.34 (m,
3H), 5.80 (t, J ) 9.8 Hz, 1H), 5.54 (s, 1H), 5.12 (d, J ) 3.7 Hz,
1H), 5.05 (dd, J ) 9.8, 3.6 Hz, 1H), 4.33 (dd, J ) 10.2, 4.7 Hz,
1H), 4.04-3.95 (m, 1H), 3.82 (t, J ) 10.2 Hz, 1H), 3.74 (t, J )
9.6 Hz, 1H), 3.40 (s, 3H), 1.99 (s, 3H); 13C NMR δ 170.0, 166.0,
137.0, 133.5, 130.0, 129.1,128.6, 128.3, 126.2, 101.7, 97.7, 79.2,
76.6, 72.5, 68.9, 68.5, 62.5, 55.5, 20.9.
4,5-Bis-O-[3-(t r iflu or om et h yl)b en zoyl]-1,2-O-isop r op y-
lid en e-r-D-xylofu r n a ose (9a ): 1H NMR (CDCl3) δ 8.25 (s, 2H),
8.21-8.18 (m, 2H), 7.86-7.80 (m, 2H), 7.65-7.53 (m, 2H), 6.10
(d, J ) 3.7 Hz, 1H), 5.65 (d, J ) 2.9 Hz, 1H), 4.80-4.75 (m, 1H),
) 5.6, 8.7 Hz, 1H), 5.66 (d, J ) 4.5 Hz, 1H), 4.75 (ABX, J AB
)
12.3, J AX )3.0, J BX ) 2.9 Hz, ∆νAB ) 36.7 Hz, 2H), 4.54 (d, J )
2.0 Hz, 1H), 2.73-2.67 (m, 1H), 2.37-2.35 (m, 1H), 1.62 (s, 3H);
13C NMR δ 166.0, 163.2, 150.1, 134.4, 133.7, 129.8, 129.5, 129.3,
129.0, 128.8, 128.6, 111.7, 84.9, 82.7, 75.0, 64.3, 38.0, 12.7.
3′-O-Acetyl-5′-O-ben zoyl-r-D-th ym id in e (13): 1H NMR δ
8.74 (br s, 1H), 8.01 (d, J ) 7.3 Hz, 2H), 7.65-7.57 (m, 1H),
7.47 (t, J ) 7.7 Hz, 2H), 7.33 (d, J ) 0.9 Hz, 1H), 6.32 (dd, J )
7.2, 2.3 Hz, 1H), 5.35 (d, J ) 6.4 Hz, 1H), 4.73 (t, J ) 4.1 Hz,
1H), 4.52-4.40 (m, 2H), 2.87 (dt, J ) 15.4, 6.7 Hz, 1H), 2.30 (d,
J ) 15.4 Hz, 1H), 2.05 (s, 3H), 1.96 (d, J ) 0.9 Hz, 3H); 13C
NMR δ 169.9, 166.1, 164.0, 150.3, 135.3, 133.5, 129.7, 129.3,
128.7, 110.3, 86.9, 84.6, 74.4, 64.1, 38.5, 20.9, 12.7
Ch olesten e (14): 1H NMR (CDCl3) δ 5.28-5.26 (m, 1H),
2.33-2.15 (m 1H), 2.05-1.65 (m 4H), 1.60-0.95 (m, 25H), 1.00
(s, 3H), 0.91 (d, J ) 6.5 Hz, 3H), 0.85 (d, J ) 6.6 Hz, 6H), 0.67
(s, 3H); 13C NMR δ 143.7, 119.0, 56.9, 56.2, 50.6, 42.3, 39.9, 39.8,
39.5, 37.5, 36.2, 35.8, 32.9, 31.9, 31.8, 28.3, 28.1, 28.0, 24.3, 23.8,
22.8, 22.6, 20.8, 19.5, 18.7, 11.9.
Met h yl 2-d eoxy-3-O-a cet yl-4,6-O-b en zylid en e-r-D-glu -
cop yr a n osid e (15):15 mp 120-122 °C (lit.10 mp 124-125 °C);
1H NMR (CDCl3) δ 7.43-7.46 (m, 2H), 7.32-7.37 (m, 3H), 5.54
(s, 1H), 5.35-5.29 (m, 1H), 4.78 (d, J ) 3.2 Hz, 1H), 4.25 (dd, J
) 10.2, 4.8 Hz, 1H), 3.92-3.86 (m, 1H), 3.75 (t, J ) 10.2 Hz,
1H), 3.65 (t, J ) 9.5 Hz, 1H), 3.33 (s, 3H), 2.33 (ddd, J ) 12.5,
5.2, 1.0 Hz, 1H), 2.03 (s, 3H), 1.74 (dt, J ) 12.5, 3.8 Hz, 1H); 13
C
(12) Collins, P. M.; Hurford, J . R.; Overend, W. G. J . Chem. Soc.,
Perkin Trans 1 1975, 2163.
(13) Iacono, S.; Rasmussen, J . R. Org Synth. 1985, 64, 57.
(14) Holy, A.; Soucek, M. Tetrahedron Lett. 1971, 185.
(15) Barton, D. H. R.; Subramanian, R. J . Chem. Soc., Perkin Trans
1 1977, 1718
(11) Somanathan, R.; Hellberg, L. H. Org. Prepr. Proc. Int. 1986,
16, 388.

8260 J . Org. Chem., Vol. 62, No. 23, 1997
Notes
1
NMR δ 170.2, 137.3, 129.1, 128.3, 127.0, 126.2, 101.8, 98.7, 80.4,
69.1, 68.0, 63.0, 54.9, 35.5, 21.2.
Deoxyla cton e 17: H NMR (CDCl3) δ 4.72 (dd, J ) 5.7, 2.5
Hz, 1H), 4.48-4.42 (m, 1H), 4.34-4.30 (m, 1H), 2.59 (dt, J )
6.3, 1.8 Hz, 1H), 2.41 (d, J ) 12.2, 1H), 2.35-2.16 (m, 2H), 2.08
(ddd, J ) 15.1, 6.4, 3.4 Hz, 1H), 1.75-1.40 (m, 10H); 13C NMR
δ 179.1, 110.2, 77.5, 72.4, 70.0, 37.0, 35.4, 33.8, 30.0, 28.1, 25.0,
24.0, 23.5.
3-Deoxy-1,2-O-isop r op ylid en e-5-O-[3-(tr iflu or om eth yl)-
ben zoyl]-r-D-xylofu r a n ose (16a ): 1H NMR (CDCl3) δ 8.31 (s,
1H), 8.24 (d, J ) 7.9 Hz, 1H), 7.82 (d, J ) 7.8 Hz, 1H), 7.59 (t,
J ) 7.8 Hz, 1H), 5.88 (d, J ) 3.7 Hz, 1H), 4.80 (t, J ) 4.3 Hz,
1H), 4.60-4.54 (m, 2H), 4.42-4.35 (m, 1H), 2.20 (dd, J ) 13.3,
4.1 Hz, 1H), 1.79-1.69 (m, 1H), 1.54 (s, 3H), 1.34 (s, 3H); 13C
NMR δ 165.1, 133.0, 131.1 (q, J C-F ) 33 Hz), 129.6, 129.1, 126.6,
123.6 (q, J C-F ) 272 Hz), 111.4, 105.7, 80.2, 75.6, 65.9, 35.4,
26.7, 26.1.
3-Deoxy-1,2-O-isop r op ylid en e-5-O-ben zoyl-r-D-xylofu r a -
n ose (16b):16 1H NMR (CDCl3) δ 8.05 (d, J ) 7.5 Hz, 2H), 7.57
(t, J ) 7.0 Hz, 1H), 7.44 (t, J ) 7.4 Hz, 2H), 5.88 (d, J ) 3.7 Hz,
1H), 4.79 (t, J ) 4.2 Hz, 1H), 4.61-4.51 (m, 2H), 4.39-4.33 (m,
1H), 2.18 (dd, J ) 13.4, 4.3 Hz, 1H), 1.81-1.71 (m, 1H), 1.53 (s,
3H), 1.33 (s, 3H); 13C NMR δ 166.4, 133.1, 129.8, 128.4, 111.4,
106.8, 80.3, 77.2, 75.8, 65.3, 35.4, 26.8, 26.2.
Ack n ow led gm en t. This work was supported by
Grant #DHP-172 from the American Cancer Society.
C.J .R. thanks the American Cancer Society for a J unior
Faculty Research Award.
Su p p or tin g In for m a tion Ava ila ble: Copies of 1H and 13C
NMR spectra for compounds 4-17 (32 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.
(16) Murray, D. H.; Prokop, J . J . Pharm. Sci. 1965, 54, 1468.
J O971332Y