Visible Light Initiated Photosensitized Electron Transfer Cyclizations of Aldehydes and Ketones to Tethered αβ-Unsaturated Esters: Stereoselective Synthesis of Optically Pure C-Furanosides

Article abstract of DOI:10.1021/jo9702812

Photosensitized one-electron reductive activation of aldehydes/ketones tethered with activated olefins leads to efficient cyclization to give diastereoselective cycloalkanols in high yield. The activation is promoted by secondary and dark electron transfer from visible light (405 nm) initiated photosensitized electron transfer generated 9,10-dicyanoanthracene radical anion (DCA^.-). The DCA^.- is produced by electron transfer using either triphenylphosphine (Ph₃P) as sacrificial electron donor (PS-A) or 1,5-dimethoxynaphthalene (DMN) as primary electron donor and ascorbic acid as sacrificial electron donor (PS-B), to light-absorbing DCA. The cyclization is suggested to involve ketyl radical intermediate. High trans diastereoselectivity is observed during the formation of cycloalkanols. This cyclization strategy is further extended for the stereoselective synthesis of optically pure C-furanoside (41), starting from naturally occuring L-tartaric acid. The stereochemistry of 41 is suggested based on the single-crystal X-ray diffraction data.

Full text of DOI:10.1021/jo9702812

5966
J . Org. Chem. 1997, 62, 5966-5973
Visible Ligh t In itia ted P h otosen sitized Electr on Tr a n sfer
Cycliza tion s of Ald eh yd es a n d Keton es to Teth er ed
r,â-Un sa tu r a ted Ester s: Ster eoselective Syn th esis of Op tica lly
P u r e C-F u r a n osid es†
Ganesh Pandey,* Saumen Hajra, and Manas K. Ghorai
Division of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411 008, India
K. Ravi Kumar
X-ray Crystallography Section, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received February 14, 1997X
Photosensitized one-electron reductive activation of aldehydes/ketones tethered with activated olefins
leads to efficient cyclization to give diastereoselective cycloalkanols in high yield. The activation
is promoted by secondary and dark electron transfer from visible light (405 nm) initiated
photosensitized electron transfer generated 9,10-dicyanoanthracene radical anion (DCA•-). The
DCA•- is produced by electron transfer using either triphenylphosphine (Ph3P) as sacrificial electron
donor (PS-A) or 1,5-dimethoxynaphthalene (DMN) as primary electron donor and ascorbic acid as
sacrificial electron donor (PS-B), to light-absorbing DCA. The cyclization is suggested to involve
ketyl radical intermediate. High trans diastereoselectivity is observed during the formation of
cycloalkanols. This cyclization strategy is further extended for the stereoselective synthesis of
optically pure C-furanoside (41), starting from naturally occuring L-tartaric acid. The stereochem-
istry of 41 is suggested based on the single-crystal X-ray diffraction data.
In tr od u ction
laboratories6 or involve toxic reagents2-5 or conditions.7
In this present era of increased ecological concern and
the requirement of a clean technology in chemical syn-
theses, it is mandatory on the part of organic chemists
to find an alternative strategy to effect this chemistry.
In this endeavor, we have developed an attractive
strategy to realize diastereoselective cyclizations of al-
dehydes or ketones to tethered olefins by visible light
initiated photosensitized one-electron reductive reactions.
We disclose herein the details of the strategy and its
application for the construction of C-furanoside frame-
work.
Reductive coupling of aldehydes and ketones to teth-
ered olefins have emerged as an attractive strategy for
the construction of bioactive cyclopentanoids,1 owing to
the retention of some useful functionalities during these
cyclizations, in contrast to the conventional radical
cyclization protocols. Usually, these reactions have been
realized by the reductive activation of a carbonyl moiety
to ketyl radicals with low-valent metallic species such
as zinc,2 lanthanide salts,3 tributyl tin hydride,4 lithium
naphthalemide,5 etc. Cathodic reductions6 have also
shown promise during the coupling of aldehyde-electron
deficient olefins or ketone-normal olefin systems. Pho-
toreductive protocol, reported by Cossy et al.7 using 254
nm light and in the presence of cancer suspect HMPA,
is also found to be useful. However, these methodologies
are either too difficult to adopt in normal synthetic
Resu lts a n d Discu ssion
Recently, our group has developed two photosystems8
useful for initiating one-electron reductive chemistry. One
such application of these photosystems has been in the
activation of R,â-unsaturated ketones as carbon-centered
radical precursors and their stereoselective cyclizations
with proximate olefins.8 The concept has involved the
secondary and dark electron transfer from 9,10-dicy-
anoanthracene radical anion (DCA•-) generated through
a primary electron transfer processes employing different
sacrificial electron donors. Photosystem A (PS-A, Figure
1) employed DCA as visible light harvesting electron
acceptor and triphenylphosphine (Ph3P) as sacrificial
electron donor whereas photosystem B (PS-B, Figure 2)
utilized DCA as usual electron acceptor, DMN (1,5-
dimethoxynaphthalene) as primary electron donor, and
ascorbate ion as secondary and sacrificial electron donor.
The design of these photosystems is based on the match-
ing thermodynamic criterion required for electron trans-
fer processes.
* Author to whom correspondence should be addressed. FAX: (91)-
212-335153. E-mail: pandey@ems.ncl.res.in.
† Dedicated to Professor M. S. Wadia on the occasion of his 60th
birthday.
X Abstract published in Advance ACS Abstracts, August 1, 1997.
(1) (a) Sowell, C. G.; Wolin, R. L.; Little, R. D. Tetrahedron Lett.
1990, 31, 485. (b) Bannai, K.; Tanaka, T.; Okamura, N.; Hazato, A.;
Sugiura, S.; Manabe, K.; Tomimori, K.; Kato, Y.; Kurozumi, S.; Noyori,
R. Tetrahedron 1990, 46, 6689. (c) Enholm, E. J .; Trivellas, A. J . Am.
Chem. Soc. 1989, 111, 6463. (d) Enholm, E. J .; Satici, H.; Trivellas,
A. J . Org. Chem. 1989, 54, 5841.
(2) Corey, E. J .; Pyne, S. G. Tetrahedron Lett. 1983, 24, 2821.
(3) (a) Enholm, E. J .; Trivellas, A. Tetrahedron Lett. 1989, 30, 1063.
(b) Shim, S. C.; Hwang, J . T.; Kang, H. Y.; Chang, M. H. Tetrahedron
Lett. 1990, 31, 4765. (c) Inokuchi, T.; Kawafuchi, H.; Torri, S. J . Org.
Chem. 1991, 56, 4983.
(4) Enholm, E. J .; Prasad, G. Tetrahedron Lett. 1989, 30, 4939.
(5) (a) Stork, G.; Malhotra, S.; Thompson, H.; Uchibayashi, M. J .
Am. Chem. Soc. 1965, 87, 1148. (b) Pradhan, S. K.; Radhakrishnan,
T. V.; Subramanian, R. J . Org. Chem. 1976, 41, 1943. (c) Pradhan, S.
K.; Kadam, S. R.; Kolhe, J . N.; Radhakrishnan, T. V.; Sohani, S. V.;
Thaker, V. B. J . Org. Chem. 1981, 46, 2622.
(6) Little, R. D.; Fox, D. P.; Hijfte, L. V.; Dannecker, R.; Sowell, G.;
Wolin, R. L.; Moens, L.; Baizer, M. M. J . Org. Chem. 1988, 53, 2287.
(7) (a) Belotti, D.; Cossy, J .; Pete, J . P.; Portella, C. Tetrahedron
Lett. 1985, 26, 4591. (b) Cossy, J .; Pete, J . P.; Portella, C. Tetrahedron
Lett. 1989, 30, 7361.
(8) (a) Pandey, G.; Hajra, S. Angew. Chem., Int. Ed. Engl. 1994, 33,
1169. (b) Pandey, G.; Hajra, S.; Ghorai, M. K.; Ravi Kumar, K. J . Am.
Chem. Soc., in press.
S0022-3263(97)00281-8 CCC: $14.00 © 1997 American Chemical Society

Stereoselective Synthesis of Optically Pure C-Furanosides
J . Org. Chem., Vol. 62, No. 17, 1997 5967
Sch em e 3
F igu r e 1.
rameter, preparative photosensitized electron transfer
activation of 5, using either PS-A or PS-B, is initiated
essentially employing the same reaction conditions as
mentioned in our earlier report.8 Photosensitized elec-
tron transfer activation of 5 involved its irradiation in
DMF:i-PrOH:H2O (88:10:2) at 405 nm using DCA as
light-absorbing electron acceptor and either Ph3P as
sacrificial electron donor (PS-A) or DMN as primary
electron donor and ascorbic acid as sacrificial electron
donor (PS-B). The irradiation is performed in a specially
designed three-chamber photoreactor made of Pyrex
glass. The 405 nm light is obtained by using CuSO4‚5H2O:
NH3 solution as filter.12 A 450 W Hanovia medium-
pressure lamp is used as light source. Before the
irradiation, the reaction mixture is deoxygenated by
bubbling argon. After almost quantitative (>98%) con-
version (∼20 h) of 5 into products, irradiation is discon-
tinued. GC analysis (SP-1000 or methyl silicon capillary
column) of the photomixture indicates the formation of
two products in the ratio of 19:1. Removal of the solvent
followed by column chromatographic (using 100-200
mesh silica gel and petroleum ether:EtOAc as eluent)
purification of the photomixture gives 6 in 80% yield. The
F igu r e 2.
Sch em e 1
Sch em e 2a
1
product 6 is characterized by detailed IR, H NMR, 13C
NMR, and mass spectral data which is in agreement with
its reported values.6 The minor product observed in the
GC is characterized as 7 by comparing with the authentic
sample;4 however, the same could not be obtained in
enough quantity for spectral details. Unchanged DCA
and DMN (PS-B) are recovered after the purification.
Ph3PdO is formed using PS-A; however, effort is not
made to isolate it.
a
Reagents: (a) Ph3PdCHCOOEt, CH2Cl2, rt, 2 d, 83%; (b)
(COCl)2, DMSO, Et3N, CH2Cl2, -78 °C, 96%.
The spectacular success of these photosystems in
initiating sequential electron transfer processes encour-
aged8 us to apply this strategy to realize the reductive
cyclization of 1 to produce cyclopentanols of type 2
(Scheme 1). Toward this endeavor, first we evaluated
to study the photosensitized electron transfer activation
behavior of ethyl 7-oxo-2(E)-heptenoate (5) employing
PS-A as well as PS-B. Compound 5 is easily obtained in
96% yield of Swern oxidation9 of compound 4, which in
turn is prepared (83%) by the Wittig olefination of
2-hydroxypyran (3) with ethyl (triphenylphosphoranyli-
dene)acetate (Scheme 2). The thermodynamic feasibility
of electron transfer from DCA•- to 5 is ascertained by
estimating negative free energy change (∆Get ) -12.45
Mechanistically, it is believed that this cyclization
involved the activation of 5 to ketyl radical intermediate
(8) by the transfer of an electron from DCA•-. The
intermediate 8 upon intramolecular addition to the
electron deficient olefin followed by termination of radical
intermediates 9 and 10 by H-abstraction, provided by
i-PrOH (Scheme 3), yields cyclized products 6 and 7,
respectively. The alternate possibility of these cycliza-
tions involving ionic intermediate 11, by one electron
reductive activation of R,â-unsaturated esters, similar to
electroreductive cyclizations,6 could be ruled out since no
trace of corresponding olefin reduction product (12) is
observed as in the case of electroreductions (Scheme 4).6
Normally, the cyclization stereochemistry of these ketyl
radicals have been reported2-7 to produce mixtures of
trans- (major) and cis- (minor) cyclopentanols in varying
ratios. However, in this reaction, high trans diastereo-
kcal/mol) utilizing the equation ∆Get ) E1/2(ox) - E1/2(red)
.
This calculation utilized the literature reported10 value
of -0.89 eV as E1/2(ox) of DCA•- and -0.35 eV as E1/2(red)
value of 5, measured by cyclic voltametry study11 (for
details, see the Experimental Section).
After ascertaining the possibility of electron transfer
from DCA•- to 5 through the above photophysical pa-
(9) Mancuso, A. J .; Swern, D. Synthesis 1981, 165.
(10) Mattes, S. L.; Farid, S. Org. Photochem. 1983, 6, 223.
(11) Since the cyclic voltamogram is irreversible, the reduction
potential and ∆Get value are only approximate; however, it agrees
generally quite well with experimental result.
(12) Calvert, J . G.; Pitts, J . N. Photochemistry; Wiley: New York,
1966; p 736.

5968 J . Org. Chem., Vol. 62, No. 17, 1997
Pandey et al.
Sch em e 4
Sch em e 7
Sch em e 5a
lactonized forms (23, 25, and 27). All of the products
displayed characteristic spectral data.
The success of photosensitized electron transfer pro-
moted generation of ketyl radicals and their efficient and
highly diastereoselective cyclizations with tethered R,â-
unsaturated esters encouraged us to extend this meth-
odology for the synthesis of C-furanosides. C-Furano-
sides are an important class of compounds as precursor
to C-nucleosides, possessing antibiotic, anticancer, and
antiviral properties,14 and to many other natural prod-
ucts.15,16 Generally, these compounds are produced by
the intramolecular Michael addition of a hydroxyl group
of an intermediate obtained from a carbohydrate precur-
sor to an activated olefins.17 However, these methods
normally produce a mixture of stereoisomers at the
“anomeric” carbon center. Similar problems are also
encountered in reactions involving radical18,19 and ionic
intermediates.20 Noyori’s21 and J ust’s22 groups have
reported the use of non-carbohydrate precursor for the
synthesis of optically pure C-furanosides, but their
strategies involved tedious optical resolution step. In an
attempt to overcome these problems, we designed an
alternative strategy of constructing C-furanoside by the
intramolecular addition of photosensitized electron trans-
fer generated ketyl radical derived from 38 to â-alkoxy-
a
Reagents: (a) PCC, Celite, CH2Cl2, rt, 52%; (b)
Ph3PdCHCOOEt, CH2Cl2, rt, 86%; (c) (COCl)2, DMSO, Et3N,
CH2Cl2, -78 °C, 96%.
Sch em e 6a
a
Reagents: (a) (CH2OH)2, PTSA, C6H6, reflux, 82-84%; (b)
LiAlH4, THF, reflux, 96%; (c) (COCl)2, DMSO, Et3N, CH2Cl2, -78
°C, 100%; (d) Ph3PdCHCOOEt, CH2Cl2, rt, 2 d; (e) PTSA, 5%
aqueous MeOH, 80%.
(14) Reviews: (a) Suhadolink, R. J . Nucleoside Antibiotics; Wiley-
Interscience: New York, 1970; p 354. (b) Daves, G. D., J r.; Cheng, C.
C. Progr. Med. Chem. 1976, 13, 303. (c) Hanessian, S.; Pernet, A. G.
Adv. Carbohydr. Chem. Biochem. 1976, 33, 111.
(15) (a) Hosova, T.; Takashiro, E.; Matsumoto, T.; Suzuki, K. J . Am.
Chem. Soc. 1994, 116, 1004. (b) Cha, J . K.; Christ, W. J .; Finan, J .
M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J .; McWhorter,
W. W., J r.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J . Am.
Chem. Soc. 1982, 104, 7369.
(16) (a) Hanessian, S.; Pernet, A. G. Adv. Carbohydr. Chem. Bio-
chem. 1976, 33, 111. (b) Daves, G. D.; Cheng, C. C. Prog. Med. Chem.
1976, 13, 303.
(17) (a) Barrett, A. G. M.; Broughton, H. B. J . Org. Chem. 1984, 49,
3673. (b) Gonzalez, M. S. P.; Aciego, R. M. D.; Herrera, F. J . L.
Tetrahedron 1988, 44, 3715.
(18) (a) Araki, Y.; Endo, T.; Tanaji, M.; Nagasawa, J .; Ishido, Y.
Tetrahedron Lett. 1988, 29, 351. (b) Barton, D. H. R.; Ramesh, M. J .
Am. Chem. Soc. 1990, 112, 891.
(19) (a) Togo, H.; Fujii, M.; Ikuma, T.; Yokoyama, M. Tetrahedron
Lett. 1991, 32, 6559. (b) Togo, H.; Aoki, M.; Yokoyama, M. Tetrahedron
Lett. 1991, 32, 6559.
(20) (a) Inuoe, T.; Kuwajima, I. J . Chem. Soc., Chem. Commun. 1980,
251. (b) Stewart, A. O.; Williams, R. M. J . Am. Chem. Soc. 1985, 107,
4289.
(21) (a) Noyori, R.; Sato, T.; Hayakawa, Y. J . Am. Chem. Soc. 1978,
100, 2561. (b) Sato, T.; Ito, R.; Hayakawa, Y.; Noyori, R. Tetrahedron
Lett. 1978, 1829.
selectivity (>90%) was found to be favored13 compared
to the earlier studies made in organic solvents.2-7
To monitor the generality of this cyclization protocol,
substrates (16, 21a , and 21b) are included in our study.
Compound 16 is prepared by following the identical
reaction sequence as described for compound 5, starting
from 6-hydroxyhexanal (14) which is obtained (52%) by
partial oxidation of 1,6-hexandiol (13) (Scheme 5). Com-
pounds 21a and 21b are prepared through the reaction
sequences as shown in Scheme 6. Photosensitized elec-
tron transfer activation of these compounds, either using
PS-A or PB-B (cf. Experimental Section) following identi-
cal experimental conditions as mentioned for 5, produced
expected cyclized products (22, 24, and 26) (Scheme 7)
in very good yields (77-89%). The corresponding cis-
isomers from these substrates are also isolated in their
(13) At this stage we are not sure of the exact mechanistic detail
about this observation; however, the effect of aqueous solvent might
be pointed out in this regard.
(22) J ust, G.; Liak, T. J .; Lim, M.; Potvin, P.; Tsantrizos, Y. S. Can.
J . Chem. 1980, 58, 2024.

Stereoselective Synthesis of Optically Pure C-Furanosides
J . Org. Chem., Vol. 62, No. 17, 1997 5969
Sch em e 8a
Sch em e 9a
a
Reagents: (h) Et3N:MeOH:H2O (1:5:1), 0 °C, 42 h (52% for 36
a
Reagents: (a) PhCHO, PTSA, C6H6, reflux (55%); (b) LiAlH4,
and 12% for 37); (i) (COCl)2, DMSO, Et3N, CH2Cl2, -78 °C (100%);
(j) PS-A or PS-B (25%); (k) Bu3SnH, AlBN, C6H6, reflux (40%); (l)
Pd/C, H2 (45 psi), MeOH, (95%).
AlCl3, Et2O: CH2Cl2 (1:1, v/v), reflux (89%); (c) (MeO)2CMe2, PTSA,
CH2Cl2, reflux (70%); (d) PhCOCl, Py, CH2Cl2 (95%); (e) PTSA,
5% aqueous MeOH (85%); (f) TBDMSCl, ImH, CH2Cl2 (95%); (g)
HC: CCOOMe, NMM, CH2Cl2 (91%).
acrylate moiety, an excellent radical acceptor,23 obtained
from the naturally occurring L-tartaric acid.
Diethyl L-tartarate (28) is converted into corresponding
benzaldehyde acetal (29, 55%) by refluxing with benzal-
dehyde in C6H6 using p-toluenesulfonic acid (PTSA) as
catalyst (Scheme 8). 29 is reduced by mixed hydride
reagent (lithium aluminum hydride-anhydrous alumi-
num chloride) to afford 2-O-benzyl-L-threitol24 (30). An
earlier report24 described the formation of this compound
only in 45% yield; however, a little modification during
the working up of the reaction mixture (for details, see
the Experimental Section) enhanced the yield of 30 to
89%. Heating (7 h) of a mixture of 30 and 2,2-dimethoxy-
propane in CH2Cl2 in the presence of 4A° molecular sieves
produced 31 in 70% yield. Benzoyl protection of the
hydroxyl group of 31 gave 32 (95%) as a thick liquid.
Deprotection of acetonide group from 32, using PTSA in
aqueous MeOH at rt, yielded white fluffy crystals of diol
33 in 86% yield. Selective protection of primary hydroxyl
group of 33 as tert-butyldimethylsilyl ether (34) is
obtained (95%) by stirring a mixture of 33 and tert-
butyldimethylsilyl chloride in CH2Cl2 at rt in the pres-
ence of imidazole. Compound 34 is converted into 35 in
91% yield by the Michael reaction25 of 34 with methyl
propiolate in the presence of N-methylmorpholine in
CH2Cl2. Our attempt to debenzoylate 35 by stirring with
K2CO3-MeOH, however, gave an unidentified mixture
of products. Milder hydrolysis26 such as by stirring 35
in Et3N:MeOH:H2O (1:5:1) at 0 °C for 42 h gave 36 (52%)
as a viscous liquid. A small amount (12%) of 37 is also
obtained in this reaction as a colorless oil (Scheme 9).
Careful (cf. Experimental Section) Swern oxidation of 36
yielded precursor aldehyde 38, which is pure enough to
proceed to the next step. Photosensitized electron trans-
fer activation of 38, using either P S-A or P S-B, led to
the cyclized product 3927 in 25% yield along with an
uncharacterized mixture of products. The low yield of
39 in this reaction is quite surprising to us. To verify
F igu r e 3. ORTEP diagram of compound 41.
F igu r e 4. ORTEP diagram of compound 41.
the cyclization behavior of ketyl radical intermediate
obtained from 38, its alternative generation using
Bu3SnH23 is also studied. The reaction of 38 with
Bu3SnH in refluxing C6H6 did not improve the cyclization
yield of 40 to any great extent (∼40%). This may be
attributed to other possible competing reaction pathways
available from the ketyl radical intermediate. Debenz-
ylation of 39 by hydrogenation using Pd/C as catalyst
gave 41 (95%). Compound 41 has been characterized by
1
detailed H NMR, 13C NMR, mass, and IR spectroscopy.
The stereochemistry of the compound 41 is confirmed by
single-crystal X-ray diffraction data (Figures 3 and 4).
In summary, we have reported a novel photosensitized
visible light initiated reductive cyclization of aldehydes/
ketones with tethered olefins to produce diastereoselec-
tive cycloalkanols. The application of this methodology
is also successfully demonstrated by the stereoselective
(23) (a) Lee, E.; Tae, J . S.; Lee, C.; Park, C. M. Tetrahedron Lett.
1993, 34, 4831. (b) Lee, E.; Park, C. M. J . Chem. Soc., Chem. Commun.
1994, 293.
(24) Al-Hakim, A. H.; Haines, A. H.; Morley, C. Synthesis 1985, 207.
(25) Winterfeldt, E.; Preuss, H. Chem. Ber. 1966, 99, 450.
(26) Tsuzuki, K.; Nakajima, Y.; Watanabe, T.; Yanagiya, M.; Mat-
sumoto, T. Tetrahedron Lett. 1978, 989.
(27) In our present experimental conditions, we always got cyclized
product 40 in desilylated form.

5970 J . Org. Chem., Vol. 62, No. 17, 1997
Pandey et al.
light (405 nm) of a 450 W Hanovia medium-pressure lamp
through a CuSO4‚5H2O:NH3 filter solution. The progress of
the reaction was monitored by GC. After 18-22 h of irradia-
tion, when substrate was almost consumed (95-98%), the
solvents were removed by distillation under reduced pressure.
The concentrate was dissolved in Et2O (50 mL), and the Et2O
layer was washed with H2O and saturated brine solution and
dried over Na2SO4. After evaporation of the solvent, the
mixture was purified by silica gel column chromatography to
give respective cyclized products.
synthesis of optically pure C-furanoside, starting with
L-tartaric acid.
Exp er im en ta l Section
Reactions were monitored by thin layer chromatography
(TLC) or gas chromatography (GC). All yields reported refer
to isolated material. Temperatures above and below ambient
temperature refer to bath temperatures unless otherwise
stated. Solvents and anhydrous liquid reagents were dried
according to established procedures by distillation under argon
atmosphere from an appropriate drying agent. Reagents were
procured from Aldrich, USA, and SD Fine Chemicals, India.
Analytical TLC was performed using precoated silica gel
plates (0.25 mm). Column chromatography was performed
using silica gel (100-200 mesh, SD Fine Chemicals, India) by
standard chromatographic techniques. Product ratios were
determined on a capillary gas chromatography (SP-1000,
methylsilicon and phenylsilicon 50 m, 0.25 mm).
All nuclear magnetic resonance spectra were recorded on
either Bruker AC 200 FT NMR or Bruker MSL 300 NMR
spectrometers. All chemical shifts are reported in parts per
million down field from TMS; coupling constants are given in
hertz. IR spectra were taken on Perkin-Elmer FTIR 1620 or
Unicam ATI Mattison RS-1 or Perkin-Elmer 599B. Mass
spectra were obtained at a voltage of 70 eV using Finnigan
MAT-1020B instrument. GC/MS was done using Shimadzu
GCMS-QP2000A. Melting points (mp) were measured by
Yanaco melting point apparatus and were uncorrected.
Cyclic Volta m m etr y. The reduction potential of com-
pound 5 was measured by a cyclic voltammetry experiment.
This experiment was carried out with a three-electrode as-
sembly on a PAR 175 Universal programmer and PAR RE0074
XY recorder. The cell consisted of a Metro E410 hanging
mercury drop electrode (HMDE) and Pt wire as auxiliary
electrode. Tetraethylammonium perchlorate was used as a
supporting electrolyte in DMF solution. Before the experi-
ment, the solution was deoxygenated by bubbling argon for
10 min. The observed cyclic voltamogram was irreversible,
and therefore, the reduction potential (E1/2(red)) as well as free
energy change (∆Get) value obtained is only approximate;
however, it agrees generally quite well with experimental
results.
X-r a y Cr ysta l a n d In ten sity Da ta . A colorless crystal of
size 0.13 × 0.10 × 0.07 mm of compound 41 was mounted and
aligned on a Siemens R3m/v diffractometer. Crystal data: a
) 5.566(1) Å, b ) 8.220(1) Å, c ) 21.551(4) Å, â ) 90.0°; space
group P2(1)2(1)2(1), V ) 986.0(1) Å3, Z ) 4, density (calc) )
1.389 mg/m3. Intensity data in the 2θ range 3.78-50.08° were
collected using ω scan with Mo KR radiation (λ ) 0.710 73 Å).
A total of 1070 independent reflections were collected, of which
511 and I g 3σ(I).
All crystallographic calculations were carried out with the
aid of the SHELXTL Plus program package. The positional
and anisotropic thermal parameters were refined for all non-
hydrogen atoms. A riding model with fixed isotropic U was
used for hydrogen atoms. For the observed data final R )
5.1%, Rw ) 5.0%, goodness-of-fit ) 1.34.
Gen er a l P h otoir r a d ia tion P r oced u r e. All irradiations
were performed in a specially designed photoreactor which
consisted of three chambers. The first and outer chamber
contained the irradiation solution, and the second one was
charged with CuSO4‚5H2O:NH3 filter solution. A 450 W
Hanovia medium-pressure mercury lamp was housed into a
water-circulated double-jacketed chamber which was im-
mersed into the second one. The whole photoreactor was made
of Pyrex glass.
DCA (0.6 mmol) was dissolved in DMF:i-PrOH:H2O (500
mL, 88:10:2) in a round bottom (RB) flask by stirring for about
2 h. Substrate (2.4 mmol) and Ph3P (1.45 mmol) or DMN (0.4
mmol) and ascorbic acid (6.2 mmol) were introduced to the
solution and stirred for an additional 5 min. The resultant
mixture was transferred into the outer chamber of the above
photoreactor and was deoxygenated by bubbling argon for 0.5
h and properly sealed. Irradiation was performed with the
P r ep a r a tion of Eth yl 7-Hyd r oxy-2(E)-h ep ten oa te (4).
To a previously dried 100 mL RB flask was added ethyl
(triphenylphosphoranylidene)acetate (11.2 g, 32.1 mmol) and
60 mL of CH2Cl2 followed by 2-hydroxypyran (2.4 g, 23.5 mmol)
under an argon atmosphere. The reaction mixture was
allowed to stir at room temperature (rt) for 2 d. After
concentrating, the residue was stirred with 40 mL of Et2O:
petroleum ether (7:3) for 45 min. The resulting suspension
was filtered, and the precipitate was washed with 10 mL of
the same solvent. The combined filtrate was concentrated in
vacuo and the mixture was separated by column chromatog-
raphy on silica gel to yield 3.36 g (83%) of 4 as a clear liquid:
1
200 MHz H NMR (CDCl3) δ 6.95 (1H, dt, J ) 15.6, 7.0 Hz),
5.8 (1H, dt, J ) 15.6, 1.4 Hz), 4.17 (2H, q, J ) 7.2 Hz), 3.62
(2H, t, J ) 6.4 Hz), 2.19 (2H, m), 2.0 (1H, br s, OH), 1.61-
1.32 (4H, m), 1.27 (3H, t, J ) 7.2 Hz); 50 MHz 13C NMR
(CDCl3) δ 166.94, 149.29, 121.50, 62.57, 60.29, 32.49, 32.19,
25.42, 14.32; IR (neat) 3400 (br), 3025, 2940, 2885, 1722, 1655,
1375, 1222, 1045, 988, 765 cm-1
.
Eth yl 7-Oxo-2(E)-h ep ten oa te (5). In a two-necked 100-
mL RB flask a solution of oxalyl chloride (0.95 mL, 11.0 mmol)
dissolved in CH2Cl2 (30 mL) was cooled to -78 °C under argon
atmosphere. DMSO (1.97 mL, 27.8 mmol) in CH2Cl2 (8 mL)
was introduced dropwise over 5 min into the flask, and the
gas evolution was observed. After 5 min of stirring, the alcohol
(4, 1.2 g, 7 mmol) dissolved in CH2Cl2 (10 mL) was added to
the reaction mixture over about 5 min. Stirring was continued
for additional 1.5 h at -78 °C. Addition of Et3N (4.85 mL,
34.8 mmol) in CH2Cl2 (5 mL) followed afterward. After the
reaction mixture was allowed to warm to rt, it was quenched
with H2O (20 mL). The organic layer was separated, and the
aqueous layer was extracted with CH2Cl2 (1 × 20 mL). The
combined organic layers were washed with H2O (5 × 30 mL)
and saturated brine solution, dried over Na2SO4, and concen-
trated in vacuo. Column purification of the concentrate gave
1
5 (1.15 g, 96%): 200 MHz H NMR (CDCl3) δ 9.8 (1H, t, J )
1.4 Hz), 6.94 (1H, dt, J ) 15.7, 6.9 Hz), 5.85 (1H, dt, J ) 15.7,
1.4 Hz), 4.2 (2H, q, J ) 7.2 Hz), 2.51 (2H, td, J ) 7.3, 1.4 Hz),
2.27 (2H, m), 1.84 (2H, m), 1.28 (3H, t, J ) 7.2 Hz); 75 MHz
13C NMR (CDCl3) δ 201.4, 166.28, 147.37, 122.21, 60.13, 42.85,
31.15, 20.28, 14.13; IR (neat) 2955, 2842, 2727, 1728, 1661,
1441, 1320, 1275, 1200, 1158, 1043, 984 cm-1
.
P h otoa ctiva tion of 5. A solution of compound 5 (0.5 g,
2.94 mmol), Ph3P (0.54 g, 2.06 mmol), and DCA (0.14 g, 0.60
mmol) in DMF:i-PrOH:H2O (500 mL, 88:10:2) was irradiated
in a specially designed photoreactor as mentioned above under
an argon atmosphere with light from a 450 W Hanovia
medium-pressure lamp filtered by a CuSO4‚5H2O:NH3 solu-
tion. The progress of the reaction was monitored by GC. After
considerable consumption (98%) of 5 (18 h), the solvent was
removed by distillation under reduced pressure. The concen-
trate was dissolved in Et2O (50 mL) and washed with H2O
and saturated brine solution. The Et2O layer was concentrated
in vacuo, and the mixture was separated by column on silica
gel (100-200 mesh) using petroleum ether:EtOAc as eluent
1
to give compound 6 (0.4 g, 80%): 200 MHz H NMR (CDCl3)
δ 4.18 (2H, q, J ) 7.2 Hz), 3.85 (1H, m), 2.7 (1H, br s, OH), 2.4
(2H, m), 2.27-1.8 (3H, m), 1.61 (3H, m), 1.25 (4H, m); 50 MHz
13C NMR (CDCl3) δ 174.28, 78.978, 60.76, 44.61, 38.67, 34.40,
30.78, 22.00, 14.36; MS m/ e 143 (M+ - electron transfer, 17),
127 (M+ - OEt, 24), 115, (16), 109 (27), 97 (27), 88 (77), 84
(96), 73 (47), 67 (52), 55 (100); IR (neat) 3420 (br OH), 2960,
2880, 1730, 1378, 1265, 1190, 1145, 1105, 1038 cm-1
.
P r ep a r a tion of Eth yl 8-Hyd r oxy-2(E)-octen oa te (15).
1,6-Hexanediol (13) (5 g, 42.3 mmol) and 160 mL of CH2Cl2
were placed in a 500 mL RB flask equipped with a magnetic

Stereoselective Synthesis of Optically Pure C-Furanosides
J . Org. Chem., Vol. 62, No. 17, 1997 5971
stirring bar and argon gas balloon. A mixture of dry pyri-
dinium chlorochromate (PCC; 7.6 g, 35.2 mmol) and Celite (7.6
g) was slowly added to the solution over 1.5 h by a solid
addition funnel at rt. The suspended mixture continued to
stir for another 2 h, and 100 mL of Et2O was added to the
reaction mixture. The resulting mixture was passed through
a silica gel column and eluted with EtOAc:petroleum ether to
give 2.25 g (55%) of a gummy liquid of 6-hydroxyhexanol (14).
Wittig reaction of 14 with ethyl (triphenylphosphoranylidene)-
acetate by following the identical reaction condition as de-
scribed for 4 gave ethyl 8-hydroxy-2(E)-octenoate (15, 86%) as
an oil: 200 MHz 1H NMR (CDCl3) δ 6.95 (1H, dt, J ) 15.8,
6.9 Hz), 5.81 (1H, dt, J ) 15.8, 1.4 Hz), 4.17 (2H, q, J ) 7.1
Hz), 3.62 (2H, t, J ) 6.4 Hz), 2.21 (2H, m), 2.04 (1H, br s),
1.61-1.31 (6H, m), 1.27 (3H, t, J ) 7.1 Hz); 50 MHz 13C NMR
(CDCl3) δ 166.94, 149.29, 121.50, 62.57, 60.29, 32.49, 32.19,
27.92, 25.42, 14.32; IR (neat) 3400 (br), 3022, 2940, 2877, 1710,
P r ep a r a tion of 20. Swern oxidation of 19a by following
the identical procedure as described for 5 gave 20a (100%):
200 MHz 1H NMR (CDCl3) δ 9.77 (1H, t, J ) 1.3 Hz), 3.97
(4H, m), 2.50 (2H, m), 2.0 (1H, m), 1.90-1.08 (10H, m); IR
(neat) 2938, 2868, 2720, 1737, 1457, 1362, 1350, 1295, 1170,
1110, 1042, 964, 940 cm-1
.
Syn th esis of 2-(4-Car beth oxy-3-bu ten yl)cycloh exan on e
(21a ). Wittig olefination of compound 20a with ethyl (tri-
phenylphosphoranylidene)acetate, as discussed earlier for
compound 4 and followed by deprotection of ketal with
catalytic PTSA in 5% aqueous MeOH, gave compound 21a
(80%): 200 MHz 1H NMR (CDCl3) δ 6.92 (1H, dt, J ) 15.8,
6.8 Hz), 5.8 (1H, dt, J ) 15.8, 1.4 Hz), 4.18 (2H, q, J ) 7.2
Hz), 2.45-2.15 (5H), 2.15-1.75 (4H, m), 1.65 (2H, m), 1.35 (2H,
m), 1.27 (3H, t, J ) 7.2 Hz); 50 MHz 13C NMR (CDCl3) δ
212.35, 166.48, 148.65, 121.54, 60.06, 49.68, 42.05, 34.01,
29.63, 27.95, 27.81, 24.97, 14.20; IR (neat) 2930, 2855, 1725,
1655, 1375, 1221, 1048, 987, 762 cm-1
.
1708, 1648, 1448, 1372, 1270, 1175, 1042, 990, 865 cm-1
.
Eth yl 8-Oxo-2(E)-octen oa te (16). This was obtained by
the Swern oxidation of 15 following the identical reaction
procedure as described for 5: 200 MHz 1H NMR (CDCl3) δ
9.75 (1H, t, J ) 1.4 Hz), 6.92 (1H, dt, J ) 15.8, 6.9 Hz), 5.81
(1H, dt, J ) 15.8, 1.4 Hz), 4.16 (2H, q, J ) 7.1 Hz), 2.45 (2H,
td, J ) 7.0, 1.4 Hz), 2.22 (2H, m), 1.69-1.44 (4H, m), 1.27 (3H,
t, J ) 7.1 Hz); 50 MHz 13C NMR (CDCl3) δ 201.92, 166.35,
148.22, 121.66, 59.99, 43.37, 31.68, 27.36, 21.38, 14.10; IR
(neat) 2988, 2942, 2885, 2725, 1720, 1658, 1372, 1315, 1275,
1
Com p ou n d 24: mixture of two isomers; 200 MHz H NMR
(CDCl3) δ 4.14 (2H, q, J ) 7.1 Hz), 2.73 (1H, br s, OH), 2.54-
2.17 (3H, m), 1.98 (2H, m), 1.81-1.1 (14H, m); 50 MHz 13C
NMR (CDCl3) δ 174.36, 77.27, 60.40, 46.80, 44.40, 34.15, 28.09,
26.57, 23.87, 23.32, 20.97, 20.17, 14.08; other isomer 173.13,
79.72, 60.23, 45.47, 44.75, 38.48, 33.34, 28.23, 27.57, 25.60,
25.42, 21.14, 14.08; MS m/ e 226 (M+, 21), 208 (M+ - H2O, 6),
181 (M+ - OEt, 8), 180 (M+ - EtOH, 52), 162 (13), 152 (37),
137 (41), 121 (49), 111 (28), 98 (56), 91 (26), 83 (24), 79 (28),
67 (41), 55 (100); IR (neat) 3480 (br OH), 2935, 2875, 1730,
1192, 1162, 1048, 990 cm-1
.
1455, 1385, 1320, 1275, 1210, 1170, 1040, 1015, 972 cm-1
.
Eth yl 2-(2-h yd r oxycycloh exyl)eth a n oa te (22): 200 MHz
1H NMR (CDCl3) δ 4.14 (2H, q, J ) 7.2 Hz), 3.9 (1H, m), 2.48
(1H, dd, J ) 15.2, 7.7 Hz), 2.26 (1H, dd, J ) 15.2, 6.7 Hz),
2.03 (1H, m), 1.76-1.35 (8H, m), 1.3 (1H, m), 1.25 (3H, t, J )
7.2 Hz); 50 MHz 13C NMR (CDCl3) δ 173.94, 69.30, 60.57,
38.61, 37.17, 32.76, 27.20, 24.79, 20.70, 14.47; MS m/ e 168
(M+ - H2O, 1), 141 (M+ - OEt, 3), 140 (M+ - EtOH, 6), 122
(4), 111 (10), 97 (21), 96 (29), 94 (9), 83 (14), 81 (100), 79 (27),
68 (63), 67 (75), 55 (64); IR (neat) 3450 (br OH), 2975, 2920,
1
Com p ou n d 25: 200 MHz H NMR (CDCl3) δ 2.87 (1H, dd,
J ) 17.3, 8.8 Hz), 2.66 (1H, td, J ) 9.7, 2.7 Hz), 2.35 (1H, d,
J ) 17.6 Hz), 2.30-2.02 (2H, m), 1.96 (1H, m), 1.85-1.5 (4H,
m), 1.5-1.02 (6H, m); 50 MHz 13C NMR (CDCl3) δ 177.27,
98.10, 44.86, 39.40, 37.40, 32.15, 31.33, 30.09, 28.49, 24.25,
23.52; GC MS m/ e 180 (M+, 2), 152 (M+ - CO, 4), 137 (6), 136
(10), 121 (5), 111 (3), 107 (3), 98 (22), 95 (10), 79 (7), 67 (7), 55
(47), 51 (10), 41 (100), 38 (70); IR (neat) 3022, 2940, 2868, 1768,
2852, 1715, 1445, 1372, 1290, 1168, 1110, 1032, 982 cm-1
.
1460, 1430, 1225, 1195, 1178, 1153, 1050, 1013, 970 cm-1
.
1
Com p ou n d 23: 200 MHz H NMR (CDCl3) δ 4.52 (1H, m),
2.71 (1H, dd, J ) 16.8, 6.0 Hz), 2.38 (1H, m), 2.26 (1H, dd, J
) 16, 3.6 Hz), 1.9-1.25 (8H, m); 50 MHz 13C NMR (CDCl3) δ
168.26, 79.36, 37.64, 35.12, 28.03, 27.36, 23.00, 20.12; GC MS
m/ e 140 (M+, 32), 112 (M+ - CO, 56), 111 (100), 97 (23), 81
(84), 68 (80), 67 (89), 55 (100), 41 (94); IR (neat) 2928, 2855,
P r ep a r a tion of 18b. This substrate was prepared (78%)
by ethylene glycol protection of methyl 3-(2-oxocyclopentyl)-
propionate28 (17b) as described for compound 18a : 200 MHz
1H NMR (CDCl3) δ 3.92 (4H, m), 3.66 (3H, s), 2.3 (2H, m), 2.0-
1.15 (9H, m); IR (neat) 2935, 2882, 1736, 1388, 1270, 1190,
1105, 1055, 956, 870 cm-1
.
1772, 1178, 1150, 995 cm-1
.
P r ep a r a tion of 19b. LiAlH4 reduction of 18b as discussed
earlier gave compound 19b (96%): 200 MHz 1H NMR (CDCl3)
δ 3.9 (4H, m), 3.62 (2H, t, J ) 6.8 Hz), 1.9 (2H, m), 1.84-1.48
(7H, m), 1.28 (2H, m); IR (neat) 3420 (br), 2990, 2918, 2852,
P r ep a r a tion of 18a . Ethyl 3-(2-oxocyclohexyl)propionate28
(17a ) (2.25 g, 11.36 mmol), 0.8 g (12.6 mmol) of ethylene glycol,
p-toluenesulfonic acid (0.05 g), and 40 mL of dry C6H6 were
charged into a 100 mL RB flask fitted with Dean-Stark
apparatus. The whole content was refluxed for 16 h. After
cooling, the reaction mixture was washed with 5% NaHCO3
solution, dried over Na2SO4, and concentrated in vacuo. Silica
gel column purification of the concentrate gave 2.25 g (82%)
1430, 1318, 1210, 1145, 1100, 1025, 946, 752 cm-1
.
Syn t h esis of 2-(4-Ca r b oet h oxy-3-b u t en yl)cyclop en -
ta n on e (21b). This product was obtained by following the
reaction sequence as enumerated for compound 21a starting
with 19b in 78% yield: 200 MHz 1H NMR (CDCl3) δ 6.92 (1H,
dt, J ) 15.9, 6.8 Hz), 5.84 (1H, dt, J ) 15.9, 1.4 Hz), 4.18 (2H,
q, J ) 7.1 Hz), 2.38-1.65 (9H, m), 1.62-1.33 (2H, m), 1.27
(3H, t, J ) 7.1 Hz); 50 MHz 13C NMR (CDCl3) δ 220.44, 166.48,
148.16, 122.0, 60.18, 48.29, 38.04, 30.03, 29.66, 28.15, 20.69,
14.29; IR (neat) 2960, 2880, 1730, 1660, 1455, 1415, 1375,
1
of 18a : 200 MHz H NMR (CDCl3) δ 4.13 (2H, q, J ) 7.2 Hz),
3.94 (4H, m), 2.33 (2H, m), 2.0 (1H, m), 1.85-1.25 (10H, m),
0.25 (3H, t, J ) 7.2 Hz); IR (neat) 2938, 2880, 1738, 1458, 1385,
1274, 1190, 1170, 1100, 1060, 962, 949, 872 cm-1
.
P r ep a r a tion of 19a . Lithium aluminum hydride (0.22 g,
5.5 mmol) and 30 mL of THF were placed in a 100 mL of two-
necked RB flask equipped with a magnetic stirring bar, reflux
condenser, and argon gas balloon. 18a 2.2 g, (9.1 mmol)
dissolved in 5 mL of THF was slowly added to the suspension
through a syringe. The whole content was refluxed for 12 h.
After cooling, the reaction mixture was quenched with con-
centrated NaOH solution. The organic layer was separated
from the precipitate, and the precipitate was washed with Et2O
(2 × 20 mL). The combined organic layer was dried over
Na2SO4 and concentrated in vacuo. The concentrate was
purified by silica gel column chromatography to yield 1.75 g
1320, 1278, 1210, 1190, 1170, 1050 cm-1
.
1
Com p ou n d 26: 200 MHz H NMR (CDCl3) δ 4.15 (2H, q, J
) 7.2 Hz), 3.15 (1H, br s, OH), 2.48 (2H, m), 2.4-2.0 (3H, m),
2.0-1.48 (5H, m), 1.45-1.15 (6H, m), 1.05 (1H, m); 50 MHz
13C NMR (CDCl3) δ 174.66, 91.11, 60.63, 51.35, 46.74, 36.92,
34.92 (2C), 31.19, 29.67, 25.67, 14.15; MS m/ e 212 (M+, 14),
194 (M+ - H2O, 4), 183 (14), 167 (M+ - OEt, 17), 166 (M+
-
EtOH, 96), 148 (15), 138 (56), 137 (88), 124 (22), 107 (43), 97
( ), 91 (17), 84 (78), 79 (39), 67 (43), 55 (100); IR (neat) 3450
(br OH), 2940, 2860, 1720, 1450, 1378, 1320, 1282, 1215, 1175,
1100, 1020 cm-1
.
1
(96%) of 19a : 200 MHz H NMR (CDCl3) δ 3.95 (4H, m), 3.58
1
(2H, t, J ) 6.5 Hz), 2.24 (1H, br s, OH), 1.88-1.0 (13 H, m);
Com p ou n d 27: 200 MHz H NMR (CDCl3) δ 2.78 (1H, dd,
J ) 17.7, 9.1 Hz)), 2.48 (1H, m), 2.35 (1H, m), 2.30 (1H, m),
2.2-1.75 (6H, m), 1.75-1.22 (4H, m); 50 MHz 13C NMR
(CDCl3) δ 176.96, 105.22, 49.68, 45.55, 38.25, 34.97, 33.05,
31.89 (2C), 25.49; GC MS m/ e 166 (M+, 2), 138 (M+ - CO, 6),
121 (6), 110 (4), 101 (8), 84 (30), 81 (8), 67 (8), 55 (30), 51 (12),
IR (neat) 3380 (br), 2920, 2855, 1640, 1446, 1358, 1340, 1285,
1230, 1163, 1146, 1092, 1060, 1030, 958, 932, 870 cm-1
.
(28) Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J .;
Terrell, R. J . Am. Chem. Soc. 1963, 85, 207.

5972 J . Org. Chem., Vol. 62, No. 17, 1997
Pandey et al.
41 (100), 38 (68), 27 (55); IR (neat) 3028, 2955, 2878, 1770,
- 1, 8), 341 (M+ - Me, 25), 298 (10), 255 (48), 192 (28), 176
(58), 158 (27), 133 (100), 122 (55), [341 (M+ - Me, 1), 176 (2),
133 (3), 105 (48), 91 (100), 77 (29), 73 (12), 55 (5)]; IR (neat)
3031, 2984, 2888, 1720, 1602, 1584, 1496, 1453, 1371, 1515,
1460, 1428, 1227, 1175, 1035, 995, 968 cm-1
.
P r ep a r a tion of (2R,3R)-Dieth yl 2,3-O-Ben zylid en eta r -
ta r a te (29). (2R,3R)-Diethyl tartarate (28; 56 g, 271 mmol),
benzaldehyde (30 g, 283 mmol), p-toluenesulfonic acid (0.1 g),
and dry C6H6 (300 mL) were charged into a 500 mL RB flask.
The whole content was heated under reflux with provision for
azeotropic removal of water for 22 h. After cooling to rt, the
solution was washed with 5% NaHCO3 solution and saturated
brine solution and dried over Na2SO4. Concentration followed
by crystallization from ethanol gave 44.0 g (55%) of 29, mp
47-49 °C (lit.29 mp 48-49 °C).
1274, 1177, 1157, 1109, 1070, 1026, 850, 739, 712 cm-1
.
P r ep a r a tion of 4-O-Ben zoyl-3-O-ben zyl-L-th r eitol (33).
A solution of 32 (8 g, 22.4 mmol) and PTSA (0.1 g) in 5%
aqueous methanol (120 mL) was stirred at rt overnight. The
reaction mixture was concentrated in vacuo, and the concen-
trate was diluted in Et2O (70 mL). The Et2O layer was washed
with 5% NaHCO3 solution and saturated brine solution, dried
over Na2SO4, and evaporated under vacuum. The residue was
recrystallized from EtOAc: petroleum ether to give 6.1 g (86%)
P r ep a r a tion of 2-O-Ben zyl-L-th r eitol (30). Lithium
aluminum hydride (5.7 g, 155 mmol) and 1:1 (v/v) Et2O:CH2Cl2
(250 mL) were placed in a 1 L two-necked RB flask equipped
with a magnetic stirring bar, reflux condenser, and argon gas
Balloon. Compound 29 (14.7 g, 50 mmol) dissolved in Et2O
(60 mL) was slowly added to the above suspension. Anhydrous
aluminum chloride (20 g, 150 mmol) in Et2O (110 mL) was
added over 0.5 h. After 1 h of stirring at rt, the reaction
mixture was heated under reflux for 4 h. After the mixture
was cooled to 0 °C, H2O (12 mL) was added carefully to destroy
excess hydride. An additional 125 mL of H2O was added to
the reaction mixture. The whole content was again heated
under reflux for 0.5 h, and organic layer was separated. The
aqueous layer was further refluxed with EtOAc (2 × 150 mL)
for 0.5 h, and organic layer was separated. The combined
organic layers were dried over Na2SO4 and concentrated in
vacuo. The residue was recrystallized from EtOAc:petroleum
ether to give 9.5 g (89%) of 30: mp 77-81 °C (lit.20 mp 73-76
of 33 as a white fluffy crystals: mp 89-91 °C; [R]22 ) -19.6°
D
(c ) 0.6, MeOH); 200 MHz 1H NMR (CDCl3) δ 8.05 (2H, m),
7.58 (1H, m), 7.45 (2H, m), 7.35 (5H, m), 4.85 (1H, d, J ) 11.4
Hz), 4.65 (1H, dd, J ) 11.8, 5.0 Hz), 4.62 (1H, d, J ) 11.4 Hz),
4.5 (1H, dd, J ) 11.8, 4.7 Hz), 3.85 (2H, br s), 3.73 (2H, m),
2.8 (1H, br s, OH), 2.35 (1H, br s, OH); 50 MHz 13C NMR
(CDCl3) δ 166.59, 137.77, 133.28, 129.94, 129.75, 128.56,
128.21, 128.11, 77.57, 73.28, 71.90, 64.00, 63.58; IR (neat) 2918,
2853, 1709, 1463, 1376, 1293, 1123, 1088, 710 cm-1 (intense
OH peak is not observed, may be due to the intramolecular
H-bonding).
4-O-Ben zoyl-3-O-b en zyl-1-[(ter t-b u t yld im et h ylsilyl)-
oxy]-L-th r eitol (34). To a stirring solution of 33 (5.0 g, 15.8
mmol) and imidazole (2.4 g, 35.3 mmol) in CH2Cl2 (60 mL)
was added tert-butyldimethylsilyl chloride (2.5 g, 16.6 mmol)
at rt, and stirring was continued for an additional 4 h. The
reaction mixture was filtered, and the filtrate was washed with
H2O (2 × 20 mL) and saturated brine solution, dried over
Na2SO4, and concentrated in vacuo. Silica gel column chro-
matographic purification of the concentrate afforded 6.46 g
°C); [R]22 ) +16.97° (c ) 1.02, MeOH; lit.30 +15.7°, c ) 1.0,
D
MeOH).
P r ep a r a tion of 3-O-Ben zyl-1,2-O-isop r op ylid en e-L-tr ei-
tol (31). Compound 30 (9 g, 42.4 mmol), 2,2-dimethoxypro-
pane (6.6 g, 63.6 mmol), p-toluenesulfonic acid (0.15 g), and
dry CH2Cl2 (200 mL) were placed in a 500 mL RB flask fitted
with Soxhlet extractor containing 4 Å molecular sieves. After
3 h of reflux, the sieves were replaced with fresh bath and the
heating was continued for additional 4 h. The reaction mixture
was cooled to rt, washed with saturated NaHCO3 solution and
brine, dried over Na2SO4, and concentrated in vacuo. The
concentrate was purified by column chromatography using
petroleum ether/EtOAc as eluent to yield 7.5 g (70%) of 31:
(95%) of 34 as a gummy liquid: [R]22 ) -6.5° (c ) 0.95,
D
1
MeOH); 200 MHz H NMR (CDCl3) δ 8.05 (2H, m), 7.58 (1H,
m), 7.45 (2H, m), 7.33 (5H, m), 4.83 (1H, d, J ) 11.6 Hz), 4.66
(1H, d, J ) 11.6 Hz), 4.56 (2H, m), 3.95 (1H, m), 3.84 (1H, br
s), 3.71 (2H, m), 2.5 (1H, br s, OH), 0.9 (9H, s), 0.08 (6H, s); 50
MHz 13C NMR (CDCl3) δ 166.44, 138.14, 133.12, 129.78,
128.53, 128.14, 128.0, 76.76, 73.45, 71.78, 64.23, 63.70, 26.00,
18.33, -5.24; MS m/ e 373 (M+ - t-Bu, 13), 265 (17), 179 (71),
159 (19), 145 (28), 131 (20), 122 (10), 117 (100), [117 (5), 105
(20), 91 (100), 77 (14), 57 (9)]; IR (neat) 3448 (br, OH), 2928,
1721, 1453, 1274, 1115, 836, 778, 711 cm-1
.
1
200 MHz H NMR (CDCl3) δ 7.4 (5H, m), 4.74 (2H, AB q, J )
Com p ou n d 35. Alcohol 34 (6 g, 13.9 mmol), N-methyl-
morpholine (1.55 g, 15.3 mmol), and dry CH2Cl2 (100 mL) were
placed in a 250 mL two-necked RB flask equipped with a
magnetic stirring bar and argon gas balloon. Methyl propi-
olate (1.3 g, 15.4 mmol) in CH2Cl2 (10 mL) was slowly added
to the stirring solution, and stirring was continued for 10 h at
rt. The reaction mixture was washed with H2O (3 × 40 mL)
and brine solution, dried over Na2SO4, and concentrated in
vacuo. The concentrate was purified by silica gel column
chromatography to give 6.5 g (91%) of 35 as a thick liquid:
11.8, 7.1 Hz), 4.33 (1H, dd, J ) 12.6, 6.7 Hz), 4.03 (1H, dd, J
) 8.4, 6.7 Hz), 3.83 (1H, dd, J ) 8.4, 7.0 Hz), 3.74 (1H, m), 3.6
(2H, m), 2.2 (1H, br s), 1.45 (3H, s), 1.4 (3H, s); 50 MHz 13C
NMR (CDCl3) δ 138.37, 128.39, 127.87, 127.73, 109.29, 79.59,
76.65, 72.78, 65.61, 61.73, 26.40, 25.37; IR (neat) 3417 (br, OH),
1641, 1070, 744 cm-1
.
P r ep a r a tion of 4-O-Ben zoyl-3-O-ben zyl-1,2-O-isop r o-
p ylid en e-L-th r eitol (32). Alcohol 31 (6 g, 23.8 mmol), pyri-
dine (3.85 mL, 47.6 mmol), and dry CH2Cl (70 mL) were
charged into a 250 mL two-necked RB flask equipped with a
magnetic stirring bar and argon gas balloon. Freshly distilled
benzoyl chloride (3.04 mL, 26.2 mmol) was slowly added at 0
°C, and the reaction mixture was allowed to stir for 12 h at rt.
Pyridine was washed off from the reaction mixture with 5%
of aqueous CuSO4 solution. The organic layer was washed
with H2O and brine, dried over Na2SO4, and concentrated in
vacuo. Column chromatographic purification of the concen-
trate gave 8.1 g (95%) of 32 as a thick liquid: 200 MHz 1H
NMR (CDCl3) δ 8.05 (2H, m), 7.58 (1H, m), 7.5-7.25 (7H, m),
4.8 (2H, AB q, J ) 12.0, 4.5 Hz), 4.58-4.3 (3H, m), 4.07 (1H,
dd, J ) 8.4, 6.6 Hz), 3.85 (2H, m), 1.48 (3H, s), 1.40 (3H, s); 50
MHz 13C NMR (CDCl3) δ 166.25, 138.12, 133.06, 129.94,
129.64, 128.38, 128.33, 127.87, 127.70, 109.50, 77.12, 76.12,
73.0, 65.61, 64.17, 26.39, 25.33; MS m/ e 356 (M+, 3), 355 (M+
1
200 MHz H NMR (CDCl3) δ 8.05 (2H, m), 7.64 (1H, m), 7.57
(1H, d, J ) 12.2 Hz), 7.45 (2H, m), 7.35 (5H, m), 5.35 (1H, d,
J ) 12.2 Hz), 4.73 (2H, AB q, J ) 15.2, 11.7 Hz), 4.5 (2H, dd,
J ) 5.1, 3.1 Hz), 4.15 (1H, m), 3.96 (1H, m), 3.83 (2H, d, J )
5.7 Hz), 3.68 (3H, s), 0.88 (9H, s), 0.05 (6H, s); 50 MHz 13C
NMR (CDCl3) δ 168.21, 166.23, 163.60, 137.60, 133.30, 129.84,
128.55, 128.28, 128.11, 97.65, 84.65, 75.80, 73.41, 63.14, 62.51,
51.01, 25.86, 18.26, -5.37; MS m/ e 457 (M+ - t-Bu, 3), 179
(14), 159 (8), 153 (25), 105 (58), 91 (100), 77 (15), 73 (11), 59
(5), [457 (18), 265 (12), 247 (6), 179 (100)]; IR (neat) 2952, 2856,
1722, 1642, 1452, 1272, 1204, 1122, 1026, 837, 780, 752, 712
cm-1
.
Com p ou n d 36. A solution of 35 (6 g, 11.6 mmol) in Et3N:
MeOH:H2O (1:5:1, v/v, 100 mL) was stirred in a 250 mL double
wall jacketed flask at 0 °C. After 42 h of stirring at 0 °C, the
reaction mixture was diluted with 200 mL of H2O and
extracted with Et2O (3 × 75 mL). The organic layer was
washed with H2O (2 × 50 mL) and saturated brine solution,
dried over Na2SO4, and concentrated in vacuo. The mixture
was separated by silica gel column chromatography to give
2.5 g (52%) of 36 as a viscous liquid and 0.6 g (12%) of 37 as
(29) Ehrlenmeyer, E. Biochem. Z. 1915, 68, 351.
(30) Fujita, K.; Nakai, H.; Kobayashi, S.; Inoue, K.; Nujima, S.;
Ohno, M. Tetrahedron Lett. 1982, 23, 3507.
(31) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
an oil, and 1.5 g (25%) of 35 was recovered: [R]22 ) + 13.71°
D

Stereoselective Synthesis of Optically Pure C-Furanosides
J . Org. Chem., Vol. 62, No. 17, 1997 5973
1
(c ) 0.96, MeOH); 200 MHz H NMR (CDCl3) δ 7.57 (1H, d, J
(3H, s), 2.96 (1H, dd, J ) 16.8, 5.2 Hz), 2.73 (1H, dd, J ) 16.8,
8.8 Hz), 1.85 (br s, OH); 75 MHz 13C NMR (CDCl3) δ 172.31,
128.28, 127.67, 127.41, 85.44, 79.88 (3C), 71.77, 61.53, 51.70,
38.09; IR (neat) 3396 (br, OH), 2925, 1728, 1456, 1439, 1398,
1348, 1280, 1215, 1175, 1132, 1111, 1090, 1063, 1041, 837, 737
) 12.2 Hz), 7.35 (5H, s), 5.37 (1H, d, J ) 12.2 Hz), 4.65 (2H,
s), 4.1 (1H, m), 3.81 (2H, d, J ) 5.6 Hz), 3.7 (3H, m), 3.68 (3H,
s), 2.2 (1H, br s, OH), 0.9 (9H, s), 0.07 (6H, s); 50 MHz 13C
NMR (CDCl3) δ 168.56, 163.97, 137.91, 128.64, 128.27, 128.16,
97.34, 85.11, 78.86, 73.44, 62.53, 60.96, 51.11, 25.92, 18.32,
-5.31; MS m/ e [411 (M+ + 1, 2), 378 (M+ - OMe, 2), 379 (M+
- MeOH, 3), 353 (M+ - t-Bu, 7), 321 (5), 251 (14), 245 (9), 231
(8), 221 (11), 189 (32), 175 (36), 161 (100)], 161 (4), 159 (4),
143 (3), 131 (7), 117 (9), 91 (100), 81 (7), 75 (22), 57 (17), 55
(13); IR (neat) 3464 (br), 2928, 2857, 1714, 1640, 1496, 1471,
cm-1
.
n -Bu 3Sn H-Med ia ted Ra d ica l Cycliza tion of Com p ou n d
38. A 50 mL two-necked RB flask and a condenser were flame-
dried and allowed to cool under an argon atmosphere. After
the flask had cooled, compound 38 (0.22 g, 0.537 mmol) and
AIBN (0.022 g, 0.134 mmol) were charged into the flask.
Freshly distilled C6H6 (20 mL) and n-Bu3SnH (0.2 mL, 0.7
mmol) were syringed into the flask. This solution was care-
fully degassed for 10 min with argon. The reaction mixture
was heated at 85 °C for 8 h. When no starting material was
observed on GC/TLC, the reaction mixture was concentrated
in vacuo, and the mixture was separated by column chroma-
tography using EtOAc:petroleum as eluent to give compound
40 (0.09 g, 40%) as a colorless liquid: 200 MHz 1H NMR
(CDCl3) δ 7.33 (5H, m), 4.63 (2H, AB q, J ) 12.0, 11.5 Hz), 4.1
(2H, m), 3.99 (2H, m), 3.82 (2H, m), 3.7 (3H, s), 2.9 (1H, dd, J
) 16.7, 5.4 Hz), 2.7 (1H, dd, J ) 16.7, 8.9 Hz), 0.88 (9H, s),
0.07 (6H, s); 50 MHz 13C NMR (CDCl3) δ 172.73, 138.49,
128.55, 127.80, 127.74, 85.06, 81.61, 81.11, 80.73, 72.30, 61.78,
51.96, 38.78, 26.17, 18.54, -5.0, -5.1; MS m/ e [411 (M+ + 1,
40), 395 (4), 379 (M+ - OMe, 6), 3.53 (M+ - t-Bu, 100)], 379
(M+ - OMe, 2), 353 (M+ - t-Bu, 32), 321 (6), 261 (6), 243 (20),
231 (20), 169 (21), 129 (25), 117 (26), 91 (100), 75 (42), 73 (42),
65 (18), 57 (28); IR (neat) 3447 (br), 2982, 2930, 2857, 1736,
1437, 1362, 1207, 1138, 835, 778, 743, 699 cm-1
.
1
Com p ou n d 37: 200 MHz H NMR (CDCl3) δ 7.33 (5H, m),
5.08 (1H, t, J ) 5.4 Hz), 4.65 (2H, AB q, J ) 17.9, 12.2 Hz),
4.23 (1H, dd, J ) 12.5, 1.4 Hz), 3.83 (1H, m), 3.79 (2H, m),
3.71 (1H, m), 3.69 (3H, s), 3.38 (1H, d, J ) 1.4 Hz), 2.76 (2H,
d, J ) 5.4 Hz), 0.9 (9H, s), 0.07 (6H, s); 50 MHz 13C NMR
(CDCl3) δ 169.77, 138.10, 128.28, 127.86, 127.63, 98.64, 79.59,
71.46, 69.34, 68.12, 61.91, 51.54, 40.23, 25.85, 18.17, -5.35,
-5.45; IR (neat) 2928, 2882, 2856, 1744, 1470, 1454, 1410,
1360, 1326, 1254, 1162, 1106, 1042, 1006, 836, 778 cm-1
.
Com p ou n d 38: In a two-necked 50 mL RB flask oxalyl
chloride (0.15 mL, 1.75 mmol) dissolved in CH2Cl2 (12 mL)
was cooled to -78 °C under argon atmosphere. DMSO (0.36
mL, 4.66 mmol) in CH2Cl2 (4 mL) was introduced dropwise
over 5 min into the flask, and the gas evolution was observed.
After 5 min of stirring the alcohol (36; 0.48 g, 1.17 mmol)
dissolved in CH2Cl2 (4 mL) was added over about 5 min.
Stirring was continued for additional 1.5 h at -78 °C.
a
solution of Et3N (0.8 mL, 5.75 mmol) in CH2Cl2 (3 mL) was
added dropwise afterward. After the reaction mixture was
allowed to warm to rt, the reaction was quenched with water
(10 mL). The organic layer was separated, and the aqueous
layer was extracted with CH2Cl2 (1 × 15 mL). The combined
organic layers were washed with H2O (5 × 30 mL) and
saturated brine solution, dried over Na2SO4, and concentrated
in vacuo to yield crude aldehyde 38 (0.48 g, 100%): 200 MHz
1H NMR (CDCl3) δ 9.68 (1H, d, J ) 1.0 Hz), 7.48 (1H, d, J )
12.3 Hz), 7.35 (5H, s), 5.34 (1H, d, J ) 12.3 Hz), 4.7 (2H, AB
q, J ) 12, 18.5 Hz), 4.25 (1H, m), 4.0 (1H, dd, J ) 4.3, 1.0 Hz),
3.8 (2H, d, J ) 5.3 Hz), 3.68 (3H, s), 0.9 (9H, s), 0.08 (6H, s);
50 MHz 13C NMR (CDCl3) δ 200.77, 168.01, 162.43, 136.78,
128.80, 128.58, 128.47, 98.47, 83.37, 81.87, 74.00, 61.39, 51.20,
25.89, 18.31, -5.39; IR (neat) 2952, 2857, 1713, 1437, 1408,
1390, 1362, 1328, 1289, 1259, 1205, 1189, 1142, 1120, 1070,
1439, 1257, 1093, 1061, 1028, 1005, 837 cm-1
.
Deben zyla tion of Com p ou n d 39. To a solution of com-
pound 39 (0.07 g, 0.236 mmol) in MeOH (20 mL) was added a
catalytic amount of 10% of Pd/C, and it was hydrogenated
using Parr apparatus at 45 psi pressure for 7 h. The solution
was filtered and concentrated in vacuo. The residue was
crystallized from acetone:petroleum ether to yield needle-
shaped colorless crystals of 41 (0.046 g, 95%): mp 87-88 °C;
[R]22 ) +41.67° (c ) 0.32, MeOH); 300 MHz 1H NMR
D
(CD3COCD3) δ 4.61 (1H, d, J ) 4.05 Hz, OH), 4.54 (1H, d, J )
4.75 Hz, OH), 4.26 (1H, m), 4.20 (1H, m), 4.14 (1H, m), 4.06
1
(1H, m), 3.90 (2H, m), 3.77 (3H, s), 2.78 (2H, m); 300 MHz H
NMR (D2O) δ 4.17 (1H, dd, J ) 4.54, 2.66 Hz), 4.08 (2H, m),
3.95 (1H, dd, J ) 4.22, 2.66 Hz), 3.78 (1H, dd, J ) 12.0, 4.4
Hz), 3.7 (3H, s), 3.68 (1H, dd, J ) 12.0, 6.53 Hz), 2.82 (1H, dd,
J ) 1.6.04, 5.03 Hz), 2.72 (1H, dd, J ) 16.04, 8.57 Hz); 75
MHz 13C NMR (CD3COCD3) δ 172.91, 82.99, 82.55, 82.49,
79.78, 62.26, 52.24, 39.93; MS m/ e 207 (M+ + 1, 2), 175 (M+
- OMe, 7), 158 (20), 157 (32), 143 (37), 139 (12), 133 (22), 125
(18), 116 (67), 115 (47), 101 (42), 97 (39), 83 (85), 84 (93), 73
(100), 69 (58), 57 (91); IR (Nujol) 3460, 3290, 3182, 2360, 2340,
1051, 1027, 1007, 838, 777 cm-1
.
P h otor ed u ctive Cycliza tion of 38. A solution of com-
pound 38 (0.48 g, 1.17 mmol) in DMF:i-PrOH:H2O (500 mL,
88:10:2) was irradiated using either PS-A [Ph3P (0.21 g, 0.82
mmol), DCA (0.06 g, 0.26 mmol)] or PS-B [DCA (0.06 g, 0.25
mmol), DMN (0.025 g, 0.14 mmol) and ascorbic acid (0.54 g,
3.06 mmol)] in a specially designed photoreactor as mentioned
above under an argon atmosphere with light from a 450 W
Hanovia medium-pressure lamp filtered by a CuSO4‚5H2O:
NH3 solution. The progress of the reaction was monitored by
GC. After 18 h, the solvent was removed by distillation under
reduced pressure. The concentrate was dissolved in EtOAc
(50 mL) and washed with H2O and saturated brine solution.
The organic layer was concentrated in vacuo, and the mixture
was separated by column chromatography on silica gel (100-
200 mesh) using petroleum ether:CH3COCH3 as eluent to give
compound 39 (0.09 g, 25%): 200 MHz 1H NMR (CDCl3) δ 7.34
(5H, m), 4.77 (1H, d, J ) 11.9 Hz), 4.58 (1H, d, J ) 11.9 Hz),
4.14 (2H, m), 4.11 (1H, m), 3.98 (1H, m), 3.83 (2H, m), 3.73
1716, 1360, 1260, 1214, 1188, 1102, 1076 cm-1
.
Ack n ow led gm en t. S.H. and M.K.G. thank UGC
and CSIR, New Delhi, respectively, for the award of
research fellowships.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR, 13C NMR,
and mass spectra of compounds (36 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 O9702812