The stereoselective preparation of an enantiomerically pure cyclopentane using intramolecular aldol cyclopentaannulation of a glucose derivative

Article abstract of DOI:10.1021/jo981225j

Methods for the annulation of carbohydrates have found extensive applications in organic synthesis. We report here a new protocol for the stereoselective conversion of glucose into an enantiomerically pure cyclopentane aldehyde 22. The readily available epoxide 15 was reacted with allyl Grignard to produce alcohol 16 in 86% yield. Swern oxidation followed by epimerization using triethylamine in N,N-dimethylformamide furnished the ketone 17 also in 86% yield. Regioselective deprotonation with lithium hexamethyldisilazane in THF was followed by methylation with methyl iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone as cosolvent to give 80% yield of ketone 18. Oxidation of ketone 18 by the Wacker procedure gave the 1,4-diketone 19 in 56% yield. Intramolecular aldol condensation occurred readily on treatment of diketone 19 with potassium tert-butoxide in toluene to furnish a 90% yield of enone 20. Treatment with N-bromosuccinimide produced the bromoester 21 in 72% yield, which was reduced to a mixture of aldehydes 22 (61%) and 23 (14%) with zinc shot in 2-propanol.

Full text of DOI:10.1021/jo981225j

8522
J . Org. Chem. 1998, 63, 8522-8529
Th e Ster eoselective P r ep a r a tion of a n En a n tiom er ica lly P u r e
Cyclop en ta n e Usin g In tr a m olecu la r Ald ol Cyclop en ta a n n u la tion
of a Glu cose Der iva tive
Andrew J . Wood, David J . Holt, Maria-Consuelo Dominguez, and Paul R. J enkins*
Department of Chemistry, Leicester University, Leicester, LE1 7RH, U.K.
Received J une 23, 1998
Methods for the annulation of carbohydrates have found extensive applications in organic synthesis.
We report here a new protocol for the stereoselective conversion of glucose into an enantiomerically
pure cyclopentane aldehyde 22. The readily available epoxide 15 was reacted with allyl Grignard
to produce alcohol 16 in 86% yield. Swern oxidation followed by epimerization using triethylamine
in N,N-dimethylformamide furnished the ketone 17 also in 86% yield. Regioselective deprotonation
with lithium hexamethyldisilazane in THF was followed by methylation with methyl iodide and
1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone as cosolvent to give 80% yield of ketone 18.
Oxidation of ketone 18 by the Wacker procedure gave the 1,4-diketone 19 in 56% yield.
Intramolecular aldol condensation occurred readily on treatment of diketone 19 with potassium
tert-butoxide in toluene to furnish a 90% yield of enone 20. Treatment with N-bromosuccinimide
produced the bromoester 21 in 72% yield, which was reduced to a mixture of aldehydes 22 (61%)
and 23 (14%) with zinc shot in 2-propanol.
In tr od u ction
molecules.2 To elucidate more closely the type of sugar
transformation process being used in any particular case,
we have found it useful to define two types of carbohy-
drate annulation based on two landmark discoveries in
this area. When all the carbon atoms of the sugar end
up in the carbocycle, we call the reaction an F-type
annulation, after Ferrier, who studied this process ex-
tensively. An example of an F-type annulation is the
cyclization of the enol ether 1 to the “carbohydrate-like”
carbocycle 2.3
The use of carbohydrates as chiral starting materials
has been an important strategy in organic synthesis for
many years.1 Examples of this strategy for the synthesis
of “carbohydrate-like” and “noncarbohydrate-like” target
molecules are widespread. The extent to which a car-
bohydrate can be used in a route to any particular
synthetic objective depends on methods which exercise
control over the proportion of the original five or six
carbon atoms of the sugar which ultimately end up in
the target molecule. It is common for pathways using
this approach to involve annulation reactions of the sugar
derivatives as a means of synthesizing cyclic target
(1) Hanessian, S., Total Synthesis of Natural Products; The Chiron
Approach; Pergamon: Oxford, 1993.
(2) Ferrier, R. J .; Middleton S. Chem. Rev. 1993, 93, 2779. Lopez,
J . C.; Fraser-Reid, B. J . Chem. Soc., Chem. Commun. 1997, 2251.
(3) Ferrier, R. J . J . Chem. Soc., Perkin Trans. 1 1979, 1455.
(4) Stork, G.; Takahashi, T.; Kawamoto, L.; Suzuki, T. J . Am. Chem.
Soc. 1978, 100, 8272.
(5) Bonnert, R. V.; J enkins, P. R. J . Chem. Soc., Chem. Commun.
1987, 6. Bonnert, R. V.; Howarth, J .; J enkins, P. R.; Lawrence, N. J .
J . Chem. Soc. Perkin Trans. 1 1991, 1225.
(6) Bonnert, R. V.; Davies, M. J .; Howarth, J .; J enkins, P. R. J .
Chem. Soc., Chem. Commun. 1987, 148. Bonnert, R. V.; Davies, M. J .;
Howarth, J .; J enkins, P. R.; Lawrence, N. J . J . Chem. Soc., Perkin
Trans. 1 1992, 27.
The alternative type of cyclization is called the S-type
annulation, after Stork, the discoverer of several carbo-
hydrate annulation reactions in which only some of the
carbons of the sugar end up in a relatively “non-
carbohydrate-like” carbocyclic product. An example of
an S-type annulation is the cyclization of the protected
cyanohydrin 3 to the cyclopentane derivative 4. The
(7) Wood, A. J .; J enkins, P. R. Tetrahedron Lett. 1997, 38, 1853.
(8) Boa, A. N.; Clark, J .; J enkins, P. R.; Lawrence, N. J . J . Chem.
Soc., Chem. Commun. 1993, 151.
(11) Ohrui, H.; Kuzuhara, H. Agric. Biol. Chem. 1980, 44, 907.
(12) Wood, A. J .; J enkins, P. R.; Fawcett, J .; Russell, D. R. J . Chem.
Soc., Chem. Commun. 1995, 1567.
(13) Pipelier, M.; Ermolenko, M. S.; Zampella, A.; Olesker, A.;
Lukacs, G.; Synlett 1996, 24.
(9) Ferrier, R. J .; Srivastava, V. K.; Carbohydr. Res. 1977, 99, 1275.
Tsang, R.; Fraser-Reid, B. J . Org. Chem. 1985, 50, 4659.
(10) Verheyden, J . P. H.; Richardson, A. C.; Bhatt, R. S.; Grant, B.
D.; Fitch, W.; Moffatt, J . G. Pure Appl. Chem. 1978, 50, 1363. Achab,
S.; Das, B. C. J . Chem. Soc., Chem. Commun. 1983, 391, J . Chem.
Soc., Perkin Trans. 1 1990, 2863. Achab, S.; Cosson, J .-P.; Das, B. C.
J . Chem. Soc., Chem. Commun. 1984, 1040. Mezzina, E.; Savoia, D.;
Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. J . Chem. Soc., Perkin
Trans. 1 1989, 845. Ferrier, R. J .; Haines, S. R. Carbohydr. Res. 1984,
130, 135. Klemer, A.; Kohla, M. Liebigs Ann. Chem. 1987, 683. Elliot,
R. P.; Fleet, G. W. J .; Pearce, L.; Smith, C.; Watkin, D. J . Tetrahedron
Lett. 1991, 32, 6227. Mann, J .; Thomas, A. J . Chem. Soc., Chem.
Commun. 1985, 737. Drew, M. G. B., Mann, J . J . Chem. Soc., Perkin
Trans. 1 1986, 2279. Mann, J .; Thomas, A. J . Chem. Soc., Perkin Trans.
1 1986, 2287.
(14) The epoxide 7 was prepared by first forming methyl-4,6-O-
benzylidene-R-D-glucopyranoside according to Evans (Evans, M. E.
Carbohydr. Res. 1972, 21, 473). Subsequent conversion to the corre-
sponding bis-mesylate and cyclization to the epoxide with sodium
methoxide was performed by the method of Richtmeyer and Hicks and
Fraser-Reid (Richtmeyer, N. K.; Hudson, C. S. J . Am. Chem. Soc. 1941,
63, 1727. Hicks, D. R.; Fraser-Reid, B. Can. J . Chem. 1975, 53, 2017).
(15) Asano, T.; Yokota, S.; Mitsonobu, O. Chem. Lett. 1983, 343.
Reaction with allylmagnesium bromide gives a different product arising
from the opening of the epoxide with bromide anion followed by attack
on the introduced bromine by the Grignard reagent; see: Mitsonobu,
O. Organic Synthesis in J apan, Past, Present and Future; Kagaaku
Dozin Co.: Tokyo, 1992; pp 215-226.
10.1021/jo981225j CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/29/1998

Cyclopentaannulation of Glucose Derivatives
J . Org. Chem., Vol. 63, No. 23, 1998 8523
Sch em e 1a
a
Reagents and conditions: i, CH2CRCH2MgCl, THF, 2 h reflux; ii, DMSO, (CF3CO)2O, DCM, 1.5 h, -78 °C, Et3N; iii, Et3N, DMF; 48
h for 9a , 7 days for 9b; iv, PdCl2, CuCl2, O2, DMF-H2O (1:1), 5 h, 92%; v, O3, DCM, 0.5 h; H2NCSNH2, 3 h, 36%; vi, NaN(SiMe3)2, THF,
0 °C, 1 h, then MeI, DMPU, 24 h, 42%; vii, PdCl2, CuCl2, O2, DMF-H2O (1:1), 5 h, 45%.
numbers 1-6 on structure 3 indicate the carbons from
glucose; clearly only three of these are involved in the
new ring.4
the synthesis of cyclopentaannulated sugars using an
intramolecular phosphonate cyclization appeared.13
Resu lts a n d Discu ssion
The objective in this project has been the cyclopen-
taannulation of glucose derivatives. Our first studies on
this topic are summarized in Scheme 1. Epoxide 7 is a
known compound,14 and this was reacted separately with
allylmagnesium chloride15 and methallylmagnesium chlo-
ride to give the alcohols 8a and 8b. Oxidation to the
ketones 9a and 9b using the Swern procedure16 was
followed by epimerization to produce the ketones 10a and
10b with the equatorial allyl groups, despite a previous
report by Ferrier that the latter reaction was not pos-
sible.17 The main evidence in favor of the epimerized
structures 10a and 10b comes from the proton NMR
spectra. The ketone 9a with the axial allyl group shows
a singlet for H-1 at δ 4.77 and a triplet for the equatorial
proton at C-2, which is coupled only to the CH2 of the
allyl group. In the epimerized structure 10a , H-1 now
appears as a doublet at δ 4.99, J ) 4.1 Hz, which is
coupled to the axial proton at C-2. Similar changes were
observed for the conversion of 9b to 10b.
We have reported examples of the S-type annulation
involving a Robinson annulation of the sugar methyl
ketone 5 to give the cyclohexenone 6,5 radical cyclizations
of cyclohexaannulated sugars,6 and cyclopentaannulated
sugars,7 and we have used these procedures in the
synthesis of a C-ring synthon of paclitaxel.8
Ketone 10a was oxidized by the Wacker reaction18 with
oxygen in the presence of palladium chloride and copper-
(II) chloride to produce the diketone 11, the first sub-
strate for cyclization. Ozonolysis of 10b occurred in a
low yield and gave a poor yield of the hemiacetal 12.
Treatment of diketone 11 with sodium hydroxide in
refluxing methanol gave no cyclization. To remove one
position of enolization, the ketone 10a was converted into
the alkylate ketone 14, which was subjected to three
different conditions of cyclization; potassium tert-butoxide
in toluene, sodium carbonate in methanol, and sodium
There are several reports of sugar annulation methods
which involve enolate cyclization reactions via alkyla-
tion,9 aldol condensation,10 and dithiane alkylation.11 We
report here full details of our studies on cyclopentaan-
nulation based on the intramolecular aldol reaction12 and
the removal of the sugar component to produce stereo-
selectively a chiral cyclopentane derivative. Shortly after
our communication of part of these results, a report on
(16) Mancuso, A. J .; Huang, S.-L.; Swern, D. J . Org. Chem. 1978,
43, 2480.
(17) Ferrier, R. J .; Lee, C.-K.; Wood, T. A. J . Chem. Soc., Chem.
Commun. 1991, 690. Compound 9a could not be induced to epimerize
by Ferrier in this publication.
(18) Pauley, D.; Anderson, F.; Hudlicky, T. Org. Synth. 1989, 67,
121.

8524 J . Org. Chem., Vol. 63, No. 23, 1998
Wood et al.
Sch em e 2a
a
Reagents and conditions: i, CH2CHCH2MgCl, THF, 2 h reflux, 86%; ii, DMSO, (CF3CO)2O, DCM, 1.5 h, -78 °C, then Et3N 24 h, 86%;
iii, LiN(SiMe3)2, THF, 0 °C, 1 h, then MeI, DMPU, 24 h, 80%; iv, PdCl2, O2, DMF-H2O (1:1), 5 h, 56%; v, ButOK, toluene, 0.5 h, 90%; vi,
NBS, BaCO3, CCl4, 3 h reflux, 72%; vii, Zn shot, IPA-H2O (10:1), 22 h reflux.
Sch em e 3
methoxide in methanol. In each case, the starting
material was isolated with a trace of benzaldehyde, and
no evidence in favor of cyclization was observed.
The search for a viable cyclopentaannulation method
was continued using the reaction sequence described in
Scheme 2. The known â-epoxide 1519 was reacted with
allylmagnesium chloride to produce the alcohol 16,15
which was oxidized16 and epimerized17 to give the ketone
17. Deprotonation and methylation of 17 furnished the
ketone 18, which was subsequently oxidized by the
Wacker procedure18 to furnish the diketone 19. Success-
ful cyclization was achieved using potassium tert-butox-
ide in toluene to give the enone 20. The structure of 20
was confirmed by an X-ray crystal structure; full details
of this were submitted with the preliminary publication
of part of these results.12 NBS bromination was surpris-
ingly clean, leading to the expected product 21.20 Treat-
ment of the bromide 21 with zinc shot gave a mixture of
two aldehydes, 22 and 23, in 61 and 14% yields, respec-
at C-3′ and C-5′. Consequently, we can assign the signals
tively. This reaction is an application of the method for
at δ 2.2 and δ 2.84 to the two R-hydrogens H-5′ and H-3′;
and the signals at δ 2.37 and δ 2.70 to the â-hydrogens
H-3′ and H-5′. Turning now to the hydrogen on C-2′ we
see a strong NOE to the â-hydrogens, confirming that
the C-2′ proton is on the â face of the molecule. This
assignment is confirmed by the NOE between the alde-
hyde proton and the methyl group.
A possible mechanism for the zinc reduction is shown
in Scheme 3. The Vasella reaction normally occurs by
attack of the zinc on the bromo substituent to give the
aldehyde 24, which can be regarded as an enedione. The
electron-transfer reduction of enediones using zinc is
known,22and in Scheme 3 we adapt this mechanism to
explain the formation of 22 and 23. Transfer of two
electrons from the zinc may be expected to produce the
dianion 25, which protonates on carbon to give the
enolate 26. Protonation of the enolate from the â face
carbohydrate ring cleavage by Vasella,21 but as explained
below, the form of zinc used on 21 was different from that
previously reported.
The configurational assignment of the major aldehyde
product 22 was determined with the aid of a NOESY
spectrum. First we are sure of the configuration of the
C-1′ center in 22 from the X-ray crystal structure of 20.
The assignment of the signals of the CH2 protons at
carbons 3′ and 5′ in the H1 NMR spectrum of 22 is clear
from the chemical shift expected of protons adjacent to a
carbonyl group. From the NOESY spectrum we see a
strong NOE between the methyl group at the quaternary
center and one of the protons of each methylene group
(19) The epoxide 15 was prepared by first forming methyl-4,6-O-
benzylidene-R-D-glucopyranoside according to Evans (Evans, M. E.
Carbohydr. Res. 1972, 21, 473). Subsequent conversion to the corre-
sponding mono-tosylate by the method of Hicks and Fraser-Reid (Hicks,
D. R.; Fraser-Reid, B. Synthesis 1974, 203) was followed by conversion
to the â epoxide following the procedure of Pougny (Pougny, J . R.;
Sinay, P. J . Chem. Res., Miniprint 1982, 186).
(22) (a) Windhaus, A., Ber. Dtsch. Chem. Ges. 1903, 36, 3752. (b)
Elks, J .; Evans, R. M.; Long, A. G.; Thomas, G. H.; J . Chem. Soc. 1954,
451. (c) Toda, M.; Hayashi, M.; Hirata, S.; Yamamura, S. Bull. Chem.
Soc. J pn. 1972, 45, 264.
(20) Hanessian, S.; Plessas, N. R. J . Org. Chem. 1969, 34, 1035.
(21) Vasella, A., Bernet, B. Helv. Chim. Acta 1979, 62, 1990.

Cyclopentaannulation of Glucose Derivatives
J . Org. Chem., Vol. 63, No. 23, 1998 8525
lithium aluminum hydride. Dichloromethane was distilled
from calcium hydride. Petroleum ether refers to the 40-60
°C boiling fraction. Flash column chromatography was per-
formed on Sorbsil C-60 silica gel (Crosfield Chemicals), 40-
60 M. Melting points are uncorrected. All chemical shifts
were taken directly from the spectra, and J values are given
in hertz.
as shown in 26â would furnish the aldehyde 22. Proto-
nation from the R face is shown in 26r yielding the
aldehyde 23.
The nature of the zinc has an important effect on the
reduction of 21. Using zinc shot we obtained the alde-
hydes 22 and 23. This form of zinc is different from the
activated powdered zinc described by Vasella,21 which we
used in our previous work.8 In fact, when we used
activated powdered zinc in the reduction of 21, we
obtained the alcohols 27a and 27b as the major products.
These alcohols were isolated and characterized as their
p-nitrobenzoate esters. We believe the explanation of
this is that powdered zinc prepared by the Vasella
method is a more reactive reducing agent, because of its
greater active surface area, than the equivalent material
prepared from zinc shot.
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-p r op en yl-r-D-
a lt r op yr a n osid e (8a ) a n d Met h yl 4,6-O-Ben zylid en e-2-
deoxy-2-C-(2-m eth yl-2-pr open yl)-r-D-altr opyr an oside (8b).
Allylmagnesium chloride (27.0 mL, 2 M solution in THF) was
added dropwise to an ice-cooled, stirred suspension of the
epoxide 7 (4.75 g, 18.00 mmol) in dry THF (65.0 mL). The
reaction mixture was heated to reflux for 2 h and then the
reaction was quenched by the dropwise addition of water (30
mL). The mixture was extracted into diethyl ether (2 × 75
mL), and the combined organic layers were washed with
saturated sodium chloride solution (2 × 50 mL), dried, and
evaporated to dryness. Chromatography on silica gel with
petroleum ether-diethyl ether (5:1 to 1:1) as the eluent yielded
8a as a white solid (4.98 g, 86%): [R]20 +59° (c 1.0, CHCl3);
D
Rf 0.45, 2:1 petroleum ether-ethyl acetate; νmax (CH2Cl2)/cm-1
3575 br s, 1650 s, 1380 s; δH (300 MHz CDCl3) 2.17-2.29 (2H,
m, 7-H), 3.13 (1H, d, J 6.9, 2-H), 3.39 (3H, s, OMe), 3.42 (1H,
t, obscured, 4-H), 3.67 (1H, dd, J 2.9, 9.8, 3-H), 3.79 (1H, t, J
10.0, 6ax-H), 4.18-4.27 (1H, m, 5-H), 4.31 (1H, dd, J 5.0, 9.9,
6eq-H), 4.55 (1H, s, 1-H), 5.08-5.16 (2H, m, 9-H), 5.61 (1H, s,
10-H), 5.72-5.83 (1H, m, 8-H), 7.29-7.52 (5H, Ph); δC (75
MHz, CDCl3) 34.1 (CH2, C7), 44.6 (CH, C2), 55.4 (CH3, OMe),
58.3 (CH, C5), 68.3 (CH, C3), 69.2 (CH2, C6), 76.7 (CH, C4),
101.2 (CH, C1), 102.1 (CH, C10), 117.3 (CH2, C9), 126.5 (CH,
Ph), 128.1 (CH, Ph), 128.9 (CH, Ph), 135.3 (CH, C8), 137.2 (C,
Ph); m/z (EI) 306 (M+, 1.9) 274 (15.8), 179 (25.9), 105 (PhCO+,
100) (found M+, 306.14665; C17H22O5 requires 306.1467).
This compound was previously communicated without full
experimental and spectroscopic data.15
In the same way, the epoxide 7 (497 mg, 1.88 mmol) was
treated with 2-methyl-2-propenylmagnesium chloride to yield
8b as a white solid (576 mg, 92%); mp 97-99 °C (lit.15 mp 98-
100 °C); Rf 0.45, 2:1 petroleum ether-ethyl acetate; νmax (CH2-
Cl2)/cm-1 3510 br w, 2940 s, 1690 w; δH (300 MHz CDCl3) 1.7
(3H, s, 11-H), 2.12-2.31 (2H, m, 7-H), 2.38-2.48 (1H, m, 2-H),
3.43 (3H, s, OMe), 3.72 (1H, dd, J 3.0, 9.7, 3-H), 3.83 (1H, t, J
9.9, 6ax-H), 3.99 (1H, br s, 4-H), 4.22-4.32 (1H, m, 5-H), 4.35
(1H, dd, J 4.9, 9.9, 6eq-H), 4.57 (1H, s, 1-H), 4.81 (1H, s, 9-H),
4.88 (1H, s, 9-H), 5.65 (1H, s, 10-H), 7.34-7.63 (5H, Ph); δC
(75 MHz, CDCl3) 21.8 (CH3, C11), 38.1 (CH2, C7), 42.5 (CH,
C3), 55.4 (CH3, OMe), 58.3 (CH, C2), 68.7 (CH, C5), 69.3 (CH2,
C6), 76.7 (CH, C4), 101.5 (CH, C1), 102.1 (CH, C10), 113.0
(CH2, C9), 126.1 (CH, Ph), 128.1 (CH, Ph), 128.9 (CH, Ph),
137.2 (C, Ph), 142.0 (CH, C8); m/z (EI) 320 (M+, 29.6) 288
(110.5), 264 (14.5), 179 (29.4), 105 (PhCO+, 100) (found: M+,
320.1625; C18H24O5 requires 320.1625).
The structural requirements for facile cyclopentaan-
nulation are very stringent; the only substrate we were
able to cyclize was 19. An especially important feature
seems to be the quaternary center R to the carbonyl
group. Wacker oxidation of 17 was used to produce the
ketone 29 without the quaternary center. However, all
attempts to cyclize this material failed. One possible
explanation of this phenomenon is that it might be
related to the Thorpe-Ingold effect23 in which the degrees
of rotational freedom of the ketone side chain of 19 are
restricted so that cyclization is favored.
In conclusion, we have developed a procedure for the
cyclopentaannulation of a glucose-derived diketone 19,
and we have used a reaction with N-bromosuccinimide
followed by reductive elimination using activated zinc
shot to stereoselectively produce an enantiomerically
pure cyclopentane 22 with a quaternary stereogenic
center, which we believe will find use in the synthesis of
steroids and vitamin D derivatives.
This compound was previously communicated without full
experimental and spectroscopic data.15
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-p r op en yl-r-D-
a r a bin o-h exop yr a n osid -3-u lose (9a ) a n d Meth yl 4,6-O-
Ben zylid en e-2-d eoxy-2-C-(2-m et h yl-2-p r op en yl)-r-D-a r -
a bin o-h exopyr an osid-3-u lose (9b). Trifluoroacetic anhydride
(0.96 mL, 6.80 mmol) in dry dichloromethane (1.0 mL) was
added dropwise to a cooled solution (-65 °C) of dimethyl
sulfoxide (0.63 mL, 6.78 mmol) in dry dichloromethane (4.0
mL) under an atmosphere of nitrogen. Once addition was
complete, the mixture was stirred for 0.3 h at -65 °C, and
then a solution of 8a (1.5 g, 4.90 mmol) in dry dichloromethane
(6.0 mL) was added slowly, dropwise, the temperature being
kept at -65 °C. Once addition was complete, the reaction
mixture was stirred for a further 1.5 h at this temperature.
Triethylamine (3.67 mL, 26.30 mmol) was then added drop-
wise, and the solution was allowed to warm to room temper-
ature. The reaction mixture was diluted with dichloromethane
(30 mL), washed with 1 M hydrochloric acid until the aqueous
layer was just acidic, and then washed with sodium hydrogen
carbonate followed by saturated sodium chloride solution (20
mL). The dichloromethane layer was then dried and evapo-
Exp er im en ta l Section
All reactions were performed under an atmosphere of
nitrogen (unless otherwise stated in the text), and solvent
extractions were dried with MgSO4. Tetrahydrofuran was
freshly distilled from sodium benzophenone ketyl. Carbon
tetrachloride was distilled from phosphorus pentoxide and
stored under nitrogen. Diethyl ether was distilled from
(23) Beesley, R. M.; Ingold, C. K.; Thorpe, J . F. J . Chem. Soc. 1915,
107, 1080. Ingold, C. K. J . Chem. Soc. 1921, 119, 305. Alinger, N. L.;
Zalkow, V. J . Org. Chem. 1960, 25, 701. Kirby, A. Adv. Phys. Org.
Chem. 1980, 17, 183. DeTar, D. F.; Luthra, N. P. J . Am. Chem. Soc.
1980, 102, 4505. J ager, J .; Graafland, T.; Schenk, H.; Kirby, A. J .;
Engberts, J . B. F. N. J . Am. Chem. Soc. 1984, 106, 139. Sternbach, D.
D.; Rosanna, D. M.; Onan, K. D. Tetrahedron Lett. 1985, 26, 591. Eliel
E. L.; Wilen, S. H. Stereochemistry of Carbon Compounds; Wiley: New
York, 1994, 682.

8526 J . Org. Chem., Vol. 63, No. 23, 1998
Wood et al.
rated to dryness. Chromatography on silica gel with petroleum
ether-ethyl acetate (5:1) as the eluent yielded 9a as a white
solid (1.27 g, 85%): Rf 0.8, 2:1 petroleum ether-ethyl acetate;
14.8, 7b-H), 2.90-3.00 (1H, m, 2-H), 3.35 (3H, s, OMe), 3.93
(1H, t, J 10.1, 6ax-H), 4.11 (1H, ddd, J 4.4, 9.8, 10.1, 5-H),
4.31 (1H, overlapping dd, J 1.3, 9.8, 4-H), 4.37 (1H, overlapping
dd, J 4.4, 9.8, 6eq-H), 4.75 (1H, br s, 9a-H), 4.83 (1H, br s,
9b-H), 4.97 (1H, d, J 4.1, 1-H), 5.57 (1H, s, 10-H), 7.32-7.57
(5H, Ph); δC (62.9 MHz, CDCl3) 22.9 (CH3, C11), 31.9 (CH2,
C7), 52.2 (CH, C2), 55.7 (CH3, OMe), 66.5 (CH, C5), 70.0 (CH2,
C6), 83.6 (CH, C4), 102.4 (CH, C1), 103.6 (CH, C10), 112.9
(CH2, C9), 126.8 (CH, Ph), 128.7 (CH, Ph), 129.6 (CH, Ph),
137.1 (C, Ph), 142.3 (C, C8), 198.9 (C, C3); m/z (EI) 318 (M+,
9.8), 256 (6.1), 167 (5.4), 149 (52.8), 145 (20.2), 105 (100) (found,
318.1467; C18H22O5 requires 318.1467). Anal. Found: C,
67.83; H, 6.77. C18H22O5 requires C, 67.91; H, 6.96.
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-(p r op a n -2-on e)-
r-D-r ibo-h exop yr a n osid -3-u lose (11). Palladium(II) chlo-
ride (23.0 mg, 0.13 mmol) and copper(II) chloride (130 mg, 1.31
mmol) were added to a solution of 10a (398 mg, 1.31 mmol) in
DMF and water (42.0 mL, 1:1). The reaction mixture was
stirred at room temperature while oxygen was bubbled through
the solution for 5 h. The reaction mixture was extracted with
dichloromethane (2 × 20 mL) and the combined organic layers
were washed with saturated sodium chloride solution (2 × 25
mL), dried, and evaporated to dryness. Chromatography on
silica gel with petroleum ether-ethyl acetate (5:1) as the
eluent yielded 11 as a white solid (388 mg, 92); mp 180-182
°C; Rf 0.75, petroleum ether-ethyl acetate (2:1); [R]19D +136.8°
(c 2.0, CHCl3); νmax (CHCl3)/cm-1 3000 w, 1745 s, 1710 w, 1410
w, 1145 m, 1050 s; δH (300 MHz, CDCl3) 2.24 (3H, s, 9-H),
2.45 (1H, dd, J 5.8, 18.5, 7a-H), 3.13 (1H, dd, J 7.1, 18.4, 7b-
H), 3.36 (3H, s, OMe), 3.42-3.47 (1H, m, 2-H), 3.96 (1H, t, J
10.1, 6ax-H), 4.10 (1H, dt, J 4.5, 10.0, 5-H), 4.37-4.41 (2H,
4-H, 6eq-H), 5.09 (1H, d, J 4.3, 1-H), 5.60 (1H, s, 10-H), 7.35-
7.54 (5H, Ph); δC (75 MHz, CDCl3) 30.1 (CH3, C9), 37.4 (CH2,
C7), 49.3 (C, C2), 55.1 (CH3, OMe), 65.6 (CH, C5), 69.3 (CH2,
C6), 82.6 (CH, C4), 101.8 (CH, C1), 102.9 (CH, C10), 126.2 (CH,
Ph), 128.1 (CH, Ph), 129.1 (CH, Ph), 136.4 (C, Ph), 197.8 (C,
C3), 206.1 (C, C8); m/z (EI) 319 ([M - H]+, 3.0) 279 (18.1), 263
(12), 171 (12.6), 149 (100) (found [M - H]+, 319.1182; C17H19O6
requires [M - H]+ 319.1182).
Ozon olysis of Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-
(2-m et h yl-2-p r op en yl)-r-D-r ibo-h exop yr a n osid -3-u lose
(10b). Olefin 10b (0.20 g, 0.63 mmol) was dissolved in
dichloromethane (25 mL), and ozone was bubbled through the
solution for 0.5 h. The flask was then flushed with nitrogen
for 0.3 h, and thiourea was added (48.0 mg, 0.63 mmol), and
the solution was stirred for 3 h. Water (30 mL) was added
portionwise, and the mixture was extracted with dichlo-
romethane (2 × 30 mL), washed with saturated sodium
chloride solution (2 × 30 mL), dried, and evaporated to
dryness. Chromatography on silica gel with petroleum ether-
ethyl acetate (5:1) as the eluent yielded 12 as a white solid
(77 mg, 36%): δH (300 MHz, CDCl3) 1.76 (3H, s, 9-H), 1.98-
2.19 (2H, m, 7-H), 2.90-2.99 (1H, m, 2-H), 3.48 (3H, s, OMe),
3.89 (1H, t, J 10.0, 6ax-H), 3.92 (1H, d, J 9.4, 4-H), 4.14 (1H,
ddd, J 4.4, 9.63, 5-H), 4.42 (1H, dd, J 4.4, 10.1, 6eq-H), 5.00
(1H, d, J 8.3, 1-H), 5.64 (1H, s, 10-H), 7.35-7.54 (5H, Ph); δC
(62.9 MHz, CDCl3) 15.1 (CH3, C9), 34.5 (CH2, C7), 47.5 (CH,
C2), 55.6 (CH3, OMe), 65.4 (CH, C5), 70.1 (CH2, C6), 76.2 (CH,
C4), 102.2 (CH, C1), 103.4 (CH, C10), 106.9 (C, C8), 115.3 (C,
C3), 126.3 (CH, Ph), 128.2 (CH, Ph), 129.2 (CH, Ph), 136.4 (C,
Ph); m/z 338 (M+, 7.2), 289 (56.8), 52 (100).
[R]23 +23.9° (c 1.89, CHCl3); δH (250 MHz, CDCl3) 2.31-2.51
D
(2H, m, 7-H), 2.69 (1H, t, J 7.9, 2-H), 3.31 (3H, s, OMe), 3.86
(1H, t, J 10.1, 6ax-H), 4.10 (1H, ddd, J 4.4, 10.1, 5-H), 4.30
(2H, overlapping d and dd, J 9.8, 4-H, J 4.4, 10.1, 6eq-H), 4.77
(1H, s, 1-H), 5.02-5.15 (2H, m, 9-H), 5.51 (1H, s, 10-H), 5.57-
5.73 (1H, m, 8-H), 7.23-7.47 (5H, Ph); δC (62.9 MHz, CDCl3)
34.0 (CH2, C7), 54.0 (CH3, OMe), 55.3 (CH, C2), 65.0 (CH, C5),
68.5 (CH2, C6), 79.9 (CH, C4), 101.3 (CH, C1), 102.1 (CH, C10),
117.4 (CH2, C9), 127.3 (CH, Ph), 128.3 (CH, Ph), 129.2 (CH,
Ph), 133.9 (CH, C8), 135.6 (C, Ph), 199.5 (C, C3); m/z (EI) 304
(M+, 4.7), 273 (8.9), 263 (6.1), 149 (40.2), 105 (PhCO+, 100)
(found M+, 304.1311; C17H20O5 requires 304.1311).
This compound was previously communicated,17 but it was
prepared by a different method.
In the same way, the alcohol 8b (1.5 g, 4.68 mmol) was
oxidized to the ketone, and the crude material was purified
by chromatography on silica gel with petroleum ether-ethyl
acetate (5:1) as the eluent to yield 9b as a white solid (1.05 g,
71%): mp 115-117 °C; Rf 0.8, 2:1 petroleum ether-ethyl
acetate; [R]23D +12.2° (c 1.26, CHCl3); νmax (CH2Cl2)/cm-1 2915
s, 1735 s (CO), 1650 m, 1400 s; δH (300 MHz CDCl3) 1.77 (3H,
s, 11-H), 2.40 (1H, dd, J 7.2, 14.1, 7a-H), 2.52 (1H, dd, J 9.2,
14.0, 7b-H), 2.90-2.96 (1H, m, 2-H), 3.38 (3H, s, OMe), 3.96
(1H, t, J 10.2, 6ax-H), 4.17 (1H, dt, J 4.8, 10.0, 5-H), 4.39 (1H,
dd, J 4.8, 10.1, 6eq-H), 4.45 (1H, obscured d, J 9.9, 4-H), 4.85
(1H, s, 1-H), 4.85-4.89 (2H, m, 9-H), 5.61 (1H, s, 10-H), 7.35-
7.55 (5H, Ph); δC (75 MHz, CDCl3) 21.6 (CH3, C11), 39.0 (CH2,
C7), 54.6 (CH3, OMe), 54.9 (CH, C2), 65.1 (CH, C5), 69.4 (CH2,
C6), 80.6 (CH, C4), 102.2 (CH, C1), 103.4 (CH, C10), 113.9
(CH2, C9), 126.3 (CH, Ph), 128.1 (CH, Ph), 129.2 (CH, Ph),
136.5 (C, Ph), 140.8 (CH, C8), 200.5 (C, C3); m/z (EI) 318 (M+,
46.6), 287 (15.5), 183 (17.4), 149 (57.3), 105 (PhCO+, 100)
(found M+, 318.1467; C18H22O5 requires M+, 318.1467).
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-p r op en yl-r-D-
er yth r o-h exop yr a n osid -3-u lose (10a ) a n d Meth yl 4,6-O-
Ben zyliden e-2-deoxy-2-C-(2-m eth yl-2-pr open yl)-r-D-er yth -
r o-h exop yr a n osid -3-u lose (10b). Ketone 9a (1.31 g, 4.30
mmol) was dissolved in DMF-triethylamine (50.0 mL, 1:1) and
stirred for 48 h. The reaction mixture was diluted with
dichloromethane (75 mL), and the resulting solution was
washed with saturated sodium chloride solution (3 × 25 mL).
The dichloromethane layer was then dried and evaporated to
dryness. Chromatography on silica gel with petroleum ether-
ethyl acetate (5:1) as the eluent yielded 10a as a white solid
(0.73 g, 56%): mp 148-152 °C; Rf 0.6, 2:1 petroleum ether-
ethyl acetate; [R]21D +75.3° (c 0.96, CHCl3); νmax (CH2Cl2)/cm-1
2920 s, 1745 s, 1595 m, 1400 m; δH (250 MHz, CDCl3) 2.12-
2.28 (1H, m, 7a-H), 2.50-2.64 (1H, m, 7b-H), 2.75-2.86 (1H,
m, 2-H), 3.35 (3H, s, OMe), 3.91 (1H, t, J 10.1, 6ax-H), 4.08
(1H, ddd, J 4.4, 9.8, 10.1, 5-H), 4.28 (1H, dd, J 1.3, 9.8, 4-H),
4.37 (1H, dd, J 4.4, 10.1, 6eq-H), 4.99 (1H, d, J 4.1, 1-H), 5.02-
5.17 (2H, m, 9-H), 5.54 (1H, s, 10-H), 5.66-5.85 (1H, m, 8-H),
7.30-7.55 (5H, Ph); δC (62.9 MHz, CDCl3) 27.6 (CH2, C7), 53.5
(CH, C2), 55.3 (CH3, OMe), 66.0 (CH, C5), 69.6 (CH2, C6), 83.1
(CH, C4), 102.0 (CH, C1), 103.2 (CH, C10), 117.3 (CH2, C9),
126.1 (CH, Ph), 128.3 (CH, Ph), 129.3 (CH, Ph), 134.9 (CH,
C8), 136.7 (C, Ph), 198.4 (C, C3); m/z (EI) 304 (M+, 26.2), 263
(11.6), 169 (19.7), 149 (64.7), 98 (100) (found M+, 304.1310;
C
17H20O5 requires 304.1310).
In the same way, the ketone 9b (1.27 g, 4.00 mmol) was
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-m eth yl-2-C-p r o-
pen yl-r-D-er yth r o-h exopyr an osid-3-u lose (13). Sodium hex-
amethyldisilazide (0.4 mL, 0.40 mmol, 1 M solution in THF)
was cooled to 0 °C, and a solution of 10a (136 mg, 0.40 mmol)
was added dropwise in THF (15.0 mL), the temperature being
maintained at 0 °C. The solution was stirred for 1 h at 0 °C,
and then methyl iodide (0.2 mL, 3.20 mmol) was added,
followed by DMPU (0.04 mL, 0.04 mmol). The solution was
allowed to warm to room temperature and stirred overnight.
Water (25 mL) was added portionwise, and the mixture was
extracted with diethyl ether (2 × 10 mL). The combined
organic layers were washed with saturated sodium chloride
solution (2 × 10 mL), dried, and evaporated to dryness.
Chromatography on silica gel with petroleum ether-ethyl
dissolved in DMF-triethylamine (100 mL, 1:1) and was stirred
for 7 days. The resulting solution was reduced in vacuo and
then diluted with dichloromethane (30 mL), and this solution
was washed with saturated sodium chloride solution (2 × 20
mL). The dichloromethane layer was then dried and evapo-
rated to dryness. Chromatography on silica gel with petroleum
ether-ethyl acetate (5:1) as the eluent yielded 10b as a white
solid (1.1 g, 84%); mp 135-137 °C (from petroleum ether); Rf
0.8, 2:1 petroleum ether-ethyl acetate; [R]17D +103.1° (c 0.99,
CHCl3); νmax (CH2Cl2)/cm-1 2940 s, 1780 s, 1650 m, 1450 m,
1410 m, 1280 m, 1210 m; δH (250 MHz, CDCl3) 1.74 (3H, s,
C8-Me), 2.26 (1H, dd, J 9.4, 14.8, 7a-H), 2.50 (1H, dd, J 5.0,

Cyclopentaannulation of Glucose Derivatives
J . Org. Chem., Vol. 63, No. 23, 1998 8527
acetate (5:1) as the eluent yielded 13 as a clear oil (but also
containing an unidentified compound) (59 mg, 42%): δH (250
MHz, CDCl3) 1.38 (3H, s, C2-Me), 2.33 (1H, dd, J 7.9, 13.5,
7a-H), 2.46 (1H, dd, J , 7.5, 13.8, 7b-H), 3.35 (3H, s, OMe), 3.94
(1H, t, J 10.1, 6ax-H), 4.12 (1H, ddd, J 4.4, 9.8, 10.1, 5-H),
4.36 (1H, dd, J 4.4, 10.1, 6eq-H), 4.55 (1H, s, 1-H), 4.59 (1H,
d, J 9.8, 4-H), 5.07-5.21 (2H, m, 9-H), 5.57 (1H, s, 10-H), 5.60-
5.82 (1H, m, 8-H), 7.30-7.56 (5H, Ph); δC (62.9 MHz, CDCl3)
21.5 (CH3, C2-Me), 36.4 (CH2, C7), 53.5 (C, C2), 55.2 (CH3,
OMe), 65.8 (CH, C5), 69.6 (CH2, C6), 80.0 (CH, C4), 102.2 (CH,
C1), 107.0 (CH, C10), 119.3 (CH2, C9), 126.5 (CH, Ph), 128.3
(CH, Ph), 129.3 (CH, Ph), 133.0 (CH, C8), 136.7 (C, Ph), 202.6
(C, C3); m/z (EI) 318 (M+, 2.8) 277 (6.1), 191 (8.9), 149 (26.6),
121 (16.4), 113 (10.6), 112 (100) (found M+ 318.1467; C18H22O5
requires 318.1467).
complete, the mixture was stirred for 0.3 h at -65 °C, and
then a solution of 16 (18.95 g, 61.90 mmol) in dry dichlo-
romethane (20 mL) was added slowly, dropwise, the internal
temperature being kept at -65 °C. Once addition was
complete, the reaction mixture was stirred for a further 1.5 h
at this temperature. Triethylamine (48.64 mL, 0.35 mol) was
then added dropwise, and the solution was allowed to warm
to room temperature. The reaction mixture was diluted with
dichloromethane (200 mL), and the resulting solution was
washed with 1 M hydrochloric acid until the aqueous layer
remained acidic and then washed with enough sodium hydro-
gen carbonate to neutralize the acid, followed by saturated
sodium chloride solution (200 mL). The dichloromethane layer
was then dried, and evaporated to dryness. Chromatography
on silica gel with petroleum ether-diethyl ether (3:1) as the
eluent yielded 17 as a white solid (16.18 g, 86%), mp 99-101
°C (from petroleum ether) (lit.17 mp 100-102 °C); Rf 0.72, 1:1
petroleum ether-diethyl ether; νmax (CH2Cl2)/cm-1 2920 s, 1740
s (CO), 1640 m; δH (250 MHz, CDCl3) 2.33-2.56 (2H, m, 7-H),
2.97-3.10 (1H, m, 3-H), 3.46 (3H, s, OMe), 3.53 (1H, dd, J
10.3, 9.4, 4-H), 3.67 (1H, t, J 10.3, 6ax-H), 4.14 (1H, ddd, J
4.9, 9.7, 10.3, 5-H), 4.31 (1H, dd, J 4.9, 10.3, 6eq-H), 4.53 (1H,
s, 1-H), 4.94-5.10 (2H, m, 9-H), 5.41 (1H, s, 10-H), 5.70-5.88
(1H, m, 8-H), 7.27-7.47 (5H, Ph); δC (62.9 MHz, CDCl3) 28.0
(CH2, C7), 51.1 (CH, C3), 56.1 (CH3, OMe), 64.6 (CH, C5), 69.5
(CH2, C6), 80.4 (CH, C4), 101.3 (CH, C1), 101.6 (CH, C10),
117.8 (CH2, C9), 126.5 (CH, Ph), 128.7 (CH, Ph), 129.6 (CH,
Ph), 135.2 (CH, C8), 137.5 (C, Ph), 200.1 (C, CO); m/z (EI) 304
(M+, 2.4), 276 (M+ - C2H4) (5.2), 105 (PhCO+, 100); (found M+,
304.1311; C17H20O5 requires M+, 304.1311). Anal. Found: C,
66.83; H, 6.58. C17H20O5 requires C, 67.14; H, 6.62%.
Meth yl 4,6-O-Ben zylid en e-2-d eoxy-2-C-m eth yl-2-C-p r o-
p a n on e-r-D-er yth r o-h exop yr a n osid -3-u lose (14). Palla-
dium(II) chloride (10.0 mg, 0.05 mmol) and copper(II) chloride
(73 mg, 0.54 mmol) were added to a solution of 13 (173 mg,
0.54 mmol) in DMF and water (20.0 mL, 1:1). The reaction
mixture was stirred at room temperature, and oxygen was
bubbled through it for 5 h. The reaction mixture was extracted
with dichloromethane (2 × 20 mL), and the combined organic
layers were washed with saturated sodium chloride solution
(2 × 25 mL), dried, and evaporated to dryness. Chromatog-
raphy on silica gel with petroleum ether-diethyl ether (10:1)
as the eluent yielded 14 as a white solid (90 mg, 45%): Rf 0.5,
petroleum ether-diethyl ether (1:2); [R]20 + 50.9 (c 0.95,
D
CHCl3); νmax (CHCl3)/cm-1 3045 m, 1765 s, 1755 s; δH (250
MHz, CDCl3) 1.53 (3H, s, C2-Me), 2.14 (3H, s, 9-H), 2.74 (1H,
d, J 18.3, 7a-H), 2.99 (1H, d, J 18.2, 7b-H), 3.29 (3H, s, OMe),
3.93 (1H, t, J 10.1, 6ax-H), 4.08 (1H, dt, J 4.4, 10.1, 5-H), 4.36
(1H, dd, J 4.4, 10.1, 6eq-H), 4.56 (1H, d, J 10.1, 4-H), 5.19 (1H,
s, 1-H), 5.58 (1H, s, 10-H), 7.31-7.55 (5H, Ph); δC (62.9 MHz,
CDCl3) 22.4 (CH3, C2), 31.7 (CH3, C9), 44.8 (CH2, C7), 53.6
(C, C2), 55.8 (CH3, OMe), 65.6 (CH, C5), 69.9 (CH2, C6), 79.9
(CH, C4), 102.6 (CH, C1), 106.3 (CH, C10), 126.8 (CH, Ph),
128.7 (CH, Ph), 129.7 (CH, Ph), 137.0 (C, Ph), 202.7 (C, C3),
207.4 (C, C8); m/z (EI) 334 (M+, 0.9), 276 (10.6), 149 (45.9),
129 (10.5), 128 (66.5), 121 (15.2), 105 (36.2), 97 (15.4), 91 (34.1),
85 (100) (found M+, 334.1416; C18H22O6 requires 334.1416).
Meth yl 4,6-O-Ben zylid en e-3-d eoxy-3-C-p r op en yl-r-D-
glu cop yr a n osid e (16). Allylmagnesium chloride (100 mL,
2 M solution in THF, 0.20 mol) was added dropwise to an ice-
cooled, stirred suspension of the epoxide 15 (17.62 g, 66.60
mmol) in dry THF (100 mL). The reaction mixture was heated
under reflux for 2 h and then the reaction was quenched by
the dropwise addition of water (50 mL). The reaction mixture
was extracted with diethyl ether (2 × 200 mL), and the
combined organic layers were washed with saturated sodium
chloride solution (2 × 75 mL), dried, and evaporated to
dryness. Chromatography on silica gel with petroleum ether-
diethyl ether (3:1 to 1:1) as the eluent yielded 16 as a clear
sticky oil (18.95 g, 86%): Rf 0.22, 1:1 petroleum ether-diethyl
ether; (found: C, 65.5; H, 7.2. C17H22O5 requires C, 66.7; H,
7.4); δH (250 MHz, CDCl3) 2.14-2.35 (1H, m, 2-H), 2.45-2.65
(3H, 3-H and 7-H), 3.37 (3H, s, OMe), 3.78 (1H, t, J 10.0, 6ax-
H), 3.9 (1H, br s, OH), 3.92-4.05 (1H, m, 5-H), 4.11 (1H, dd,
J 9.7, 5.3, 4-H), 4.28 (1H, dd, J 10.1, 4.8, 6eq-H), 4.55 (1H, s,
1-H), 5.03-5.20 (2H, m, 9-H), 5.59 (1H, s, 10-H), 5.74-5.94
(1H, m, 8-H), 7.32-7.57 (5H, Ph); δC (62.9 MHz, CDCl3) 29.2
(CH2, C7), 42.7 (CH, C3), 55.7 (CH3, OMe), 55.9 (CH, C5), 69.6
(CH, C2), 70.0 (CH2, C6), 76.4 (CH, C4), 102.5 (CH, C1), 102.8
(CH, C10), 117.2 (CH2, C9), 126.7 (CH, Ph), 128.8 (CH, Ph),
129.6 (CH, Ph), 137.6 (CH, C8), 138.1 (C, Ph); m/z (EI) 306
(M+, 1.9) 305 [M - H]+ (3.6), 274 (2.9), 256 (3.3), 105 (PhCO+,
100) (found M+, 306.14665; C17H22O5 requires 306.1467).
This compound was previously communicated without full
experimental and spectroscopic data.15
This compound was previously communicated,17 but it was
prepared by a different method.
Meth yl 4,6-O-Ben zylid en e-3-d eoxy-3-C-m eth yl-3-C-p r o-
p en yl-r-D-er yth r o-h exop yr a n osid e (18). Lithium hexa-
methyldisilazide (18.08 mL, 18.08 mmol, 1 M solution in THF)
was cooled to 0 °C, and a solution of 17 (5.0 g, 16.44 mmol)
was added dropwise in THF (15 mL), the temperature being
maintained at 0 °C. The solution was stirred for 1 h at 0 °C,
and then methyl iodide (7.8 mL, 98.64 mmol) was added,
followed by DMPU (1.0 mL, 8.22 mmol). The solution was
allowed to warm to room temperature and stirred overnight.
Water (200 mL) was added portionwise, the mixture was
extracted with diethyl ether (2 × 200 mL), and the combined
organic layers were washed with saturated sodium chloride
solution (2 × 25 mL), dried, and evaporated to dryness.
Chromatography on silica gel with petroleum ether-diethyl
ether (10:1) as the eluent yielded 18 as a clear oil (4.19 g,
80%): Rf 0.75, 1:1 petroleum ether-diethyl ether (1:1); [R]20
D
-3.3° (c 2.07, CHCl3); δH (250 MHz, CDCl3) 1.26 (3H, s, C3-
Me), 2.21 (1H, dd, J 13.8, 9.15, 7a-H), 2.59 (1H, dd, J 13.8,
5.5, 7b-H), 3.37 (3H, s, OMe), 3.64 (1H, t, J 10.1, 6ax-H), 3.73
(1H, d, J 10.0, 4-H), 4.23 (1H, dt, J 10.0, 5.16, 5-H), 4.33 (1H,
dd, J 10.1, 5.2, 6eq-H), 4.48 (1H, s, 1-H), 4.94-5.08 (2H, m,
9-H), 5.4 (1H, s, 10-H), 5.56-5.75 (1H, m, 8-H), 7.25-7.46 (5H,
Ph); δC (62.9 MHz, CDCl3) 19.3 (CH3, C3-CH3), 38.5 (CH2, C7),
51.8 (C, C3), 55.6 (CH3, OMe), 60.0 (CH, C5), 69.8 (CH2, C6),
77.5 (CH, C4), 101.5 (CH, C1), 101.7 (CH, C10), 119.21 (CH2,
C9), 126.5 (CH, Ph), 128.7 (CH, Ph), 129.5 (CH, Ph), 134.5 (CH,
C8), 137.9 (C, Ph), 203.7 (C, C2); m/z (EI) 318 (M+, 0.9), 290
(M+ - CH2CH2) (1.3), 174 (100) (found M+, 318.1467; C18H22O5
requires 318.1467). Anal. Found: C, 67.83; H, 7.21. C18H22O5
requires C, 67.96; H 6.97).
Meth yl 4,6-O-Ben zylid en e-3-d eoxy-3-C-m eth yl-3-C-p r o-
p a n on e-r-D-er yth r o-h exop yr a n osid -2-u lose (19). Palla-
dium(II) chloride (233 mg, 1.32 mmol) and copper(II) chloride
(2.24 g, 13.16 mmol) were added to a stirred solution of 18
(4.17 g, 13.16 mmol) in DMF and water (80 mL, 1:1). The
reaction was stirred at room temperature while oxygen was
bubbled through the solution for 5 h. The product was
extracted into dichloromethane (2 × 75 mL), and the combined
organic layers were washed with saturated sodium chloride
solution (2 × 25 mL), dried, and evaporated to dryness.
Chromatography on silica gel with petroleum ether-diethyl
ether (10:1) as the eluent yielded 19 as a white solid (2.48 g,
Meth yl 4,6-O-Ben zylid en e-3-d eoxy-3-C-p r op en yl-r-D-
a r a bin o-h exop yr a n osid e-2-u lose (17). Trifluoroacetic an-
hydride (12.67 mL, 89.73 mmol) in dry dichloromethane (40
mL) was added dropwise to a cooled solution (-65 °C) of
dimethyl sulfoxide (8.36 mL, 0.12 mol) in dry dichloromethane
(130 mL) under an atmosphere of nitrogen. Once addition was

8528 J . Org. Chem., Vol. 63, No. 23, 1998
Wood et al.
56%): mp 112-114 °C; Rf 0.75, petroleum ether-diethyl ether
(1:1); [R]20D -78° (c 1.0, CHCl3); νmax (CHCl3)/cm-1 3940 w, 1760
m, 1730 m; δH (250 MHz, CDCl3) 1.19 (3H, s, C3-Me), 2.01
(3H, s, 9-H), 2.77 (1H, d, J 18.6, 7a-H), 2.98 (1H, d, J 18.6,
7b-H), 3.36 (3H, s, OMe), 3.70 (1H, t, J 10.0, 6ax-H), 4.06 (1H,
d, J 10.1, 4-H), 4.18 (1H, dt, J 10.1, 4.97, 5-H), 4.31 (1H, dd,
J 10.1, 4.97, 6eq-H), 4.63 (1H, s, 1-H), 5.40 (1H, s, 10-H), 7.23-
7.43 (5H, Ph); δC (62.9 MHz, CDCl3) 19.2 (CH3, C3-CH3), 30.4
(CH3, C9), 48.1 (CH2, C7), 49.0 (C, C3), 56.6 (CH3, OMe), 60.1
(CH, C5), 69.7 (CH2, C6), 79.5 (CH, C4), 100.7 (CH, C1), 101.7
(CH, C10), 126.7 (CH, Ph), 128.7 (CH, Ph), 129.6 (CH, Ph),
137.9 (C, Ph), 204.4 (C, C2), 206.8 (C, C8); m/z (EI) 334 (M+,
4.8) 228 (M+ - PhCHO) (5.8), 188 (88.7), 159 (100) (found M+,
334.1416; C18H22O6 requires 334.1416). Anal. Found: C, 64.83;
H, 6.59. C18H22O6 requires C, 64.70; H, 6.63).
Meth yl 4,6-O-Ben zylid en e-3-d eoxy-3-C-p r op en on e-r-D-
a r a bin o-h exop yr a n osid -2-u lose (29). Palladium(II) chlo-
ride (40 mg, 0.21 mmol) and copper(II) chloride (106 mg, 2.1
mmol) were added to a stirred solution of 17 (657 mg, 2.10
mmol) in DMF and water (25 mL, 1:1). The reaction mixture
was stirred at room temperature while oxygen was bubbled
through the solution for 0.5 h. The product was extracted into
dichloromethane (2 × 25 mL), and the combined organic layers
were washed with saturated sodium chloride solution (2 × 15
mL), dried, and evaporated to dryness. Chromatography on
silica gel with petroleum ether-diethyl ether (2:1) as the
eluent yielded 29 as a clear oil (429 mg, 62%): Rf 0.50,
petroleum ether-diethyl ether (2:1); νmax (CHCl3)/cm-1 3940
w, 1760 m, 1730 m; δH (250 MHz, CDCl3) 2.20 (3H, s, 9-H),
2.75 (1H, dd, J 3.9, 17.7, 7a-H), 2.87 (1H, dd, J 6.9, 17.6, 7b-
H), 3.44-3.55 (1H, m, 3-H), 3.50 (3H, overlapping s, OMe),
3.67 (1H, dd, J 9.4, 11.6, 4-H), 3.78 (1H, t, J 10.0, 6ax-H), 4.23
(1H, ddd, J 5.0, 9.4, 10.0, 5-H), 4.39 (1H, dd, J 5.0, 10.0, 6eq-
H), 4.65 (1H, s, 1-H), 5.49 (1H, s, 10-H), 7.33-7.50 (5H, Ph);
δC (62.9 MHz, CDCl3) 30.2 (CH3, C9), 37.3 (CH2, C7), 47.6 (CH,
C3), 55.7 (CH3, OMe), 64.4 (CH, C5), 69.0 (CH2, C6), 79.9 (CH,
C4), 100.6 (CH, C1), 101.5 (CH, C10), 126.2 (CH, Ph), 128.4
(CH, Ph), 129.3 (CH, Ph), 136.9 (C, Ph), 199.2 (C, C2), 205.8
(C, C8); m/z (EI) 320 (M+, 2.1), 292 (15.5), 174 (30.8), 145 (100)
(found M+, 320.1260; C17H20O6 requires 320.1260).
combined organic layers were washed with water (2 × 75 mL),
dried, and evaporated to dryness. Chromatography on silica
gel with petroleum ether-diethyl ether (3:1) as the eluent
yielded 21 as a white solid (654 mg, 72%): mp 131-132 °C
(petroleum ether 40-60 °C); Rf 0.50, petroleum ether-ethyl
acetate (1:1); [R]22D + 128.2° (c 2.0, CHCl3); νmax (CH2Cl2)/cm-1
2960 m, 1730 s, 1710 s, 1640 w, 1600 w, 1450 m, 1260 s, 1180
m, 1110 s; δH (250 MHz, CDCl3) 1.47 (3H, s, C3-Me), 2.18 (1H,
d, J 18.7, 9a-H), 2.66 (1H, d, J 18.6, 9b-H), 3.37 (1H, dd, J
11.0, 7.6, 6a-H), 3.46 (1H, obscured dd, J 11.0, 2.5, 6b-H), 3.77
(3H, s, OMe), 4.36 (1H, dt, J 9.8, 7.4, 2.5, 5-H), 5.06 (1H, d, J
9.8, 4-H), 5.40 (1H, s, 1-H), 6.00 (1H, s, 7-H), 7.41-7.69 (3H,
Ph), 8.00-8.11 (2H, Ph); δC (62.9 MHz, CDCl3) 20.1 (CH3, C3-
CH3), 31.0 (CH2, C6), 45.7 (C, C3), 49.6 (CH2, C9), 54.6 (CH3,
OMe), 66.8 (CH, C5), 76.1 (CH, C4), 96.1 (CH, C1), 127.7 (2CH,
m-Ph), 127.0 (CH, C7), 128.5 (CH, p-Ph), 128.8 (CH, o-Ph),
132.9 (C, Ph), 164.2 (CO, OBz), 205.0 (C, C8); m/z (EI) 394/
396 (M+, 3), 365, 353, 315 (M+ - Br), 105 (PhCO+, 100) (found
M+, 394.0518; C18H19O5Br requires 394.0518).
(3R,1′R,2′R)-2′-F or m yl-1′-m eth yl-3-cyclop en ta n -4′-on e-
2-p r op en yl-3-ben zoa te (22) a n d (3R,1′R,2′S)-2′-F or m yl-1′-
m eth yl-3-cyclop en ta n -4′-on e-2-p r op en yl-3-ben zoa te (23).
Zinc shot (100 g) was activated by washing with 2 M hydro-
chloric acid (6 × 50 mL), water (5 × 60 mL), 10% w/v aqueous
potassium carbonate solution (50 mL), water (4 × 70 mL),
2-propanol (2 × 60 mL), and ether (3 × 60 mL). The bromo
compound 21 (356 mg, 0.90 mmol) was heated to reflux with
the activated zinc (7.66 g, 0.117 mol) in 2-propanol-water (20:2
mL) for 22 h. The zinc was removed by filtration and washed
with diethyl ether (3 × 40 mL), and the combined organic
layers were washed with saturated sodium chloride solution
(2 × 40 mL), dried, and evaporated to dryness. Separation
by the chromatotron technique24 on
a 2 mm plate with
petroleum ether-diethyl ether (2:1) as the eluent yielded
starting material 21 (64 mg, 18%), 22 as a colorless oil (100
mg, 39%), and a 1:1 mixture of 22 and 23 (58 mg, 23%). 22: Rf
0.47, diethyl ether-petroleum ether (2:1); [R]18D -80.0° (c 1.2,
CHCl3); νmax (CH2Cl2)/cm-1 3050 w, 2920 m, 2840 w, 1745 s,
1725 s, 1715 s, 1600 w, 1450 m, 1245 s, 1105 m, 1095 s; δH
(250 MHz, CDCl3) 1.17 (3H, s, C1′-Me), 2.20 (1H, d, J 17.6,
5′R-H), 2.37 (1H, dd, J 8.8, 19.5, 3′â-H), 2.70 (1H, d, J 17.6,
5′â-H), 2.84 (1H, ddd, J 1.5, 10.3, 19.5, 3′R-H), 3.32 (1H, ddd,
J 1.4, 8.8, 10.3, 2′-H), 5.44 (1H, d, J 10.4, 1cis-H), 5.51 (1H, d,
J 17.0, 1trans-H), 5.76 (1H, d, J 7.2, 3-H), 5.93 (1H, ddd, J 7.2,
10.4, 17.0, 2-H), 7.42-7.67 (3H, Ph), 8.00-8.09 (2H, Ph), 9.98
(1H, d, J 1.4, CHO); δC (62.9 MHz, CDCl3) 19.9 (CH3, C1′-CH3),
36.6 (CH2, C5′), 46.8 (C, C1′), 49.2 (CH2, C3′), 52.3 (CH, C2′),
79.3 (CH, C3), 121.6 (CH2, C1), 129.1 (CH, C2), 129.9 (C, Ph),
Meth yl 4,6-O-Ben zylid en e-2,3-d id eoxy-3-C-m eth yl-3,2-
C-(2′-oxa p r op a n -1′-yl-3′-ylid en e)-r-D-a r a bin o-h exop yr a -
n osid e (20). Potassium tert-butoxide (91 mg, 0.86 mmol) was
added to a solution of 19 (239 mg, 0.79 mmol) in dry toluene
(5.0 mL). The solution was stirred at room temperature under
an atmosphere of nitrogen for 0.5 h. Water (100 mL) was
added portionwise. The mixture was extracted with dichlo-
romethane (2 × 200 mL), and the combined organic layers
were washed with saturated sodium chloride solution (2 × 25
mL), dried, and evaporated to dryness. Chromatography on
silica gel with petroleum ether-diethyl ether (2:1) as the
eluent yielded 20 as a white solid (204 mg, 90%): mp 134-
136 °C (petroleum ether); Rf 0.75, petroleum ether-diethyl
130.0 (CH, Ph), 132.4 (CH, Ph), 134.0 (CH, Ph), 165.7 (CO,
+
OBz), 201.1 (CH, CHO), 213.6 (C, C4′); m/z (CI) 304 (MNH4
,
100) (found MNH4+, 304.1549; C17H22NO4 requires 304.1549).
Anal. Found: C, 70.76; H, 6.62. C17H18O4 requires C, 71.31;
H, 6.34). 23: δC (62.9 MHz, CDCl3) 25.8 (CH3, C1′-CH3), 38.1
(CH2, C5′), 47.5 (C, C1′), 48.6 (CH2, C3′), 57.9 (CH, C2′), 78.8
(CH, C3), 121.1 (CH2, C1), 129.9 (CH, C2), 130.2 (C, Ph), 130.4
(CH, Ph), 132.7 (CH, Ph), 133.9 (CH, Ph), 165.0 (CO, OBz),
200.6 (CH, CHO), 214.4 (C, C4′).
ether (1:2); [R]23 +25.5° (c 1.73, CHCl3); νmax (CHCl3)/cm-1
D
3000 w, 1720 s, 1090 s; δH (250 MHz, CDCl3) 1.42 (3H, s, C3-
Me), 2.28 (1H, d, J 18.8, 9a-H), 2.47 (1H, d, J 18.8, 9b-H), 3.41
(1H, d, J 9.4, 4-H), 3.42 (3H, s, OMe), 3.65 (1H, t, J 10.2, 6ax-
H), 4.12 (1H, ddd, J 10.0, 9.37, 5.08, 5-H), 4.27 (1H, dd, J 10.1,
5.06, 6eq-H), 5.29 (1H, s, 1-H), 5.48 (1H, s, 10-H), 5.96 (1H, s,
7-H), 7.27-7.46 (5H, Ph); δC (62.9 MHz, CDCl3) 20.5 (CH3, C3-
CH3), 46.2 (C, C3), 50.5 (CH2, C9), 55.9 (CH3, OMe), 61.2 (CH,
C5), 69.6 (CH2, C6), 86.3 (CH, C4), 98.1 (CH, C1), 102.3 (CH,
C10), 126.6 (CH, Ph), 128.7 (CH, Ph), 129.7 (CH, Ph), 130.2
(CH, C7), 137.7 (C, Ph), 174.0 (C, C2), 207.4 (C, C8); m/z (EI)
316 (M+, 6.5), 273 (9.2), 167 (73.8), 138 (100), (found M+,
(3R,1′R,2′R)-2′-Hydr oxym eth yl-1′-m eth yl-3-cyclopen tan -
4′-on e-2-p r op en yl-3-ben zoa te (27a ) a n d (3R,1′R,2′S)-2′-
Hyd r oxym eth yl-1′-m eth yl-3-cyclop en ta n -4′-on e-2-p r op e-
n yl-3-ben zoa te (28a ). Zinc was activated by washing with
2 M hydrochloric acid (2 × 50 mL), water (50 mL), 2-propanol
(75 mL), and ether (2 × 100 mL). This was left to stand open
to the air for up to 1 month. The bromo compound 21 (200
mg, 0.51 mmol) was heated to reflux with the activated zinc
in 2-propanol (28.0 mL) for 3 h. The zinc was removed by
filtration and washed with diethyl ether (3 × 25 mL), and the
combined organic layers were washed with saturated sodium
chloride solution (2 × 25 mL), dried, and evaporated to
dryness. Chromatography on silica gel with petroleum ether-
diethyl ether (4:6) as the eluent yielded 27a and 28a as a
mixture of diastereoisomers (105 mg, 72%): Rf 0.26, diethyl
316.1310.
C18H20O5 requires 316.1311). Anal. Found: C,
68.14; H, 6.24. C18H20O5 requires C, 68.39; H, 6.37.
4-Ben zoyloxy-5-br om om eth yl-2,3-C-(2-p r op en -2′-on e)-
3-d eoxy-3-C-m eth yl-r-D-a r a bin o-h exop yr a n osid -2-u lose
(21). Barium carbonate (2.6 g, 13.2 mmol) followed by
N-bromosuccinimide (507 mg, 2.85 mmol) was added to a
solution of 20 (708 mg, 2.31 mmol) in dry carbon tetrachloride
(73.0 mL). This solution was stirred under an atmosphere of
nitrogen at reflux for 3 h. The barium carbonate was removed
by filtration and washed with diethyl ether (75 mL), and the
(24) Instruction Manual, Model 7924T, Chromatotron. Harrison
Research, 840 Moana Court, Palo Alto, CA.

Cyclopentaannulation of Glucose Derivatives
J . Org. Chem., Vol. 63, No. 23, 1998 8529
ether-petroleum ether (7:3); νmax (Et2O)/cm-1 3440 s, 2920 w,
2890 w, 1745 s, 1720 s, 1605 w, 1270 s, 1100 w, 1110 s; δH
(250 MHz, CDCl3) 1.10 (3H, s, C1′-Me minor), 1.21 (3H, s, C1′-
Me major), 1.72 (1H, br s, OH minor), 1.86 (1H, br s, OH
major), 1.97-2.73 (10H, minor and major), 3.64-3.87 (4H,
CH2OH major and minor), 5.6 (2H, d, J 6.3, 3-H major, minor
obscured), 5.74-5.91 (2H, 2-H major and minor), 7.32-7.57
(6H, Ph major and minor), 7.81-8.00 (4H, Ph major and
minor). Major compound only: δC (62.9 MHz, CDCl3) 24.0
(CH3, C1′ Me), 40.8 (CH2, C3′), 43.3 (C, C1′), 47.1 (CH, C2′),
47.8 (CH2, C5′), 61.3 (CH2, CH2OH), 77.2 (CH, C3), 118.2 (CH2,
C1), 127.6 (2CH, Ph), 128.6 (CH, C2), 128.6 (CH, Ph), 131.6
(CH, Ph), 132.4 (C, Ph), 164.2 (CO, OBz), 217.0 (C, C4′); m/z
(EI) 288 (M+, 12), 257 (M+ - CH2OH) (4), 183 (M+ - PhCO+)
(18), 166 (M+ - PhCO2H) (65), 105 (PhCO+, 100) (found M+,
288.1365; C17H20O4 requires 288.1365).
H), 2.54 (1H, dd, J 9.44, 18.9, 3′b-H), 2.60-2.75 (1H, m, 2-H),
2.78 (1H, d, J 18.3, 5′b-H), 4.42 (1H, dd, J 11.3, 7.2, CHHO),
4.52 (1H, dd, J 11.3, 6.3, CHHO), 5.28 (1H, d, J 4.4, 1a-H),
5.33 (1H, d, J 11.3, 1b-H), 5.62 (1H, d, J 6.3, 3-H), 5.85 (1H,
ddd overlapping, J 4.4, 6.0, 10.7, 2-H), 7.33-7.57 (3H, Ph),
7.82-7.90 (2H, Ph), 8.06 (2H, dd, J 6.9, 1.9, Ph), 8.18 (2H, dd,
J 6.9, 1.9, Ph); δC (62.9 MHz, CDCl3) 25.5 (CH3, C1′-Me), 42.1
(CH2, C3′), 44.9 (C, C1′), 45.9 (CH, C2′), 48.9 (CH2, C5′), 65.6
(CH2, CH2O), 78.4 (CH, C3), 120.4 (CH2, C1), 124.0 (CH, Ph),
129.1 (CH, Ph), 129.8 (C, Ph), 130.1 (CH, Ph), 131.1 (CH, Ph),
132.6 (CH, Ph), 134.0 (CH, Ph), 135.5 (C, Ph), 151.0 (C, p-NO2-
Ph), 164.8 (C, OBz), 165.3 (C, OBz), 214.4 (C, C4′). 28b: Rf
0.35 petroleum ether-ethyl acetate (4:1); [R]22D-31.3° (c 0.8,
CHCl3); δH (250 MHz, CDCl3) 1.48 (3H, s, C1′-Me), 2.07-2.25
(2H, 5′a-H and 3′a-H), 2.54 (1H, dd, J 8.8, 18.9, 3′b-H), 2.74
(1H, d, J 18.3, 5′b-H), 2.80-2.93 (1H, m, 2′-H), 4.38 (1H, dd,
J 11.3, 6.92, CHHO), 4.52 (1H, dd, J 11.3, 6.6, CHHO), 5.33
(2H, m, 1-H), 5.59 (1H, d, J 7.2, 3-H), 5.71-5.90 (1H, m, 2-H),
7.34-7.59 (3H, Ph), 7.93-8.28 (6H, Ph).
(3R ,1′R ,2′R )-1′-Me t h yl-2′-p -n it r ob e n zoyloxym e t h yl-
cyclop en t a n -4′-on e-2-p r op en yl-3-b en zoa t e (27b ) a n d
(3R,1′R,2′S)-3-1′-Meth yl-2′-p-n itr oben zoa te-m eth yl-cyclo-
p en ta n -4′-on e-2-p r op en yl-3-ben zoa te (28b). The mixture
of alcohols 27a and 28a (57 mg, 0.20 mmol) in dry toluene
(2.0 mL) was stirred magnetically at 0 °C with triethylamine
(0.07 cm, 0.49 mmol). p-Nitrobenzyl chloride was added, and
the solution was stirred until no starting material remained
by TLC. Water (25 mL) was added portionwise, and the
mixture was extracted with diethyl ether (2 × 10 mL), washed
with saturated sodium chloride solution (2 × 5 mL), dried, and
evaporated to dryness. Chromatography on silica gel with
petroleum ether-diethyl ether (2:1) as the eluent yielded 27b
and 28b (5:1) (72 mg, 96%). 27b: Rf 0.75, petroleum ether-
Ack n ow led gm en t. We are grateful to the EPSRC
(D.J .H.), Pharmachemie B.V. of Holland (A.J .W.), and
the Erasmus Scheme of the European Union (M.-C.D.)
for financial support.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
for 8a ,b 9a ,b, 10a ,, 11-14, 16, 17, 21-23 and 27a ,b, 28a ,b,
and 29 (21 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.
ethyl acetate (4:1); [R]22 +20.4° (c 3.3, CHCl3); νmax (CH2Cl2)/
D
cm-1 2960 m, 1730 s, 1710 s, 1640 w, 1600 w, 1450 m, 1260 s,
1180 m, 1110 s; δH (250 MHz, CDCl3) 1.30 (3H, s, C1′-Me),
2.15 (1H, d, J 18.3, 5′a-H), 2.22 (1H, ddd, J 1.6, 9.8, 18.9, 3′a-
J O981225J