A carbohydrate approach to the enantioselective synthesis of 1,3-polyols

Article abstract of DOI:10.1021/jo960042z

Treatment of per-O-benzoyl-D-glycero-D-gulo-heptono-1,4-lactone (2) with tertiary amines afforded selectively and with good yields the (5H)-furan-2-one derivatives 3, 4, and 5, formed by controlled elimination of one, two, or three molecules of benzoic acid, respectively. The stereochemistry for the exocyclic double bonds of 4 and 5 was determined by means of NMR techniques. Particularly, the furanone 4 was obtained from 2 (～90% yield) as a mixture of the E and Z diastereoisomers, which were separated by column chromatography or, more efficiently, by HPLC. The catalytic hydrogenation of compounds 4-E and 4-Z took place diastereoselectively, due to the chiral induction of the stereocenter located in the lateral chain. Thus, hydrogenation of 4-E led to a mixture of the 4,5-dihydro-(3H)-furan-2-ones having 3R,5S,2′S (D-xylo, 6) and 3S,5R,2′S (D-arabino, 7) configurations, with 6 as the major product; whereas the 4-Z isomer gave the same mixture, but being 7 preponderant. On hydrogenation of the original 4-E / Z mixture, compound 6 was obtained pure after recrystallization. O-Debenzoylation of 6 gave 9, which was reduced with NaBH₄ to the 3,5-dideoxy-meso-xylo-heptitol (11). The peracetate (12) and perbenzoate (13) of the latter were prepared, and the 1-(tert-butyldiphenylsilyl)oxy derivative (16) was also synthesized via the 3′-(silyloxy)-4,5-dihydro-(3H)-furan-2-one 14. Chemoselective reduction of the lactone function of 6 with diisoamylborane gave the 2,5,6-tri-O-benzoyl-3,6-dideoxy-D-xylo-heptofuranose (17). The 3,5-dideoxy-D-arabino-heptitol (18), a diastereoisomer of 11, was also isolated and characterized.

Full text of DOI:10.1021/jo960042z

J . Org. Chem. 1996, 61, 4007-4013
4007
A Ca r boh yd r a te Ap p r oa ch to th e En a n tioselective Syn th esis of
1,3-P olyols
Christia´n Di Nardo, Lucio O. J eroncic, Rosa M. de Lederkremer, and Oscar Varela*
Departamento de Quı´mica Orga´nica, Facultad de Ciencias Exactas y Naturales,
Universidad de Buenos Aires, Ciudad Universitaria, Pabello´n II, 1428, Buenos Aires, Argentina
Received J anuary 4, 1996X
Treatment of per-O-benzoyl-D-glycero-D-gulo-heptono-1,4-lactone (2) with tertiary amines afforded
selectively and with good yields the (5H)-furan-2-one derivatives 3, 4, and 5, formed by controlled
elimination of one, two, or three molecules of benzoic acid, respectively. The stereochemistry for
the exocyclic double bonds of 4 and 5 was determined by means of NMR techniques. Particularly,
the furanone 4 was obtained from 2 (∼90% yield) as a mixture of the E and Z diastereoisomers,
which were separated by column chromatography or, more efficiently, by HPLC. The catalytic
hydrogenation of compounds 4-E and 4-Z took place diastereoselectively, due to the chiral induction
of the stereocenter located in the lateral chain. Thus, hydrogenation of 4-E led to a mixture of the
4,5-dihydro-(3H)-furan-2-ones having 3R,5S,2′S (D-xylo, 6) and 3S,5R,2′S (D-arabino, 7) configura-
tions, with 6 as the major product; whereas the 4-Z isomer gave the same mixture, but being 7
preponderant. On hydrogenation of the original 4-E/ Z mixture, compound 6 was obtained pure
after recrystallization. O-Debenzoylation of 6 gave 9, which was reduced with NaBH4 to the 3,5-
dideoxy-meso-xylo-heptitol (11). The peracetate (12) and perbenzoate (13) of the latter were
prepared, and the 1-(tert-butyldiphenylsilyl)oxy derivative (16) was also synthesized via the 3′-
(silyloxy)-4,5-dihydro-(3H)-furan-2-one 14. Chemoselective reduction of the lactone function of 6
with diisoamylborane gave the 2,5,6-tri-O-benzoyl-3,6-dideoxy-D-xylo-heptofuranose (17). The 3,5-
dideoxy-D-arabino-heptitol (18), a diastereoisomer of 11, was also isolated and characterized.
In tr od u ction
Furthermore, previous work from our laboratory9 has
shown that 3,5-dideoxylactones are readily prepared from
aldonolactones. Particularly, starting from an aldohep-
tono-1,4-lactone, such as commercially available D-glyc-
ero-D-gulo-heptono-1,4-lactone (1), a furanone (4), and
hence a 3,5-dideoxylactone (6 or 7), similar to those
involved as intermediates in the Hanessian’s procedure,8
could be obtained. The chiral center in the furanone is
expected to induce stereoselection during the hydrogena-
tion.
In recent years, diverse strategies for the synthesis of
extended 1,3-polyol chains have been developed.1,2 The
interest in pursuing such studies arises from the occur-
rence of a complex array of 1,3-polyhydroxyl functions
in polyene macrolide antibiotics, which are employed in
the treatment of systemic fungal infections.3 Those
studies culminate in the total synthesis of some members
of such a class of antibiotics, as amphotericin B,4 pima-
rolide,5 mycoticin A,6 and roxaticin.7
Hanessian et al.8 used the “replicating chiron” proce-
dure for the synthesis of seven carbon subunits having a
predictable 1,3-substitution pattern. The sequence em-
ploys (S)-glutamic acid as chiral template, and 3,5-
dideoxyheptonolactones are involved as intermediates.
The attraction of using a carbohydrate as a chiral
template resides in its appropriate functionalization, its
flexibility in the length of carbon chains, and that its
manipulation usually provides stereochemical control.
We describe here the above-mentioned carbohydrate
approach to the enantioselective synthesis of 1,3-polyol
fragments.
Resu lts a n d Discu ssion
Benzoylation of D-glycero-D-gulo-heptono-1,4-lactone (1)
at room temperature for 2 h afforded the per-O-benzoyl-
D-glycero-D-gulo-heptono-1,4-lactone (2) in good yield.10
However, the benzoylation of 1 with a large excess of
benzoyl chloride and pyridine, for long periods (16 h), led
to a mixture of furanone derivatives (3-5), resulting from
successive eliminations of benzoic acid.11 The extent of
the elimination can be controlled by adjusting the reac-
tion conditions. Thus, treatment of 2 with 1 mol equiv
of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in dichlo-
romethane (-15 °C, 15 min) gave crystalline 3 in 67%
yield.12 Under optimized conditions (20% triethylamine
in chloroform, room temperature, 45 min) the furanone
X Abstract published in Advance ACS Abstracts, May 1, 1996.
(1) Oishi, T.; Nakata, T. Synthesis 1990, 635-645.
(2) Masamune, S.; Choy, W. Aldrichim. Acta 1982, 15, 45-63.
(3) Omura, S.; Tanaka, H. In Macrolide Antibiotics: Chemistry,
Biology and Practice; Omura, S., Ed.; Academic Press: New York, 1984;
pp 351-404.
(4) (a) Nicolau, K. C.; Daines, R. A.; Uenishi, J .; Li, W. S.; Papahatjis,
D. P.; Chakraborty, T. K. J . Am. Chem. Soc. 1988, 110, 4672-4685.
(b) Nicolau, K. C.; Daines, R. A.; Chakraborty, T. K.; Ogawa, Y. J . Am.
Chem. Soc. 1988, 110, 4685-4696. (c) Nicolau, K. C.; Daines, R. A.;
Ogawa Y.; Chakraborty, T. K. J . Am. Chem. Soc. 1988, 110, 4696-
4705. (d) Kennedy, R. M.; Abiko, A.; Tekemasa, T.; Okumoto, H.;
Masamune, S. Tetrahedron Lett. 1988, 29, 451-454.
(5) Duplantier, A. J .; Masamune, S. J . Am. Chem. Soc. 1990, 112,
7079-7081.
(6) Poss, C. S.; Rychnovsky, S. D.; Schreiber, S. L. J . Am. Chem.
Soc. 1993, 115, 3360-3361.
(7) (a) Mori, Y.; Asai, M.; Okumura, A.; Furukawa, H. Tetrahedron
1995, 51, 5299-5314. (b) Ibid. 1995, 51, 5315-5330. (c) Rychnovsky,
S. D.; Hoyle, R. C. J . Am. Chem. Soc. 1994, 116, 1753-1765.
(8) Hanessian, S.; Sahoo, S. P.; Murray, P. J . Tetrahedron Lett. 1985,
26, 5631-5634.
(9) Lederkremer, R. M.; Varela, O. Adv. Carbohydr. Chem. Biochem.
1994, 50, 125-209.
(10) Kohn, P.; Samaritano, R. H.; Lerner, L. M. J . Org. Chem. 1966,
31, 1503-1506.
(11) (a) Litter, M. I.; Lederkremer, R. M. Anales Asoc. Quim. Argent.
1974, 62, 147-150. (b) Litter, M. I.; Lederkremer, R. M. Carbohydr.
Res. 1973, 26, 431-434.
(12) Di Nardo, C.; Varela, O.; Lederkremer, R. M.; Baggio, R. F.;
Vega, D. R.; Garland, M. T. Carbohydr. Res. 1995, 269, 99-109.
S0022-3263(96)00042-4 CCC: $12.00 © 1996 American Chemical Society

4008 J . Org. Chem., Vol. 61, No. 12, 1996
Di Nardo et al.
Sch em e Ia
rivatives, is acidic, as on removal produces a resonance-
stabilized carbanion, which may rearrange with elimi-
nation of the benzoyloxy group at C-4. We have proposed15
an E1cB mechanism for the formation of (5H)-furan-2-
ones, such as 3. The introduction of an endocyclic double
bond favors the abstraction of H-5, being the resulting
carbanion stabilized by conjugation with an R,â-unsatur-
ated carbonyl group, and also an E1cB mechanism would
operate during the second elimination, which leads to 4.
A further elimination of benzoic acid from 4 afforded the
triunsaturated derivative 5. However, the elimination
from 4 to give 5 follows a different pathway, as the
benzoyloxy group remains on C-3′, and that on C-2′ is
eliminated. A mechanism similar to that proposed for
the elimination of the allylic substituents in pyran-2-
ones16 could be involved. This process would start with
the formation of an incipient allylic carbocation on C-2′,
by breaking of the C-2′-OCOPh bond, followed by
abstraction of H-3′ by a base. Since allylic esters produce
carbocation intermediates on treatment with hard Lewis
acids,17 the furanone 4 was allowed to react with tin(IV)
chloride in dichloromethane. Gradual conversion of 4
into 5 was observed, although tarry polymeric byproducts
were formed. On the other hand, 5 can be readily
prepared by prolonged treatment of 2 with triethy-
lamine.15
a
(i) DBU, CH2Cl2, -15 °C 15 min (67%); (ii) Et3N, CHCl3, rt,
45 min (90% from 2); (iii) Et3N, CHCl3, rt, 6-10 h (60-80% from
2); (iv) SnCl4, CH2Cl2, rt.
The spectral data of the furanone 5 showed that we
1
were dealing with a single stereoisomer. The H NMR
spectrum was completely assigned by single-frequency
resonance (SFD) experiments. The coupling constant
between H-2′ and H-3′ (J 2′,3′ 6.2 Hz) suggests a cis
relationship for those protons, whereas the large J 1′,2′
value (11.8 Hz) would indicate a s-trans conformation
along the C-1′-C-2′ bond. The stereochemistry for the
exocyclic double bonds was conclusively confirmed by
NOEDS experiments. Thus, selective irradiation at the
H-1′ frequency (6.42 ppm) afforded positive NOE (20%)
over the H-4 signal (7.62 ppm), indicating a Z configu-
ration for the double bond on C-5. Similarly, saturation
of the H-2′ signal resulted in an enhancement (18%) of
the H-3′ signal (7.59 ppm), dictating also a Z configura-
tion for the C-2′-C-3′ double bond. Interestingly, the 5
(Z,Z) was the only crystalline isomer (60-80% yield)
isolated on reaction of 2 with 20% triethylamine in
chloroform for 6 h. Also, when pure 4-E and 4-Z were
treated separately with triethylamine, the 5 (Z,Z) isomer
was obtained. This result indicates that 4-E undergoes
isomerization of the exocyclic double bond during (or
before) the last elimination. In fact, we have observed
that the isomerization of 4-E into 4-Z (and vice versa) is
faster than the elimination of the allylic benzoyloxy
group.
4 was now obtained in ∼90% yield from 2. The product
showed two close spots by TLC, and its spectral data
indicated that the two theoretically possible diastereo-
isomers for the C-5-C-1′ double bond had been formed.
The mixture was partially separated by column chroma-
1
tography. The H NMR spectrum (Table 1) of the less
polar product showed the H-1′ resonance at lower field
(5.91 ppm) than that of the other isomer (5.49 ppm),
suggesting a cis disposition for H-1′ and the furanone-
ring oxygen atom,13 and hence an E configuration for the
exocyclic double bond. Furthermore, this compound
showed, in agreement with the assigned structure, a long-
4
range coupling constant J 4,1′ (0.8 Hz)snot observed for
the other isomerscharacteristic of a transoid disposition14
for H-4 and H-1′. The identity of both diastereoisomers
was firmly established by nuclear Overhauser effect
difference spectroscopy (NOEDS). Selective saturation
of the H-1′ signal (5.49 ppm) of the more polar isomer
gave rise to a positive NOE (23%) over the H-4 signal
(7.53 ppm), indicating a Z configuration. On the other
hand, on saturation of H-1′ (5.91 ppm) of the other
isomer, no enhancement of the H-4 signal was observed.
Once the structure of the furanones 4-E and 4-Z were
established, their ratio in the original mixture was
determined by the integral of the H-1′ signal for each
diastereoisomer. Thus, the 4-Z:4-E ratio was estimated
as 1.2:1. Similar proportions were obtained by HPLC
separation of 4-E,Z. This procedure allowed us to
recover, almost quantitatively, each of the pure diaste-
reoisomers.
The elimination of benzoic acid from the perbenzoy-
lated aldoheptonolactone 2, which leads to the furanones
3-5, takes place in successive steps. The H-3, vicinal to
the carbonyl group in 4,5-dihydro-(3H)-furan-2-one de-
Hydrogenation of 4-E,Z with Pd/charcoal as a catalyst
afforded a syrup, which crystallized from ethanol. After
successive recrystallizations from methanol, a single
isomer from the four theoretically possible was obtained.
1
The 500 MHz H NMR spectrum of this product showed
nicely resolved signals, which were readily assigned. The
assignments were confirmed by a homonuclear 2D NMR
COSY experiment. As we have previously described,18
and in agreement with earlier studies on the elucidation
(15) J eroncic, L. O.; Varela, O.; Ferna´ndez Cirelli, A.; Lederkremer,
R. M. Tetrahedron 1984, 40, 1425-1430.
(16) (a) Varela, O.; Ferna´ndez Cirelli, A.; Lederkremer, R. M.
Carbohydr. Res. 1980, 79, 219-224. (b) Nelson, C. R.; Gratzl, J . S.
Carbohydr. Res. 1978, 60, 267-273.
(13) Ingham, C. F.; Massy-Westropp, R. A.; Reynolds, G. D. Aust.
J . Chem. 1974, 27, 1477.
(14) Sternhell, S. Q. Rev. Chem. Soc. 1969, 23, 256-270.
(17) Priebe, W.; Zamojski, A. Tetrahedron 1980, 36, 287-297.

Enantioselective Synthesis of 1,3-Polyols
Ta ble 1. 1H NMR Da ta for Com p ou n d s 4-12 a n d 14-18
δ (ppm), J (Hz)
J . Org. Chem., Vol. 61, No. 12, 1996 4009
H-3
(J 3,4) (J 3,4′
H-4
(J 4,5
H-4′
(J 4′,5) (J 4,4′
H-5
(J 5,1′) (J 5,1′′
H-1′
H-1′′
(J 1′′,2′) (J 1′,1′′
H-2′
H-3′
(J 3′,3′′
H-3′′
(J 2′,3′′)
compd
)
)
)
)
(J 1′,2′
)
)
(J 2′,3′
)
)
4-E
7.60
(J 4,1′ 0.8 Hz)
7.53
5.91
(9.8)
5.49
(8.3)
6.42
6.22
(5.3)
6.43
(5.2)
6.23
(6.2)
5.72
(3.8)
5.66
(3.5)
5.78
(3.9)
3.89
(3.8)
5.22
(3.7)
4.01
(3.6)
3.95
(3.5)
4.68
4.70
4-Z
5
7.62
(J 4,1′ 0.5 Hz)
2.97
(5.6)
3.06
(5.5)
a
(1.8)
2.80
(5.0)
2.79
(5.5)
2.71
(5.2)
2.28
(5.3)
7.59
(11.8)
(J 1′,3′ 1.0 Hz)
4.68
6
5.70
(8.6) (10.6)
5.69
2.15
(10.4) (12.7)
2.17
4.73
2.31
4.54
(5.7)
4.61
(5.6)
4.56
(5.4)
3.49
(6.2)
4.05
(5.4)
3.52
(7.0)
3.49
(7.0)
(9.9) (4.6)
∼4.73
(12.0)
4.64
(12.1)
4.72
(12.0)
3.60
(11.7)
4.31
(12.0)
3.69
(10.2)
3.69
7
2.52
(∼7.5)
2.49
2.24
(8.6) (10.5)
(10.5) (12.7)
(∼7.5) (4.8)
(5.8) (14.7)
2.12
(3.9) (14.8)
8
5.31
(9.4) (3.8)
∼4.70
(9.1)
9b
10
14
15
∼4.70
1.85c
1.85c
(8.0)
5.45
(8.6) (10.6)
4.54
(8.4) (10.9)
4.46
(8.1) (10.7)
2.01c
(10.5) (12.7)
1.89
(10.8) (13.3)
1.90
(10.7) (12.6)
4.50
4.66
4.40
2.01c
1.74c
1.65
(10.2)
H-1
H-1′
(J 1′,2) (J 1,1′
H-2 (J 2,3
(J 2,3′
)
H-3
(J 3,4
H-3′
(J 3,3′
H-4
(J 3′,4
(J 1,2
)
)
)
)
)
H-5
H-5′
)
H-6
H-7
H-7′
11b
12
3.61
(4.0)
4.23
(4.0)
3.49
(6.8) (11.6)
3.95
3.94
1.59c
4.05
3.94
3.61
3.49
5.06c
1.83c
5.06c
4.23
3.95
(6.0) (12.0)
16
3.67-3.43
4.00
5.33
1.57
4.19
4.60c
(6.0)
4.01
4.00
5.70
3.67-3.43
17d
5.58
(<1)
2.66
(8.0)
1.82
(14.0)
1.68-1.59
2.20
4.60c
(6.0) (2.2)
18b
3.67-3.35
3.89c
3.89c
3.67-3.35
a
b
d
Overlapped with H-aromatic. In D2O. c Center of a complex multiplet. Data for the â anomer.
Ta ble 2. 13C NMR Da ta for Com p ou n d s 4-18
δ (ppm) (50.3 MHz)
of the geometry of 4,5-dihydro-3,5-disubstituted-(3H)-
furan-2-ones,19 the large values for the coupling constants
between H-4,4′ with H-3 and H-5 indicate a threo
relationship for the substituents on C-3 and C-5. There-
fore, the chiral centers of the compound should have a
3R,5S,2′S (D-xylo) or 3S,5R,2′S (D-arabino) configuration.
As described later, the absolute configuration was estab-
lished as D-xylo (6), as chemical transformations per-
formed on the compound led to a meso alditol.
The mother liquors of recrystallization of 6 showed
by TLC two spots, the major product having Rf 0.35
(as 6) and the other Rf 0.43. The mixture was separated
by column chromatography. The NMR spectral data
demonstrated that, against our expectations, the less
polar component was not the D-arabino isomer 7 but the
(5H)-furan-2-one 8, produced by saturation of the exo-
cyclic double bond of 4. The 1H NMR spectrum of 8
clearly showed the ABX pattern of the lateral chain-
methylene groups at C-1′ and C-3′ coupled with H-2′. The
configuration for 8 was established as threo, as on
hydrogenation the dideoxylactone 6 was exclusively
obtained. Therefore, the addition of hydrogen to the
double bond of 8 took place with excellent diastereofacial
selectivity from the side opposite to the exocyclic chain.
This result agrees with previous observations from this18
and other laboratories20 on the stereochemistry of the
hydrogenation of analogous (5H)-substituted-furan-2-
ones.
compd
C-2
C-3
C-4
C-5
C-1′
C-2′
C-3′
4-E
4-Z
5
6
7
162.5 140.2
162.5 139.4
162.6 138.4
120.1 150.4 108.5
122.7 147.8 109.3
123.5 145.4 107.2
67.6
67.7
106.0
68.9*
68.8
65.1
64.8
137.9
65.2
65.1
65.1
66.3
64.2
67.9
67.9
171.4
171.6
69.2* 37.7#
73.5
73.4
75.8
76.1
73.0
74.1
72.8
35.5#
35.2#
36.0
68.8
36.9#
a
8
162.6 137.9
69.1
9b
10
14
15
180.4
171.3
177.3
175.0
69.1* 39.0#
68.0* 36.3#
68.5
69.8
37.9#
34.4#
37.5*
38.7*
68.9*
67.9*
68.5
38.9*
39.0*
68.5
C-1
C-2
C-3
C-4
C-5
C-6
C-7
11b
12
66.8
64.9
69.5
67.4
68.6
68.6#
74.6
41.1
35.6
35.6
65.3
65.6
67.8
41.1
35.6
35.6
69.5
67.4
68.6
66.8
64.9
65.3
66.7#
65.9
66.6*
13
65.3
16c
17d
18b
68.0#
106.6
42.1* 63.8
38.2* 79.2
42.3* 68.8#
35.9* 70.2
70.6
66.8* 69.3
40.9#
66.2* 40.4#
a
b
d
Overlapped with C-aromatic. In D2O. c In DMSO-d6. Data
for the â anomer. * and # signals may be interchanged.
The second component of the mixture isolated from the
column, which had the same Rf as 6, gave more complex
NMR spectra than 6. For example, the 500 MHz 1H
NMR spectrum showed additional signals at δ 3.06 (ddd,
H-4), 2.17 (q, H-4′), 2.52 (ddd, H-1′), and 2.24 (ddd, H-1′′).
In the 13C NMR spectrum (Table 2) of the product,
distinctive signals appeared in the region of the meth-
ylene carbons (C-4,1′). The presence of the D-arabino
isomer 7 was therefore established.
(18) (a) Varela, O.; Nin, A. P.; Lederkremer, R. M. Tetrahedron Lett.
1994, 35, 9359-9362. (b) Marino, M. C.; Varela, O.; Lederkremer, R.
M. Carbohydr. Res. 1991, 220, 145-153. (c) Moradei, O.; du Mortier,
C.; Varela, O.; Lederkremer, R. M. J . Carbohydr. Chem. 1991, 10, 469-
479.
(19) Hussain, S. A. M. T.; Ollis, W. D.; Smith, C.; Stoddart, J . F. J .
Chem. Soc., Perkin Trans. 1 1975, 1480-1492.
(20) Vekemans, S. A.; de Bruyn, R. G. M.; Caris, R. C. H. M.; Kokx,
A. J . P. M.; Konings, J . J . H. G.; Godefroi, E. F.; Chittenden, G. J . F.
J . Org. Chem. 1987, 52, 1093-1099.

4010 J . Org. Chem., Vol. 61, No. 12, 1996
Di Nardo et al.
agreement with the Kishi’s empirical rule23 for the
osmylation of allylic alcohol systems.
Sch em e 2
The O-debenzoylation of 6 was accomplished with
sodium methoxide in methanol, to afford syrupy hep-
tonolactone 9. Conventional acetylation of 9 afforded the
tri-O-acetyl derivative 10 in 92% yield (from 6). Direct
reduction of 6 with lithium aluminum hydride led to the
corresponding polyol (11) in 89% yield. The 13C NMR
spectrum of the product showed only four signals, indi-
cating a symmetric structure for the 3,5-dideoxyheptitol
11 and, hence, a meso-xylo absolute configuration. The
conversion of 6 into 11 was also performed by employing
lithium borohydride in tetrahydrofurane,24 affording a
yield similar to that obtained in the reaction with lithium
aluminum hydride. On the other hand, reduction of the
free dideoxyheptonolactone 9 with excess of sodium
borohydride in methanol gave 11 in 99% yield.
In order to facilitate the spectroscopic characterization
of 11, some derivatives were synthesized. Thus, acety-
lation of 11 afforded the meso-1,2,4,6,7-pentaacetoxypen-
tane (12). The 13C NMR spectrum of 11 showed three
close signals in the region of 64-69 ppm, which were
assigned by a 13C NMR-APT experiment. Signals at 64.9
and 35.6 ppm, having inverse phase, were atributed to
C-1,7 and C-3,5, respectively. The normal phase signals
at 67.4 and 65.6 ppm, with an intensity ratio of aproxi-
mately 2:1, were identified as the resonances of C-2,6 and
C-4, respectively. The benzoylated polyol 13 was also
prepared, and its 13C NMR spectrum was assigned by
comparison with that of 11.
A polyol derivative having one of the primary hydroxyl
groups selectively protected would be useful for the
elongation of the polyol chain from the opposite extreme.
Such a derivative could be readily achieved by selective
protection of the primary hydroxyl group (HO-3′) of 9 by
silylation, followed by reduction of the lactone function.
Thus, treatment of 9 with 1.2 equiv of tert-butylchlo-
rodiphenylsilane and imidazole gave mainly the 3′-O-silyl
derivative 14, together with the 3,3′-di-O-silyl derivative
15 as a byproduct. Besides the primary hydroxyl group,
the HO-3 of saturated furanones is also reactive, and
disubstituted products are usually obtained on silyla-
tion25 or esterification.26 The lactone function of 14 was
reduced with NaBH4, to give the desired 1-O-silylated
polyol 16. As expected, the 13C NMR spectrum of 16
showed differentiated resonances for the seven carbons
of the polyol chain.
In order to determine the ratio of 6 and 7, the crude
mixture of hydrogenation of 4-E,Z was subjected to
quantification on the basis of the NMR integral of the
characteristic signals for each isomer. The data were
confirmed by HPLC quantification of the free alditols,
which were obtained by O-debenzoylation followed by
NaBH4 reduction of 6 and 7 (see later), as the alditols
could be readily separated by that technique. Thus, on
catalytic hydrogenation (10% Pd/C) of 4-E,Z, a 1.4:1 ratio
for 6:7 was obtained. This result indicates that the
stereocenter at C-2′ exerts some stereocontrol during the
hydrogenation. When 4-E was hydrogenated under
conditions identical to those employed for 4-E,Z, a
moderately higher diastereoselectivity was observed
(ratio 6:7, 2:1). Interestingly, although less selective,
hydrogenation of 4-Z led to the D-arabino (7) as the major
stereoisomer (ratio 7:6, 1.2:1). When the furanones 4-E
and 4-Z were hydrogenated using Pd/BaSO4 as catalyst
a somewhat higher selectivity was observed. Thus, 4-E
afforded 6 and 7 in a 3:1 ratio, whereas 4-Z gave a 1:1.4
ratio for the same products. However, attempted hydro-
genations in homogeneous phase with a rhodium catalyst
(Wilkinson catalyst) were extremely slow, and starting
material was found to remain unreacted even after 40 h
of reaction.
The diastereofacial selectivity observed for the fura-
nones having a different configuration for the exocyclic
double bond may be explained if the hydrogenation occurs
under conformational control. Conformations having the
C-H bond eclipsing the CdC bond are known to be
preferred for allylic systems.21,22 The large value for J 1′,2′
in 4-E and 4-Z is indicative that they adopt preferentially
such a conformation, as depicted in Scheme 2. Assuming
that this conformational preference is reflected in the
transition state, the stereochemistry of the major product
would arise from the preferential approach of hydrogen
to the face of the exocyclic double bond opposite to that
containing the allylic benzoyloxy group. This explanation
agrees with the fact that the stereoselection is higher for
4-E than for 4-Z; since the smaller J 1′,2′ value for the
latter suggests the presence of other eclipsed rotamers
in the conformational equilibrium, which might react by
a different reagent approach. Our results are in excellent
On the other hand, the lactone group of 6 may be
selectively reduced to give a benzoylated derivative of the
3,5-dideoxy-D-xylo-heptofuranose (17), having the ano-
meric hydroxyl group unprotected. The reduction of the
carbonyl lactone of 6 was chemoselectively performed
with diisoamylborane,27 affording the lactol derivative 17
1
with a very good yield (∼80%). The H NMR spectrum
of 17 showed a singlet (J 1,2 < 1 Hz) in the anomeric region
(5.58 ppm). The small value for J 1,2 indicates28 a â-con-
(23) Cha, J . K.; Christ, W. J .; Kishi, Y. Tetrahedron 1984, 40, 2247-
2255.
(24) (a) Soai, K.; Ookawa, A. J . Org. Chem. 1986, 51, 4000-4005.
(b) Brown, H. C.; Narisimhan, S.; Choi, Y. M. J . Org. Chem. 1982, 47,
4702-4708.
(25) Mark, E.; Zbiral, E. Monatash. Chem. 1981, 112, 215-239.
(26) J eroncic, L. O.; Gallo-Rodr´ıguez, C.; Varela, O.; Lederkremer,
R. M. J . Carbohydr. Chem. 1993, 12, 841-851.
(27) (a) Kohn, P.; Samaritano, R. H.; Lerner, L. M. J . Am. Chem.
Soc. 1965, 87, 5475-5480. (b) Lerner, L. M. Methods Carbohydr. Chem.
1972, 6, 131-134.
(21) Gung, B. W.; Karipides, A.; Wolf, M. A. Tetrahedron Lett. 1992,
33, 731-716.
(22) Karabastos, G. J .; Fenoglio, D. J . In Topics in Stereochemistry;
Eliel, E. L., Allinger, N. L., Eds.; Wiley-Interscience: New York, 1970;
pp 167-203.
(28) Marino, C.; Varela, O.; Lederkremer, R. M. Carbohydr. Res.
1989, 190, 65-76.

Enantioselective Synthesis of 1,3-Polyols
J . Org. Chem., Vol. 61, No. 12, 1996 4011
Sch em e 3a
Analytical TLC was performed on silica gel 60 F254 (Merck)
precoated plates (0.2 mm), with 9:1 toluene-EtOAc as solvent,
except when otherwise specified. Visualization of the spots
was effected by exposure to UV light or charring with a
solution of 10% sulfuric acid in EtOH, containing 0.5%
p-anisaldehyde.
(5E )-3-(Ben zoyloxy)-5-[(2′S)-2′,3′-b is(b en zoyloxy)p r o-
pyliden e]-(5H)-fu r an -2-on e (4-E) an d (5Z)-3-(Ben zoyloxy)-
5-[(2′S)-2′,3′-b is(b en zoyloxy)p r op ylid en e]-(5H )-fu r a n -2-
on e (4-Z). To a solution of 2,3,5,6,7-penta-O-benzoyl-D-
glycero-D-gulo-heptono-1,4-lactone10 (2, 2.20 g, 3.02 mmol) in
dry chloroform (20 mL) was added triethylamine (1.9 mL, 13.3
mmol) under nitrogen. The mixture was stirred in the dark,
at room temperature (rt) for 45 min, when monitoring by TLC
showed two main spots (Rf 0.56 and 0.61) and no starting
material (Rf 0.37). The solution was diluted with CH2Cl2 (300
mL), washed with 1 M aqueous HCl (2 × 100 mL), saturated
aqueous NaCl (100 mL), and saturated aqueous NaHCO3 (100
mL), dried (MgSO4), and concentrated. The 1H NMR spectrum
of the resulting syrup showed almost exclusively the presence
of the E- and Z-furanone derivatives (4). The mixture was
partially separated by column chromatography, employing 10:1
hexane-EtOAc.
Fractions containing the faster moving product (Rf 0.61)
were combined and concentrated to afford syrupy 4-E (0.29 g,
20%), which gave the following: [R]D ) -97.2 (c 1.3, CHCl3);
IR (film, cm-1) 1780 (CO-1,4-lactone), 1740 (CO-enolic ben-
zoate), 1710 (CO-benzoate); UV (methanol) λmax (nm) 232 (ꢀ
38 000), 276 (ꢀ 31 000). Anal. Calcd for C28H20O8: C, 69.42;
H, 4.16. Found: C, 69.58; H, 4.19.
On concentration of the fractions which gave a single spot
having Rf 0.56, syrupy compound 4-Z (0.37 g, 25%) was
obtained: [R]D ) -61.1 (c 1.9, CHCl3); IR (film, cm-1) 1780,
1740, 1710; UV (methanol) λmax (nm) 230 (ꢀ 37 000), 275 (ꢀ
30 000). Anal. Calcd for C28H20O8: C, 69.42; H, 4.16.
Found: C, 69.50; H, 4.21.
From intermediate fractions of the column was obtained a
mixture 4-E,Z (0.59 g, overall yield 85%) was obtained.
HPLC separation of the original 4-E,Z mixture (0.50 g) was
carried out employing an Ultrasphere ODS 5 µm (Alltech)
column, with 15% MeOH-water (3 mL/min). The products
were eluted as follows: 4-E (tR 15.2 min, 0.19 g, 38%), 4-Z (tR
20.2 min, 0.25 g, 50%), and a mixture 4-E,Z (0.05 g, 10%).
(5Z)-3-(Be n zoyloxy)-5-[(Z)-3′-(b e n zoyloxy)-2′-p r op e -
n ylid en e]-(5H)-fu r a n -2-on e (5). (a ) By Tr ea t m en t of 2
w ith Ter tia r y Am in es. It was synthesized15 by reaction of
2 with 20% Et3N in CHCl3 for 6 h (mp 151-152 °C). Other
amines, such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or
pyridine, were also effective for the preparation of 5, but the
yields were lower than when Et3N was used.
(b) By Tin (IV) Ch lor id e-P r om oted Elim in a tion fr om
4. To a solution of 4-E/ Z (0.10 g, 0.21 mmol) in CH2Cl2 (2
mL) was added SnCl4 (0.051 mL, 0.42 mmol) at 0 °C under
nitrogen. The mixture was stirred at rt, and TLC showed
gradual conversion of 4 (Rf 0.56 and 0.61) into 5 (Rf 0.71). After
15 h, spots of similar intensity, corresponding to 4 and 5, were
observed, but the solution darkened and a tarry precipitate
(Rf 0.0) appeared. After 24 h of reaction, complete decomposi-
tion was observed.
a
(i) NaMeO-MeOH, 2 h, rt; (ii) (MeCO)2O, C5H5N, 16 h, rt;
(iii) LiAlH4, THF, 6 h, rt (from 6); or LiBH4, THF, 6 h, reflux (from
6); or NaBH4, MeOH, 2 h, rt (from 9); (iv) PhCOCl, C5H5N, 2 h,
rt; (v) Ph2ButSiCl, imidazole, DMF, 14 h, rt; (vi) NaBH4, MeOH,
4 h, rt; (vii) (Me2CHCHMe)2BH, THF, 20 h, rt.
Sch em e 4
figuration for the major anomer. This assignment was
confirmed by the 13C NMR spectrum of 17, which showed
two signals at 100.6 and 94.6 ppm, in a 7:1 ratio, due to
the resonances of C-1â and C-1R. Compound 17 also
constitutes a synthetic equivalent of an alternate anti,
anti polyol fragment with a different functionalization
on each extreme.
In order to obtain the free alditol having the D-arabino
configuration (18), the crude mixture of hydrogenation
of 4-E,Z, containing almost equal proportions of 6 and 7,
was subjected to O-debenzoylation followed by sodium
borohydride reduction. The separation of the resulting
mixture of meso-xylo- (11) and D-arabino- (18) 3,5-
dideoxyalditols could be readily accomplished by HPLC.
Compound 11 showed the same physical and spectro-
scopic properties as the product previously synthesized
from pure 6. The H and 13C NMR spectra of 18 were
more complex than those of 11, as expected for an
asymmetric compound.
1
In summary, we report here easy routes for the access
to 1,3-polyol chains of defined stereochemistry. Particu-
larly, compound 11, which was readily prepared from
furanones 4-E/Z can be identified in the C-16-C-22 and
C-18-C-24 fragment constituents of the polyene mac-
rolide antibiotics roxaticin7 and mycoticin A and B,6
respectively. Those fragments may undergo chain elon-
gation from each of the extremes by procedures already
described1,7 to generate the required syn or anti geometry
between hydroxyl groups.
(3R,5S)-3-(Ben zoyloxy)-5-[(2′S)-2′,3′-b is(b en zoyloxy)-
p r op yl]-4,5-d ih yd r o-(3H)-fu r a n -2-on e (6), Its (3S,5R,2′S)
Dia ster eom er (7), a n d (5S)-3-(Ben zoyloxy)-5-[(2′S)-2′,3′-
bis(ben zoyloxy)p r op yl]-(5H)-fu r a n -2-on e (8). (a ) Hyd r o-
gen a tion of 4-E/Z. The diastereomeric mixture 4-E/ Z (3.14
g, 6.48 mmol) dissolved in EtOAc (20 mL) was hydrogenated
in the presence of 10% Pd/C (0.30 g) at atmospheric pressure
for 12 h. The catalyst was filtered, and the filtrate concen-
trated to a syrup, which slowly crystallized upon addition of
EtOH (2.22 g, 70%). After four successive recrystallizations
from MeOH, compound 6 was obtained as white needles (0.950
g, 30% yield): mp 139-140 °C; [R]D ) -50 (c 1, CHCl3); Rf
0.35; IR (Nujol, cm-1) 1790, 1720. Anal. Calcd for C28H24O8:
C, 68.85; H, 4.95. Found: C, 68.96; H, 5.20.
Exp er im en ta l Section
Gen er a l P r oced u r es. All NMR spectra were performed
in CDCl3, unless otherwise indicated. Column chromatogra-
phy was carried out on silica gel 60, 240-400 mesh (Merck).
The mother liquors of crystallization and recrystallization
were combined and concentrated. The resulting syrup showed
by TLC a main product, having the same Rf (0.35) as 6, and a
(29) Bock, K.; Pedersen, C. Adv. Carbohydr. Chem. Biochem. 1983,
41, 27-66.

4012 J . Org. Chem., Vol. 61, No. 12, 1996
Di Nardo et al.
small proportion of a faster migrating component (Rf 0.43).
The mixture was chromatographed using 12:1 toluene-EtOAc
as eluent. The compound having Rf 0.43 was obtained as an
amorphous solid (0.022 g, 0.7%), and it was characterized as
(5S)-3-(benzoyloxy)-5-[(2′S)-2′,3′-bis(benzoyloxy)propyl]-(5H)-
mixture was allowed to reach rt, and it was stirred for 6 h,
when the starting material (6) had been completely converted
into a product of Rf 0.45 (2:2:1 nPrOH-EtOH-water). The
solution was cooled at 0 °C and wet Et2O was added, in order
to destroy the remaining LiAlH4. The mixture was carefully
diluted with water (100 mL) and filtered. The solid residue
was washed with water (3 × 30 mL) and then with boiling
methanol (5 × 40 mL). The filtrate and washings were
combined, concentrated to ∼20 mL, and desalted with Am-
berlite MB-3 resin. Compound 11 was obtained as a colorless
oil (0.186 g, 95%): Rf 0.45 (2:2:1 nPrOH-EtOH-water),
essentialy pure according to its NMR spectra. Column chro-
matography (1.5:1 EtOAc-MeOH) of a portion of the crude
oil (0.08 g) afforded an analytical sample of 11 (0.071 g, 89%):
[R]D ) 0.0 (c 1.7, H2O); HPLC tR 9.3 min in a LiChrospher 100
NH2 5 µm (Merck) column, with 8:1 acetonitrile-water (1.5
mL/min). Anal. Calcd for C7H16O5: C, 46.66; H, 8.95.
Found: C, 46.55; H, 9.11.
furan-2-one (8): [R]D ) -19 (c 1.3, CHCl3); IR (Nujol, cm-1
)
1775, 1735, 1720. Anal. Calcd for C28H22O8: C, 69.13; H, 4.56.
Found: C, 69.03; H, 4.67.
Evaporation of the solvent from the fractions that contained
the product of Rf 0.35 gave a syrup (0.28 g) which did not
1
crystallized from EtOH. The H and 13C NMR spectra of the
product revealed that 6 was mixed with another fully satu-
rated furanone, which was further identified as the (3S,5R,2′S)
diastereoisomer 7.
The mixture of 6 and 7 could not be separated at this stage
by chromatographic techniques, including HPLC. However,
the proportions of 6 and 7 in the crude mixtures of hydrogena-
tion were determined by the integral of differentiated signals
1
in the H and 13C NMR spectra of such mixtures. The ratio of
(b) By LiBH4 Red u ction of 6. Compound 6 (0.89 g, 1.82
mmol) was added, under nitrogen, to a freshly prepared 0.36
M solution of LiBH4 in THF (10 mL). The mixture was heated
under reflux for 6 h and then stirred at rt for an additional 12
h. Anhydrous MeOH (2 mL) was added, and after 1 h of
stirring, the solution was treated with Dowex 50W (H+) resin,
filtered, and concentrated. The residue was dissolved in
MeOH and the solvent evaporated, in order to eliminate the
boric acid. This procedure was repeated 5 times. The polyol
11 was obtained as an essentially pure, colorless syrup (0.308
g, 94%), with the same properties as the product described in
a.
6 and 7 was also established by the sequence of O-debenzoy-
lation followed by lactone reduction, which led to the corre-
sponding alditols 11 and 18. The proportions of both polyols
in the mixtures was determined by HPLC, since they gave
peaks having different tR, as described below.
(b) Hyd r ogen a tion of 4-E. Compound 4-E (0.593 g, 1.224
mmol) was hydrogenated in the presence of 10% Pd/C under
the conditions described above. The crude product showed a
6:7 ratio of 2:1. Two recrystallizations from MeOH afforded
6 (0.281 g, 47%), which gave the same physical constants as
those reported in a.
(c) Hyd r ogen a tion of 4-Z. Compound 4-Z (0.402 g, 0.83
mmol) was hydrogenated as described in a. The ratio of 6:7
in the crude product was determined as 1:1.2. The product
did not crystallize. After chromatographic purification with
solutions of increasing polarity of hexane-EtOAc, a syrupy
mixture of 6 and 7 (0.29 g, 71%) was obtained.
Hydrogenations of pure 4-E and 4-Z and of the original
mixture 4-E/ Z were also performed by employing 10% Pd/
BaSO4. The hydrogenation mixtures were processed and
quantified as described above. The following ratios for 6:7
were obtained: 3:1 (from 4-E), 1:1.4 (from 4-Z), 1.5:1 (from
4-E/ Z).
(3R,5S)-3-Hyd r oxy-5-[(2′S)-2′,3′-d ih yd r oxyp r op yl]-4,5-
d ih yd r o-(3H)-fu r a n -2-on e (9). To a suspension of 6 (1.135
g, 2.317 mmol) in anhydrous MeOH (30 mL) was added a 1.18
M solution of NaOMe in MeOH (5.9 mL) at 0 °C. The mixture
was allowed to reach rt, and it was stirred until complete
consumption of 6 (2 h). The solution was made neutral upon
addition of Dowex 50W (H+) resin suspended in MeOH. The
resin was filtered and the filtrate concentrated to a syrup,
which showed by TLC an intense spot having Rf 0.45 (4:1
EtOAc-EtOH). The syrup was dissolved in water (100 mL),
and the solution was extracted with 2:1 toluene-Et2O (45 mL,
twice). Upon evaporation of the water, the colorless oil
obtained (0.40 g, 98%) was purified by column chromatography
(c) By Na BH4 Red u ction of 9. To a solution of 9 (0.364
g, 2.066 mmol) in MeOH (6 mL) was added an excess of NaBH4
(0.20 g). The mixture was stirred for 2 h at rt, when TLC
showed complete conversion of 9 (Rf 0.68, 3:2 CHCl3-MeOH)
into a more polar compound (Rf 0.48). The solution was
neutralized with Dowex 50W (H+) resin, filtered, and evapo-
rated twice with MeOH, to give syrupy 11 (0.368 g, 99%),
whose NMR spectrum was identical to that of the product
described in a.
Isola tion of 11 a n d 3,5-Did eoxy-D-a r a bin o-h ep titol (18)
fr om th e Mixtu r es of 6 a n d 7. The crude mixture of
hydrogenation of 4-E/ Z was treated with 0.15 M NaOMe,
followed by decationization with Dowex 50W (H+) resin, and
then reduced with an excess of NaBH4 in MeOH (2 h). The
solution was neutralized again with resin and concentrated
to a syrup, which was redissolved in a small volume of MeOH
and filtered through a C-8 MAXI-CLEAN cartridge (Alltech).
The resulting mixture of polyols 11 and 18 was separated by
HPLC, employing a LiChrospher 100 NH2 5 µm (Merck)
column, with 8:1 acetonitrile-water (1.5 mL/min). Com-
pounds 18 and 11 gave peaks having tR 7.9 and 9.3 min,
respectively. Syrupy 18 gave [R]D ) -22 (c 0.7, H2O).
(3R,5S)-3-Hyd r oxy-5-[(2′S)-3′-ter t-[(bu tyld ip h en ylsilyl)-
oxy]-2′-h yd r oxyp r op yl]-4,5-d ih yd r o-(3H)-fu r a n -2-on e (14)
a n d (3R,5S)-3[(ter t-Bu t yld ip h en ylsilyl)oxy]-5-[(2′S)-3′-
[(ter t-bu tyld ip h en ylsilyl)oxy]-2′-h yd r oxyp r op yl]-4,5-d i-
h yd r o-(3H)-fu r a n -2-on e (15). Compound 6 (1.20 g, 2.46
mmol) was O-debenzoylated as described above. The resulting
crude syrup was dissolved in anhydrous DMF (3 mL), and
imidazole (0.42 g, 6.15 mmol) and tert-butylchlorodiphenylsi-
lane (TBDPSCl, 0.39 mL, 1.48 mmol) were added. The
mixture was stirred for 4 h at rt, and an equal amount of
TBDPSCl was added. The stirring was maintained for a
further 10 h, when TLC (3:2 hexane-acetone) showed two
main spots having Rf 0.41 and 0.80. The mixture was diluted
with CH2Cl2 (100 mL), and the solution was washed with
dilute aqueous HCl (100 mL) and water (2 × 100 mL), dried
(MgSO4), filtered, and evaporated, to yield a colorless oil (1.19
g). The oil was subjected to column chromatography, employ-
ing mixtures of increassing polarity of toluene-EtOAc (from
5:1 to 1:1). Compound 15 (0.353 g, 22%) was isolated first.
Further fractions from the column afforded the lower moving
component (Rf 0.41), which was characterized as 14 (0.612 g,
60%). It gave [R]D ) -5.0 (c 1, CHCl3). Anal. Calcd for
C23H30O5Si: C, 66.64, H; 7.29. Found: C, 66.53; H, 7.60.
(4:1 EtOAc-EtOH) to give syrupy 9 (0.36 g, 88%): [R]D
)
-55.1 (c 0.9, H2O). Anal. Calcd for C7H12O5: C, 47.58; H, 6.87.
Found: C, 47.36; H, 7.00.
(3R,5S)-3-Acetoxy-5-[(2′S)-2′,3′-d ia cetoxyp r op yl]-4,5-d i-
h yd r o-(3H)-fu r a n -2-on e (10). Compound 6 (0.15 g, 0.85
mmol) was O-debenzoylated as described above. The crude
syrup obtained was dissolved in pyridine (5 mL), and acetic
anhydride (4 mL) was added at 0 °C. The mixture was stirred
overnight at rt and then poured into ice-water (120 mL). After
0.5 h, it was extracted with CH2Cl2 (4 × 50 mL) and the extract
washed with 2 M aqueous HCl (60 mL), water (60 mL), and
saturated aqueous NaHCO3 (60 mL), dried (MgSO4), and
concentrated. The residue (Rf 0.44, 9:1 toluene-iPrOH) was
chromatographed with 15:1 chloroform-acetone, affording
syrupy 10 (0.21 g, 81% from 6): [R]D ) -26.3 (c 2.5, CHCl3).
Anal. Calcd for C13H18O5: C, 51.65; H, 6.00. Found: C, 51.72;
H, 6.17.
3,5-Did eoxy-m eso-xylo-h ep titol (11). (a ) By LiAlH4
Red u ction of 6. To a 0.5 M solution of LiAlH4 in THF (18
mL), cooled at 0 °C was slowly added a solution of 6 (0.532 g,
1.09 mmol) in THF (8 mL) under nitrogen. The reaction

Enantioselective Synthesis of 1,3-Polyols
J . Org. Chem., Vol. 61, No. 12, 1996 4013
1-O-(ter t-Bu tyld ip h en ylsilyl)-3,5-d id eoxy-L-xylo-h ep ti-
tol (16). Lactone 14 (93 mg, 0.224 mmol) was reduced under
the same conditions as described for 9, to give a colorless syrup
(97 mg) of Rf 0.18 (3:2 hexane-acetone). After purification
by column chromatography (2:1 hexane-acetone), pure 16 (47
mg, 50%) was obtained. It gave [R]D ) -0.7 (c 1.3, CHCl3).
Anal. Calcd for C23H34O5Si: C, 65.99; H, 8.19. Found: C,
66.20; H, 8.38.
2,6,7-Tr i-O-b en zoyl-3,5-d id eoxy-r,â-D-xylo-h ep t ofu r a -
n ose (17). To a freshly prepared solution of bis(3-methyl-2-
butyl)borane27 (10 mmol) in THF (8 mL), cooled at -10 °C,
was added compound 6 (1.20 g, 2.4 mmol) dissolved in THF (5
mL). The solution was stirred for 20 h at rt, and water (1
mL) was added dropwise. The mixture was stirred for an
additional 0.5 h and then cooled at 0 °C; 30% H2O2 was slowly
added, while the pH was maintained between 7 and 8 with 1
M NaOH. The THF was evaporated, and the residue was
extracted with CH2Cl2 (3 × 75 mL); the extract was washed
with saturated aqueous NaCl (80 mL), dried (MgSO4), and
concentrated. The resulting syrup was dissolved in methanol,
followed by evaporation, in order to eliminate boric acid. The
procedure was repeated four times, affording 17 (1.14 g, 95%)
as a chromatographically homogeneous syrup (Rf 0.33, 4:1
toluene-EtOAc). Column chromatography led to syrup 17
(0.94 g, 78%): [R]D ) -16 (c 2.5, CHCl3). The 13C NMR
spectrum (25 MHz, CDCl3) showed the two signals for the â
and R anomers at 106.6 and 94.6 ppm, respectively, in a 7:1
ratio. Anal. Calcd for C28H26O8: C, 68.56; H, 5.34. Found:
C, 68.71; H, 5.42.
Ack n ow led gm en t. We are indebted to the Univer-
sidad de Buenos Aires and CONICET (Consejo Nacional
de Investigaciones Cient´ıficas y Te´cnicas de la Repu´blica
Argentina) for financial support and UMYMFOR
(CONICET-FCEN-UBA) for the microanalyses. R.M.L.
and O.V. are Research Members of CONICET.
J O960042Z