Synthesis of chiral spiroacetals from carbohydrates

Article abstract of DOI:10.1021/jo960060g

Chiral spiroacetals of the 1,7-dioxaspiro[5.5]undecane, 1,6-dioxaspiro[4.5]decane, and 1,6-dioxaspiro[4.4]nonane types have been prepared from carbohydrates in pyranose or furanose forms. The spirocyclization reaction has been accomplished from a conveniently homologated carbohydrate by an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals. Thus, 2,3,4,6-tetraO-benzyl-1-deoxy-1-(3′-hydroxypropyl)-α-D-glucopyranose (2) was photolyzed with visible light in the presence of (diacetoxyiodo)benzene and iodine to give a mixture of (1R)-(3) and (1S)-2,3,4,6-tetra-O-benzyl-1-deoxy-D-glucopvranose-1-spiro-2′- tetrahydrofuran (4). The photolysis of methyl 6-deoxy-6-(2′-hydroxyethyl)-2,3,4-tri-O-methyl-α-D-glucopyranoside (8) gave the isomeric spiroacetals methyl (5S)- (9) and (5R)-6-deoxy-5,2′-epoxy-6-ethyl-2,3,4-tri-O-methyl-α-D- glucopyranoside (10) in which the spirocenter is now located at C-5. The spiroacetals of the [5.5]undecane series: methyl (5R)- (19) and (5S)-6-deoxy-5,3′-epoxy-2,3,4-tri-O-methyl-6-propyl-/a-D-glucopyranoside (20) have been prepared starting from methyl 6-deoxy-6-(3′-hydroxypropyl)-2,3,4-tri-O-methyl-β-D-glucopyranoside (18). The reaction has also been applied to hexofuranoses and 1-deoxy-1-(3′-hydroxypropyl)-2,3:5,6-di-O-isopropylidene-α-D- mannofuranose (21) gave rise to (1S)- (22) and (1R)-1-deoxy-2,3: 5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′-tetrahydrofuran (23); and 1-deoxy-1-(4′-hydroxybutyl)-2,3:5,6-di-O-isopropylidene-α-D- mannofuranose (28) to (1R)- (30) and (1S)-1-deoxy2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′- tetrahydropyran (32). Both spiroacetal enantiomers are formally available from the same carbohydrate.

Full text of DOI:10.1021/jo960060g

J . Org. Chem. 1996, 61, 3999-4006
3999
Syn th esis of Ch ir a l Sp ir oa ceta ls fr om Ca r boh yd r a tes
Angeles Mart´ın, J ose´ A. Salazar, and Ernesto Sua´rez*
Instituto de Productos Naturales y Agrobiologı´a del C.S.I.C., Carretera de La Esperanza 3,
38206-La Laguna, Tenerife, Spain
Received J anuary 9, 1996X
Chiral spiroacetals of the 1,7-dioxaspiro[5.5]undecane, 1,6-dioxaspiro[4.5]decane, and 1,6-dioxaspiro-
[4.4]nonane types have been prepared from carbohydrates in pyranose or furanose forms. The
spirocyclization reaction has been accomplished from a conveniently homologated carbohydrate by
an intramolecular hydrogen abstraction reaction promoted by alkoxy radicals. Thus, 2,3,4,6-tetra-
O-benzyl-1-deoxy-1-(3′-hydroxypropyl)-R-D-glucopyranose (2) was photolyzed with visible light in
the presence of (diacetoxyiodo)benzene and iodine to give a mixture of (1R)-(3) and (1S)-2,3,4,6-
tetra-O-benzyl-1-deoxy-D-glucopyranose-1-spiro-2′-tetrahydrofuran (4). The photolysis of methyl
6-deoxy-6-(2′-hydroxyethyl)-2,3,4-tri-O-methyl-R-D-glucopyranoside (8) gave the isomeric spiroacetals
methyl (5S)- (9) and (5R)-6-deoxy-5,2′-epoxy-6-ethyl-2,3,4-tri-O-methyl-R-D-glucopyranoside (10) in
which the spirocenter is now located at C-5. The spiroacetals of the [5.5]undecane series: methyl
(5R)- (19) and (5S)-6-deoxy-5,3′-epoxy-2,3,4-tri-O-methyl-6-propyl-â-D-glucopyranoside (20) have
been prepared starting from methyl 6-deoxy-6-(3′-hydroxypropyl)-2,3,4-tri-O-methyl-â-D-glucopy-
ranoside (18). The reaction has also been applied to hexofuranoses and 1-deoxy-1-(3′-hydroxypropyl)-
2,3:5,6-di-O-isopropylidene-R-D-mannofuranose (21) gave rise to (1S)- (22) and (1R)-1-deoxy-2,3:
5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′-tetrahydrofuran (23); and 1-deoxy-1-(4′-
hydroxybutyl)-2,3:5,6-di-O-isopropylidene-R-D-mannofuranose (28) to (1R)- (30) and (1S)-1-deoxy-
2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′-tetrahydropyran (32). Both spiroacetal
enantiomers are formally available from the same carbohydrate.
The characterization of many important natural prod-
ucts which exhibit a spiroacetal ring system in their
structures has stimulated the development of several
methodologies for the synthesis of this substructural
unit.1 These metabolites isolated from a large variety of
natural sources can have very simple structures such as
the 1,7-dioxaspiro[5.5]undecane itself which is the major
component of the pheromone of the olive fruit fly (Dacus
oleae)2 or can be very complex antiparasitic agents
(avermectins and milbemycins)3 or polyether antibiotics4
of the monensin5 and lonomycin6 type.
Most common routes to spiroacetals are based on the
preparation of the dihydroxy ketone, the typical method
for the ring closure being the usual acid-promoted spi-
rocyclization. This may be inconvenient in complex
molecules bearing acid-sensitive protective groups. We
wish to report here on a convenient methodology for the
synthesis of optically active spiroacetals from carbohy-
drates in which the spirocyclization is achieved by an
intramolecular hydrogen abstraction reaction promoted
by alkoxy radicals.7,8 Thus, chiral 1,7-dioxaspiro[5.5]-
undecane, 1,6-dioxaspiro[4.5]decane, and 1,6-dioxaspiro-
[4.4]nonane derivatives can be prepared in good yields.
Most natural products having a spiroacetal moiety in
their structures fall into one of these three categories.
Racemic spiroacetals have been previously prepared
using a radical methodology9 and different approaches
to these compounds from carbohydrates have recently
been reported.10
As depicted in Scheme 1, the first step is the formation
of a C-glycopyranoside if the spirocenter is going to be
generated at C-1 (A) or a homologation of the carbohy-
drate side chain if it is at C-5 (B). The second step is a
remote functionalization of the C-1 or C-5 carbon atom
from an alkoxy radical generated from the corresponding
alcohol by photolysis in presence of (diacetoxyiodo)-
benzene (DIB) and iodine. In previous papers from this
laboratory we have developed hypervalent iodine re-
X Abstract published in Advance ACS Abstracts, May 15, 1996.
(1) For reviews of spiroacetals see: (a) Vaillancourt, V.; Praft, N.
E.; Perron, F.; Albizati, K. F. In The Total Synthesis of Natural
Products; ApSimon, J ., Ed.; Wiley: New York, 1992; Vol. 8, pp 533-
691. (b) Perron, F.; Albizati, K. F. Chem. Rev. 1989, 89, 1617-1661.
(c) Boivin, T. L. B. Tetrahedron 1987, 43, 3309. (d) Kluge, A. F.
Heterocycles 1986, 24, 1699-1740.
(2) Davies, H. G.; Green, R. H. Chem. Soc. Rev. 1991, 20, 211-269,
271-339.
(3) (a) Baker, R.; Herbert, R.; Howse, P. E.; J ones, O. T.; Francke,
W.; Reith, W. J . Chem. Soc., Chem. Commun. 1980, 52-53. For a
review on pheromone spiroacetals see: (b) Mori, K. In The Total
Synthesis of Natural Products; ApSimon, J ., Ed.; Wiley: New York,
1992; Vol. 9, pp 1-534.
(4) For reviews on polyether antibiotics see: (a) Polyethers Antibiot-
ics: Naturally Occurring Acid Ionophores; Westley, J . W., Ed.; Marcel
Dekker: New York, 1982; Vols. 1 and 2. (b) Wierenga, W. In The Total
Synthesis of Natural Products; ApSimon, J ., Ed.; Wiley: New York,
1992; Vol. 4, pp 533-691.
(5) For recent synthesis of monensin see: (a) Ireland, R. E.;
Armstrong, J . D., III; Leberton, J .; Meissner, R. S.; Rizzacasa, M. A.
J . Am. Chem. Soc. 1993, 115, 7152-7156. (b) Ireland, R. E.; Meissner,
R. S.; Rizzacasa, M. A. J . Am. Chem. Soc. 1993, 115, 7166-7172.
(6) For recent synthesis of lonomycin A see: Evans, D. A.; Ratz, A.
M.; Huff, B. E.; Sheppard, G. S. J . Am. Chem. Soc. 1995, 117, 3448-
3467.
(7) For a recent review on intramolecular free radical functional-
izations see: Majetich, G.; Wheless, K. Tetrahedron 1995, 51, 7095-
7129.
(8) For a preliminary communication see: Mart´ın, A.; Salazar, J .
A.; Sua´rez, E. Tetrahedron Lett. 1995, 36, 4489-4492.
(9) (a) Kay, I. T.; Williams, E. G. Tetrahedron Lett. 1983, 24, 5915-
5918. (b) Kay, I. T.; Bartholomew, D. Tetrahedron Lett. 1984, 25,
2035-2038. (c) Baker, R.; Brimble, M. A. J . Chem. Soc., Perkin Trans.
1 1988, 125-131. (d) Wincott, F. E.; Danishefsky, S. J .; Schulte, G.
Tetrahedron Lett. 1987, 28, 4951-4954.
(10) (a) Cubero, I. I.; Lo´pez Espinosa, M. T. P.; Richardson, A. C.;
Aamlid, K. H. Carbohydr. Res. 1993, 242, 281-296. (b) Cubero, I. I.;
Lo´pez Espinosa, M. T. P.; Kari, N. Carbohydr. Res. 1994, 261, 231-
242. (c) Cubero, I. I.; Lo´pez Espinosa, M. T. P.; Kari, N. Carbohydr.
Res. 1995, 268, 187-200. (d) Preuss, R.; Karl-Heinz, J .; Schmidt, R.
R. Liebigs Ann. Chem. 1992, 377-382. (e) Grondin, R.; Leblanc, Y.;
Hoogsteen, K. Tetrahedron Lett. 1991, 32, 5021-5024. (f) Remy, G.;
Cottier, L.; Descotes, G. Can. J . Chem. 1983, 61, 434. (g) Bernasconi,
C.; Cottier, L.; Descotes, G. Carbohydr. Res. 1983, 2, 159. (h) Remy,
G.; Cottier, L.; Descotes, G. J . Carbohydr. Chem. 1983, 1, 37.
S0022-3263(96)00060-6 CCC: $12.00 © 1996 American Chemical Society

4000 J . Org. Chem., Vol. 61, No. 12, 1996
Mart´ın et al.
Sch em e 1
Sch em e 2a
a
(a) BH3‚THF, 0 °C f rt, 5 h; NaOH, H2O2, 40 °C, 0.5 h; (b)
see Table 1; (c) HCl, AcOH, 50 °C, 6 h.
informative interactions with the C-3′ protons are il-
lustrated by arrows in the structures of 3 and 4.
The minor compound 4 is the thermodynamically more
stable, as indicated by the acid-catalyzed isomerization
of 3 to 4. The equilibrium (3:4, 1:4) is reached after 6 h
at 50 °C in AcOH containing traces of HCl. Since all the
sugar substituents are in equatorial positions, the pre-
ferred configuration of the spirocenter of this dioxaspiro-
[4.5]decanyl ring system is then determined primarily
by the anomeric effect as occurs in the [5.5] variety.16
In order to prepare a 1,6-dioxaspiro[4.5]decane deriva-
tive with the spirocenter at C-5 the necessary two-
carbons homologation of the carbohydrate side chain was
accomplished from commercially available methyl R-D-
glucopyranoside as shown in Scheme 3. The tosylate 6
was prepared from alcohol 5 which in turn was obtained
by a three-step protocol from the above-mentioned glu-
copyranose in 60% overall yield.17 Compound 6 was
converted into allyl derivative 7 using freshly prepared
allylmagnesium bromide in ether (88%).18 The required
alcohol 8 was obtained by ozonolysis of 7 in a mixture of
CH2Cl2-MeOH followed by in situ reduction with NaBH4.
The hydrogen abstraction reaction was then carried out
by treating 8 with the DIB/iodine system, as shown in
Table 1 (entry 2) to yield the spiroacetal isomers 9 and
10 in a ratio of 1.7:1. The reaction proceeded in good
overall yield (75%), and the expected 1,3-diaxial steric
interaction by the 1R-methoxy group did not seem to
influence the six-membered transition state necessary for
the hydrogen abstraction. Assignment of the C-5 ster-
eochemistry was by examination of NOE difference
experiments as shown in Scheme 3. Reaction of the
minor isomer 10 with TsOH in AcOH gave after 7 h at
rt an approximately equimolecular mixture of 9 and 10.
agents as mild oxidizing agents for the generation of
alkoxy radicals from alcohols.11
This methodology allows both spiroacetal enantiomers
to be formally obtained from the same carbohydrate
depending on the carbon atom (C-1 or C-6) in which the
additional side chain si formed, since a hydroxymethyl-
enation12 of the anomeric carbon of B gives rise to the
optical isomer of A. Taking into account the relatively
limited variety in Nature of carbohydrates,13 particularly
hexoses, this feature is synthetically interesting because
it allows the required absolute configuration of the
stereogenic centers in natural spiroacetals to be achieved.
Resu lts a n d Discu ssion
Allyl derivative 1 was prepared following Kishi meth-
odology.14 Treatment of p-nitrobenzoyl 2,3,4,6-tetra-O-
benzyl-R-D-glucopyranoside with allyltrimethylsilane and
BF3‚Et2O gave a (R:â, 9:1) mixture of allylglucopyrans
from which the R-isomer 1 was separated by chromatog-
raphy (Scheme 2). Hydroboration-oxidation of the major
stereoisomer 1 gave rise to alcohol 2 which underwent
intramolecular hydrogen abstraction when submitted to
reaction with (diacetoxyiodo)benzene (DIB) and iodine
under the conditions summarized in Table 1 (entry 1).
Two C-1 isomeric dioxaspiro[4.5]decanyl derivatives 3
and 4 were formed in 68% overall yield in a ratio of 3:1.
By HETCOR and ROESY experiments15 both diastere-
omeric spiroacetals were found to possess the C-1 ster-
eochemistry illustrated in Scheme 2 in which the most
(15) (a) Bothner-By, A. A.; Stephens, R. L.; Lee, J .; Warren, C. D.;
J eanloz, R. W. J . Am. Chem. Soc. 1984, 106, 811-813. (b) Bax, A.;
Davis, D. G. J . Magn. Reson. 1985, 63, 207-213. (c) Kessler, H.;
Griesinger, C.; Kerssebaum, R.; Wagner, K.; Ernst, R. R. J . Am. Chem.
Soc. 1987, 109, 607-609.
(16) (a) Deslongchamps, P. Stereoelectronic Effects in Organic
Chemistry; Pergamon Press: New York, 1983. (b) Deslongchamps, P.;
Rowan, D. D.; Pothier, N.; Sauve´, T.; Saunders, J . K. Can. J . Chem.
1981, 59, 1105. (c) Pothier, N.; Rowan, D. D.; Deslongchamps, P.;
Saunders, J . K. Can. J . Chem. 1981, 59, 1132.
(17) (a) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 1990. (b)
Hirst, E. L.; Percival, E. In Methods in Carbohydrate Chemistry; Vol.
2; Whistler, R. L.; Wolfrom, M. L.; Eds.; Academic Press: New York,
1963; p 147.
(18) Aged solutions of allylmagnesium bromide, addition of CuI, or
changing the solvent to tetrahydrofuran, lead to complex mixtures.
(11) (a) Concepcio´n, J . J .; Francisco, C. G.; Herna´ndez, R.; Salazar,
J . A.; Sua´rez, E. Tetrahedron Lett. 1984, 25, 1953-1956. (b) Armas,
P.; Concepcio´n, J . J .; Francisco, C. G.; Herna´ndez, R.; Salazar, J . A.;
Sua´rez, E. J . Chem. Soc., Perkin Trans. 1 1989, 405-411. (c) Dorta,
R. L.; Francisco, C. G.; Herna´ndez, R.; Salazar, J . A.; Sua´rez, E. J .
Chem. Res. 1990, 240-241.
(12) Chatani, N.; Ikeda, T.; Sano, T.; Sonoda, N.; Kurosawa, H.;
Kawasaki, Y.; Murai, S. J . Org. Chem. 1988, 53, 3387-3389.
(13) Lichtenthaler, F. W.; Cuny, E.; Martin, D.; Ro¨nninger, S.;
Weber, T. In Carbohydrates as Organic Raw Materials; Lichtenthaler,
F. W., Ed.; VCH: Weinhein, 1991; pp 207-246.
(14) Lewis, M. D.; Cha, J . K.; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976-4978.

Synthesis of Chiral Spiroacetals from Carbohydrates
J . Org. Chem., Vol. 61, No. 12, 1996 4001
Ta ble 1. Syn th esis of Ch ir a l Sp ir oa ceta lsa
entry
substrate
reagentsb (mmol)
time (h)
T (°C)
products (yield, %)
3(51); 4(17)
1
2
3
4
5
6
7
8
9
2
8
11
11
11
18
18
18
DIB/I2(1.1/1)
DIB/I2(1.1/1)
DHSA/I2(2.5/1)
DIB/I2(1.1/1)
HgO/I2(1.5/1.5)
DIB/I2(1.1/1)
DHSA/I2(2.3/1.1)
HgO/I2(2.5/2.5)
DIB/I2(1.2/1)
DIB/I2(1.8/1)
1
0.6
6
3
9
0.5
5
5
3
2.5
40
40
80
40
20
40
80
20
40
40
9(47); 10(28)
12(7); 13(12); 14(8)
complex mixture
complex mixture
19(53); 20(33)
19(33); 20(24)
19(18); 20(33)
21
28+29
22(42); 23(25)
30(16); 31(9); 32(17); 33(7)
10
a
b
All reactions were performed in cyclohexane by irradiation with two 100 W tungsten-filament lamps. Per mmol of substrate; DIB
) (diacetoxyiodo)benzene; DHSA ) diphenylhydroxyselenium acetate [Ph2Se(OH)(OAc)].
Sch em e 3a
Sch em e 4a
a
(a) BH3‚THF; NaOH, H2O2; (b) see Table 1.
Sch em e 5a
a
(a) TsCl, Py, rt, 7 h; (b) CH2dCHCH2MgBr, Et2O, 0 °C f rt,
3 h; (c) O3, MeOH/CH2Cl2, -78 °C; (d) NaBH4, 0 °C f rt, 2.25 h;
(e) see Table 1; (f) TsOH, AcOH, rt, 7 h.
A study by molecular mechanics using the MMX force
field19 is in accord with the stability observed for the pair
of stereoisomers of the dioxaspiro[4.5]decanyl series 3 and
4 (4 is favored over 3 by 2.89 kcal/mol of MMX steric
energy) and also with the similar stability of stereoiso-
mers 9 and 10 (9 favored over 10 only by 0.4 kcal/mol).
With compound 7 at hand we decided to study the
formation of spiroacetals of the [5.5]undecane series.
Hydroboration-oxidation of olefin 7 afforded the alcohol
11 in 90% yield (Scheme 4). The photolysis of 11 in
presence of DIB/I2 or HgO/I2 led to complex mixtures that
were not studied (Table 1, entries 4 and 5). Nevertheless,
the use of diphenylhydroxyselenium acetate (DHSA) as
oxidant20 gave three compounds in low yield (entry 3) for
which we propose structures 12-14. By studies of
molecular mechanics and ROESY experiments the ste-
reochemistries were tentatively assigned as shown in
Scheme 4. The formation of compounds 13 and 14,
a
(a) TsCl, Py, rt, 16 h; (b) CH2dCHCH2MgBr, Et2O, rt, 4 h; (c)
BH3‚THF; NaOH, H2O2; 0 °C f rt, 4 h (d) see Table 1.
through a six-membered transition state, seems to indi-
cate difficulties for the radical abstraction of the C-5
proton, very probably due to 1,3-diaxial steric interactions
with the methoxyl group at C-1.
In an effort to avoid 13 and 14 we have prepared the
alcohol 18 in three steps from methyl 2,3,4-tri-O-methyl-
â-D-glucopyranoside (15) (Scheme 5), following an identi-
cal methodology with that used to obtain 8 (Scheme 3).17
The photolysis of 18 with DIB/I2 gave a good overall yield
(86%) of isomeric 1,7-dioxaspiro[5.5]undecane derivatives
19 and 20 (Table 1, entry 6). The use of other oxidant
systems DHSA and HgO led to poorer yields (entries 7
and 8). The C-5 sterochemistries were determined using
(19) MMX force field as implemented in PCMODEL (v. 4.0), Serena
Software, Bloomington IN, 47402-3076. See: Gajewski, J . J .; Gilbert,
K. E.; McKelvey, J . Advances in Molecular Modelling; J AI Press:
Greenwich, CT, 1992; Vol. 2.
(20) (a) Dorta, R. L.; Francisco, C. G.; Freire, R.; Sua´rez, E.
Tetrahedron Lett. 1988, 29, 5429-5432. (b) Dorta, R. L.; Francisco,
C. G.; Sua´rez, E. Tetrahedron Lett. 1994, 35, 1083-1086. (c) Dorta,
R. L.; Francisco, C. G.; Sua´rez, E. Tetrahedron Lett. 1994, 35, 2049-
2052.

4002 J . Org. Chem., Vol. 61, No. 12, 1996
Mart´ın et al.
a
Sch em e 6
Sch em e 7a
a
(a) See Table 1.
difference NOE and ROESY experiments in combination
with DEPT and HETCOR spectra to assign carbons and
protons as shown in Scheme 5. The major compound 19
is now the thermodynamically more stable by 2.7 kcal/
mol as established by molecular mechanics. It is also
clear from these calculations that the new ring adopts
the chair conformation that has a maximum number of
anomeric effects. We have not isolated, in this case, any
compound coming from a hydrogen abstraction through
a six-membered transition state as it occurred in the
photolysis of compound 11. As observed 1,3-diaxial
interactions seem to be critical for the synthesis of these
dioxaspiro[5.5]undecane derivatives using this methodol-
ogy (compare entries 3, 4 and 5 to 6). Contrarily, these
steric interactions have little effect on the synthesis of
dioxaspiro[4.5]decanes 9 and 10 (compare entries 1 and
2).
1-Allyl-1-deoxy-2,3:5,6-di-O-isopropylidene-R-D-manno-
furanose, prepared by radical allylation of the corre-
sponding 1-chloro-mannose derivative following the Keck
and Yates procedure,21 was transformed via hydrobora-
tion-oxidation into the desired alcohol 21. Photolysis
of 21 with the DIB/I2 system gave a mixture of the 1,6-
dioxaspiro[4.4]nonane derivatives 22 and 23 (entry 9).
The stereochemistries at C-1 were clearly assigned on
the basis of the ROESY spectra (principal correlations
shown by arrows in Scheme 6). As may be expected
compound 22 is the more stable (by 5 kcal/mol) as well
as being the major component of the C-1 isomeric
mixture.
a
(a) CCl4, Ph3P, reflux, 4.5 h; (b) CH2dCHCH2CH2MgBr, Et2O,
0 °C, 22 h; (c) BH3‚THF, 0 °C f rt, 5 h; NaOH, H2O2, 40 °C, 1 h;
(d) see Table 1.
pound 30 was confirmed by the observed ROESY interac-
tions of the proton at C-3′ with protons at C-2, C-3, and
C-4. The reduction of iodine derivatives 31 and 32 with
Bu3SnH to give, respectively, compounds 30 and 32 in
good yields established the C-1 stereochemistry of those
compounds.
The iodine compounds are probably formed by hydro-
gen abstraction at C-3′ through a more favorable six-
membered cyclic transition state before the abstraction
and spirocyclization at C-1 takes place.
Exp er im en ta l Section
Gen er a l. Melting points were determined with a hot-stage
apparatus and are uncorrected. Optical rotation measure-
ments were recorded at room temperature in CHCl3. IR
spectra were recorded in CHCl3 solutions. NMR spectra were
determined at 200 or 400 MHz for 1H and 50.3 MHz for 13C
for CDCl3 solutions unless otherwise stated in the presence of
TMS as internal standard. Phase sensitive ROESY spectra
were measured with a mixing time of 700 ms. Mass spectra
were determined at 70 eV unless otherwise specified. Merck
silica gel 60 PF254 and 60 (0.063-0.2 mm) were used for
preparative thin-layer chromatography (TLC) and column
chromatography, respectively. Circular layers of 1 mm of
Merck silica gel 60 PF254 were used on a chromatotron for
centrifugally assisted chromatography. Commercial reagents
and solvents were analytical grade or were purified by
standard procedures prior to use.23 All reactions involving air-
or moisture-sensitive materials were carried out under an
argon atmosphere. The spray reagent for TLC was vanillin
(1 g) in H2SO4-EtOH (4:1; 200 mL). (Diacetoxyiodo)benzene
(DIB) 98% was purchased from Aldrich. Diphenylhydroxyse-
lenium acetate (DHSA) [Ph2Se(OH)(OAc)] has been previously
prepared in this laboratory.20a
The synthesis of spiroacetals of the [4.5]decane type
in which the tetrahydropyran ring is formed during the
radical reaction was accomplished from the mannofura-
nosyl chloride 25. Treatment of 25 with 3-butenylmag-
nesium bromide gave the mixture of isomers 26 and 27
which could only be partially resolved by careful chro-
matography (Scheme 7).22 The mixture of alcohols 28
and 29, obtained by hydroboration of olefins 26 and 27,
was then submitted to the radical cyclization reaction
conditions (entry 10). In this case two iodine compounds
31 and 33 were formed besides the expected spiroacetals
30 and 32. The proposed C-1 stereochemistry for com-
(21) (a) Keck, G. E.; Yates, J . B. J . Am. Chem. Soc. 1982, 104, 5829-
5831. (b) Keck, G. E.; Enholm, E. J .; Yates, J . B.; Wiley, M. R.
Tetrahedron 1985, 41, 4079-4094.
(22) Franc¸ois, P.; Perilleux, D.; Kempener, Y.; Sonveaux, E. Tetra-
hedron Lett. 1990, 31, 6347-6350.
(23) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals, 3rd ed.; Pergamon Press: New York, 1988.

Synthesis of Chiral Spiroacetals from Carbohydrates
J . Org. Chem., Vol. 61, No. 12, 1996 4003
2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-(3′-h yd r oxyp r op yl)-r-
D-glu cop yr a n ose (2). To a solution of compound 114 (455 mg,
0.807 mmol) in dry THF (40 mL) at 0 °C and under Ar was
added dropwise a 1 M solution of BH3-THF complex (4.4 mL,
4.4 mmol) and stirred at rt for 5 h. The mixture was then
cooled to 0 °C and treated with a 3 M aqueous solution of
NaOH (25 mL). The oxidation was carried out by slow
dropwise addition of 30% H2O2 (25 mL), the temperature being
maintained below 40 °C. After stirring for an additional 0.5
h, the reaction mixture was poured into water and extracted
with CH2Cl2. The combined extracts were washed with brine,
dried over Na2SO4, and concentrated under reduced pressure.
Chromatotron chromatography of the residue (n-hexane-
EtOAc, 75:25) gave compound 2 (345 mg, 73%) as a crystalline
solid: mp 91.5-92.5 °C (from acetone-n-hexane); [R]D +21.3°
spiroacetals 4 (12 mg, 0.021 mmol, 80%) and 3 (3 mg, 0.005
mmol, 20%).
Meth yl 2,3,4-Tr i-O-m eth yl-6-O-tosyl-r-D-glu cop yr a n o-
sid e (6). To a solution of alcohol 517 (3.71 g, 15.7 mmol) in
dry pyridine (70 mL) was added, under Ar, tosyl chloride (9 g,
47.1 mmol), and the solution was stirred at rt for 16 h. The
reaction mixture was then poured into ice-water and ex-
tracted with CHCl3. The organic extracts were washed with
dilute HCl and water, dried over Na2SO4, and concentrated
under reduced pressure to give the title compound 6 (6 g, 15
1
mmol, 98%): IR 1364, 1177 cm-1; H NMR 2.45 (3H, s), 3.05
(1H, dd, J ) 8.8, 10 Hz), 3.11 (1H, dd, J ) 3.5, 9.5 Hz), 3.34
(3H, s), 3.46 (3H, s), 3.47 (1H, dd, J ) 9.5, 10 Hz), 3.48 (3H,
s), 3.59 (3H, s), 3.62 (1H, ddd, J ) 2.4, 4.1, 8.5 Hz), 4.20 (1H,
dd, J ) 2.4, 10.7 Hz), 4.25 (1H, dd, J ) 4.1, 10.7 Hz), 4.72
(1H, d, J ) 3.5 Hz), 7.35 (2H, d, J ) 8.2 Hz), 7.81 (2H, d, J )
8.3 Hz); 13C NMR 21.56 (q), 55.22 (q), 58.92 (q), 60.40 (q), 60.72
(q), 68.42 (d), 68.66 (t), 78.75 (d), 81.45 (d), 83.33 (d), 97.31
(d), 127.92 (2 × d), 129.76 (2 × d), 132.99 (s), 144.79 (s); MS
(CI, CH4) m/ z (rel intensity) 389 ([M - H]+, 1), 359 (8), 327
(100), 295 (23), 219 (6), 187 (47), 155 (100).
1
(c ) 0.474); IR 3650, 3500 cm-1; H NMR 1.63-1.82 (4H, m),
3.57-3.80 (8H, m), 4.03 (1H, m), 4.45 (1H, d, J ) 10.7 Hz),
4.48 (1H, d, J ) 11.9 Hz), 4.57 (1H, s), 4.63 (1H, s), 4.70 (1H,
d, J ) 11.9 Hz), 4.79 (1H, d, J ) 10.9 Hz), 4.81 (1H, d, J )
10.7 Hz), 4.92 (1H, d, J ) 10.9 Hz), 7.11-7.36 (20H, m); 13C
NMR 20.84 (t), 29.01 (t), 62.15 (t), 69.02 (t), 71.00 (d), 72.98
(t), 73.37 (t), 74.20 (d), 74.90 (t), 75.33 (t), 78.11 (d), 80.07 (d),
82.27 (d), 127.48-128.30 (20 × d), 137.78 (s), 138.03 (s), 138.14
(s), 138.59 (s); MS (EI) m/ z (rel intensity) 583 ([M + H]+, 1),
491 (3), 385 (29), 277 (12), 259 (14), 253 (31), 181 (100); HRMS
calcd for C30H35O6 491.2434, found 491.2424.
Meth yl 6-Allyl-6-d eoxy-2,3,4-tr i-O-m eth yl-r-D-glu cop y-
r a n osid e (7). To a solution of p-toluenesulfonate 6 (615 mg,
1.577 mmol) in dry Et2O (30 mL) was added, under Ar at 0
°C, allylmagnesium bromide in Et2O (6.5 mL, 6.31 mmol). The
mixture was stirred at rt for 4 h, poured into brine, and
extracted with Et2O. The organic layer was washed with
aqueous saturated NaHCO3 and brine, dried over Na2SO4, and
concentrated under reduced pressure. Chromatotron chroma-
tography (n-hexane-EtOAc, 85:15) of the residue gave the title
P h otolysis of 2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-(3′-h y-
d r oxyp r op yl)-r-D-glu cop yr a n ose (2). A solution of com-
pound 2 (33 mg, 0.06 mmol) in cyclohexane (7 mL) containing
DIB (22 mg, 0.066 mmol) and iodine (15 mg, 0.06 mmol) under
Ar was irradiated with two 100 W tungsten-filament lamps
at 40 °C for 1 h. The reaction mixture was then poured into
aqueous saturated Na2S2O3 and extracted with CH2Cl2, dried
over Na2SO4, and concentrated. Chromatotron chromatogra-
phy of the residue (n-hexane-EtOAc, 90:10) gave (1R)-2,3,4,6-
tetra-O-benzyl-1-deoxy-D-glucopyranose-1-spiro-2′-tetrahydro-
furan (3) (16.8 mg, 0.029 mmol, 51%) and (1S)-2,3,4,6-tetra-
O-ben zyl-1-deoxy-D-glu copyr a n ose-1-spir o-2′-t et r a h ydr o-
furan (4) (5.6 mg, 0.01 mmol, 17%). Compound 3: mp 69.8-
71.3 °C (from acetone-n-hexane); [R]D +29.8° (c ) 0.416); IR
2990, 1355, 1060, 1022 cm-1; 1H NMR 1.93-2.00 (2H, m), 2.04
(1H, m), 2.19 (1H, m), 3.47 (1H, m), 3.54-3.63 (2H, m), 3.66-
3.74 (3H, m), 3.95 (1H, dd, J ) 6.8, 13.6 Hz), 4.10 (1H, dd, J
) 7.5, 13.6 Hz), 4.52 (1H, d, J ) 10.7 Hz), 4.55 (1H, d, J )
11.9 Hz), 4.61 (1H, d, J ) 11.9 Hz), 4.74 (1H, d, J ) 11.1 Hz),
4.78 (1H, d, J ) 10.9 Hz), 4.83 (1H, d, J ) 10.7 Hz), 4.86 (1H,
d, J ) 11.1 Hz), 4.92 (1H, d, J ) 10.9 Hz), 7.14-7.36 (20H,
m); 13C NMR 25.02 (t), 27.73 (t), 68.20 (t), 69.46 (t), 73.41 (t),
73.83 (d), 75.08 (t), 75.08 (t), 75.63 (t), 78.13 (d), 82.28 (d), 84.40
(d), 109.88 (s), 127.52-128.50 (20 × d), 138.10 (s), 138.22 (s),
138.66 (s), 138.73 (s); MS (EI) m/ z (rel intensity) 580 (M+, 1),
489 (2), 459 (1), 397 (3), 383 (4), 365 (2), 273 (1), 240 (100);
HRMS calcd for C37H40O6 580.2825, found 580.2827. Com-
pound 4: IR 2980, 1355, 1070, 1020 cm-1; 1H NMR 1.78-1.98
(4H, m), 3.55 (1H, d, J ) 9.5 Hz), 3.62 (1H, dd, J ) 1.9, 10.8
Hz), 3.68 (1H, t, J ) 9.5 Hz), 3.72 (1H, dd, J ) 3.7, 10.8 Hz),
3.82-3.89 (2H, m), 3.99 (1H, m), 4.02 (1H, t, J ) 9.5 Hz), 4.52
(1H, d, J ) 12.2 Hz), 4.54 (1H, d, J ) 10.9 Hz), 4.58 (1H, d, J
) 12.2 Hz), 4.68 (1H, d, J ) 11.4 Hz), 4.83 (1H, d, J ) 10.9
Hz), 4.88 (1H, d, J ) 11 Hz), 4.91 (1H, d, J ) 11 Hz), 4.95
(1H, d, J ) 11.4 Hz), 7.15-7.34 (20H, m); 13C NMR 24.02 (t),
33.44 (t), 68.13 (t), 68.74 (t), 71.24 (d), 73.31 (t), 74.73 (t), 75.46
(t), 75.55 (t), 78.50 (d), 80.05 (d), 84.52 (d), 107.34 (s), 127.52-
128.80 (20 × d), 138.04 (s), 138.15 (s), 138.36 (s), 138.68 (s);
MS (EI) m/ z (rel intensity) 580 (M+, 1), 489 (4), 397 (5), 365
(2), 291 (5), 274 (5), 253 (40); HRMS calcd for C37H40O6
580.2825, found 580.2826.
compound 7 (361 mg, 1.39 mmol, 88%): IR 3079, 1640 cm-1
;
1H NMR 1.45 (1H, m), 1.86 (1H, m), 2.05 (1H, m), 2.22 (1H,
m), 2.75 (1H, t, J ) 9.4 Hz), 3.12 (1H, dd, J ) 3.6, 9.5 Hz),
3.32-3.55 (2H, m), 3.34 (3H, s), 3.46 (3H, s), 3.50 (3H, s), 3.57
(3H, s), 4.71 (1H, d, J ) 3.6 Hz), 4.93 (1H, dd, J ) 1.5, 10.3
Hz), 5.00 (1H, dd, J ) 1.5, 17.4 Hz), 5.78 (1H, dddd, J ) 6.6,
6.6, 10.2, 17.0 Hz); 13C NMR 29.74 (t), 30.88 (t), 54.87 (q), 58.79
(q), 60.56 (q), 60.68 (q), 69.38 (d), 81.98 (d), 83.44 (d), 84.06
(d), 97.06 (d), 114.69 (t), 138.23 (d); MS (CI, CH4) m/ z (rel
intensity) 260 (M+, 1), 259 (5), 229 (100), 197 (98), 173 (9),
165 (29), 145 (63); HRMS calcd for C12H21O4 229.1440, found
229.1439.
Meth yl 6-Deoxy-6-(2′-h yd r oxyeth yl)-2,3,4-tr i-O-m eth yl-
r-D-glu cop yr a n osid e (8). A solution of compound 7 (200 mg,
0.769 mmol) in CH2Cl2/MeOH (51 mL, 1:1) was cooled to -78
°C, and ozone was introduced into the solution until it became
blue. Then Ar was bubbled through the solution to expel
excess of ozone, and the mixture was heated to 0 °C. NaBH4
(73 mg, 1.92 mmol) was added and the solution stirred for 2.25
h at rt. The reaction mixture was then poured into water and
extracted with CHCl3, dried over Na2SO4, and concentrated.
Chromatotron chromatography of the residue (first n-hexane-
EtOAc, 45:55 and then 30:70) gave compound 8 (174 mg, 0.66
mmol, 86%): mp 59.8-60.6 °C (from n-hexane); [R]D +141.5°
1
(c ) 0.260); IR 3622, 3464 cm-1; H NMR 1.39-1.98 (4H, m),
2.81 (1H, dd, J ) 8.9, 9.6 Hz), 3.16 (1H, dd, J ) 3.6, 9.7 Hz),
3.39 (3H, s), 3.47 (1H, t, J ) 9.5 Hz), 3.49 (1H, m), 3.50 (3H,
s), 3.55 (3H, s), 3.61 (3H, s), 3.67 (2H, t, J ) 6.2 Hz), 4.76 (1H,
d, J ) 3.6 Hz); 13C NMR 27.92 (t), 28.86 (t), 55.01 (q), 58.84
(q), 60.64 (q), 60.75 (q), 62.54 (t), 69.98 (d), 81.90 (d), 83.43
(d), 83.94 (d), 97.12 (d); MS (EI) m/ z (rel intensity) 247 ([M -
OH]+, 2), 233 (2), 201 (5), 169 (8), 145 (4), 131 (22), 101 (78),
88 (100); HRMS calcd for C11H21O5 233.1389, found 233.1375.
P h otolysis of Meth yl 6-Deoxy-6-(2′-h ydr oxyeth yl)-2,3,4-
tr i-O-m eth yl-r-D-glu cop yr a n osid e (8). A solution of alcohol
8 (117 mg, 0.443 mmol) in cyclohexane (8 mL) containing DIB
(158 mg, 0.487 mmol) and iodine (111 mg, 0.443 mmol) under
Ar was irradiated at 40 °C for 0.5 h in a similar manner to
that described above for the photolysis of 2. Chromatotron
chromatography of the reaction residue (n-hexane-EtOAc, 60:
40) gave methyl (5S)-6-deoxy-5,2′-epoxy-6-ethyl-2,3,4-tri-O-
methyl-R-D-glucopyranoside (9) (55 mg, 0.21 mmol, 47%) and
methyl (5R)-6-deoxy-5,2′-epoxy-6-ethyl-2,3,4-tri-O-methyl-R-D-
glucopyranoside (10) (32 mg, 0.122 mmol, 28%). Compound
9: IR 2838, 1446, 1375, 1167, 1077 cm-1; 1H NMR 1.96-2.12
(4H, m), 3.20 (1H, d, J ) 9.2 Hz), 3.28 (1H, dd, J ) 4, 9.1 Hz),
Isom er iza tion of (1R)-2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-
D-glu cop yr a n ose-1-sp ir o-2′-t et r a h yd r ofu r a n (3). To a
solution of spiro compound 3 (15 mg, 0.026 mmol) in acetic
acid (1 mL) was added a solution of HCl (2 µL) in acetic acid
(0.075 mL). The mixture was stirred at 50 °C for 6 h, poured
into an aqueous solution of KOH (0.5%), and extracted with
CH2Cl2. The combined extracts weredried over Na2SO4 and
concentrated under reduced pressure. Chromatotron chroma-
tography of the residue (n-hexane-EtOAc, 92:8) gave the

4004 J . Org. Chem., Vol. 61, No. 12, 1996
Mart´ın et al.
3.34 (1H, t, J ) 9.2 Hz), 3.45 (3H, s), 3.49 (3H, s), 3.51 (3H, s),
3.59 (3H, s), 3.82 (1H, m), 4.01 (1H, m), 4.79 (1H, d, J ) 3.9
Hz), irradiation at δ 1.96-2.12 (6-H2) gave rise to a NOE
enhancement of the 3-H signal (δ 3.34, 10%); 13C NMR 24.85
(t), 31.07 (t), 56.26 (q), 58.97 (q), 60.76 (q), 60.80 (q), 67.80 (t),
80.42 (d), 81.07 (d), 83.91 (d), 98.09 (d), 110.29 (s); MS (EI)
m/ z (rel intensity) 261 ([M - H]+, 3), 231 (90), 199 (41), 171
(13), 167 (9), 145 (8), 101 (67), 88 (100); HRMS calcd for
C11H19O5 231.1232, found 231.1206. Compound 10: IR 2836,
1445, 1376, 1171, 1089 cm-1; 1H NMR 1.86-2.16 (4H, m), 3.12
(1H, d, J ) 9.6 Hz), 3.22 (1H, dd, J ) 4.0, 9.7 Hz), 3.42 (3H,
s), 3.51 (3H, s), 3.61 (3H, s), 3.64 (3H, s), 3.80 (1H, t, J ) 9.7
Hz), 3.98-4.08 (2H, m), 4.79 (1H, d, J ) 4.0 Hz), irradiation
at δ 1.86-2.16 (6-H2) gave rise to a NOE enhancement of the
4-H signal (δ 3.12, 6.5%); 13C NMR 24.09 (t), 36.07 (t), 55.49
(q), 58.92 (q), 60.75 (q), 61.40 (q), 70.25 (t), 80.30 (d), 82.14
(d), 83.11 (d), 98.14 (d), 108.50 (s); MS (EI) m/ z (rel intensity)
231 ([M - OMe]+, 6), 199 (3), 167 (2), 159 (3), 114 (98), 101
(44), 88 (100); HRMS calcd for C11H19O5 231.1232, found
231.1264.
Isom er iza tion of Meth yl 5(R)-6-Deoxy-5,2′-ep oxy-6-
eth yl-2,3,4-tr i-O-m eth yl-r-D-glu cop yr a n osid e (10). To a
solution of spiro compound 10 (4 mg, 0.015 mmol) in acetic
acid (0.4 mL) was added a 0.1 M solution of TsOH in acetic
acid (0.015 mL). The mixture was stirred at rt for 7 h, poured
into an aqueous solution of NaOH (10%), and extracted with
CH2Cl2. The combined extracts were dried over Na2SO4 and
concentrated under reduced pressure. Chromatotron chroma-
tography of the residue (n-hexane-EtOAc, 92:8) gave the
spiroacetals 10 (1.6 mg, 0.006 mmol, 40%) and 9 (1.4 mg, 0.005
mmol, 35%).
3.53 (3H, s), 3.54 (3H, s), 3.57 (3H, s), 3.73 (1H, m), 3.96 (1H,
ddd, J ) 2.8, 11.2, 12.4 Hz), 4.87 (1H, d, J ) 3.6 Hz); 13C NMR
18.43 (t), 25.15 (t), 29.21 (t), 56.99 (q), 59.09 (q), 60.09 (q), 60.23
(q), 61.91 (t), 79.47 (d), 80.69 (d), 86.02 (d), 97.61 (d), 100.67
(s); MS (CI, CH4) m/ z (rel intensity) 276 (M+, 1), 275 (7), 245
(100), 213 (83), 181 (49), 153 (100), 88 (100); HRMS calcd for
C12H21O5 245.1389, found 245.1377. Compound 13: IR 2934,
2830, 1160, 1097, 1050 cm-1; 1H NMR 1.86-1.97 (4H, m), 3.23
(1H, dd, J ) 3.6, 9.6 Hz), 3.28 (1H, dd, J ) 8.8, 10 Hz), 3.39
(3H, s), 3.46 (1H, dd, J ) 8.8, 9.6 Hz), 3.50 (3H, s), 3.58 (3H,
s), 3.61 (1H, m), 3.62 (3H, s), 3.75 (1H, m), 3.91 (1H, m), 4.15
(1H, m), 4.82 (1H, d, J ) 3.6 Hz); 13C NMR 25.97 (t), 26.70 (t),
55.03 (q), 58.95 (q), 60.63 (q), 60.81 (q), 68.73 (t), 70.95 (d),
75.90 (d), 80.48 (d), 81.62 (d), 83.78 (d), 97.52 (d); MS (CI, CH4)
m/ z (rel intensity) 275 ([M - H]+, 7), 245 (95), 213 (100), 185
(12), 181 (29), 153 (11), 88 (95); HRMS calcd for C12H21O5
245.1389, found 245.1400. Compound 14: IR 2933, 2835,
1158, 1096, 1055 cm-1; 1H NMR 1.82-1.97 (4H, m), 2.96 (1H,
t, J ) 9.6 Hz), 3.16 (1H, dd, J ) 3.6, 9.6 Hz), 3.40 (3H, s), 3.51
(3H, s), 3.52 (3H, s), 3.55 (1H, t, J ) 9.6 Hz), 3.62 (3H, s), 3.76
(1H, dd, J ) 2.2, 10 Hz), 3.77 (1H, m), 3.90 (1H, dd, J ) 6.4,
13.6 Hz), 4.16 (1H, ddd, J ) 2.2, 6.4, 6.4 Hz), 4.79 (1H, d, J )
3.6 Hz); 13C NMR 25.14 (t), 25.96 (t), 54.86 (q), 58.89 (q), 60.23
(q), 60.90 (q), 68.44 (t), 70.84 (d), 78.10 (d), 81.54 (d), 81.93
(d), 83.65 (d), 96.94 (d); MS (CI, CH4) m/ z (rel intensity) 277
([M + H]+, 13), 275 (7), 245 (47), 213 (100), 205 (2), 181 (37),
88 (100); HRMS calcd for C11H17O4 213.1127, found 213.1107.
Photolysis was also performed with DIB/I2 (Table 1, entry 4)
and with HgO/I2 (Table 1, entry 5) but complex mixtures were
obtained in both cases.
Meth yl 2,3,4-tr i-O-m eth yl-6-O-tosyl-â-D-glu cop yr a n o-
sid e (16). To a solution of alcohol 1517 (2.95 g, 12.5 mmol) in
dry pyridine (60 mL) was added, under Ar, tosyl chloride (7.14
g, 37.5 mmol), and the solution was stirred at rt for 7 h. The
reaction mixture was then poured into ice-water and ex-
tracted with CH2Cl2. The organic extracts were washed with
dilute HCl and water, dried over Na2SO4, and concentrated
under reduced pressure to give the title compound 16 (4.8 g,
12.3 mmol, 98%): mp 72.5-74.1 °C (from n-hexane-EtOAc);
Meth yl 6-Deoxy-6-(3′-h yd r oxyp r op yl)-2,3,4-tr i-O-m eth -
yl-r-D-glu cop yr a n osid e (11). To a solution of compound 7
(328 mg, 1.26 mmol) in dry THF (20 mL) at 0 °C and under
Ar was added dropwise a 1 M solution of BH3-THF complex
(5 mL) and stirred at rt for 4 h. The mixture was then cooled
to 0 °C and treated with a 3 M aqueous solution of NaOH (52
mL). The oxidation was carried out by slow dropwise addition
of 30% H2O2 (52 mL), the temperature being maintained below
40 °C. After stirring for an additional 1 h, the reaction mixture
was poured into water and extracted with CH2Cl2. The
combined extracts were washed with brine, dried over Na2-
SO4, and concentrated under reduced pressure. Chromatotron
chromatography of the residue (n-hexane-EtOAc, 40:60) gave
1
[R]D -13.3° (c ) 0.346); IR 1599, 1448, 1364, 1176 cm-1; H
NMR 2.45 (3H, s), 2.91 (1H, dd, J ) 7.7, 8.5 Hz), 3.02 (1H, t,
J ) 9.0 Hz), 3.13 (1H, t, J ) 8.6 Hz), 3.34 (1H, ddd, J ) 2.2,
4.9, 9.5 Hz), 3.43 (3H, s), 3.48 (3H, s), 3.54 (3H, s), 3.59 (3H,
s), 4.08 (1H, d, J ) 7.6 Hz), 4.18 (1H, dd, J ) 4.9, 10.4 Hz),
4.27 (1H, dd, J ) 2.2, 10.4 Hz), 7.34 (2H, d, J ) 8.2 Hz), 7.81
(2H, d, J ) 8.3 Hz); 13C NMR 21.5 (q), 56.67 (q), 60.24 (q),
60.29 (q), 60.57 (q), 68.56 (t), 72.36 (d), 78.62 (d), 83.31 (d),
86.19 (d), 103.8 (d), 127.89 (2 × d), 129.67 (2 × d), 132.79 (s),
144.72 (s); MS (EI) m/ z (rel intensity) 389 ([M - H]+, <1),
359 (<1), 327 (10), 295 (2), 219 (1), 187 (5), 88 (100); HRMS
calcd for C15H19O6S 327.0902, found 327.0901.
compound 11 (315 mg, 1.13 mmol, 90%): IR 3623, 3475 cm-1
;
1H NMR 1.36-1.50 (2H, m), 1.52-1.71 (2H, m), 1.78-1.86 (2H,
m), 2.78 (1H, t, J ) 9.2 Hz), 3.15 (1H, dd, J ) 3.7, 9.6 Hz),
3.36-3.59 (2H, m), 3.37 (3H, s), 3.49 (3H, s), 3.52 (3H, s), 3.60
(3H, s), 3.64 (2H, t, J ) 6.3 Hz), 4.73 (1H, d, J ) 3.6 Hz); 13C
NMR 21.77 (t), 31.15 (t), 32.59 (t), 54.89 (q), 58.78 (q), 60.57
(q), 60.72 (q), 62.41 (t), 69.95 (d), 81.94 (d), 83.45 (d), 83.97
(d), 97.02 (d); MS (CI, CH4) m/ z (rel intensity) 277 ([M - H]+,
2), 261 (52), 247 (80), 229 (36), 215 (100), 183 (98). HRMS
calcd for C11H19O4 215.1283, found 215.1279.
Meth yl 6-Allyl-6-d eoxy-2,3,4-tr i-O-m eth yl-â-D-glu cop y-
r a n osid e (17). To a solution of p-toluenesulfonate 16 (4.5 g,
11.5 mmol) in dry Et2O (200 mL) was added, under Ar at 0
°C, allylmagnesium bromide in Et2O (48.6 mL, 46 mmol). The
mixture was stirred at rt for 3 h, poured into brine, and
extracted with Et2O. The organic layer was washed with
aqueous saturated NaHCO3 and water, dried over Na2SO4, and
concentrated under reduced pressure. Dry column chroma-
tography (n-hexane-EtOAc, 90:10) of the residue gave the title
compound 17 (2.38 g, 9.15 mmol, 79%): IR 3078, 1640, 1086,
1061 cm-1; 1H NMR 1.53 (1H, m), 1.88 (1H, m), 2.06-2.30 (2H,
m), 2.81 (1H, t, J ) 9.1 Hz), 2.93 (1H, dd, J ) 7.7, 9.2 Hz),
3.09 (1H, ddd, J ) 2.4, 9.5, 9.5 Hz), 3.11 (1H, t, J ) 8.9 Hz),
3.50 (3H, s), 3.52 (3H, s), 3.54 (3H, s), 3.59 (3H, s), 4.06 (1H,
d, J ) 7.7 Hz), 4.95 (1H, dddd, J ) 1.7, 1.7, 1.7, 10.0 Hz), 5.01
(1H, dddd, J ) 1.6, 1.6, 1.6, 17.0 Hz), 5.80 (1H, dddd, J ) 7.0,
7.0, 10.1, 17.0 Hz); 13C NMR 29.68 (t), 30.79 (t), 56.73 (q), 60.33
(q), 60.60 (q), 60.68 (q), 73.67 (d), 83.87 (d), 83.95 (d), 86.58
(d), 104.08 (d), 114.82 (t), 138.12 (d); MS (CI, CH4) m/ z (rel
intensity) 259 ([M - H]+, 2), 229 (5), 197 (9), 173 (4), 165 (13),
101 (31), 88 (100); HRMS calcd for C12H21O4 229.1440, found
229.1430.
P h otolysis of Meth yl 6-Deoxy-6-(3′-h yd r oxyp r op yl)-
2,3,4-tr i-O-m eth yl-r-D-glu cop yr a n osid e (11). A solution of
compound 11 (102 mg, 0.367 mmol) in cyclohexane (6 mL)
containing DHSA (205 mg, 0.66 mmol) and iodine (92 mg,
0.367 mmol) under Ar was irradiated with two 100 W
tungsten-filament lamps at reflux temperature for 3 h. Fur-
thermore DHSA (79 mg, 0.257 mmol) was added and the reflux
continued for 3 h. The reaction mixture was then poured into
aqueous saturated Na2S2O3 and extracted with CH2Cl2, dried
over Na2SO4, and concentrated. Chromatotron chromatogra-
phy (n-hexane-EtOAc, 85:15) of the residue afforded methyl
(5R)-6-deoxy-5,3′-epoxy-2,3,4-tri-O-methyl-6-propyl-R-D-glu-
copyranoside (12) (7 mg, 0.025 mmol, 7%) and a mixture of
two compounds 13 and 14 which was separated by flash
chromatography over neutral alumina (benzene-EtOAc, 97.5:
2.5) to afford: methyl (6S)-6-deoxy-6,3′-epoxy-2,3,4-tri-O-meth-
yl-6-propyl-R-D-glucopyranoside (13) (12 mg, 0.043 mmol, 12%)
and methyl (6R)-6-deoxy-6,3′-epoxy-2,3,4-tri-O-methyl-6-pro-
pyl-R-D-glucopyranoside (14) (8 mg, 0.027 mmol, 8%). Com-
pound 12: IR 2935, 2840, 1081, 1045 cm-1
1.69 (3H, m), 1.79-1.91 (3H, m), 3.03 (1H, d, J ) 8 Hz), 3.39
(1H, dd, J ) 3.6, 8 Hz), 3.42 (1H, t, J ) 8 Hz), 3.52 (3H, s),
;
1H NMR 1.63-
Meth yl 6-Deoxy-6-(3′h yd r oxyp r op yl)-2,3,4-tr i-O-m eth -
yl-â-D-glu cop yr a n osid e (18). To a solution of compound 17
(200 mg, 0.77 mmol) in dry THF (12 mL) at 0 °C and under

Synthesis of Chiral Spiroacetals from Carbohydrates
J . Org. Chem., Vol. 61, No. 12, 1996 4005
Ar was added dropwise a 1 M solution of BH3-THF complex
(4.62 mL) and stirred at rt for 5 h. The mixture was then
cooled to 0 °C and treated with a 3 M aqueous solution of
NaOH (32 mL). The oxidation was carried out by slow
dropwise addition of 30% H2O2 (32 mL), the temperature being
maintained below 40 °C. After stirring for an additional 1 h,
the reaction mixture was poured into water and extracted with
CH2Cl2. The combined extracts were washed with brine, dried
over Na2SO4, and concentrated under reduced pressure. Chro-
matotron chromatography of the residue (n-hexane-EtOAc,
1:1) gave the compound 18 (196 mg, 0.7 mmol, 92%): mp 56.5-
58.5 °C (from acetone-n-hexane); [R]D -4.5° (c ) 0.334); IR
3620, 3450 cm-1; 1H NMR 1.39-1.89 (6H, m), 2.87 (1H, t, J )
9 Hz), 2.95 (1H, dd, J ) 7.7, 9 Hz), 3.09 (1H, m), 3.13 (1H, t,
J ) 9 Hz), 3.51 (3H, s), 3.54 (3H, s), 3.56 (3H, s), 3.61 (3H, s),
3.65 (2H, t, J ) 6.3 Hz), 4.10 (1H, d, J ) 7.7 Hz); 13C NMR
21.66 (t), 31.11 (t), 32.39 (t), 56.65 (q), 60.23 (q), 60.50 (q), 60.58
(q), 62.32 (t), 74.40 (d), 83.68 (d), 83.79 (d), 86.42 (d), 103.97
(d); MS (EI) m/ z (rel intensity) 261 ([M - OH]+, 6), 247 (3),
229 (3), 215 (7), 187 (5), 183 (14), 145 (23), 101 (100), 88 (100);
HRMS calcd for C13H25O5 261.1702, found 261.1700.
(t), 29.03 (t), 62.08 (t), 66.77 (t), 73.36 (d), 79.77 (d), 80.57 (d),
84.10 (d), 85.28 (d), 109.02 (s), 112.51 (s); MS (EI) m/ z (rel
intensity) 287 ([M - CH3]+, 73), 229 (4), 211 (3), 201 (4), 187
(4), 169 (10), 101 (100); HRMS calcd for C14H23O6 287.1495,
found 287.1488.
P h otolysis of 1-Deoxy-1-(3′-h yd r oxyp r op yl)-2,3:5,6-d i-
O-isop r op ylid en e-r-D-m a n n ofu r a n ose (21). A solution of
compound 21 (50 mg, 0.165 mmol) in cyclohexane (10 mL)
containing DIB (95 mg, 0.29 mmol) and iodine (42 mg, 0.165
mmol) under Ar was irradiated at 40 °C for 3 h in a similar
manner to that described above for the photolysis of 2.
Chromatotron chromatography of the reaction residue (n-
hexane-EtOAc, 85:15) gave (1S)-1-deoxy-2,3:5,6-di-O-isopro-
pylidene-D-mannofuranose-1-spiro-2′-tetrahydrofuran (22) (20
mg, 0.067 mmol, 42%) and (1R)-1-deoxy-2,3:5,6-di-O-isopro-
pylidene-D-mannofuranose-1-spiro-2′-tetrahydrofuran (23) (12.5
mg, 0.042 mmol, 25%). Compound 22: IR 3015, 1388, 1378,
1070 cm-1 1H NMR 1.34 (3H, s), 1.37 (3H, s), 1.44 (3H, s),
;
1.46 (3H, s), 1.88 (1H, m), 1.94-2.01 (2H, m), 2.14 (1H, m),
3.85 (1H, dd, J ) 3.7, 8.2 Hz), 3.91 (2H, t, J ) 6.6 Hz), 4.01
(1H, dd, J ) 4.4, 8.8 Hz), 4.08 (1H, dd, J ) 6.4, 8.8 Hz), 4.35
(1H, ddd, J ) 4.4, 6.4, 8.4 Hz), 4.52 (1H, d, J ) 6 Hz), 4.81
(1H, dd, J ) 3.7, 6 Hz); 13C NMR 23.53 (t), 24.69 (q), 25.23 (q),
25.95 (q), 26.67 (q), 31.01 (t), 67.01 (t), 67.91 (t), 73.12 (d), 78.99
(d), 80.08 (d), 84.98 (d), 109.19 (s), 112.51 (s), 115.08 (s); MS
(EI) m/ z (rel intensity) 285 ([M - CH3]+, 100), 242 (7), 199
(53), 184 (4), 167 (82), 141 (52), 101 (99); HRMS calcd for
C14H21O6 285.1338, found 285.1333. Compound 23: IR 3010,
1388, 1377, 1072 cm-1; 1H NMR 1.33 (6H, s), 1.41 (3H, s), 1.43
(3H, s), 1.74 (1H, m), 1.94-2.06 (3H, m), 3.48 (1H, dd, J ) 4,
8 Hz), 3.95 (1H, ddd, J ) 0.8, 7, 15 Hz), 4.02 (1H, dd, J ) 4.2,
8.8 Hz), 4.07 (1H, dd, J ) 6, 8.8 Hz), 4.08 (1H, m), 4.43 (1H,
ddd, J ) 4.4, 6.2, 8.2 Hz), 4.48 (1H, d, J ) 6 Hz), 4.75 (1H, dd,
J ) 4, 6 Hz); 13C NMR 24.20 (t), 24.77 (q), 25.15 (q), 25.77 (q),
27.06 (q), 34.08 (t), 67.09 (t), 69.18 (t), 73.28 (d), 77.04 (d), 79.20
(d), 83.01 (d), 109.26 (s), 112.55 (s), 113.48 (s); MS (EI) m/ z
(rel intensity) 285 ([M - CH3]+, 51), 243 (6), 199 (22), 167 (15),
141 (38), 101 (65); HRMS calcd for C14H21O6 285.1338, found
285.1350.
P h otolysis of Meth yl 6-Deoxy-6-(3′h yd r oxyp r op yl)-
2,3,4-tr i-O-m eth yl-â-D-glu cop yr a n osid e (18). A solution of
compound 18 (50 mg, 0.18 mmol) in cyclohexane (5 mL)
containing DIB (64 mg, 0.198 mmol) and iodine (45 mg, 0.18
mmol) under Ar was irradiated at 40 °C for 0.5 h in a similar
manner to that described above for the photolysis of 2.
Chromatotron chromatography of the reaction residue (n-
hexane-EtOAc, 85:15) gave methyl (5R)-6-deoxy-5,3′-epoxy-
2,3,4-tri-O-methyl-6-propyl-â-D-glucopyranoside (19) (16.5 mg,
0.059 mmol, 53%) and methyl (5S)-6-deoxy-5,3′-epoxy-2,3,4-
tri-O-methyl-6-propyl-â-D-glucopyranoside (20) (26.5 mg, 0.095
mmol, 33%). Compound 19: IR 2836, 1128, 1086, 1049 cm-1
;
1H NMR 1.50-1.53 (2H, m), 1.66-1.71 (2H, m), 1.81-1.93 (2H,
m), 2.83 (1H, d, J ) 9.6 Hz), 2.99 (1H, t, J ) 8.6 Hz), 3.50
(1H, t, J ) 9.4 Hz), 3.56 (3H, s), 3.57 (3H, s), 3.58 (3H, s), 3.60
(3H, s), 3.66-3.77 (2H, m), 4.42 (1H, d, J ) 8 Hz), irradiation
at δ 2.83 (4-H) gave rise to a NOE enhancement of the 6-H2
signal (9.5%); 13C NMR 18.11 (t), 24.41 (t), 30.05 (t), 56.86 (q),
60.35 (q), 60.83 (q), 61.15 (t), 61.53 (q), 82.65 (d), 84.10 (d),
85.17 (d), 97.25 (s), 98.99 (d); MS (EI) m/ z (rel intensity) 275
([M - H]+, 3), 245 (71), 213 (21), 181 (13), 153 (18), 128 (100),
101 (31), 88 (100); HRMS calcd for C12H21O5 245.1389, found
245.1389. Compound 20: IR 2837, 1446, 1089, 1008 cm-1; 1H
NMR 1.53-1.76 (6H, m), 3.12 (1H, d, J ) 7.1 Hz), 3.16 (1H, t,
J ) 7.2 Hz), 3.32 (1H, t, J ) 7.2 Hz), 3.52 (3H, s), 3.54 (3H, s),
3.54 (3H, s), 3.56 (3H, s), 3.71 (1H, m), 4.02 (1H, ddd, J ) 2.6,
11.7, 11.7 Hz), 4.38 (1H, d, J ) 6.9 Hz); 13C NMR 17.88 (t),
25.11 (t), 27.07 (t), 56.15 (q), 59.66 (q), 59.70 (q), 59.83 (q),
61.72 (t), 82.96 (d), 83.37 (d), 85.75 (d), 98.99 (s), 100.57 (d);
MS (EI) m/ z (rel intensity) 245 ([M - OMe]+, 6), 213 (4), 181
(5), 153 (7), 128 (100), 101 (20), 88 (94); HRMS calcd for
C12H21O5 245.1389, found 245.1391. Photolysis was also
performed with DHSA/I2 (Table 1, entry 7) and with HgO/I2
(Table 1, entry 8).
1-(3′-Bu ten yl)-1-d eoxy-2,3:5,6-d i-O-isop r op ylid en e-r-D-
m a n n ofu r a n ose (26) a n d 1-(3′-Bu ten yl)-1-d eoxy-2,3:5,6-
d i-O-isop r op ylid en e-â-D-m a n n ofu r a n ose (27). To a solu-
tion of 2,3:5,6-di-O-isopropylidene-D-mannofuranose (24) (1 g,
3.85 mmol) in dry THF (18 mL) were added under Ar CCl4
(2.7 mL, 28 mmol) and Ph3P (2.52 g, 9.6 mmol). The mixture
was heated at reflux for 4.5 h, cooled at rt, filtered over Celite
545, and concentrated under reduced pressure. To a solution
of the crude residue containing compound 25 (3.2 g) in dry
Et2O (40 mL) was added freshly prepared 3-butenylmagnesium
bromide in Et2O (49 mL, 53.9 mmol) under Ar at 0 °C and the
reaction kept at rt for 22 h. The reaction mixture was then
poured into brine and extracted with Et2O, dried over Na2-
SO4, and concentrated. Dry column chromatography (n-
hexane-EtOAc, 93:7) gave a mixture of compounds 26 and
27 (825 mg, 2.77 mmol, 72%, 26:27 ) 65:35). The mixture
could be partially resolved by careful chromatotron chroma-
1-D e o x y -1-(3′-h y d r o x y p r o p y l)-2,3:5,6-d i-O -is o p r o -
p ylid en e-r-D-m a n n ofu r a n ose (21). To a solution of 1-allyl-
1-deoxy-2,3:5,6-di-O-isopropylidene-R-D-mannofuranose21 (443
mg, 1.56 mmol) in dry THF (50 mL) at 0 °C and under Ar was
added dropwise a 1 M solution of BH3-THF complex (4.7 mL,
4.7 mmol) and stirred at rt for 4 h. The mixture was then
cooled to 0 °C and treated with a 3 M aqueous solution of
NaOH (50 mL). The oxidation was carried out by slow
dropwise addition of 30% H2O2 (50 mL), the temperature being
maintained below 40 °C. After stirring for an additional 1 h,
the reaction mixture was poured into water and extracted with
CH2Cl2. The combined extracts were washed with brine, dried
over Na2SO4, and concentrated under reduced pressure. Chro-
matotron chromatography of the residue (n-hexane-EtOAc, 60:
40) gave compound 21 (310 mg, 70%): IR 3660, 3500 cm-1; 1H
NMR 1.32 (3H, s), 1.36 (3H, s), 1.43 (3H, s), 1.48 (3H, s), 1.39-
1.66 (4H, m), 3.66 (2H, t, J ) 5.9 Hz), 3.77 (1H, dd, J ) 3.7,
7.4 Hz), 4.02 (1H, dd, J ) 4.8, 8.6 Hz), 4.07 (1H, t, J ) 7.2
Hz), 4.09 (1H, dd, J ) 6, 8.6 Hz), 4.39 (1H, ddd, J ) 4.9, 6.0,
7.3 Hz), 4.49 (1H, d, J ) 6.3 Hz), 4.75 (1H, dd, J ) 3.7, 6.1
Hz); 13C NMR 24.52 (q), 25.05 (q), 25.99 (q), 26.78 (q), 27.04
1
tography. Compound 26: IR 3080, 1640 cm-1; H NMR 1.34
(3H, s), 1.38 (3H, s), 1.40-1.65 (2H, m), 1.46 (3H, s), 1.50 (3H,
s), 2.13 (2H, m), 3.72 (1H, dd, J ) 3.7, 7.6 Hz), 4.04 (1H, dd,
J ) 4.7, 8.7 Hz), 4.07 (1H, m), 4.11 (1H, dd, J ) 6.1, 8.7 Hz),
4.40 (1H, ddd, J ) 4.8, 6.0, 7.6 Hz), 4.51 (1H, d, J ) 6.2 Hz),
4.77 (1H, dd, J ) 3.7, 6.1 Hz), 5.00 (1H, dddd, J ) 1.6, 1.6,
1.6, 10.2 Hz), 5.05 (1H, dddd, J ) 1.7, 1.7, 1.7, 17.0 Hz), 5.82
(1H, dddd, J ) 6.5, 6.5, 10.2, 16.9 Hz); 13C NMR 24.61 (q),
25.31 (q), 26.07 (q), 26.94 (q), 29.68 (t), 29.80 (t), 67.03 (t), 73.43
(d), 79.93 (d), 80.71 (d), 83.56 (d), 85.28 (d), 109.14 (s), 112.52
(s), 115.26 (t), 137.43 (d); MS (EI) m/ z (rel intensity) 299 ([M
+ H]+, 16), 283 (100), 241 (44), 225 (29), 197 (7), 181 (17), 123
(98), 101 (100); HRMS calcd for C16H26O5 298.1780, found
298.1782. Compound 27: mp 35.7-37.3 °C (from n-hexane);
[R]D -5.6° (c ) 0.250): IR 3079, 1640 cm-1; 1H NMR 1.33 (3H,
s), 1.38 (3H, s), 1.45 (3H, s), 1.47 (3H, s), 1.70-1.86 (2H, m),
2.18 (2H, m), 3.45 (1H, dd, J ) 3.6, 7.6 Hz), 3.48 (1H, ddd, J
) 3.6, 6.7, 6.7 Hz), 4.05 (1H, dd, J ) 5.1, 8.7 Hz), 4.10 (1H,
dd, J ) 5.8, 8.7 Hz), 4.40 (1H, ddd, J ) 5.3, 5.3, 7.6 Hz), 4.60
(1H, dd, J ) 3.6, 6.2 Hz), 4.73 (1H, dd, J ) 3.6, 6.2 Hz), 4.98

4006 J . Org. Chem., Vol. 61, No. 12, 1996
Mart´ın et al.
(1H, dddd, J ) 1.6, 1.6, 1.6, 10.2 Hz), 5.04 (1H, dddd, J ) 1.7,
1.7, 1.7, 17.1 Hz), 5.82 (1H, dddd, J ) 6.6, 6.6, 10.2, 16.9 Hz);
13C NMR 24.71 (q), 25.32 (q), 25.78 (q), 26.90 (q), 27.35 (t),
30.22 (t), 66.97 (t), 73.23 (d), 80.83 (d), 81.35 (d), 81.50 (d),
81.55 (d), 108.98 (s), 112.24 (s), 114.74 (t), 138.20 (d); MS (EI)
m/ z (rel intensity) 299 ([M + H]+, 3), 298 (M+, 1), 283 (100),
241 (10), 225 (5), 197 (3), 165 (10), 123 (91), 101 (98); HRMS
calcd for C16H26O5 298.1780, found 298.1761.
(1H, m), 1.88 (1H, m), 2.35 (1H, m), 2.51 (1H, dddd, J ) 4.1,
12.8, 12.8, 12.8 Hz), 3.85 (1H, m), 3.97 (1H, ddd, J ) 2.5, 11.3,
11.3 Hz), 4.10 (1H, dd, J ) 6.4, 8.6 Hz), 4.14 (1H, dd, J ) 4.8,
8.6 Hz), 4.27 (1H, dd, J ) 4.5, 12.4 Hz), 4.31 (1H, dd, J ) 4.6,
6.9 Hz), 4.41 (1H, ddd, J ) 4.9, 6.5, 6.5 Hz), 4.86 (1H, dd, J )
4.6, 6.2 Hz), 4.90 (1H, d, J ) 6.2 Hz); 13C NMR 25.32 (q), 25.56
(q), 25.56 (q), 26.91 (q), 28.44 (t), 34.16 (t), 34.34 (d), 61.97 (t),
66.57 (t), 74.15 (d), 79.86 (d), 81.64 (d), 85.80 (d), 101.74 (s),
109.23 (s), 114.72 (s); MS (EI) m/z (rel intensity) 441 ([M +
H]+, 8), 425 (69), 397 (9), 383 (20), 339 (13), 313 (89), 255 (23),
141 (35), 101 (100); HRMS calcd for C15H22O6I 425.0461, found
425.0463. Compound 32: IR 2945, 1373, 1162, 1085 cm-1; 1H
NMR 1.32 (3H, s), 1.39 (3H, s), 1.46 (6H, s), 1.54-1.80 (6H,
m), 3.58 (1H, m), 3.72 (1H, ddd, J ) 2.7, 11.5, 11.5 Hz), 3.83
(1H, dd, J ) 3.7, 8.0 Hz), 4.05 (1H, dd, J ) 4.4, 8.6 Hz), 4.13
(1H, dd, J ) 6.2, 8.6 Hz), 4.34 (1H, d, J ) 6.0 Hz), 4.40 (1H,
ddd, J ) 4.4, 6.2, 8.0 Hz), 4.78 (1H, dd, J ) 3.7, 6.0 Hz); 13C
NMR 19.25 (t), 24.55 (q), 25.19 (t), 25.29 (q), 25.91 (q), 26.89
(q), 28.50 (t), 61.28 (t), 67.17 (t), 73.17 (d), 78.81 (d), 80.02 (d),
85.85 (d), 105.71 (s), 109.16 (s), 112.43 (s); MS (EI) m/z (rel
intensity) 315 ([M + H]+, 9), 313 (3), 299 (94), 257 (18), 241
(12), 213 (29), 181 (43), 141 (65), 101 (100); HRMS calcd for
1-Deoxy-1-(4′-h yd r oxyb u t yl)-2,3:5,6-d i-O-isop r op yli-
den e-r-D-m an n ofu r an ose (28) an d 1-Deoxy-1-(4′-h ydr oxy-
bu tyl)-2,3:5,6-di-O-isopr opyliden e-â-D-m an n ofu r an ose (29).
To a solution of compounds 26 and 27 (514 mg, 1.72 mmol) in
dry THF (17 mL) at 0 °C and under Ar was added dropwise a
1 M solution of BH3-THF complex (10.3 mL) and stirred at rt
for 5 h. The mixture was then cooled to 0 °C and treated with
a 3 M aqueous solution of NaOH (35 mL). The oxidation was
carried out by slow dropwise addition of 30% H2O2 (35 mL),
the temperature being maintained below 40 °C. After stirring
for an additional 1 h, the reaction mixture was poured into
water and extracted with CH2Cl2. The combined extracts were
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure. Dry column chromatography of the residue
(n-hexane-EtOAc, 1:1) gave compounds 28 and 29 (480 mg,
1.52 mmol, 88%). An aliquot of the mixture could be partially
resolved by careful chromatotron chromatography. Compound
C
16H25O6 313.1651, found 313.1658. Compound 33: IR 2934,
1
1375, 1099, 1065 cm-1; H NMR 1.12 (1H, brd, J ) 13.8 Hz),
1.35 (3H, s), 1.41 (3H, s), 1.47 (3H, s), 1.73 (3H, s), 2.18 (1H,
m), 2.69 (1H, ddd, J ) 2.8, 2.8, 14.6 Hz), 2.98 (1H, ddd, J )
4.1, 12.5, 14.6 Hz), 3.69-3.81 (2H, m), 3.99 (1H, dd, J ) 4.2,
5.6 Hz), 4.16 (1H, dd, J ) 6.5, 8.7 Hz), 4.25 (1H, dd, J ) 5.4,
8.7 Hz), 4.47 (1H, d, J ) 6.1 Hz), 4.47 (1H, ddd, J ) 5.5, 5.5,
6.5 Hz), 4.72 (1H, dd, J ) 4.2, 6.1 Hz); 13C NMR 24.04 (q),
25.36 (q), 25.60 (q), 26.59 (q), 26.97 (t), 50.45 (t), 60.03 (t), 66.34
(t), 73.53 (d), 79.10 (d), 80.48 (d), 87.96 (d), 103.16 (s), 108.85
(s), 113.63 (s), the C-3′(s) could not be observed; MS (EI) m/z
(rel intensity) 567 ([M + H]+, 3), 551 (49), 509 (16), 439 (28),
424 (10), 381 (11), 323 (6), 312 (100), 196 (29), 101 (100); HRMS
calcd for C15H21O6I2 550.9428, found 550.9432.
1
28: IR 3620, 3488 cm-1; H NMR 1.34 (3H, s), 1.38 (3H, s),
1.41-1.69 (6H, m), 1.46 (3H, s), 1.50 (3H, s), 3.66 (1H, t, J )
6.3 Hz), 3.73 (1H, dd, J ) 3.7, 7.7 Hz), 4.04 (1H, dd, J ) 4.6,
8.7 Hz), 4.06 (1H, m), 4.11 (1H, dd, J ) 6.1, 8.7 Hz), 4.40 (1H,
ddd, J ) 4.6, 6.0, 7.7 Hz), 4.51 (1H, d, J ) 6.4 Hz), 4.77 (1H,
dd, J ) 3.7, 6.1 Hz); 13C NMR 22.01 (t), 24.64 (q), 25.14 (q),
26.10 (q), 26.94 (q), 30.29 (t), 32.22 (t), 62.69 (t), 67.01 (t), 73.46
(d), 79.98 (d), 80.75 (d), 84.08 (d), 85.29 (d), 109.14 (s), 112.56
(s); MS (EI) m/z (rel intensity) 317 ([M+H]+, 8), 301 (100), 259
(81), 243 (9), 215 (6), 200 (10), 183 (22), 165 (43), 101 (97);
HRMS calcd for C15H25O6 301.1651, found 301.1647. Com-
1
pound 29: IR 3620, 3496 cm-1; H NMR 1.26-1.79 (6H, m);
1.34 (3H, s), 1.38 (3H, s), 1.45 (3H, s), 1.48 (3H, s), 3.47 (1H,
dd, J ) 3.6, 7.3 Hz), 3.47 (1H, ddd, J ) 3.6, 6.8, 6.8 Hz), 3.67
(1H, t, J ) 6.2 Hz), 4.05 (1H, dd, J ) 5.1, 8.6 Hz), 4.10 (1H,
dd, J ) 5.8, 8.6 Hz), 4.40 (1H, ddd, J ) 5.2, 5.2, 7.4 Hz), 4.62
(1H, dd, J ) 3.6, 6.2 Hz), 4.74 (1H, dd, J ) 3.6, 6.2 Hz); 13C
NMR 22.22 (t), 24.70 (q), 25.30 (q), 25.76 (q), 26.92 (q), 27.76
(t), 32.59 (t), 62.59 (t), 66.97 (t), 73.22 (d), 80.78 (d), 81.42 (d),
81.60 (d), 82.16 (d), 109.00 (s), 112.32 (s); MS (EI) m/z (rel
intensity) 317 ([M + H]+, 8), 301 (100), 259 (58), 243 (6), 215
(5), 183 (21), 165 (45), 101 (96); HRMS calcd for C15H25O6
301.1651, found 301.1658.
Red u ction of (1S,3′R)-1-Deoxy-2,3:5,6-d i-O-isop r op yl-
id en e-D-m a n n ofu r a n ose-1-sp ir o-2′-(3′-iod otetr a h yd r op y-
r a n ) (31). To a solution of compound 31 (4 mg, 0.009 mmol)
in dry benzene (1 mL) were added Bu3SnH (0.012 mL, 0.045
mmol) and AIBN (1 mg, 0.006 mmol) and stirred at reflux
temperature for 40 min. The reaction mixture was then
poured into water, extracted with Et2O, dried over Na2SO4,
and concentrated. The residue was purified by chromatotron
chromatography (n-hexane-EtOAc, 87:13) to give compound
30 (2.3 mg, 0.007 mmol, 80%).
Red u ction of (1R)-1-Deoxy-2,3:5,6-d i-O-isop r op ylid en e-
D-m a n n ofu r a n ose-1-sp ir o-2′-(3′,3′-d iiod ot et r a h yd r op y-
r a n ) (33). To a solution of compound 33 (5 mg, 0.009 mmol)
in dry benzene (1 mL) were added Bu3SnH (0.024 mL, 0.09
mmol) and AIBN (1 mg, 0.006 mmol) and stirred at reflux
temperature for 0.5 h. The reaction mixture was then poured
into water, extracted with Et2O, dried over Na2SO4, and
concentrated. The residue was purified by chromatotron
chromatography (n-hexane-EtOAc, 93:7) to give compound 32
(2.5 mg, 0.008 mmol, 90%).
P h otolysis of 1-Deoxy-1-(4′-h yd r oxybu tyl)-2,3:5,6-d i-O-
isop r op ylid en e-D-m a n n ofu r a n ose (28+29). A solution of
the mixture of alcohols 28 and 29 (40 mg, 0.126 mmol) in
cyclohexane (4 mL) containing DIB (73 mg, 0.227 mmol) and
iodine (32 mg, 0.126 mmol) under Ar was irradiated at 40 °C
for 2.5 h in a similar manner to that described above for the
photolysis of 2. Chromatotron chromatography of the reaction
residue (n-hexane-EtOAc, 93:7) gave (1R)-1-deoxy-2,3:5,6-di-
O-isopropylidene-D-mannofuranose-1-spiro-2′-tetrahydropy-
ran (30) (6.4 mg, 0.02 mmol, 16%), (1S,3′R)-1-deoxy-2,3:5,6-
di-O-isopropylidene-D-mannofuranose-1-spiro-2′-(3′-iodo-
tetrahydropyran) (31) (5.1 mg, 0.011 mmol, 9%), (1S)-1-deoxy-
2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′-tet-
rahydropyran (32) (6.8 mg, 0.022 mmol, 17%), (1R)-1-deoxy-
2,3:5,6-di-O-isopropylidene-D-mannofuranose-1-spiro-2′-(3′,3′-
diiodotetrahydropyran) (33) (5.1 mg, 0.009 mmol, 7%).
Compound 30: IR 2942, 1373, 1236, 1066 cm-1; 1H NMR 1.36
(3H, s), 1.38 (3H, s), 1.46 (3H, s), 1.50-1.79 (6H, m), 1.56 (3H,
s), 3.73 (1H, dd, J ) 4.4, 7.9 Hz), 3.85-3.88 (2H, m), 4.11 (2H,
d, J ) 5.3 Hz), 4.35 (1H, d, J ) 6.1 Hz), 4.45 (1H, ddd, J )
5.3, 5.3, 7.9 Hz), 4.77 (1H, dd, J ) 4.4, 6.1 Hz); 13C NMR 19.18
(t), 24.80 (t), 25.26 (q), 25.42 (q), 25.73 (q), 27.00 (q), 31.65 (t),
63.67 (t), 66.96 (t), 73.69 (d), 77.80 (d), 79.67 (d), 84.87 (d),
102.96 (s), 109.23 (s), 114.05 (s); MS (EI) m/z (rel intensity)
315 ([M + H]+, 3), 299 (30), 257 (9), 239 (6), 213 (22), 181 (12),
141 (52), 101 (100); HRMS calcd for C15H23O6 299.1495, found
Ack n ow led gm en t. This work was supported by the
Investigation Programme no. PB93-0171 of the Direc-
cio´n General de Investigacio´n Cient´ıfica y Te´cnica and
Programmes no. 93/030 and 93/014 of the Direccio´n
General de Universidades e Investigacio´n del Gobierno
de Canarias. A.M. thanks the Ministerio de Educacio´n
y Ciencia, Spain, for a fellowship.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
and 13C NMR spectra of compounds 2-4, 6-14, 16-23, and
26-33 (56 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.
1
299.1487. Compound 31: IR 2992, 1373, 1075, 994 cm-1; H
NMR 1.36 (3H, s), 1.39 (3H, s), 1.48 (3H, s), 1.55 (3H, s), 1.73
J O960060G