Intramolecular hydrogen abstraction reaction promoted by alkoxy radicals in carbohydrates. Synthesis of chiral 2,7-dioxabicyclo[2.2.1]heptane and 6,8-dioxabicyclo[3.2.1]octane ring systems

Article abstract of DOI:10.1021/jo026004z

The reaction of specifically protected anhydroalditols with (diacetoxyiodo)benzene or iodosylbenzene and iodine is a mild and selective procedure for the synthesis of chiral 6,8-dioxabicyclo [3.2.1]octane and 2,7-dioxabicyclo[2.2.1]heptane ring systems under neutral conditions. This reaction can be considered to be an intramolecular glycosidation that goes through an intramolecular hydrogen abstraction promoted by an alkoxy radical followed by oxidation of the transient C-radical intermediate to an oxycarbenium ion. This methodology is useful not only for the preparation of chiral synthons but also for the selective oxidation of specific carbons of the carbohydrate skeleton, constituting a good procedure for the synthesis of protected uloses.

Full text of DOI:10.1021/jo026004z

In tr a m olecu la r Hyd r ogen Abstr a ction Rea ction P r om oted by
Alk oxy Ra d ica ls in Ca r boh yd r a tes. Syn th esis of Ch ir a l
2,7-Dioxa bicyclo[2.2.1]h ep ta n e a n d 6,8-Dioxa bicyclo[3.2.1]octa n e
Rin g System s
Cosme G. Francisco, Antonio J . Herrera, 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
esuarez@ipna.csic.es
Received J une 3, 2002
The reaction of specifically protected anhydroalditols with (diacetoxyiodo)benzene or iodosylbenzene
and iodine is a mild and selective procedure for the synthesis of chiral 6,8-dioxabicyclo[3.2.1]octane
and 2,7-dioxabicyclo[2.2.1]heptane ring systems under neutral conditions. This reaction can be
considered to be an intramolecular glycosidation that goes through an intramolecular hydrogen
abstraction promoted by an alkoxy radical followed by oxidation of the transient C-radical
intermediate to an oxycarbenium ion. This methodology is useful not only for the preparation of
chiral synthons but also for the selective oxidation of specific carbons of the carbohydrate skeleton,
constituting a good procedure for the synthesis of protected uloses.
The most representative examples of the 2,7-dioxabicy-
clo[2.2.1]heptane and 6,8-dioxabicyclo[3.2.1]octane sys-
tems are the 1,5-anhydrofuranoses, 1,4-anhydropyra-
noses, and 1,6-anhydropyranoses, a series of anhydro-
sugars to which the trivial name glycosans was given.1
1,6-Anhydropyranoses are generally formed by acid
treatment of the corresponding carbohydrates, by ther-
mal depolymerization of some polysaccharides, and by
specific intramolecular glycosidation reactions by O-6
nucleophilic attack of a good leaving group at the ano-
meric center. In this latter case the opposite reaction,
displacement of a 6-leaving group by the anomeric
oxygen, may also be possible.2 1,5-Anhydrofuranoses and
1,4-anhydropyranoses, both possessing a 2,7-dioxabicyclo-
[2.2.1]heptane ring system, are more strained compounds
and require a more specific synthesis.3
organic chemistry for the preparation of enantiomerically
pure non-carbohydrate compounds,4 and also for the
synthesis of complex oligosaccharides5 and C-disaccha-
rides.6 The ether bridge locks the conformation of the
carbohydrate ring and simultaneously protects two of the
hydroxylic groups, which may be important features in
a synthetic process.7 Of special interest are the acid-
catalyzed transformation of the 6,8-dioxabicyclo[3.2.1]-
octane into the 2,8-dioxabicyclo[3.2.1]octane ring system
present in the core of zaragozic acids,8 and the synthesis
of oxepanes by stereoselective reduction of the acetal
group.9
Furthermore, 6,8-dioxabicyclo[3.2.1]octane structural
units are widespread in bioactive natural products. These
compounds can have relatively simple structures such
as the pheromones frontalin,10 multistriatin, and exo-
brevicomin11 or can be very complex substances isolated
These compounds are considered intramolecular gly-
cosides and are important building blocks in synthetic
(4) (a) Bols, M. Carbohydrate Building Blocks; J ohn Wiley: New
York, 1996; pp 43-48. (b) Hanessian, S. Total Synthesis of Natural
Products: The ‘Chiron’ Approach; Pergamon Press: Oxford, UK, 1983.
(c) Carbohydrate Chemistry; Ferrier, R. J ., Ed.; Specialist Periodical
Report; Royal Society of Chemistry: London, UK, 2001; Vol. 32, pp
353-395 and previous volumes of the series.
* To whom correspondence should be addressed. Fax: 34-922
260135.
(1) (a) Carbohydrate Chemistry; Ferrier, R. J ., Ed.; Specialist
Periodical Report; Royal Society of Chemistry: London, UK, 2001; Vol.
32, pp 85-91 and previous volumes of the series. (b) Levoglucosenone
and Levoglucosans, Chemistry and Applications; Proceedings from the
Symposium at the 204th National Meeting of the American Chemical
Society, Washington, D.C.; Witczak, Z. J ., Ed.; ATL Press: IL, 1994.
(c) Collins, P. M.; Ferrier, R. J . Monosaccharides, Their Chemistry and
Their Roles in Natural Products; J ohn Wiley: Chichester, UK, 1995;
pp 89-90.
(2) (a) Boons, G.-J .; Isles, S.; Seta¨la¨, P. Synlett 1995, 755-756. (b)
Bernlind, C.; Oscarson, S. J . Org. Chem. 1998, 63, 7780-7788. (c)
Lafont, D.; Boullanger, P.; Cadas, O.; Descotes, G. Synthesis 1989,
191-194.
(3) (a) Bols, M.; Thomsen, I. B. Chem. Commun. 1998, 1869-1870.
(b) Balu, N.; Bhat, S. V. J . Chem. Soc., Chem. Commun. 1994, 903-
904. (c) Sharma, G. V. M.; Chander, A. S.; Krishma, P. R. Tetrahe-
dron: Asymmetry 2001, 12, 539-544. (d) J aoven, V.; J e´gou, A.; Leme´e,
L.; Veyrie`res, A. Tetrahedron 1999, 55, 9245-9260. (e) Taba, K. M.;
Ko¨ster, R.; Dahlhoff, W. V. Synthesis 1983, 1036-1037.
(5) Paulsen, H. Angew. Chem., Int. Ed. 1982, 21, 155-173.
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481.
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I.; Febner, K.; Finlay, R. V. Tetrahedron Lett. 1997, 38, 4301-4304.
(c) Evans, D. A.; Polniaszek, R. P.; DeVries, K. M.; Guin, D. E.; Mathre,
D. J . J . Am. Chem. Soc. 1991, 113, 7613-7630.
(8) (a) Caron, S.; McDonald, A. I.; Heathcock, C. H. J . Org. Chem.
1995, 60, 2780-2785. (b) Caron, S.; Stoermer, D.; Mapp, A. K.;
Heathcock, C. H. J . Org. Chem. 1996, 61, 9126-9134.
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4595-4612. (b) Fujiwara, K.; Amano, A.; Tokiwano, T.; Murai, A.
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Berranger, T.; Langlois, Y.; Tran-Huu-Dau, M. E.; Riche, C. J . Org.
Chem. 1998, 63, 5123-5128.
10.1021/jo026004z CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/21/2002
J . Org. Chem. 2002, 67, 7439-7445
7439

Francisco et al.
SCHEME 1
SCHEME 2. Su bstr a tes for th e
2,7-Dioxa bicyclo[2.2.1]h ep ta n e Ser iesa
from marine organisms such as palytoxin,12 pinnatoxin
A,13 didemniserinolipid A,14 and cyclodidemniserinol.15 On
the other hand, the system 2,7-dioxabicyclo[2.2.1]heptane
is also present in natural products such as isogosterone,16
loukacinol B,17 and salpichrolide J .18
The general route for the preparation of these dioxabi-
cyclo[n.2.1]alkane ring systems during the synthesis of
these natural products is the acid-catalyzed cyclization
of the corresponding keto diols. Here we report on an
alternative methodology for the synthesis of chiral 2,7-
dioxabicyclo[2.2.1]heptane and 6,8-dioxabicyclo[3.2.1]-
octane ring systems, under neutral conditions, using an
intramolecular hydrogen abstraction (IHA) reaction.19
The reaction was triggered by alkoxy radicals generated
in situ by reaction of alcohols with (diacetoxyiodo)benzene
(DIB) or iodosylbenzene in the presence of iodine. The
C-radical generated by the IHA is subsequently oxidized
with an excess of reagent to give an oxycarbenium ion
that is then internally trapped by the nucleophilic alcohol
(Scheme 1). In a previous communication, we described
some preliminary results obtained,20 and we now disclose
herein full details of these experiments. The reaction was
tested in the pentose and hexose series of carbohydrates
a
Key: (a) methyl (triphenylphosphoranylidene)acetate, MeCN,
rt, overnight, 83%; (b) Bu4NF, THF, rt; (c) LiAlH4, THF, rt, 1 h,
98%; (d) NaH, trimethylsulfoxonium iodide, DMSO, rt, 2 h, 23%;
(e) triphosgene, CH2Cl2/Py, -70 °C, 96%.
by using models in pyranose and furanose forms as
depicted in Schemes 2 and 3.
Syn th esis of Su bstr a tes a n d Resu lts. The aldonic
ester 3 and 2,5-anhydro-alditols 4 and 6 were prepared
from 2,3-O-isopropylidene-D-ribofuranose21 by using a
well-established method for the C-glycosidation of car-
bohydrates (Scheme 2).22 The Wittig reaction with methyl
(triphenylphosphoranylidene)acetate and subsequent cy-
clization left the tether preferentially on the R-side of the
molecule, due to the presence of the bulky TBDPS-
protecting group (2R/2â, 5.5:1).23 The reaction of the free
lactol with trimethylsulfoxonium ylide afforded exclu-
sively the required R-isomer 5.24 Reaction of the known25
diol 7 with triphosgene26 afforded the cyclic carbonate 8
that was subsequently desilylated to give the desired
alcohol 9. 3,6-Anhydro-1,2:4,5-di-O-isopropylidene-D-glyc-
ero-D-manno-heptitol (10) was prepared from D-mannose
as previously described (Table 1, entry 5).24
(11) Recent synthesis of multistriatin and exo-brevicomin: Tanigu-
chi, T.; Ohnishi, H.; Ogasawara, K. J . Chem. Soc., Chem. Commun.
1996, 1477-1478.
(12) Synthesis of palytoxin: Armstrong, R. W.; Beau, J .-M.; Cheon,
S. H.; Christ, W. J .; Fujioka, H.; Ham, W.-H.; Hawkins, L. D.; J in, H.;
Kang, S. H.; Kishi, Y.; Martinelli, M. J .; McWhorter, W. W., J r.;
Mizuno, M.; Nakana, M.; Stutz, A. E.; Talamas, F. X.; Taniguchi, M.;
Tino, J . A.; Ueda, K.; Uenishi, J .; White, J . B.; Yonaga, M. J . Am. Chem.
Soc. 1989, 111, 7525-7530.
(13) Synthesis of pinnatoxin: McCauley, J . A.; Nagasawa, K.;
Lander, P. A.; Mischke, S. G.; Semones, M. A.; Kishi, Y. J . Am. Chem.
Soc. 1998, 120, 7647-7648.
We have also prepared a number of C-glycosides of the
tetrahydropyran group in order to extend the IHA
(14) Gonza´lez, N.; Rodr´ıguez, J .; J ime´nez, C. J . Org. Chem. 1999,
64, 5705-5707.
(15) Mitchell, S. S.; Rhodes, D.; Bushman, F. D.; Faulkner, D. J .
Org. Lett. 2000, 2, 1605-1607.
(21) (a) Dudfield, P. J .; Le, V.-D.; Lindell, S. D.; Rees, C. W. J . Chem.
Soc., Perkin Trans. 1 1999, 2929-2936. (b) Chiacchio, U.; Coesano,
A.; Gumina, G.; Rescifina, A.; Iannazzo, D.; Piperno, A.; Romeo, G.;
Romeo, R. J . Org. Chem. 1999, 64, 9321-9327.
(22) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides; Pergamon
Press: Oxford, UK, 1995.
(16) Tomono, Y.; Hirota, H.; Fusetani, N. J . Org. Chem. 1999, 64,
2272-2275.
(17) Loukaci, A.; Kayser, O.; Bindseil, K.-U.; Siems, K.; Frevert, J .;
Abreu, P. M. J . Nat. Prod. 2000, 63, 52-56.
(18) Tettamanzi, M. C.; Veleiro, A. S.; Fuente, J . R.; Burton, G. J .
Nat. Prod. 2001, 64, 783-786.
(23) Ohrui, H.; J ones, G. H.; Moffatt, J . G.; Maddox, M. L.; Christen-
sen, A. T.; Byram, S. K. J . Am. Chem. Soc. 1975, 97, 4602-4613.
(24) Fre´chou, C.; Dheilly, L.; Beaupe`re, D.; Uzan, R.; Demailly, G.
Tetrahedron Lett. 1992, 33, 5067-5070.
(19) Recent reviews: (a) Majetich, G.; Wheless, K. Tetrahedron 1995,
51, 7095-7129. (b) Feray, L.; Kuznetsov, N.; Renaud P. In Radicals
in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, Germany, 2001; Vol. 2, pp 246-278. (c) Robertson, J .; Pillai,
J .; Lush, R. K. Chem. Soc. Rev. 2001, 30, 94-103.
(20) Francisco, C. G.; Herrera, A. J .; Sua´rez, E. Tetrahedron Lett.
2000, 41, 7869-7873.
(25) (a) Bennek, J . A.; Gray, G. R. J . Org. Chem. 1987, 52, 892-
897. (b) McDevitt, J . P.; Lansbury, P. T. J . Am. Chem. Soc. 1996, 118,
3818-3828.
(26) Burk, R. M.; Roof, M. B. Tetrahedron Lett. 1993, 34, 395-398.
7440 J . Org. Chem., Vol. 67, No. 21, 2002

Intramolecular Hydrogen Abstraction Reaction
TABLE 1. Syn th esis of An h yd r osu ga r s of th e
2,7-Dioxa bicyclo[2.2.1]h ep ta n e Typ ea
SCHEME 3. Su bstr a tes for th e
6,8-Dioxa bicyclo[3.2.1]octa n e Ser iesa
a
Key: (a) (i) KOH, MeOH, rt, 1 h; (ii) NaH, MeI, DMF, rt; (b)
(i)O3, CH2Cl2/MeOH, -78 °C;(ii)Me2S, NaBH4, rt;(c)(PhCN)2PdCl2,
PhH, reflux, 24 h, 60%; (d) (i) O3, CH2Cl2/MeOH, -78 °C; (ii) Me2S,
Et2AlCN, toluene, 0 °C, 10 min, 56.4% overall. The terms D-galacto,
D-manno, L-fuco, and L-rhamno refer to the starting sugar.
reaction to the synthesis of anhydrosugars of the 6,8-
dioxabicyclo[3.2.1]octane type. The first substrate, 2,6-
anhydro-1,3,4,5-tetra-O-benzyl-D-glycero-L-gulo-heptitol
(11) (Table 2, entry 1), was synthesized from D-glucose
by using the Wittig-oxymercuration process developed by
Sinay¨ et al.27 Several other models of 2,6-anhydrohep-
titols 14, 17, 21, 24, and 25 were prepared starting from
suitable derivatives of D-galactose, D-mannose, L-fucose,
and L-rhamnose, respectively (Scheme 3). The syntheses
were efficiently accomplished by using a three-step
protocol: Lewis acid catalyzed C-glycosidation with al-
lyltrimethysilane,28 treatment with bis(benzonitrile) dichlo-
ropalladium(II) in refluxing benzene in order to promote
the isomerization of the olefin,29 and ozonolysis followed
by reductive workup with NaBH4. The allylation reaction
proceeded in all cases with good stereoselectivity to give
the required R-isomer, while the olefin isomerization gave
an unseparated E/Z mixture. The mixture of cyanohy-
drins 25 was prepared by ozonolysis of olefin 20 and in
a
All reactions were performed at room temperature under
nitrogen containing (diacetoxyiodo)benzene (DIB) (1.1 mmol) and
iodine per mmol of substrate in the solvents specified in the
Experimental Section. b Under irradiation with two 80-W tungsten
filament lamps. c DIB (2 mmol) was used. 1-O-Acetyl-2,3:3,6-di-
d
O-isopropylidene-R-D-mannofuranose (7%) was also obtained.
situ reaction of the aldehyde with diethylaluminum
cyanide.30
The IHA reaction of alcohol 3 gave exclusively the 3,7-
anhydro-heptonate 26 by selective abstraction of the
hydrogen at C3 (Table 1, entry 1). In principle, the
primary O-radical could abstract either of the hydrogen
atoms at C3 or C4, both through a six-membered transi-
tion state (TS). Indeed, a study of the rotation of the
H-C6-C7-O dihedral angle gave conformations of
minimum energy for distances of approximately 3 Å
between the oxygen and either H-C3 or H-C4.31 Not-
withstanding, the TS energy should favor the abstraction
(27) (a) Pougny, J .-R.; Nassr, M. A. M.; Sinay¨, P. J . Chem. Soc.,
Chem. Commun. 1981, 375-376. (b) Zhai, D.; Zhai, W.; Williams, R.
M. J . Am. Chem. Soc. 1988, 110, 2501-2505.
(28) (a) Giannis, A.; Sandhoff, K. Tetrahedron Lett. 1985, 26, 1479-
1482. (b) Luengo, J . I.; Gleason, J . G. Tetrahedron Lett. 1992, 33, 6911-
6914. (c) Nicolaou, K. C.; Patron, A. P.; Ajito, K.; Richter, P. K.;
Khatuya, H.; Bertinato, P.; Miller, R. A.; Tomaszewski, M. J . Chem.
Eur. J . 1996, 2, 847-868. (d) Singh, G.; Vankayalapai, H. Tetrahe-
dron: Asymmetry 2001, 12, 1727-1735.
(30) Nagata, W.; Yoshioka, M. Tetrahedron Lett. 1966, 1913-1918.
(31) Molecular mechanics calculations were performed with the
AMBER* all-atom force field and the GB/SA solvation model for CHCl3
as implemented in version 7.0 of the MacroModel and BatchMin
packages.
(29) (a) Brooks, G.; Edwards, P. D.; Hatto, J . D. I.; Smale, T. C.;
Southgate, R. Tetrahedron 1995, 51, 7999-8014. (b) Wilcox, C. S.;
Long, G. W.; Suh, H. Tetrahedron Lett. 1984, 25, 395-398.
J . Org. Chem, Vol. 67, No. 21, 2002 7441

Francisco et al.
TABLE 2. Syn th esis of An h yd r osu ga r s of th e
6,8-Dioxa bicyclo[3.2.1]h ep ta n e Typ ea
simple transformation of a ribose derivative into 2,5-
anhydro-â-D-psicopyranose 28, a protected ketose with
one more carbon, is worth noting. The carbonate 9 was
synthesized in order to have a method to deprotect the
5,6-diol under basic conditions compatible with the
2,7-dioxabicyclo[2.2.1]heptane, the reaction proceeding
smoothly to give the anhydro derivative 29 in good yield
(Table 1, entry 4).
The IHA reaction of D-glycero-D-manno-heptitol 10,
easily prepared from 2,3:5,6-di-O-isopropylidene-D-man-
nofuranose, took place by the R-side of the molecule to
yield L-altro-hept-3-ulose 30 (Table 1, entry 5). The yield
of this reaction was 86% and was amenable to scale-up
(13 mmol) with only a nominal decrease in yield (80%).
In addition to 30, the side product 1-O-acetyl-2,3:5,6-di-
O-isopropylidene-R-D-mannofuranose, a compound com-
ing from a â-fragmentation of the alkoxy radical, was
formed in low yield (7%).
The 6,8-dioxabicyclo[3.2.1]octane system can also be
obtained from conveniently functionalized carbohydrate
precursors (Table 2). Thus, the D-glycero-L-gulo-heptitol
derivative 11 reacted with iodosylbenzene and iodine to
give the D-ido-hept-2-ulopyranose derivative 31 (Table
2, entry 1).32 In this series iodosylbenzene gave somewhat
better yields than DIB (compare entries 1-2 and 7-8);
the acetate group in the latter may act as an external
nucleophile and compete with the primary alcohol during
the cyclization reaction. The IHA reaction occurred under
a more stable 4C1 chair conformation, allowing a 1,3-
diaxial interaction between the involved substituents, the
hydrogen atom at C2, and the hydroxymethyl group at
C6. We were unable to detect any compound arising from
the geometrically possible abstraction of the axial hy-
drogen at C4 in this or any other example of this series.
Probably steric and stereoelectronic factors favor the
abstraction at C2 over C4.33 Comparison of the IHA
reaction of compounds 14 and 17 shows that changes in
the stereochemistries of the nearby carbons 3 and 5 do
not significantly influence the course and yield of the
reaction (Table 2, entries 3 and 4). Under similar condi-
tions the L-glycero-D-galacto-heptitol 21 afforded â-L-gulo-
hept-2-ulopyranose derivative 34. In this substrate the
hydrogen transfer occurred with the pyranose ring under
a
All reactions were performed at room temperature under
nitrogen containing iodosylbenzene and iodine (1 mmol) per mmol
of substrate in the solvent specified in the Experimental Section
and under irradiation with two 80-W tungsten filament lamps.
a
1C4 chair conformation, which allowed the maximum
approximation between the alkoxy radical and the hy-
drogen at C2. A small amount of camphorsulfonic acid
that may catalyze the intramolecular glycosidation in-
creased notably the yield of the reaction (Table 2,
compare entries 5 and 6). In the case of the L-glycero-L-
manno-heptitol derivative 24 irradiation was unneces-
sary, the reaction occurring smoothly in excellent yield
only with ambient light (Table 2, entry 7). Once more,
the use of DIB as oxidant gave an inferior result (entry
8). It is worth noting that compounds 34 and 35 were
obtained in better yields than their pseudoenantiomers
32 and 33, respectively, with which the only difference
DIB was used. c A catalytic amount of BF3‚EtO2 was added.
A
b
d
catalytic amount of camphorsulfonic acid was added. e Irradiation
was omitted. f 1-O-Acetyl-6-deoxy-2,3,4-tri-O-methyl-L-galactopy-
ranose (37%) was also obtained.
of H-C3 over the bicycle[3.3.0] bridgehead hydrogen at
C4, and this may be the reason for the observed regiose-
lectivity.
As may be expected, diol 4 cyclized through the most
favorable six-membered TS to give exclusively 2-deoxy-
D-ribo-hept-3-ulose 27; no products derived from the
alternative O-radical at C1 were detected in the crude
reaction mixture (Table 1, entry 2). The IHA reaction of
D-altritol derivative 6 occurred on the â-side of the
molecule to give the 2,5-anhydro-â-D-psicopyranose 28 as
the sole product of the reaction. The alternative hydrogen
atom transfer of the H-C5 promoted by the alkoxy
radical at C1 is inhibited by the isopropylidene group that
hinders the R-side of the molecule (Table 1, entry 3). This
(32) Recently the DIB/I2 system has been used for the deprotection
of carbohydrate benzyl ethers in the presence of a suitably located
hydroxyl group. We have not detected debenzylation or formation of
benzylidene to an appreciable extent in this case (Madsen, J .; Viuf,
C.; Bols, M. Chem. Eur. J . 2000, 6, 1140-1146).
(33) For studies on stereoelectronic effects in intermolecular hydro-
gen abstraction reactions see: (a) Malatesta, V.; Ingold, K. U. J . Am.
Chem. Soc. 1981, 103, 609-614. (b) Beckwith, A. L. J .; Easton, C. J .
J . Am. Chem. Soc. 1981, 103, 615-619.
7442 J . Org. Chem., Vol. 67, No. 21, 2002

Intramolecular Hydrogen Abstraction Reaction
involving air- or moisture-sensitive materials were carried out
under a nitrogen atmosphere. The spray reagent for TLC
analysis was 0.5% vanillin in H2SO4-EtOH (4:1) and further
heating until development of color.
is the 1-methoxy group. Probably the presence of a
supplementary â-oxygen could deactivate to some degree
the hydrogen abstraction at C2.34
The cyanohydrins 25 were prepared in order to test
the stability of this grouping (Table 2, entry 9). Unfor-
tunately, we were unable to separate both isomers
completely, but a reaction performed with the mixture
(1:1) allowed us to reach the following conclusions: the
25-R isomer cyclized efficiently to give 36 with the cyano
group in the exo position in an estimated yield of 60%;
on the other hand, the 25-S isomer, which should leave
the cyano group in the endo position, only gave 1-O-
acetyl-6-deoxy-2,3,4-tri-O-methyl-L-galactopyranose com-
ing from the â-fragmentation of the alkoxy radical. This
was confirmed since pure 25-S gave exclusively frag-
mented material in 52% yield. The possible transfer of
the cyano group to C2 was not observed. Probably the
oxidation of the C-radical was too fast, preventing the
radical addition to the nitrile.35
These examples demonstrate the utility of the IHA
reaction in the synthesis of dioxabicyclic[n.2.1]alkane (n
) 2, 3) systems. The synthesized compounds could be of
interest as chiral synthons in the preparation of more
complex natural products. It is noteworthy that the
reaction conditions are sufficiently mild as to be compat-
ible with the sensitive 1,2-isopropylidene group of the
mannofuranose 10. Consequently, common protective
groups should be compatible and this should increase the
usefulness of this methodology.36 The reaction also may
be useful for the selective oxidation of specific carbons of
the carbohydrate skeleton and constitute a mild proce-
dure for the preparation of protected uloses which are
not readily accessible by conventional synthetic methods.
Meth yl 2-Deoxy-3,6:3,7-dian h ydr o-4,5-O-isopr opyliden e-
D-r ibo-h ep ton a te (26). A solution of the alcohol 3 (84 mg,
0.34 mmol) in a mixture of CH2Cl2-cyclohexane (4 mL, 1:1)
containing (diacetoxyiodo)benzene (DIB) (120 mg, 0.37 mmol)
and iodine (43 mg, 0.17 mmol) was stirred at room temperature
under nitrogen for 2 h. The usual workup followed by chro-
matotron chromatography of the residue (hexanes-EtOAc, 85:
15) afforded the anhydrosugar 26 (62 mg, 0.25 mmol, 75%) as
a colorless oil: [R]D -62 (c 0.72); IR 2985, 2901, 1747, 1372,
1208 cm-1; 1H NMR δ 1.27 (3H, s), 1.41 (3H, s), 2.93 (1H, d, J
) 15.5 Hz), 3.1 (1H, d, J ) 15.5 Hz), 3.39 (1H, d, J ) 7.4 Hz),
3.53 (1H, dd, J ) 7.2, 3.8 Hz), 3.70 (3H, s), 4.38 (1H, d, J )
5.5 Hz), 4.44 (1H, d, J ) 5.5 Hz), 4.6 (1H, d, J ) 3.9 Hz); 13C
NMR δ 25.4 (CH3), 25.9 (CH3), 33.8 (CH2), 51.9 (CH3), 64.6
(CH2), 77.8 (CH), 80.1 (CH), 81.5 (CH), 105.9 (C), 112.3 (C),
168.8 (C); MS (EI) m/z (rel intensity) 244 (M+, 1), 243 (8), 229
(22), 213 (31); HRMS calcd for C11H16O6 244.094678, found
244.090878. Anal. Calcd for C11H16O6: C, 54.09; H, 6.60.
Found: C, 54.16; H, 6.81.
3,7-An h ydr o-2-deoxy-4,5-O-isopr opyliden e-D-r ibo-h ept-
3-u lofu r a n ose (27). A solution of the alcohol 4 (43 mg, 0.197
mmol) in CH2Cl2 (2 mL) containing DIB (70 mg, 0.217 mmol)
and iodine (51 mg, 0.2 mmol) was stirred at room temperature
under nitrogen for 0.5 h. The usual workup followed by column
chromatography (hexanes-EtOAc, 6:4) afforded the anhydro-
sugar 27 (28 mg, 0.13 mmol, 66%) as a colorless oil: [R]D -68
(c 0.116); IR 3500, 2938, 2898, 1742, 1373, 1058 cm-1; 1H NMR
δ 1.29 (3H, s), 1.45 (3H, s), 2.20 (1H, ddd, J ) 15.1, 6.2, 3.9
Hz), 2.28 (1H, ddd, J ) 15.3, 7.1, 4.2 Hz), 3.4 (1H, d, J ) 7.4
Hz), 3.55 (1H, dd, J ) 7.1, 3.9 Hz), 3.88 (2H, m), 4.2 (1H, d, J
) 5.6 Hz), 4.41 (1H, d, J ) 5.4 Hz), 4.66 (1H, d, J ) 3.8 Hz);
13C NMR δ 25.2 (CH3), 25.9 (CH3), 30.7 (CH2), 58.2 (CH2), 64.3
(CH2), 77.9 (CH), 80.2 (CH), 81.9 (CH), 108.6 (C), 112.2 (C);
MS (EI) m/z (rel intensity) 201 (M+ - Me, 23), 171 (11), 158
(8); HRMS calcd for C9H13O5 201.076290, found 201.083736.
Anal. Calcd for C10H16O5: C, 55.54; H, 7.46. Found: C, 55.41;
H, 7.31.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with
a hot-stage apparatus. Optical rotations were measured at the
sodium line at ambient temperature in CHCl3 solutions. IR
spectra were obtained as a thin film smeared onto NaCl plates
unless otherwise stated. NMR spectra were determined at 500
MHz for 1H and 125.7 MHz for 13C in CDCl3 unless otherwise
stated, in the presence of TMS as internal standard. Mass
spectra were determined at 70 eV. Merck silica gel 60 PF
(0.063-0.2 mm) was used for column chromatography. Cir-
cular layers of 1 mm of Merck silica gel 60 PF254 were used on
a Chromatotron for centrifugally assisted chromatography.
Commercially available reagents and solvents were analytical
grade or were purified by standard procedures prior to use.
“Usual workup” means aqueous treatment, extraction with
CH2Cl2, washing with 10% aqueous sodium thiosulfate, drying
with Na2SO4, filtration, and evaporation in vacuo. All reactions
2,6-An h yd r o-3,4-O-isop r op ylid en -D-r ibo-h ex-2-u lofu r a -
n ose (2,5-An h yd r o-3,4-O-isop r op ylid en e-â-D-p sicop yr a -
n ose) (28). A solution of the alcohol 6 (40 mg, 0.196 mmol) in
dry MeCN (3 mL) containing DIB (97 mg, 0.3 mmol) and iodine
(36 mg, 0.137 mmol) was stirred at room temperature, under
nitrogen, for 0.75 h. The usual workup followed by column
chromatography (hexanes-EtOAc, 1:1) afforded the anhydro-
sugar 28 (28 mg, 0.14 mmol, 70%) as a crystalline solid: mp
118-119 °C (from n-hexanes-EtOAc); [R]D -58 (c 0.228); IR
1
(CHCl3) 3601, 2983, 2900, 1734, 1602, 1384 cm-1; H NMR δ
1.28 (3H, s), 1.45 (3H, s), 3.42 (1H, d, J ) 7.2 Hz), 3.56 (1H,
dd, J ) 3.8, 7.2 Hz), 4.03 (1H, dd, J ) 6.6, 12.5 Hz), 4.07 (1H,
dd, J ) 5.9, 12.5 Hz), 4.29 (1H, d, J ) 5.5 Hz), 4.42 (1H, d, J
) 5.5 Hz), 4.69 (1H, d, J ) 3.8 Hz); 13C NMR δ 25.2 (CH3),
25.9 (CH3), 59.1 (CH2), 64.4 (CH2), 78.3 (CH), 80.3 (CH), 81.2
(CH), 107.1 (C), 112.6 (C); MS (EI) m/z (rel intensity) 201 (M+
- H, 7), 187 (16); HRMS calcd for C9H13O5 201.076290, found
201.071293. Anal. Calcd for C9H14O5: C, 53.46; H, 6.98.
Found: C, 53.68; H, 6.62.
4,8-An h ydr o-1,2,3-tr ideoxy-5,6-O-(oxom eth ylen e)-D-r ibo-
oct-1-en -4-u lofu r a n ose (29). A solution of alcohol 9 (102 mg,
0.51 mmol) in dry CH2Cl2 (5 mL) containing DIB (197 mg,
0.612 mmol) and iodine (91 mg, 0.357 mmol) was irradiated
with one 80-W tungsten-filament lamp at room temperature
under nitrogen for 0.75 h. The usual workup followed by
chromatotron chromatography (hexanes-EtOAc, 70:30) af-
forded the anhydrosugar 29 (90 mg, 0.45 mmol, 88%) as a
crystalline solid: mp 93.5 °C (from n-hexanes-EtOAc); [R]D
-70 (c 0.39); IR 2915, 1791, 1157, 1091 cm-1; 1H NMR δ 2.79
(2H, d, J ) 7.2 Hz), 3.59 (1H, d, J ) 7.8 Hz), 3.69 (1H, dd, J
) 3.8, 7.8 Hz), 4.63 (1H, d, J ) 6.0 Hz), 4.86 (1H, d, J ) 3.8
(34) (a) Francisco, C. G.; Freire, R.; Herrera, A. J .; Pe´rez-Mart´ın,
I.; Sua´rez, E. Org. Lett. 2002, 4, 1959-1961. Evidence for a deactivating
influence of a â-oxygen in the intermolecular hydrogen abstraction
reaction has been described: (b) Busfield, W. K.; Grice, I. D.; J enkins,
I. D.; Monteiro, M. J . J . Chem. Soc., Perkin Trans. 2 1994, 1071-1077.
(c) Busfield, W. K.; Grice, I. D.; J enkins, I. D. J . Chem. Soc., Perkin
Trans. 2 1994, 1079-1086.
(35) (a) Kalvoda, J .; Botta, L. Helv. Chim. Acta 1972, 55, 356-366.
(b) Freerksen, R. W.; Pabst, W. E.; Raggio, M. L.; Sherman, S. A.;
Wroble, R. R.; Watt, D. S. J . Am. Chem. Soc. 1977, 99, 1536-1542.
(36) For the use of this methodology with carbohydrates possessing
sensitive protecting groups see: (a) Gonza´lez, C. C.; Kennedy, A. R.;
Leo´n, E. I.; Riesco-Fagundo, C.; Sua´rez, E. Angew. Chem., Int. Ed.
2001, 40, 2326-2328. (b) Francisco, C. G.; Freire, R.; Gonza´lez, C. C.;
Leo´n, E. I.; Riesco-Fagundo, C.; Sua´rez, E. J . Org. Chem. 2001, 66,
1861-1866. (c) Armas, P.; Francisco, C. G.; Sua´rez, E. J . Am. Chem.
Soc. 1993, 115, 8865-8866.
J . Org. Chem, Vol. 67, No. 21, 2002 7443

Francisco et al.
Hz), 4.89 (1H, d, J ) 6.0 Hz), 5.20 (1H, d, J ) 9.1 Hz), 5.28
(1H, d, J ) 15.1 Hz), 5.86 (1H, m); 13C NMR (50.4 MHz) δ
32.1 (CH2), 65.1 (CH2), 78.3 (CH), 78.9 (CH), 79.4 (CH), 107.6
(C), 119.8 (CH2), 129.8 (CH), 154.1 (C); MS (EI), m/z (rel
intensity) 198 (M+, 15), 154 (2); HRMS calcd for C9H10O5
198.0528165, found 198.057854. Anal. Calcd for C9H10O5: C,
54.54; H, 5.09. Found: C, 54.84; H, 4.70.
2,7-An h yd r o-1,3,4,5-tetr a -O-m eth yl-â-D-gu lo-h ep t-2-u l-
op yr a n ose (32). A solution of the alcohol 14 (20 mg, 0.08
mmol) in a mixture of CH2Cl2-cyclohexane (1:1) (3 mL)
containing iodosylbenzene (35 mg, 0.16 mmol), iodine (20 mg,
0.08 mmol), and BF3‚OEt (0.01 mL, 0.08 mmol) was irradiated
with two 80-W tungsten-filament lamps at reflux temperature
under nitrogen for 2 h. The usual workup followed by column
chromatography (hexanes-EtOAc, 25:75) afforded the anhy-
drosugar 32 (13 mg, 0.052 mmol, 65%) as a colorless oil: [R]D
3,7-An h yd r o-1,2:4,5-d i-O-isop r op ylid en e-D-a llo-h ep t-3-
u lofu r a n ose (30). A solution of the alcohol 1024 (105 mg, 0.38
mmol) in CH2Cl2 (3 mL) containing DIB (244 mg, 0.76 mmol)
and iodine (48 mg, 0.19 mmol) was irradiated with two 80-W
tungsten-filament lamps at room temperature under nitrogen
for 1.5 h. The usual workup followed by column chromatog-
raphy (hexanes-EtOAc, 7:3) afforded the anhydrosugar 30 (89
mg, 0.327 mmol, 86%) and 1-O-acetyl-2,3:3,6-di-O-isopropy-
lidene-R-D-mannofuranose (8 mg, 0.026 mmol, 7%). The reac-
tion is also amenable to scale-up (3.5 g, 13 mmol) with only
nominal decrease in yield (80%). Compound 30: colorless oil;
[R]D -59.4 (c 0.16); IR (CHCl3) 3014, 2992, 2938, 2900, 1383,
1
+20 (c 0.52); IR 2904, 2828, 1452, 1195, 1105, 1052 cm-1; H
NMR δ 3.38 (1H, d, J ) 9.9 Hz), 3.41 (1H, dd, J ) 4.4, 4.1
Hz), 3.43 (3H, s), 3.46 (3H, s), 3.49 (3H, s), 3.52 (3H, s), 3.55
(1H, dd, J ) 9.2, 4.1 Hz), 3.67 (1H, dd, J ) 7.6, 4.8 Hz), 3.74
(1H, d, J ) 4.4 Hz), 3.77 (1H, d, J ) 10.0 Hz), 3.95 (1H, d, J
) 7.6 Hz), 4.46 (1H, dd, J ) 4.4, 4.4 Hz); 13C NMR δ 58.3 (CH3),
58.7 (CH3), 59.5 (CH3), 60.8 (CH3), 64.9 (CH2), 71.8 (CH2), 72.7
(CH), 76.2 (CH), 78.5 (CH), 80.2 (CH), 106.8 (C); MS (EI) m/z
(rel intensity) 248 (M+, <1), 233 (<1), 217 (<1), 187 (<1);
HRMS calcd for C11H20O6 248.125976, found 248.128181. Anal.
Calcd for C11H20O6: C, 53.21; H, 8.12. Found: C, 53.01; H,
8.48.
1371, 1228 cm-1 1H NMR δ 1.27 (3H, s), 1.37 (3H, s), 1.43
;
(3H, s), 1.45 (3H, s), 3.44 (1H, d, J ) 7.3 Hz), 3.54 (1H, dd, J
) 7.3, 3.9 Hz), 4.09 (1H, dd, J ) 8.3, 7.0 Hz), 4.14 (1H, dd, J
) 8.5, 5.3 Hz), 4.37 (1H, d, J ) 5.5 Hz), 4.39 (1H, d, J ) 5.5
Hz), 4.61 (1H, dd, J ) 6.9, 5.3 Hz), 4.64 (1H, d, J ) 3.9 Hz);
13C NMR δ 25.1 (2 × CH3), 25.8 (CH3), 25.9 (CH3), 64.6 (CH2),
64.6 (CH2), 71.4 (CH), 78.4 (CH), 80.1 (CH), 81.2 (CH), 107.0
(C), 110.0 (C), 112.3 (C); MS (EI) m/z (rel intensity) 257 (M+
- Me, 49), 214 (11), 199 (73); HRMS calcd for C12H17O6
257.102503, found 257.09977. Anal. Calcd for C13H20O6: C,
57.34; H, 7.40. Found: C. 57.04; H, 7.49. 1-O-Acetyl-2,3:3,6-
di-O-isopropylidene-R-D-mannofuranose: [R]D +76 (c 0.42); IR
2,7-An h yd r o-1,3,4,5-tetr a -O-m eth yl-â-D-a ltr o-h ep t-2-u l-
op yr a n ose (33). A solution of the alcohol 15 (80 mg, 0.32
mmol) in
a mixture of CH2Cl2-cyclohexane (2:1) (3 mL)
containing iodosylbenzene (141 mg, 0.64 mmol) and iodine (81
mg, 0.32 mmol) was irradiated with two 80-W tungsten-
filament lamps at room temperature under nitrogen for 2 h.
The usual workup followed by column chromatography (hex-
anes-EtOAc, 6:4) afforded the anhydrosugar 33 (60 mg, 0.242
mmol, 76%) as a colorless oil: [R]D -112 (c 0.79); IR 2902, 2831,
1454, 1365, 1268, 1112, 1026 cm-1 1H NMR δ 3.40 (3H, s),
;
2988, 2939, 1748, 1374, 1231 cm-1 1H NMR δ 1.33 (3H, s),
;
3.41 (1H, d, J ) 10.6 Hz), 3.44 (1H, dd, J ) 8.8, 4.4 Hz), 3.45
(3H, s), 3.48 (3H, s), 3.51 (3H, s), 3.51 (1H, d, J ) 8.8 Hz),
3.56 (1H, dd, J ) 4.3, 2.6 Hz), 3.66 (1H, d, J ) 7.9 Hz), 3.76
(1H, d, J ) 10.6 Hz), 3.81 (1H, dd, J ) 7.9, 5.7 Hz), 4.74 (1H,
dd, J ) 5.5, 1.8 Hz); 13C NMR δ 57.5 (CH3), 57.8 (CH3), 59.5
(CH3), 60.6 (CH3), 65.8 (CH2), 71.0 (CH2), 73.8 (CH), 76.8 (CH),
80.3 (CH), 80.81 (CH), 107.6 (C); MS (EI) m/z (rel intensity)
247 (M+ - H, 1), 233 (54), 201 (12); HRMS calcd for C11H19O6
247.118152, found 247.118824. Anal. Calcd for C11H20O6: C,
53.21; H, 8.12. Found: C, 53.33; H, 8.16.
1.37 (3H, s), 1.45 (3H, s), 1.47 (3H, s), 2.06 (3H, s), 4.02 (1H,
dd, J ) 4.2, 8.5 Hz), 4.04 (1H, d, J ) 6.2 Hz), 4.085 (1H, dd, J
) 6.2, 8.9 Hz), 4.39 (1H, ddd, J ) 4.3, 6.2, 7.9 Hz), 4.69 (1H,
d, J ) 5.9 Hz), 4.84 (1H, dd, J ) 3.6, 5.9 Hz), 6.11 (1H, s); 13
C
NMR (50.3 MHz) δ 21.0 (CH3), 24.6 (CH3), 25.0 (CH3), 25.9
(CH3), 26.9 (CH3), 66.8 (CH2), 72.8 (CH), 79.3 (CH), 82.2 (CH),
85.0 (CH), 100.7 (CH), 109.3 (C), 113.2 (C), 169.4 (C); MS (EI)
m/z (rel intensity) 287 (M+ - Me, 100), 243 (7), 229 (51); HRMS
calcd for C13H19O7 287.113066, found 287.109016. Anal. Calcd
for C14H22O7: C, 55.62; H, 7.33. Found: C, 55.68; H, 6.94.
2,7-An h yd r o-1-d eoxy-3,4,5-tr i-O-m eth yl-â-L-gu lo-h ep t-
2-u lop yr a n ose (34). Meth od A: A solution of the alcohol 21
(13 mg, 0.059 mmol) in dry MeCN (3 mL) containing iodosyl-
benzene (26 mg, 0.118 mmol), iodine (15 mg, 0.059 mmol), and
camphorsulfonic acid (7 mg, 0.03 mmol) was irradiated with
two 80-W tungsten-filament lamps at reflux temperature
under nitrogen for 25 min. The usual workup followed by
column chromatography (hexanes-EtOAc, 25:75) afforded the
anhydrosugar 34 (11 mg, 0.05 mmol, 85%) as a colorless oil:
[R]D -27 (c 0.53, CH2Cl2); IR 2918, 2829, 1746, 1455, 1382,
2,7-An h yd r o-1,3,4,5-t et r a -O-b en zyl-â-D-id o-h ep t -2-u l-
op yr a n ose (31). Meth od A: A solution of the alcohol 1127 (61
mg, 0.11 mmol) in a mixture of CH2Cl2-cyclohexane (1:1) (8
mL) containing DIB (39 mg, 0.12 mmol) and iodine (28 mg,
0.11 mmol) was irradiated with two 80-W tungsten-filament
lamps at room temperature under nitrogen for 1 h. The usual
workup followed by column chromatography (hexanes-EtOAc,
85:15) afforded the anhydrosugar 31 (32 mg, 0.06 mmol, 54%)
as an oil: [R]D -10.5 (c 1.49); IR (CHCl3) 3064, 3031, 2902,
1230, 1106 cm-1 1H NMR δ 1.52 (3H, s), 3.42 (1H, dd, J )
;
1
1455, 1072 cm-1; H NMR δ 3.46 (1H, d, J ) 10.3 Hz), 3.74
10.7, 4.1 Hz), 3.44 (1H, dd, J ) 4.1, 8.8 Hz), 3.47 (3H, s), 3.51
(3H, s), 3.54 (1H, ddd, J ) 8.8, 4.3, 4.3 Hz), 3.58 (3H, s), 3.68
(1H, dd, J ) 7.2, 4.8 Hz), 3.91 (1H, d, J ) 7.2 Hz), 4.45 (1H,
dd, J ) 4.3, 4.3 Hz); 13C NMR δ 20.6 (CH3), 58.5 (CH3), 58.7
(CH3), 61.5 (CH3), 64.8 (CH2), 73.1 (CH), 78.4 (CH), 80.6
(CH), 80.9 (CH), 107.4 (C); MS (EI) m/z (rel intensity) 218 (M+,
<1), 203 (1); HRMS calcd for C10H19O5 218.115424, found
218.105984. Anal. Calcd for C10H18O5: C, 55.03; H, 8.31.
Found: C, 55.18; H, 8.62. Meth od B: A solution of the alcohol
21 (57 mg, 0.259 mmol) in dry MeCN (7 mL) containing
iodosylbenzene (114 mg, 0.518 mmol) and iodine (49 mg, 0.194
mmol) was stirred at room temperature, under nitrogen, for
35 min. Workup analogously afforded compound 34 (39 mg,
0.179 mmol, 69%).
2,7-An h yd r o-1-d eoxy-3,4,5-tr i-O-m eth yl-r-L-a ltr o-h ep t-
2-u lop yr a n ose (35). Meth od A: A solution of the alcohol 24
(18 mg, 0.082 mmol) in CH2Cl2 (1.5 mL) containing iodosyl-
benzene (35 mg, 0.16 mmol) and iodine (20 mg, 0.08 mmol)
was stirred at room temperature under nitrogen for 40 min.
The usual workup followed by column chromatography (hex-
(1H, dd, J ) 7.3, 5.5 Hz), 3.83 (1H, m), 3.92 (1H, d, J ) 10.4
Hz), 4.17 (1H, d, J ) 7.9 Hz), 4.44 (1H, dd, J ) 4.3, 4.3 Hz),
4.52 (1H, d, J ) 11.6 Hz), 4.61 (1H, d, J ) 11.6 Hz), 4.62 (1H,
d, J ) 12.2 Hz), 4.68 (1H, d, J ) 11.0 Hz), 4.71 (1H, d, J )
12.2 Hz), 4.78 (1H, d, J ) 11.6 Hz), 4.81 (1H, d, J ) 11.6 Hz),
4.89 (1H, d, J ) 11.0 Hz), 7.21-7.31 (20H, m); 13C NMR δ
65.9 (CH2), 69.2 (CH2), 72.9 (CH2), 73.6 (CH2), 74.2 (CH), 74.7
(CH2), 75.3 (CH2), 79.8 (CH), 81.3 (CH), 83.2 (CH), 107.5 (C),
125.9-128.5 (20 × CH), 137.6 (C), 138.0 (C), 138.3 (C), 138.6
(C); MS (EI) m/z (rel intensity) 461 (M+ - Bn, 15), 369 (5),
355 (17), 91 (100); HRMS calcd for C35H36O6 552.251170, found
552.245819. Anal. Calcd for C35H36O6: C, 76.06; H, 6.57.
Found: C, 75.99; H, 6.59. Meth od B: A solution of the alcohol
1127 (25 mg, 0.05 mmol) in a mixture of CH2Cl2-cyclohexane
(1:1) (3 mL) containing iodosylbenzene (22 mg, 0.10 mmol) and
iodine (15 mg, 0.059 mmol) was irradiated with two 80-W
tungsten-filament lamps at room temperature under nitrogen
for 50 min. The usual workup followed by column chromatog-
raphy (hexanes-EtOAc, 85:15) afforded the anhydrosugar 31
(15 mg, 0.03 mmol, 60%).
7444 J . Org. Chem., Vol. 67, No. 21, 2002

Intramolecular Hydrogen Abstraction Reaction
anes-EtOAc, 25:75) afforded the anhydrosugar 35 (16 mg,
0.073 mmol, 90%) as a colorless oil: [R]D +122 (c 0.42); IR 2939,
2829, 1238, 1123, 1000 cm-1; 1H NMR δ 1.49 (3H, s), 3.24 (1H,
d, J ) 8.6 Hz), 3.38 (1H, dd, J ) 8.6, 4.6 Hz), 3.45 (3H, s),
3.50 (3H, s), 3.53 (3H, s), 3.55 (1H, dd, J ) 4.5, 2.7 Hz), 3.62
(1H, d, J ) 7.9 Hz), 3.83 (1H, dd, J ) 7.9, 5.8 Hz), 4.65 (1H,
dd, J ) 5.6, 2.3 Hz); 13C NMR δ 19.8 (CH3), 57.8 (CH3), 57.8
(CH3), 61.0 (CH3), 65.9 (CH2), 73.6 (CH), 77.1 (CH), 80.3 (CH),
84.5 (CH), 107.9 (C); MS (EI) m/z (rel intensity) 218 (M+, <1),
203 (5), 187 (43), 88 (100); HRMS calcd for C10H18O5 218.115413,
found 218.117867. Anal. Calcd for C10H18O5: C, 55.03; H, 8.31.
Found: C, 55.18; H, 8.62. Meth od B: A solution of the alcohol
24 (24 mg, 0.109 mmol) in CH2Cl2 (2 mL) containing DIB (39
mg, 0.12 mmol) and iodine (28 mg, 0.11 mmol) was stirred at
room temperature under nitrogen for 40 min. The usual
workup followed by column chromatography (hexanes-EtOAc,
25:75) afforded the anhydrosugar 35 (19 mg, 0.09 mmol, 83%).
(7S)-2,7-An h yd r o-7-C-cya n o-1-d eoxy-3,4,5-tr i-O-m eth -
yl-â-L-gu lo-h ep t-2-u lop yr a n ose (36). A solution of the cy-
anohydrins mixture 25 (26 mg, 0.106 mmol, 1:1) in CH2Cl2/
cyclohexane (2 mL, 1:1) containing DIB (53 mg, 0.164 mmol)
and iodine (28 mg, 0.11 mmol) was stirred at room temperature
under nitrogen for 6 h. The usual workup followed by chro-
matotron chromatography (hexanes-EtOAc, 6:4) afforded the
anhydrosugar 36 (7 mg, 0.03 mmol, 28%) and acetyl 6-deoxy-
2,3,4-tri-O-methyl-â-L-galactopyranoside (6 mg, 0.024 mmol,
22%) and acetyl 6-deoxy-2,3,4-tri-O-methyl-R-L-galactopyra-
noside (4 mg, 0.016 mmol, 15%). Compound 36 [R]D -30.5 (c
0.22); IR (CHCl3) 2936, 2832, 2359, 1744, 1463, 1386, 1125,
2,3,4-tri-O-methyl-â-L-galactopyranoside: [R]D -31 (c 0.48); IR
2984, 2937, 2833, 1748, 1372, 1230, 1089 cm-1; 1H NMR δ 1.30
(3H, d, J ) 6.4 Hz), 2.12 (3H, s), 3.22 (1H, dd, J ) 9.9, 3.0
Hz), 3.39 (1H, d, J ) 3.0 Hz), 3.46 (1H, dd, J ) 10.3, 8.6 Hz),
3.53 (3H, s), 3.54 (3H, s), 3.60 (3H, s), 3.62 (1H, q, J ) 6.3
Hz), 5.42 (1H, d, J ) 8.2 Hz); 13C NMR δ 16.4 (CH3), 21.1 (CH3),
58.3 (CH3), 60.7 (CH3), 61.8 (CH3), 71.2 (CH), 78.1 (CH), 79.1
(CH), 84.2 (CH), 94.2 (CH), 159.6 (C); MS (EI) m/z (rel
intensity) 189 (M+ - OAc, 4), 173 (1); HRMS calcd for C9H17O4
189.112674, found 189.11454. Anal. Calcd for C11H20O6: C,
53.21; H, 8.12. Found: C, 53.27; H, 8.01. Acetyl 6-deoxy-2,3,4-
tri-O-methyl-R-L-galactopyranoside: [R]D -122 (c 0.4); IR 2983,
2937, 2830, 1747, 1372, 1234, 1136, 1108 cm-1; 1H NMR δ 1.23
(3H, d, J ) 6.9 Hz), 2.10 (3H, s), 3.43 (3H, s), 3.48 (1H, d, J )
2.5 Hz), 3.50 (1H, dd, J ) 10.2, 2.5 Hz), 3.51 (3H, s), 3.58 (3H,
s), 3.70 (1H, dd, J ) 10.0, 3.5 Hz), 3.94 (1H, q, J ) 6.7 Hz),
6.33 (1H, d, J ) 3.4 Hz); 13C NMR δ 16.5 (CH3), 21.1 (CH3),
58.1 (CH3), 59.0 (CH3), 61.8 (CH3), 68.9 (CH), 76.7 (CH), 78.8
(CH), 80.2 (CH), 90.1 (CH), 169.6 (C); MS (EI) m/z (rel
intensity) 248 (M+, <1), 189 (5), 173 (1). Anal. Calcd for
C
11H20O6: C, 53.21; H, 8.12. Found: C, 53.26; H, 8.38. In the
same conditions pure 25-S (25 mg, 0.1 mmol) in CH2Cl2/
cyclohexane (5 mL, 1:1) containing DIB (38 mg, 0.12 mmol)
and iodine (25 mg, 0.1 mmol) afforded the above-mentioned
L-galactopyranosides (13 mg, 0.052 mmol, 52%, R-â, 52:42).
Ack n ow led gm en t. This work was supported by the
Investigation Programmes Nos. BQU2000-0650 and
BQU2001-1665 of the Direccio´n General de Investiga-
cio´n Cient´ıfica y Te´cnica, Spain. A.J .H. thanks the
Ministerio de Educacio´n y Ciencia, Spain for fellowships.
1104, 1058 cm-1 1H NMR δ 1.63 (3H, s), 3.26 (1H, dd, J )
;
8.9, 4.3 Hz), 3.42 (1H, d, J ) 4.4 Hz), 3.50 (6H, s), 3.57 (3H,
s), 3.58 (1H, dd, J ) 8.9, 4.3 Hz), 4.66 (1H, s), 4.67 (1H, d, J
) 4.4 Hz); 13C NMR δ 20.5 (CH3), 58.7 (CH3), 59.0 (CH3), 61.6
(CH3), 63.3 (CH), 77.1 (CH), 77.6 (CH), 79.8 (CH), 80.1 (CH),
110.5 (C), 117.6 (C); MS (EI) m/z (rel intensity) 244 (M+ + H,
4), 217 (8), 212 (3); HRMS calcd for C11H18NO5 244.118486,
found 244.120144. Anal. Calcd for C11H17O5N: C, 54.31; H,
7.04; N, 5.76. Found: C, 54.38; H, 7.19; N, 5.39. Acetyl 6-deoxy-
Su p p or tin g In for m a tion Ava ila ble: A complete descrip-
tion of experimental details and characterization data for
compounds 2-9, 12-17, and 19-25. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O026004Z
J . Org. Chem, Vol. 67, No. 21, 2002 7445