Two unusual carbohydrate reactions: Nucleophilic ring opening of an anhydrosugar and reductive elimination with co-occurring hydrogenation

Article abstract of DOI:10.1080/07328300802272389

Treatment of the 1,6-anhydrosugar epoxide 5 with a cyano-Gilman cuprate [(CuCN (6 eq.), MeLi (12 eq.)] surprisingly led to the open chain rearranged (2S,3R)-1,2-dihydroxy-3,6-dimethylheptan-4-one (7), structurally confirmed by conversion to the correspond

Full text of DOI:10.1080/07328300802272389

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Two Unusual Carbohydrate Reactions:
Nucleophilic Ring Opening of an
Anhydrosugar and Reductive Elimination with
Co‐occurring Hydrogenation
Karsten Krohn a , Ishtiaq Ahmed a & Mohammed Al Sahli a
a Department of Chemistry , University of Paderborn , Paderborn, Germany
Published online: 07 Aug 2008.
To cite this article: Karsten Krohn , Ishtiaq Ahmed & Mohammed Al Sahli (2008) Two Unusual Carbohydrate
Reactions: Nucleophilic Ring Opening of an Anhydrosugar and Reductive Elimination with Co‐occurring
Hydrogenation, Journal of Carbohydrate Chemistry, 27:6, 379-387, DOI: 10.1080/07328300802272389
To link to this article: http://dx.doi.org/10.1080/07328300802272389
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Journal of Carbohydrate Chemistry, 27:379–387, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300802272389
Two Unusual Carbohydrate
Reactions: Nucleophilic
Ring Opening
of an Anhydrosugar
and Reductive Elimination
with Co-occurring
Hydrogenation
Karsten Krohn, Ishtiaq Ahmed, and Mohammed Al Sahli
Department of Chemistry, University of Paderborn, Paderborn, Germany
Treatment of the 1,6-anhydrosugar epoxide 5 with a cyano-Gilman cuprate [(CuCN
(6 eq.), MeLi (12 eq.)] surprisingly led to the open chain rearranged (2S,3R)-1,2-dihy-
droxy-3,6-dimethylheptan-4-one (7), structurally confirmed by conversion to the corre-
sponding diacetate 8. Another unusual reaction was found by hydrogenation of the
2-tosyl-1-bromosugar 11, leading in one operation to the twofold deoxygenated chiral
pyran derivative 14. This procedure might prove to be useful in the rapid deoxygenation
of sugar derivatives.
Keywords Cyano cuprates, Epoxide opening, 1,6-Anhydro sugars, Hydrogenation,
Deoxygenation
INTRODUCTION
In connection with our ongoing investigation on the use of carbohydrates as
building blocks for complex natural products,[1,2] we investigated further reac-
tions of anhydrosugar derivatives. In the course of these transformations, by
serendipity, we observed two unusual transformations that are mechanisti-
cally interesting and may be of general use with related substrates.
Received April 28, 2008; accepted June 13, 2008.
Address correspondence to Karsten Krohn, Department of Chemistry, University of
Paderborn, Paderborn, Germany. E-mail: k.krohn@uni-paderborn.de
379

K. Krohn et al.
380
RESULTS AND DISCUSSION
Epoxide Opening
Aiming at new chiral functionalized methyl-branched stereotriads as
building blocks for macrolides, the opening of sugar epoxides with methyl
cuprates was one of the key reactions. Thus, in the first of the unusual reac-
tions described here, we investigated the reaction of epoxide 5 with the
cyano-Gilman cuprate or Lipshutz “higher-order” methyl cyanocuprate.[3]
The epoxide 5 was prepared using a known sequence starting with levogluco-
san (1)[4] via the bis-tosylate 2 and the galacto epoxide 3 (Sch. 1).[5,6] The
opening of the epoxide 3 was achieved by reaction with methylmagnesium
bromide at 2448C to 08C, catalyzed with a small amount of CuI, to afford the
methylated alcohol 4 regioselectively.[5] The key epoxide 5 was then generated
nearly quantitatively by base (NaH) catalyzed ring closure.[7,8]
To arrive at the dimethyl anhydro sugar 6, a useful macrolide building
block,[8] the epoxide 5 was first reacted with the Gilman cuprate Me2CuLi
(generated from MeLi and CuI) as the methyl nucleophile and the expected
methyl adduct 6 was formed stereo- and regioselectively and isolated in 67%
yield.[5,8,9] In a second reaction, the conversion with the cyano-Gilman
cuprate was also tested since these cuprates have been shown to have
unusual reactivity toward sugar epoxides.[1,2] Surprisingly, in addition to the
expected compound 6 (31%), a very polar ring opened product was also
formed as the major product and identified as the ketone 7 in 67% yield
(Sch. 1). In the 13C NMR spectrum of 7, the signal for a tertiary carbon atom
at C-1 at 101 ppm is shifted to 48 ppm. Furthermore, a signal for a new qua-
ternary carbon atom for C-3 at 215 ppm was typical for a carbonyl group and
also signals at 51 ppm for a secondary carbon at C-2 and at 22.4 ppm and
22.5 ppm for two primary carbons at C-1 could be detected. To further
Scheme 1: a) TsCl (2.6 eq.), pyridine/acetone (1:1, 2 h, 71%); b) NaOMe (2 eq.), MeOH, 4 h,
96%; c) MeMgCl (4 eq.), CuI (kat.), THF, 2448C to 08C 72%; d) NaH, THF, 08C, 4 h, RT, 96%; e) CuI
(5 eq), MeLi (10 eq.), Et2O/THF, 2768C to 208C, 12 h, 67%; f) CuCN (6 eq.), MeLi (12 eq.), Et2O/
THF, 2788C to 08C, 2 h 208C: 6, 63%, 7, 31%; g) Ac2O, pyridine, DMAP, 71%.

Two Unusual Carbohydrate Reactions
381
confirm the unusual structure, the diol was acetylated. However, under
the action of the basic dimethylaminopyridine, the methyl group in the
a-position to the carbonyl was epimerized to a 1:1 mixture of the diacetates
8. However, the gross structure of 7 was confirmed by all spectroscopic data,
in particular the mass spectra and the typical downfield shift of the signals
1
for the acetylated hydrogens by ca. 1 ppm in the H NMR spectrum.
The mechanism of the reaction is not entirely clear. However, reaction of
the cyclic acetal, activated by the mild cuprate Lewis acid, with a methyl
nucleophile may be the first step. This could be followed by rearrangement of
the epoxide to a ketone, b-elimination with opening of the pyran ring to an
enone, and Michael addition to the enone to yield the dimethylated product 7.
Hydrogenative Deoxygenation
In the second part, we describe a new variation to remove two heteroatoms
(originally sugar oxygen atoms) from sugar derivatives in one easily performed
hydrogenative step. The reaction was found in an attempt to synthesize natu-
rally occurring pyrans such as 9, isolated together with a number of stereoi-
[10]
´
somers by Reategui et al.
from the fungus Ophioceras venezuelense
(Sch. 2). In our synthetic scheme, we planned to use the same intermediate
3, which should provide the 4-deoxy sugar 10 under reductive conditions. In
the remaining steps, the three oxygen functions at C-1, C-2, and C-5 had to
be removed.
ˇ
´
The first step of reduction of the epoxide in 3 was described by Cerny et al.,
who employed sodium borohydride in dimethoxyethane and boron trifluoride
catalysis.[11] This last procedure provided the deoxygenation product 10 in
92% yield. Opening of the anhydro bridge with hydrogen bromide in acetic
acid gave a mixture of the bromo acetate 11 and the dibromide 12 in 45%
and 34% yield, respectively.[12] We attempted several methods for the reductive
.
Scheme 2: a) NaBH4, BF3 Et2O, 1,2-dimethoxyethane, 508C, 92%; b) 33% HBr in CH3COOH,
(CH3CO)2O, 24 h 208C, 6 h reflux: 11: 45%; 12: 34%; c) Raney nickel, H2, EtOH, RT, 30 min, 64%.

K. Krohn et al.
382
removal of the bromides in 11 and 12. Whereas the dibromide reacted to form a
complex mixture of different products not yet fully analyzed, the Raney nickel-
catalyzed hydrogenation in ethanol of the monobromide 11 rapidly led to one
single isolable product. Surprisingly, not only the anomeric bromine was
reduced, but also the neighboring tosylate group. Normally, carbohydrate tosy-
lates are not easily reduced by hydrogenation. We assume that the anomeric
bromine plays an active part in this transformation. Related to the sodium
iodide-mediated elimination of 1,2-bis-tosylates, the attack of hydrogen on
the bromine atom may induce elimination to the intermediate olefin 13 that
is hydrogenated to the pyran 14. The process may as well proceed via radical
intermediates, not shown in Scheme 2. The reaction might prove useful in
the rapid and easy 1,2-deoxygenation of sugar derivatives, in particular for
generation of chiral tetrahydropyran derivatives.
EXPERIMENTAL
General
Thin-layer chromatography was performed on precoated TLC plates (silica
gel). Melting points were measured with a Gallenkamp apparatus and are not
corrected. NMR spectra were recorded on a Bruker Avance 500 at the following
frequencies: 500.13 MHz (1H) and 125.76 MHz (13C). Chemical shifts of 1H and
13C NMR spectra are reported in ppm downfield from TMS as an internal
standard. Optical rotations were measured at 258C on a Perkin-Elmer Polari-
meter 241. Mass spectra were recorded using a Finnigan MAT 8430 spec-
trometer in the electron-impact mode at 70 eV and chemical ionization, and
are reported as m/z values and relative abundances. The infrared spectra
were recorded using a FT-IR Spectrometer Nicolet 510 P.
4-Methyl-1,6:2,3-dianhydro-b-D-mannopyranose (5)
The epoxide was generated from the known hydroxy tosylate 4[5] in a modi-
fication using sodium hydride instead of MeONa. A solution of 4 (7.00 g,
21.4 mmol) in THF (300 mL) was treated at 08C with NaH (60% in oil, 1.7 g,
31.1 mmol) in THF (60 mL). The mixture was stirred 3 h at 208C. For
workup, an aqueous NH4Cl solution (10 mL) was added. After stirring for
1 h, the product was extracted with diethyl ether (3 ꢀ 30 mL), the organic
phase was dried (MgSO4) and filtered, and the solvent was removed at
reduced pressure. The epoxide was purified by chromatography on silica gel
using petroleum ether/EtOAc 7:3 as the eluent to afford 5 as an oil (3.03 g,
19.5 mmol, 96%). [a]D ¼ –23.28 (c ¼ 1.43, CHCl3), (ref. [5] –24.68 (c ¼ 1.57,
CHCl3)). 1H NMR (200 MHz, CDCl3): 1.20 (d, J7,4 ¼ 7.4 Hz, 3H, 7-H), 2.00
(m, 1H, 4-H), 2.76 (dd, J3,2 ¼ 4.0 Hz, J3,4 ¼ 0.6 Hz, 1H, 3-H), 3.26 (m, 1H,

Two Unusual Carbohydrate Reactions
383
2-H), 3.55–3.60 (m, 2H, 5-H, 6-Ha), 4.00 (m, 1H, 6-Hb), 5.54 (d, J1,2 ¼ 3.2 Hz,
1H, 1-H). 13C NMR (50 MHz, CDCl3): 16.7 (q, C-7), 34.6 (d, C-4), 51.6
(d, C-2), 53.9 (d, C-3), 68.7 (t, C-6), 73.7 (d, C-5), 98.3 (d, C-1). MS (EI, 70eV):
m/z (%) ¼ 142 (56) [Mþ], 101 (55), 98 (44), 97 (12), 83 (65), 73 (50), 71 (70),
57 (100), 55 (98), 47 (60), 43 (57), 39 (40). IR (Film): v˜ ¼ 2962 (s, C-H), 2957
(s, C-H), 2889 (s, C-H), 2360 (w, O-C-O), 1458 (s, C-H), 1381 (s, C-H), 1170
(s, C-H), 1127, (s, C-O), 1034 (s, C-O), 1003 (s, C-O), 998 (s, C-O).
2,4-Dimethyl-1,6-anhydro-b-D-glucopyranose (6)
A suspension of CuI (5.3 g, 28 mmol) in dry THF (25 mL) was treated at
–108C under argon with methyl lithium (40 mL, 1.6 M, 55 mmol). After stirring
this mixture for 10 min at 08C, the epoxide 5 (1.0 g, 7 mmol) in THF (10 mL)
was added. After 40 min at 08C, stirring was continued at 208C for 12 h. The
solution was diluted with diethyl ether (50 mL) and quenched by addition of
a saturated aqueous solution of NH4Cl (50 mL). The aqueous phase was
extracted with diethyl ether (3 ꢀ 10 mL), the combined organic phases dried
(Na2SO4) and filtered, and the solvent removed under reduced pressure. The
residue was purified by column chromatography on silica gel (elution pet-
roleum ether/EtOAc 7:3) to afford 6 as a colorless oil (690 mg, 4.34 mmol,
67%). [a]D ¼ –63.38 (c ¼ 1.13, CHCl3), (ref. [5] –62.48 (c ¼ 0.82, CHCl3)).
1H NMR (200 MHz, CDCl3): 1.06 (d, J8,2 ¼ 6.1 Hz, 3H, 8-H), 1.20
(d, J7,4 ¼ 7.6 Hz, 3H, 7-H), 1.74 (m, 2H, 2-H, 4-H), 2.65 (brs, 1H, OH), 3.34
(s, 1H, 3-H), 3.72 (dd, J6a,5 ¼ 5.2 Hz, J6a,6b ¼ 6.9 Hz, 1H, 6-H), 4.15
(d, J6b,6a ¼ 6.9 Hz, 1H, 6-H), 4.26 (m, 1H, 5-H), 5.23 (d, J1,2 ¼ 13.2 Hz, 1H,
1-H). 13C NMR (50 MHz, CDCl3): 16.3 (q, C-8), 18.8 (q, C-7), 41.0 (d, C-4),
43.0 (d, C-2), 68.5 (t, C-6), 75.4 (d, C-3), 78.0 (d, C-5), 105.0 (d, C-1). IR
(Film): v˜ ¼ 3505 (brs, O-H), 2960 (m, C-H), 2918 (m, C-H), 2898 (m, C-H),
1503 (w, C-H), 1377 (m, C-H), 1268 (s, C-H), 1170 (s, C-O), 1093 (s, C-O),
1063 (s, C-O).
(2S,3R)-1,2-Dihydroxy-3,6-dimethylheptan-4-one (7)
In a two-neck flask, CuCN (1.88 g, 21 mmol, 6 eq.) was suspended under
argon in dry diethyl ether (50 mL). The mixture was cooled to –788C and
treated with methyl lithium (1.6 M in diethyl ether, 26.2 mL, 42 mmol,
12 eq.) and stirred for 15 min at 08C. The clear solution was then cooled
to –788C and a solution of the epoxide 5 (0.50 g, 3.5 mmol) in dry THF
(20 mL) was added by means of a syringe. The reaction vessel was maintained
for 1 h at this temperature and then warmed to 208C. The starting material
was converted after 2 h (TLC monitoring) and the reaction was quenched by
addition of water (5 mL) and aqueous NH4Cl solution (25 mL). The mixture
was extracted with diethyl ether (3 ꢀ 20 mL), the combined organic phases

K. Krohn et al.
384
dried (Na2SO4) and filtered, and the solvent removed under reduced pressure.
The residue was separated by column chromatography on silica gel (elution
with petroleum ether/EtOAc 7:3) to afford 7 (63%) as the major product
together with 31% of the cyclic dimethylanhydro sugar 6 (31%), both as color-
less oils.
[a]D ¼ –26.58 (c ¼ 0.87, MeOH). 1H NMR (500 MHz, CDCl3): 0.86
(d, J8,6 ¼ 6.9 Hz, 3H, 8-H), 0.88 (d, J7,6 ¼ 6.9 Hz, 3H, 7-H), 1.03
(d, J9,3 ¼ 15.4 Hz, 3H, 9-H), 2.09 (m, 1H, 6-H), 2.35 (d, J5,6 ¼ 6.8 Hz, 2H,
5-H), 2.71 (m, 1H, 3-H), 3.50 (m, 1H, 1a-H), 3.64 (m, 1H, 2-H), 3.77 (br, 1H,
1b-H). 13C NMR (125 MHz, CDCl3): 11.5 (q, C-9), 22.4 (q, C-8), 22.5 (q, C-7),
23.9 (d, C-6), 48.2 (d, C-3), 51.5 (t, C-5), 64.7 (t, C-1), 73.7 (d, C-2), 215.2
(s, C-4). IR (Film): v˜ ¼ 3505 (brs, O-H), 2968 (m, C-H), 2910 (m, C-H), 2897
(m, C-H), 1713 (C55O), 1376 (m, C-H), 1267 (s, C-H), 1168 (s, C-O), 1093
(s, C-O), 1063 (s, C-O), 989 (s, C-H), 860 (s, C-H). MS (EI, 70 eV): m/z
(%) ¼ 175 (7) [M þ H]þ, 157 (42), 103 (9), 99 (13), 85 (76), 57 (87), 43 (100).
MS (CI, 70 eV): m/z (%) ¼ 175 (13) [M þ H]þ, 157 (60), 141 (60), 57 (100), 85
(2), 57 (87), 43 (23).
(2S,3R)-1,2-Diacetoxy-3,6-dimethylheptan-4-one (8)
A solution of diol 7 in pyridine (0.5 mL) was treated with acetic anhydride
(0.1 mL) and DMAP (10 mg). The solution was kept at 208C for 2 h, quenched
by addition of 2 N HCl (2 mL), and extracted with diethyl ether (3 ꢀ 20 mL).
The combined organic phases were dried (Na2SO4) and filtered, and the
solvent removed under reduced pressure. The residue was purified by
column chromatography on silica gel (elution petroleum ether/EtOAc 7:3) to
afford the diacetate as an oil (18.3 mg, 71%). [a]D ¼ þ22.448 (c ¼ 0.18,
1
MeOH). H NMR (500 MHz, CDCl3): d ¼ 0.89 (d, J8,6 ¼ 4.2 Hz, 3H, 8-H), 0.90
(d, J8,6 ¼ 4.2 Hz, 3H, 8-H), 0.91 (d, J7,6 ¼ 4.6 Hz, 3H, 7-H), 0.92
(d, J7,6 ¼ 4.6 Hz, 3H, 7-H), 1.08 (d, J9,3 ¼ 7.2 Hz, 3H, 9-H), 1.12
(d, J9,3 ¼ 7.1 Hz, 3H, 9-H), 2.00 (s, 3H, 10-H), 2.04 (s, 3H, 10-H), 2.05 (s, 3H,
11-H), 2.06 (s, 3H, 11-H), 2.11 (m, 1H, 6-H), 2.15 (m, 1H, 6-H), 2.35
(d, J5,6 ¼ 6.9 Hz, 2H, 5-H), 2.36 (br, 2H, 5-H), 2.84 (m, 1H, 3-H), 2.93 (m, 1H,
3-H), 4.06 (dd, J1a,1b ¼ 5.7 Hz, J1a,2 ¼ 11.8 Hz 1H, 1a-H), 4.10 (dd,
J1a,1b ¼ 5.3 Hz, J1a,2 ¼ 11.8 Hz 1H, 1a-H), 4.26 (dd, J1b,1a ¼ 3.4 Hz,
J1b,2 ¼ 12.4 Hz 1H, 1b-H), 4.37 (dd, J1b,1a ¼ 2.8 Hz, J1b,2 ¼ 12.4 Hz 1H, 1b-H),
5.24 (m, 1H, 2-H), 5.33 (m, 1H, 2-H). 13C NMR (125 MHz, CDCl3): d ¼ 12.3
(q, C-9), 12.3 (q, C-9), 20.6 (q, C-10), 20.8 (q, C-10), 22.4 (q, C-11), 22.4 (q, C-11),
22.5 (q, C-8), 22.5 (q, C-7), 24.0 (d, C-6), 24.1 (d, C-6), 46.7 (d, C-3), 46.9 (d, C-3),
50.9 (t, C-5), 50.9 (t, C-5), 62.7 (t, C-1), 63.5 (t, C-1), 71.6 (d, C-2), 72.2 (d, C-2),
169.8 (s, C-12), 170.1 (s, C-12), 170.4 (s, C-13), 170.5 (s, C-13), 210.2 (s, C-4),
210.4 (s, C-4). MS (EI, 70 eV): m/z (%) ¼ 259 (3) [M þ H]þ, 199 (6), 159 (25),
139 (33), 85 (100), 57 (92). MS (CI, 70 eV): m/z (%) ¼ 259 (54) [M þ H]þ, 199

Two Unusual Carbohydrate Reactions
385
(16), 157 (42), 139 (26), 97 (6), 85 (100), 57 (100), 33 (45). IR (Film): v˜ ¼ 2958 (C-H),
1747 (C55O, ester), 1461 (C-H), 1371 (C-H), 1222 (C-O).
1,6-Anhydro-4-deoxy-2-O-tosyl-b-D-xylohexopyranose (10)
A
solution of 2-O-tosyl-1,6:3,4-dianhydro-b-D-galactopyranose (3)[5,6]
(11.00 g, 37 mmol) and sodium borohydride (5.50 g, 145 mmol) in 1,2-dimethox-
yethane (110 mL) was treated dropwise at 208C over 1 h with boron trifluoride
diethyl etherate (11 mL). The mixture was stirred for 20 h (TLC monitoring)
and then adjusted to pH ¼ 7 by addition of 5% HCl. The solvents were comple-
tely removed at reduced pressure and the residue was diluted with cold water
(200 mL) and extracted with CH2Cl2 (5 ꢀ 100 mL). The combined organic
phases were dried (CaCl2) and filtered, the solvent evaporated, and the
residue crystallized from CH2Cl2/Et2O/PE to yield 3 (10.20 g, 35.1 mmol,
92%) as
a
colorless solid. m.p. ¼ 89–908C (ref. [11] m.p. 89–918C).
[a]D ¼ –428 (c ¼ 1.1, CHCl3), (ref. [11] –408 (c ¼ 1.0, CHCl3)). 1H NMR
(200 MHz, CDCl3): 1.61 (d, J4a,4b ¼ 15 Hz 1H, 4a-H), 2.20 (dd, J4b,3 ¼ 1.3 Hz,
J4b,4a ¼ 15.3 Hz, 4b-H), 2.35 (s, 3H, Ar-CH3), 3.15 (brs, 1H, OH), 3.57 (m, 1H,
3-H), 2.38 (m, 1H, 4-H), 3.85 (m, 1H, 6b-H), 4.08 (d, J6a,6b ¼ 6.9 Hz, 1H, 6a-
H), 4.17 (d, J2,1 ¼ 4.5 Hz, 1H, 2-H), 4.44 (m, 1H, 5-H), 5.18 (d, J1,2 ¼ 4.5 Hz
1H, 1-H), 7.29 (d, JAr,Ar ¼ 8.1 Hz, 2H, Ar-H), 7.74 (d, JAr,Ar ¼ 8.3 Hz, 2H, Ar-
H). 13C NMR (50 MHz, CDCl3): 21.6 (q, Ar-CH3) 32.5 (t, C-4), 64.8 (d, C-3),
67.6 (t, C-6), 72.1 (d, C-5), 76.9 (d, C-2), 99.0 (d, C-1), 127.8 (d, C-Ar), 127.9
(d, C-Ar), 130.0 (d, C-Ar), 130.1 (d, C-Ar), 133.1 (s, C-Ar), 145.3 (s, C-Ar). MS
(EI, 70 eV): m/z (%) ¼ 300 [Mþ], 188 (10), 155 (38), 145 (80), 99 (100), 91
(80), 71 (64), 69 (88), 65 (30), 58 (30), 44 (41), 41 (66), 31 (20). HREIMS: Calc.
for C7H12O3 300.3275. Found 300.0775.
3,6-O-Diacetyl-4-desoxy-2-O-tosyl-D-xyloyranosylbromide
(11)
A solution of tosylate (3) (1.000 g, 3.33 mmol) in acetic acid anhydride
(6.5 mL) was treated with a 33% solution of HBr in acetic acid (14.5 mL). The
mixture was initially stirred for 24 h at 208C and then heated for 6 h at 708C
(TLC monitoring). The solvent was completely removed at reduced pressure,
and the residue treated with a saturated solution of NaHCO3 and then
extracted with CH2Cl2 (2 ꢀ 100 mL). The organic phase was washed with
water (2 ꢀ 30 mL) and dried (Na2SO4), and the solvent removed at reduced
pressure. The residue was separated by flash chromatography on silica gel (pet-
roleum ether/EtOAc 1:5) to afford the monobromide 11 (696 mg, 1.5 mmol,
45%) and the dibromide 12 (542 mg, 34%), both as unstable oils. 1H NMR
(200 MHz, CDCl3): 1.61 (m, 1H, 4a-H), 1.87 (s, 3H, Ac-CH3), 2.04 (s, 3H, Ac-
CH3), 2.20 (m, 1H, 4b-H), 2.42 (s, 3H, Ar-CH3), 4.11 (m, 2H, 6a-H, 6b-H),

K. Krohn et al.
386
4.29–4.43 (m, 2H, 2-H, 3-H), 5.29 (m, 1H, 5-H), 6.42 (d, J1,2 ¼ 3.9 Hz, 1H, 1-H),
7.32 (d, JAr,Ar ¼ 8.1 Hz, 2H, Ar-H), 7.78 (d, JAr,Ar ¼ 7.8 Hz, 2H, Ar-H). 13C NMR
(50 MHz, CDCl3): 21.0 (q, Ac-CH3), 21.1 (q, Ac-CH3), 22.1 (q, Ar-CH3) 32.3
(t, C-4), 64.7 (d, C-3), 67.6 (t, C-6), 70.7 (d, C-5), 76.6 (d, C-2), 88.4 (d, C-1),
128.3 (d, 2 ꢀ C-Ar), 130.2 (d, C-Ar), 130.3 (d, C-Ar), 133.5 (s, C-Ar), 145.9
(s, C-Ar), 170.0 (s, Ac-C55O), 170.9 (s, Ac-C55O).
Data for 3-O-Acetyl-6-bromo-2-O-tosyl-4,6-desoxy-D-
glucopyranosyl bromide (12)
1H NMR (200 MHz, CDCl3): 1.62 (m, 1H, 4a-H), 1.87 (s, 3H, Ac-CH3), 2.18
(m, 1H, 4b-H), 2.39 (s, 3H, Ar-CH3), 3.43–3.51 (m, 2H, 6a-H, 6b-H), 4.29–4.43
(m, 2H, 2-H, 3-H), 5.17 (m, 1H, 5-H), 6.34 (d, J1,2 ¼ 3.7 Hz 1H, 1-H), 7.37
(d, JAr,Ar ¼ 8.1 Hz, 2H, Ar-H), 7.72 (d, JAr,Ar ¼ 7.8 Hz, 2H, Ar-H). 13C NMR
(50 MHz, CDCl3): 21.0 (q, Ac-CH3), 22.2 (q, Ar-CH3) 30.3 (t, C-6), 32.1
(t, C-4), 64.8 (d, C-3), 71.2 (d, C-5), 76.5 (d, C-2), 88.2 (d, C-1), 128.4 (d,
2 ꢀ C-Ar), 130.1 (d, C-Ar), 130.4 (d, C-Ar), 133.3 (s, C-Ar), 145.9 (s, C-Ar), 170.1
(s, Ac-C55O).
3,6-Di-O-acetyl-1,5-anhydro-2,4-dideoxy-D-threitol (14)
A solution of monobromide 11 (500 mg, 1.07 mmol) in ethanol (9 mL) was
treated with Et3N (0.7 mL) and Raney nickel (600 mg) and the suspension
was stirred under hydrogen at 208C for 2 h. The mixture was filtered, the
solvent removed at reduced pressure, and the residue purified by chromato-
graphy on silica gel (petroleum ether/EtOAc) to afford 14 (148 mg,
1
0.69 mmol, 64%) as an oil. [a]D ¼ þ1.58 (c 0.9, MeOH). H NMR (200 MHz,
CDCl3): 1.32 (m, 1H, 2a-H), 1.61 (m, 1H, 4a-H), 1.85–1.94 (m, 2H, 2b-H,
4b-H), 1.97 (s, 3H, Ac-CH3), 2.01 (s, 3H, Ac-CH3), 3.38–3.45 (m, 1H, 1a-H),
3.51–3.61 (m, 1H, 1b-H), 3.91–4.96 (m, 3H, 6a-H, 6b-H, 3-H), 4.80–4.91
(m, 1H, 5-H). 13C NMR (50 MHz, CDCl3): 21.1 (q, Ac-CH3), 21.5 (q, Ac-CH3),
31.9 (t, C-4), 34.0 (t, C-2), 66.1 (t, C-1), 67.0 (t, C-6), 70.1 (d, C-3), 74.1
(d, C-5), 170.6 (s, Ac-C55O), 171.1 (s, Ac-C55O). MS (EI, 70 eV): m/z
(%) ¼ 216 [Mþ], 172 (14), 172 (13), 145 (3), 101 (18), 99 (10), 91 (25), 86 (100),
58 (33), 44 (22), 30 (34). HREIMS: Calc. C7H12O3 (216.2310). Found 216.0997.
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