Vitamin b12 catalysis of zinc-mediated 6-deoxy-6-iodopyranoside fragmentation: A mild and convenient preparation of ω-unsaturated hexose derivatives (5-hexenoses)

Article abstract of DOI:10.1055/s-2000-6305

The known zinc-mediated preparation of 5-hexenoses by fragmentation of 6-iodopyranosides can be performed in a simple, fast, and mild way, with less side reactions, when vitamin B₁₂ is employed as a catalyst.

Full text of DOI:10.1055/s-2000-6305

PAPER
1027
Vitamin B Catalysis of Zinc-Mediated 6-Deoxy-6-iodopyranoside
1
2
Fragmentation: A Mild and Convenient Preparation of w-Unsaturated Hexose
Derivatives (5-Hexenoses)
Martin Kleban, Ulrich Kautz, Jörg Greul, Petra Hilgers, Rolf Kugler, Han-Qing Dong, Volker Jäger*
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, D-70569 Stuttgart, Germany
Fax +49(711)6854321; E-mail: jager.ioc@po.uni-stuttgart.de
Received 21 February 2000
Dedicated to Professor Franz Xaver Effenberger on the occasion of his 70th birthday
number of other reagents have been proposed for the
Abstract: The known zinc-mediated preparation of 5-hexenoses by
crucial fragmentation step with such w-bromo- or w-iodo
fragmentation of 6-iodopyranosides can be performed in a simple,
compounds. Some of the reagent combinations reported
fast, and mild way, with less side reactions, when vitamin B is em-
1
2
10
ployed as a catalyst.
Key words: fragmentation, zinc, vitamin B12 catalysis, 6-deoxy-
-iodopyranosides, 5-hexenoses
for these or similar cases are zinc-copper pair, zinc acti-
4
a,9b
11
vated with CeCl ,
zinc/silver-graphite, or lithium
3
alkyls.5
,8,12
Another combination, zinc with vitamin B
6
12
1
3
added as a catalyst, had been mentioned in related
eliminations for syntheses of long-chain alkenol
pheromones1 and of tri-O-acetylglucal.
3b
13c
Unsaturated polyols (enitols) and aminopolyols or hex-
enose derivatives are versatile intermediates for the syn- In a project designed to find new structures for glycosi-
1
thesis of optically active target compounds. In particular, dase inhibition, aminocyclopentanepolyols A were con-
cyclizations or cycloadditions of such substrates to yield sidered promising candidates,6
,14-16
and respective
heterocyclic or carbocyclic compounds have found wide- hexenoses D were needed for the preparation of the obvi-
1
-7
6
spread application. Starting from hexoses, Bernet and ous intermediates, i. e. bicyclic isoxazolidines B (vide su-
Vasella had shown that transformation to protected 5-hex- pra) and related isoxazolines C6
a,7,17
(Scheme 1).
enoses, via 6-bromo-6-deoxypyranosides, provided
straightforward access to one of these classes. The key
6
-Bromo-6-deoxypyranosides E from the series of the
5
hexose stereoisomers were first taken as starting materi-
als. With the zinc or zinc-copper reagents difficulties were
met in several case:
step, a fragmentation including a reductive elimination
8
(
Boord reaction), was effected with zinc or activated zinc
15a,b
In the gluco series with tri-O-ben-
in refluxing propanol (93%). The hexenoses were further
developed into bicyclic isoxazolidines by dipolar cy-
cloadditions of intermediate nitrones, thus effecting an el-
egant overall conversion of hexoses into highly
functionalized cyclopentane derivatives. This sequence
zyl compounds 2-deoxygenation indeed proved trouble-
5a,15
some;
in the GlcNAc case and similarly with the
16
galactose bis(acetonide) (vide infra) yields proved diffi-
cult to reproduce, and byproducts were found.
18
1
-4,6,9
Finally, a new and milder procedure was developed, sub-
mitting 6-iodopyranosides to zinc in methanol with 0.5 to
has been useful in many other cases likewise.
Since
the hexenose products are somewhat unstable and
byproducts from further deoxygenation may be formed, a
2
mol% of vitamin B added as a catalyst. In all cases de-
12
scribed, the reaction was complete after 3 hours at room
O
N
O (N)
O
O
X
O
N
B
O
O
OR
O
O (N)
O
O (N)
O
O (N)
O
O
O
O
A
N
D
E
O
O (N)
O
C
Scheme 1
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

1
028
M. Kleban et al.
PAPER
temperature; it was not necessary to employ activated amounts, reductive elimination/fragmentation in metha-
zinc. Side reactions were not observed, reproducibility nol was complete after 0.5 to 3 hours, as monitored by
was very good, and various O-protecting groups could be TLC analyses. From the gluco-iodides 3 and 12 with tri-
carried through without trouble, see Equations 1-6 O-benzyl and tri-O-acetyl protection and the analogous
(
Scheme 2) and Table 1.
manno compounds 4 and 13, the respective hexenoses 5,
4, 6, and 15 were obtained in good yield and in spectro-
1
The 6-deoxy-6-iodo compounds 3, 4, 8, 12, 13, 20, and 23
were prepared from the respective protected a-pyrano-
sides 1, 2, 7, 10, 11, 19, and 22, using the reliable I /triph-
enylphosphane procedure of Garegg and Samuelsson. In
the GlcNAc series the iodide 17 was obtained by mesylate
substitution, see Equation 4. Upon action of an excess (ca.
scopically pure form, albeit with some deviating elemen-
tal analyses. For these cases the oximes or other
derivatives were prepared and proved satisfactory regard-
ing the latter aspect (see Experimental Part and Table 1).
The other manno derivative, the 4-O-acetyl-2,3-acetonide
2
19
8
, was transformed likewise, and the crude product of the
1
0 equiv) of zinc and cyanocobalamin in catalytic
1
) I2, PPh3,
imidazole,
toluene,
reflux
X
Zn (10 eq),
vit. B12 (0.005-0.02 eq),
NH4Cl (10 eq)
O
OMe
OR
O
(1)
3, 4
2
) Ac2O,
DMAP,
NEt3
MeOH, r.t.,
0.5 - 3 h
RO
AcO
OAc
(X = I,
R = Ac)
OR
OAc
5, 6
1
, 2 (X = OH, R = H)
X
O
OMe
O
O
dto.
dto.
(2)
8
RO
AcO
O
(
X = I,
R = Ac)
O
O
7
(X = OH, R = H)
9
X
I2, PPh3,
O
OMe
OBn
imidazole
O
dto.
(3)
12, 13
toluene,
reflux
BnO
BnO
OBn
(X = I)
OBn
OBn
10, 11 (X = OH)
14, 15
1
) Zn (10 eq),
vit. B12 (0.006 eq),
X
1) MsCl, pyridine
OH
N
2) Ac2O, DMAP,
NH Cl (10 eq),
4
O
OH
3) NaI, 2-butanone
MeOH, r.t., 1.5 h
(4)
17
2) H2NOH•HCl,
pyridine, 1 h
HO
NHAc
AcO
NHAc
(X = I, Ac)
OH
OAc
16 (X = OH, R=H)
18
X
Zn (10 eq),
I2, PPh3,
vit. B12 (0.005 eq),
O
OMe
O
imidazole
NH Cl (10 eq)
OH
4
(5)
20
toluene,
reflux
MeOH, r.t., 1.5 h
HO
O
(X = I)
O
O
O
19 (X = OH)
21
X
HO
O
O
O
O
dto.
dto.
(6)
D-23
O
O
O
(
X = I)
O
O
D-22 (X = OH)
L-24
Scheme 2
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Vitamin B12 Catalysis of Zinc-Mediated 6-Deoxy-6-iodopyranoside Fragmentation
1029
Table 1 Yields and IR Data of Compounds Prepared
Staring Material,
Configuration
Product,
Configuration
Yield Molecular
IRa
n (cm )
−
1
(%)
Formula
03
04
08
12
13
17
20
D-gluco
D-manno
D-manno
D-gluco
D-manno
D-gluco
05
D-xylo
79,c
C H O
2987 (w), 1750 (br s, C=O), 1422 (m), 1373 (m), 1266 (s), 1217 (s), 1055
(m), 896 (w), 736 (s), 705 (s)
12
16
7
7
5
4
4
(
272.3)
06
D-lyxo
79b c
96b ,
83b c
C H O
3055 (m), 2987 (m), 1748 (s, C=O), 1647 (w, C=C), 1422 (m), 1222 (s),
1042 (m), 946 (w), 705 (m)
12
16
(
272.3)
09
D-lyxo
C H O
2985 (s), 1744 (vs, C=O), 1647 (w, C=C), 1428 (m), 1373 (s), 1234 (s),
1091 (m), 988 (m), 940 (m), 854 (m)
11
17
(
229.2)
14
D-xylo
C H O
3054 (s), 2986 (m), 1730 (s, C=O), 1605 (w, C=C), 1451 (s), 1422(m),
1072 (s), 1028 (m), 896 (m)
27
28
(
416.5)
15
D-lyxo
75b ,c C H O
2868 (m), 1731 (s, C=O), 1605 (w), 1454 (s), 1330 (w), 1207 (m) 1068
(s), 1028 (s), 933 (m), 736 (s), 698 (s)
27
28
(
416.5)
18
D-xylo
92c ,c C H N O
3399 (br s, OH, NH), 2935 (m), 1745 (s, C=O), 1664 (m, C=N), 1652 (w,
C=C), 1375 (m), 1220 (m), 943 (m)
12
18
2
6
(GlcNAc)
(286.3)
D-manno
a-21
D-lyxo
84d ,c C H O
3475 (br s, OH), 2943 (s), 1649 (w, C=C), 1379 (s), 1215 (s), 1163 (m),
1072 (m), 944 (s), 879 (s), 853 (s)
9
14
4
(
186.2)
D-23 D-galacto L-24
L-arabino 83b,c
D-arabino 55a,c
C H O
3444 (br s, OH), 2987 (s), 1644 (w, C=C), 1431 (m), 1381 (m), 1212 (s),
1163 (s), 1071 (s), 932 (m)
12
20
5
(
244.3)
L-23 L-galacto D-24
as above
as above with L-24
a
Recorded as film, except for 21 (KBr).
b
c
d
Satisfactory microanalysis only obtained from derivative, see Experimental Part.
Hexenose not isolated, directly converted to oxime, yield: 92% over 2 steps; IR data from 75:25 E/Z-mixture of oximes.
a-Furanose form.
hexenose 9 was then converted to the analytically pure ni- compounds as catalysts will see further applications with
troaldol product on nitromethane/Bu NF∑3 H O treat- sensitive, highly functionalized substrates.
4
2
2
0
ment. The sequence was also applied to the N-
acetylglucosamine derivative 16, via the iodo compound
Solvents were purified and dried according to standard proce-
dures. Methy a-D-glucopyranoside, methyl a-D-mannopyranoside,
1
1
7, which when treated as above led to the stable oxime N-acetylglucosamine, D-galactose, Ph P, I , imidazole, Zn (Fluka),
8 of the respective D-xylo-hexenose in 92% yield.
3
2
and vitamin B12 (Aldrich) were purchased and used without further
1
9b
19b
19c
22
23
19b
purification. The iodo compounds 3, 4, 12, 17, 20, 23
The mannose-acetonide derivative 20 (from 19), with free
-OH, under these conditions led to the a-furanose form
were prepared according to procedures described in literature.
4
20
3
: yield 73%; mp 150-151 °C; [a] +113.0 (c = 1.00, CHCl3)
D
1
9b
20
of the hexenose 21 (analytically pure), which proved more {Lit. mp 151-152 °C; [a] +115.0 (c = 1.00, CHCl )}; 4: yield
D
3
2
0
19b
stable than the other open-chain aldehydes. Finally, the 72%; mp 88-90 °C; [a]
+48.5 (c = 1.00, CHCl ) {Lit. mp 90-
D
3
2
0
9
6
(
(
(
1 °C; [a]D +45.0 (c = 1.2, CHCl )}; 12: yield 84%, mp 68-
3
20 19c 20
1
,2:3,4-di-O-isopropylidenegalactose derivative 22, via
9 °C; [a]D +36.0 (c = 1.05, CHCl ) {Lit. oil; [a]D +61.0
3
the iodide 23, on zinc/vitamin B treatment afforded the
bis(acetonide) 24, with intact hemiacetal moiety. This -
presumably labile - structure, not obtainable with the
1
2
20
c = 1, EtOAc)}; 17: yield 75%; mp 204 °C (dec.); [a] +86.0
D
22 20
c = 0.96, CHCl ) {Lit. mp 196-197 °C (dec.); [a]D +92.2
3
20
c = 1.2, CHCl )}; 20: yield 86%; mp 110-111 °C; [a] +45.7
3
D
1
1c
2
3
20
zinc/silver-graphite procedure, underlines the advan- (c = 1.10, CHCl ) {Lit. mp 111-112 °C; [a] +46.0 (c = 1.3,
3
D
0
2
tages of the new procedure; actually, the hemiacetal 24 CHCl )}; 23: yield 82%; mp 59-60 °C; [a] - 48.0 (c = 1.16,
3
D
1
9b
20
CHCl ) {Lit. mp 58 °C; [a]D -49.0 (c = 1.00, CHCl )}.
also survived silica gel chromatography as well as Kugel-
rohr distillation.
3
3
TLC was performed on silica F254-coated aluminum sheets (E. Mer-
ck) using mixtures of EtOAc/petroleum ether (bp 40-70 °C) and
propan-2-ol/petroleum ether, with detection by UV at 254 nm or by
heating with a solution of cerium(IV) sulfate (1 g), ammonium mo-
The mechanism of such vitamin B -catalyzed reactions is
well understood: Co of cyanocobalamin with zinc is re-
duced to Co , a powerful nucleophile.
1
2
III
I
13a,21
With alkyl ha-
24
lybdate (2.1 g), and concd H SO (31 mL) in H O (500 mL). Silica
2
4
2
III
lides or the like, intermediate Co species are formed that gel (Merck, 32-63 mm) was used for chromatography. MPLC was
decompose to give an alkene when a leaving group is done using a Lewa pump with a column (4 cm × 40 cm) packed with
LiChroprep Si 60 (15-25 mm, Merck, ca. 11500 theoretical
present in the b-position (cf. reaction modes of coenzyme
2
5
1
3a,21b
plates), detection by a UV/VIS spectrometer 97.00 (Knauer). Mps
were determined on a Fisher-Johns apparatus and are uncorrected.
The optical rotations were measured on a Perkin-Elmer 241 MC po-
B ).
It is easy to predict that the ease and mildness
1
2
of this 6-halopyranoside fragmentation and of selected
Boord eliminations using vitamin B12 or related cobalt
larimeter using the Drude method to calculate [a] from the values
D
found at 546 and 579 nm. IR spectra were recorded on a Bruker IFS
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

1
030
M. Kleban et al.
PAPER
2
8 spectrometer. NMR spectra were obtained from Bruker AC 250,
Methyl 2,3,4-Tri-O-benzyl-6-deoxy-6-iodo-a-D-mannopyrano-
1
ARX 300 and ARX 500 spectrometers ( H: 250.1, 300.1, or 500.1
side (13)
MHz, 13C: 62.9, 75.5, or 125.8 MHz) with TMS as internal stan-
According to Ref. to a stirred solution of methyl 2,3,4-tri-O-ben-
19
1
5b
dard; evaluation of H NMR spectra according to 1st order interpre-
tation; multiplicity of C NMR signals from broad-band decoupled
zyl-a-D-mannopyranoside
(4.50 g, 9.69 mmol) in toluene
1
3
(100 mL) at 80 °C was added I (3.60 g, 14.2 mmol), Ph P (7.30 g,
2
3
or DEPT spectra. The NMR data of compounds 5, 6, 9, 14, 15, 18,
27.8 mmol), and imidazole (3.80 g, 55.8 mmol) and then kept at
80 °C for 4 h. The solvent was removed by evaporation and the re-
sulting oil purified by column chromatography (silica gel, 150 g,
petroleum ether/EtOAc, 90:10 Æ 80:20) to yield 4.77 g (86%) of a
2
1 and 24 prepared are shown in Tables 2 and 3.
Methyl 4-O-Acetyl-6-deoxy-6-iodo-2,3-O-isopropylidene-a-D-
mannopyranoside (8)
2
0
colorless oil; [a]D +22 (c = 0.95, CHCl ).
3
According to Ref.,19 isopropylidenemannopyranoside 7 (2.75 g,
C H IO calc.
C 58.49
58.27
H
5.43
5.38
I
22.07
21.85
2
8
31
5
8
.00 mmol) and DMAP (20 mg) were dissolved in Et N (4.00 g) and
3
(575.0)
found
cooled to 0 °C. Within 20 sec Ac O (1. 02 g, 10.00 mmol) was add-
2
ed dropwise. After 30 min the ice-bath was removed and the yellow-
ish solution stirred for another 4 h at r.t. Evaporation of volatiles and
filtration over silica gel (40 g, petroleum ether/EtOAc, 70:30) af-
forded 3.09 g (99%) of a colorless oil, which crystallized at -30 °C;
5
(
,6-Dideoxy-2,3-O-isopropylidene-a-D-lyxo-5-hexenofuranose
21); Typical Procedure
To a stirred suspension of Zn (916 mg, 14.0 mmol) and NH Cl
4
(
750 mg, 14.0 mmol) in MeOH (20 mL) a catalytic amount of vita-
20
mp 39-40 °C; [a]D +25.2 (c = 0.63, CHCl ).
3
min B12 (5 mg, 0.006 mmol) was added at r.t. After 10 min, a solu-
tion of 20 (480 mg, 1.40 mmol) in MeOH (2 mL) was added. The
resulting suspension was stirred for 90 min at r.t. Undissolved ma-
terial was filtered off and washed with MeOH. The filtrate was
C H IO calc.
C 37.32
37.18
H
4.96
4.92
I
32.86
32.64
1
2
19
6
(386.2)
found
1
Table 2 H NMR Data Hexenoses Prepared (CDCl /TMS)
3
Com-
pound
Chemical Shifts d (ppm)
1
-H
2-H
5.28
5.24
4.42
3.87
-b
3-H
4-H
5.54a
5.63
5.33
4.15
-b
5-H
6-HE
5.35
5.35
5.33
5.24
5.34
5.30
5.34
5.29
5.33
6-HZ
Others
05
06
09
14
15
1
8c
9.49
9.48
9.67
9.64
9.65
7.42
5.41
5.40
5.39
5.53a
5.47
4.52
3.79
3.89
5.29
4.73
4.48
4.20
5.77
5.74
5.87
5.82
5.85
5.80
5.99
6.02
5.94
5.38
2.06, 2.10, 2.22 (3 COCH3)
2.09, 2.09, 2.20 (3 COCH3)
1.42, 1.63 [C(CH ) ], 2.09 (COCH )
5.43
5.38
3
2
3
5.27
4.35, 4.47, 4.53, 4.57, 4.70, 4.71 (3 CH Ph), 7.15-7.42 (C H )
2
6
5
5.37
4.31-4.76 (m, 2-H, 4-H, 3 CH Ph), 7.15-7.45 (C H )
2
6
5
5.02
4.64
4.01
3.99
5.49
4.62
4.69
4.66
5.34
2.04, 2.08, 2.10 (3 COCH ), 6.75 (NH), 9.55 (OH)
3
a-21
5.42
1.32, 1.47 [C(CH ) ], 3.00 (OH)
3
2
d
a-L-24
5.40
1.38, 1.42, 1.57, 1.58 [2 C(CH ) ], 3.61 (OH)
3 2
b-L-24d
5.40
1.40, 1.49, 1.52, 1.55 [2 C(CH ) ], 3.61 (OH)
3 2
Com-
pound
Coupling Constants J (Hz)
J1,2
~0
J2,3
J3,4
J4,5
6.5
6.4
6.8
7.7
7.8
5.9
7.4
8.2
8.2
J5,6E
J5,6Z
17.1
17.0
17.3
16.0
17.5
16.8
17.5
17.1
17.1
J6E,6Z
1.8
1.2
1.8
1.8
1.8
-b
Others
05
06
09
14
15
1
8c
1.6
5.2
7.7
4.4
5.6
4.5
5.8
6.3
5.1
1.3
5.4
3.8
5.0
3.7
5.5
3.7
6.6
6.8
10.4
10.4
10.5
11.6
10.3
10.4
10.4
10.1
10.2
J4,6E = J4,6Z = 0.9
J4,6E = J4,6Z = 0.9
J4,6E = J4,6Z = 1.0
J4,6E = J4,6Z = 0.9, J
J4,6E = J4,6Z = 1.0
J2,NH = 9.0
0.7
2.3
1.0
1.5
4.0
~0
= 11.6 (3 ×)
CH Ph
2
a-21
1.7
1.6
1.6
J4,6E = 0.8, J4,6Z = 1.0, J1,OH = 2.3
J4,6E = J4,6Z = 0.9
a-L-24d
3.9
3.6
d
b-L-24
J4,6E = J4,6Z = 0.9
a
b
Assignments may be reversed. Not identified due to overlapping signals.
c 1
H NMR Data from (E)-oxime; from the (Z)-isomer only few data were identified due to overlapping signals [E/Z-mixture = 75:25]: 6.28
(
J2,NH = 6.3 Hz, NH), 6.62 (J1,2 = 5.7 Hz, 1-H), 10.23 (br s, OH), see Experimental.
d
Data obtained from a 40:60-mixture of a/b-anomers; signals for 6-H and OH coinciding.
Z
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Table 3
Vitamin B12 Catalysis of Zinc-Mediated 6-Deoxy-6-iodopyranoside Fragmentation
1031
1
3
a
C NMR Chemical Shifts of Hexenoses Prepared, d (ppm)
Compound C-1
C-2
C-3
C-4
C-5
C-6
Others
05
06
09
193.8
195.1
200.0
70.3b
71.1b
79.9b
72.4b
71.6b
80.3b
75.5b
75.4b
71.3
130.9
131.2
132.0
120.4
120.4
119.6
20.1, 20.2, 20.5 (3 COCH ), 169.1, 169.3, 169.5 (3 COCH )
3
3
20.2, 20.4, 20.6 (3 COCH ), 169.3, 169.5, 169.7 (3 COCH )
3
3
24.9, 26.5 [C(CH ) ], 111.0 [C(CH ) ], 20.9 (COCH ), 169.1
3
2
3 2
3
(
COCH3)
1
1
4
201.4
201.7
79.8
81.3
82.2
134.6
135.1
119.3
119.9
70.8, 73.1, 74.3(3 OCH Ph), 127.1 - 128.4 (3o-, m-, p-C H ), 137.1,
2
6
5
1
37.5, 137.7 (3 i-C H )
6 5
5
80.5b
82.8b
83.6b
70.7, 72.7, 74.1(3 OCH Ph), 127.6 - 128.5 (3o-, m-, p-C H ), 137.3,
2 6 5
1
37.8, 138.0 (3 i-C H )
6 5
(
(
E)-18c
Z)-18c
147.1
147.0
101.1
97.3
48.8
50.5
81.5
82.1
77.3b
72.2b
72.7b
81.5
72.5b
73.0b
85.8
131.6
131.5
132.1
134.1
133.7
119.7
120.1
119.3
120.0
119.1
20.6, 21.0, 22.9 (3 COCH ), 170.1, 170.4, 170.6 (3 COCH )
3 3
20.7, 21.0, 23.1 (3 COCH ), 170.2, 170.3, 170.9 (3 COCH )
3
3
a-21
24.9, 26.1 [C(CH ) ], 112.7 [C(CH ) ]
3
2
3 2
d
77.3b
78.2b
78.9b
78.5b
a-L-24
26.9, 27.1, 27.5, 28.6 [2 C(CH ) ], 110.5, 111.1 [2 C(CH ) ]
3 2 3 2
b-L-24d
95.0
25.4, 25.4, 26.2, 27.4 [2 C(CH ) ], 109.4, 109.6 [2 C(CH ) ]
3 2 3 2
a
Recorded in CDCl3.
Assignments may be reversed.
From 75:25-mixture of Z/E-oximes, see Experimental.
Data received from a 40:60-mixture of a/b-anomers.
b
c
d
evaporated, the reddish residue dissolved in EtOAc (20 mL),
C H NO calc.
C 49.82
49.61
H
6.62
6.74
N 4.84
4.53
1
2
19
7
washed with a mixture of H O and brine (5 mL each), the organic
(289.3)
found
2
layer re-extracted with EtOAc (3 ¥ 10 mL) and then the combined
2
,3,4-Tri-O-benzyl-5,6-dideoxy-D-xylo-5-hexenose (14)
organic layers were dried (Na SO ). Evaporation afforded the crude
2
4
From 12 (6.00 g, 10.7 mmol) according to the Typical Procedure;
yield: 14 3.73 g (83%); colorless oil; [a]D -15.2 (c = 1.05,
CHCl ); spectroscopically pure, deviating elemental analysis.
product 21 as a yellowish oil. For correct elemental analysis purifi-
20
cation of this by filtration over silica gel (20 g, eluent Et O) gave a
2
3
pale yellow oil (21, 233 mg, 90%). Further purification by MPLC
Oxime derivative: yield 75%; E/Z = 67:33; mp 60-62 °C; [a]D20
(petroleum ether/propan-2-ol, 95:5, 210 nm) afforded 21 as a color-
+
20.0 (c = 1.01, CHCl3).
less oil (218 mg, 84%), which crystallized at -30 °C; mp 55-56 °C;
20
[
a
]
-
2
9
.
0
(
c
=
0
.
5
7
,
C
H
C
l
)
.
D
3
C H NO calc.
C 75.17
75.28
H
6.77
6.86
N 3.24
3.22
2
7
29
4
(
431.5)
found
C H O
4
calc.
found
C 58.05
57.92
H
7.58
7.61
9
14
(
186.2)
2
,3,4-Tri-O-benzyl-5,6-dideoxy-D-lyxo-5-hexenose (15)
According to the Typical Procedure; from 13 (575 mg, 1.00 mmol),
2
,3,4-Tri-O-acetyl-5,6-dideoxy-D-xylo-5-hexenose (5)
2
0
yield: 15 312 mg (75%); colorless oil; [a]D -9.5 (c = 1.21,
From 3 (1g, 2.32 mmol) following the Typical Procedure; purifica-
tion by chromatography (eluent petroleum ether/EtOAc, 90:10 Æ
7
CHCl ); spectroscopically pure, deviating elemental analysis.
3
2
0
0:30), yield: 502 mg (79%); colorless oil; [a] -20.4 (c = 1.22,
20
D
Oxime derivative: colorless oil, yield 69%; E/Z = 75:25; [a]D
-11.0 (c = 1.05, MeOH).
11d
20
CHCl ) {Lit. [a]D +3.9 (c = 13.3, CH Cl ); no analysis given}.
3
2
2
C H O calc.
C 52.95
52.75
H
5.92
6.04
1
2
16
7
C H NO calc.
C 75.16
75.09
H
6.77
6.83
N 3.25
3.24
2
7
29
4
(
272.3)
found
(
431.5)
found
2
,3,4-Tri-O-acetyl-5,6-dideoxy-D-lyxo-5-hexenose (6)
Prepared from 4 (400 mg, 0.93 mmol) according to the Typical Pro-
cedure; yield: 220 mg (79%), colorless oil; [a]D +41.2 (c = 0.92,
CHCl ), spectroscopically pure, but incorrect elemental analysis.
2-Acetamido-3,4-di-O-acetyl-2,5,6-trideoxy-D-xylo-5-hexenose
oxime (18)
2
0
To a solution of vitamin B12 (20 mg, 15 mmol) in MeOH (50 mL)
3
was added Zn (2.60 g, 26.9 mmol) and NH Cl (2.14 g, 26.9 mmol).
1
6b
4
Isoxazolidine derivative with MeNHOH: 63%; colourless oil;
After the mixture had become green, 17 (1.23 g, 2.69 mmol) was
added and the suspension stirred at r.t. for 90 min. Then pyridine
20
[
a]D -75.0 (c = 1.33, CHCl3).
C H NO calc.
C
51.82
51.80
H
6.36
6.50
N 4.66
4.58
(2 mL) and H NOH∑HCl (374 mg, 5.38 mmol) were added. After
1
3
19
7
2
(
301.3)
found
stirring for another 90 min the solids were filtered off and the solu-
tion was evaporated. The residue then was purified by chromatog-
4
-O-Acetyl-5,6-dideoxy-2,3-O-isopropylidene-D-lyxo-5-hex-
raphy (CH Cl /MeOH, 97:3) to give 710 mg (92%) of the oxime 18;
enose (9)
2
2
colorless, analytically pure oil; E/Z = 75:25.
Following the Typical Procedure; from 8 (3.09 g, 8.00 mmol), yield
of 9: 1.77 g (96%); colorless oil; [a]D -44.2 (c = 0.53, CHCl3);
spectroscopically pure, deviating elemental analysis.
2
0
(E)-Isomer from repeated chromatography as above; mp 139-
2
0
1
40 °C, [a]D -2.5 (c = 1.05, CHCl3).
Nitromethane adduct (with Bu NF∑3H O); colorless oil; yield:
4
2
C
12
H
18
N
2
O calc.
5
found
C 50.34
50.07
H
6.34
6.41
N 9.78
9.26
4%;20 dr = 90:10; [a]D -22.0 (c = 0.40, CHCl3).
20
6
(286.3)
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

1
032
M. Kleban et al.
PAPER
5
(
,6-Dideoxy-1,2:3,4-di-O-isopropylidene-L-arabino-5-hexenose
L-24)
According to the Typical Procedure; D-23 (3.58 g, 9.6 mmol) gave
.95 g (83%) of L-24, colourless oil; anomer ratio a:b = 33:67;
submitted.
(b) Hilgers, P.; Kleban, M.; Picasso, S.; Jäger, V., submitted.
(c) Greul, J.; Kleban, M.; Schneider, B.; Picasso, S.; Jäger, V.,
submitted.
1
20
[
a]D +15.0 (c = 1.08, CHCl ), spectroscopically pure, deviating el-
(7) Intramolecular nitrile oxide cycloadditions producing
carbocyclic derivatives:
3
emental analysis.
2
0
(a) Jäger, V; Günther, H. J. Angew. Chem., Int. Ed. Engl. 1977,
Corresponding oxime: colorless oil; yield 95%; E/Z = 81:19; [a]D
16, 246.
-24.0 (c = 1.06, CHCl3).
(b) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410.
C H NO calc.
C 53.72
53.59
H
7.51
7.61
N 6.96
6.97
9
15
4
(c) Curran, D. P. Adv. Cycloadd. 1988, 1, 129.
8) (a) Schlosser, M. in Houben-Weyl, Methoden der
Organischen Chemie, Müller, E. , Ed.; Thieme: Stuttgart
(
201.2)
found
(
(
5
(
,6-Dideoxy-1,2:3,4-di-O-isopropylidene-D-arabino-5-hexenose
1
972, Vol. 5/1b, p 134ff.
b) Bernet, B.; Vasella, A. Helv. Chim. Acta 1984, 62, 1328.
9) (a) Bernotas, R. C.; Ganem, B. Tetrahedron Lett. 1985, 1123.
b) Bernotas, R. C.; Pezzone, M. A.; Ganem, B. Carbohydr.
Res. 1987, 305.
c) Egbertson, M.; Danishefsky, S. J. J. Org. Chem. 1989, 54,
2.
d) Farr, R. A.; Peet, N. P.; Kang, M. S. Tetrahedron Lett.
990, 49, 7109.
e) Kobayashi, Y.; Miyazaki, H.; Shiozaki, M. J. Org. Chem.
994, 59, 813.
f) Moutel, S.; Shipman, M. Synlett 1998, 1333.
D-24)
As described for L-24, starting from L-galactose via L-22 and L-23
659 mg, 1.8 mmol); D-24: 240 mg (55%); colorless, analytically
pure oil after purification by chromatography with petroleum ether/
(
(
(
2
0
EtOAc (1:1), anomer ratio a:b = 41:59; [a]D -20.0 (c = 0.96,
(
1
(
1
(
1
(
CHCl ).
3
C H O calc.
C 59.00
58.66
H
8.25
8.30
1
2
20
5
(
244.3)
found
Acknowledgement
We thank the Volkswagen-Stiftung (Hannover), the Fonds der Che-
mischen Industrie, the Alexander von Humboldt-Stiftung (fel-
lowship for Han-Qing Dong), the Landesgraduiertenförderung
Baden-Württemberg (scholarships for Martin Kleban and Petra Hil-
gers née Pruschek) for financial support, and Dr. B. Ernst (Novartis,
Basel) for a generous gift of L-galactose. We are further grateful to
Dr. T. Gracza, Dr. E. Dubois, and Dr. Jing Li for carrying out some
related experiments.
(g) Ovaa, H.; Codee, J. D. C.; Lastdrager, B.; Overkleeft, H.
S.; van der Marel, G. A.; van Boom, J. H. Tetrahedron Lett.
1999, 27, 5063.
(10) (a) Jäger,V.; Grund, H., Schwab, W. Angew. Chem., Int. Ed.
Engl. 1979, 18, 78.
(b) Jäger, V.; Häfele, B. Synthesis 1987, 801.
(c) Heinzer, F.; Belluš, D. Helv. Chim. Acta 1981, 2279.
(11) (a) Csuk, R.; Fürstner, A.; Glänzer, B. I.; Weidmann, H. J.
Chem. Soc., Chem. Commun. 1986, 1149.
(
(
b) Fürstner, A.; Weidmann, H. J. Org. Chem. 1989, 54, 2307.
c) Fürstner, A.; Koglbauer, U.; Weidmann, H. J. Carbohydr.
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1) (a) Collins, P.; Ferrier, R. R. Monosaccharides, Wiley:
(
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(
(
b) Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93, 2279.
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(
Int. Ed. Engl. 1993, 32, 164.
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(
12) Gallos, J. K.; Gogga, E. G.; Koumbis, A. E. J. Chem. Soc.,
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10.9.-12. 9. 1998.
(
(
2) Giuliano, R. M. Cycloadditions in Carbohydrate Chemistry,
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Bierer, L. Dissertation, Universität Stuttgart, 1999.
(
(
13) (a) Scheffold, R.; Rytz, G.; Walder, L. Mod. Synth. Meth.
1
(
(
983, 3, 355.
b) Mentioned as unpublished work in Ref.
c) Forbes, C. L.; Franck, R. W. J. Org. Chem. 1999, 64, 1424.
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1
3a
(
(
a) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321.
b) Cardillo, G.; Orena, M. in Houben-Weyl, Methoden der
14) (a) Jäger, V.; Picasso, S. 16th ICHC, Montana State
Organischen Chemie, Stereoselective Synthesis; Helmchen,
G.; Hofmann, R. W.; Mulzer, J.; Schaumann, E. , Eds.;
Thieme: Stuttgart, 1995; Vol. E21e, pp 4698-4817.
University, Bozeman, Aug 1997, Abstr. IL-V-I2.
(b) Greul, J.; Pruschek, P.; Kleban, M.; Picasso, S.; Jäger, V.
16th Internat. Symp. Synthesis in Organic Chemistry,
(
c) Jäger, V.; Bierer, L.; Dong, H.-Q.; Palmer, A.; Shaw, D.
Lect. Heterocycl. Chem., in print.
4) See, e.g.:
a) Liotta, J. L.; Lee, J.; Ganem, B. Tetrahedron 1991, 47,
433.
b) Gracza, T.; Hasenöhrl, T.; Stahl, U.; Jäger, V. Synthesis
991, 1108.
Cambridge, 9-22 July 1999, Abstr. P36.
(
15) (a) Kleban, M. Diplomarbeit, Universität Würzburg, 1993.
(
(
(
(
(
b) Kleban, M. Dissertation, Universität Stuttgart, 1996.
c) Hilgers, P. Dissertation, Universität Stuttgart (planned).
(
2
(
1
(
(
(
16) Greul, J. Dissertation, Universität Stuttgart (planned).
1
0a
17) cf. Ref.
18) cf. Hümmer, W.; Dubois, E.; Gracza, T.; Jäger, V. Synthesis
997, 634.
5) Intramolecular cycloaddition of hexenose-nitrones (gluco,
manno, and galacto series):
1
(
19) (a) Garegg, P. J.; Samuelsson, B. J. Chem. Soc., Chem.
Commun. 1979, 978.
(a) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 1990.
(b) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 2401.
(c) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979, 62, 2411.
(b) Garegg, P. J.; Samuelsson, B. J. Chem. Soc., Perkin Trans.
1
1980, 2866.
6) For recent examples see:
a) Kleban, M.; Li, J.; Hilgers, P.; Picasso, S.; Jäger, V.,
(
Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Vitamin B12 Catalysis of Zinc-Mediated 6-Deoxy-6-iodopyranoside Fragmentation
1033
(
c) Semeria, D.; Philippe, M.; Delaumeny, J.-M.; Sepulchre,
(b) Bundle, D. R.; Gerken, M.; Peters, T. Carbohydr. Res.
1988, 174, 239.
A.-M.; Gero, S. D. Synthesis 1983, 710.
(
(
(
(
20) (a) Kautz, U. Dissertation, Universität Stuttgart (planned).
(24) York, H.; Funk, W.; Fischer, W.; Wimmer, H. Dünnschicht-
Chromatographie. Reagenzien und Nachweismethoden, Bd.
1 a, VCH: Weinheim, 1989.
(25) Helmchen, G.; Glatz, B. Ein apparativ einfaches System und
Säulen höchster Trennleistung zur präparativen
Mitteldruckchromatographie, Anhang zur
(b) cf. Jäger, V.; Öhrlein, R.; Wehner, V.; Poggendorf, P.;
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Enantiomer 1999, 4, 205.
21) (a) Eckert, H.; Ugi, I. Angew. Chem., Int. Ed. Engl. 1975, 14,
8
25.
b) Jensen, M. P.; Halpern, J. J. Am. Chem. Soc. 1999, 121,
181.
22) (a) Akagi, M.; Tejima, S.; Haga, M. Chem. Pharm. Bull. 1963,
1, 559.
b) Kadokawa, J.-i.; Sato, M.; Karasu, M.; Tagaya, H.; Chiba,
(
2
Habilitationsschrift, Stuttgart, 1978.
1
(
Article Identifier:
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K. Angew. Chem. Int. Ed. Engl. 1998, 37, 2373.
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Synthesis 2000, No. 7, 1027–1033 ISSN 0039-7881 © Thieme Stuttgart · New York