Preparation of 23-dideoxy-2,3-epimino and 3,4-dideoxy-3,4-epimino derivatives of 1,6-anhydro-β-D-hexopyranoses by Mitsunobu reaction

Article abstract of DOI:10.1135/cccc19980813

A series of new 2-, 3-and 4-benzylamino-2-, 3-and 4-deoxy derivatives of 1,6-anhydro-β-D-hexopyranoses were prepared from 1,6:2,3-and 1.6:3,4-dianhydro-β-D-hexopyranoses by treatment with benzylamine and converted into 2,3-(N-benzylepimino)-2,3-dideoxy-and 3,4-(N-benzylepimino)-3,4-dideoxy-β-D-hexopyranoses of the D-allo, D-galacto and D-talo configuration by Mitsunobu reaction. The structures of benzylamino and benzylimino derivatives were confirmed by ¹H and ¹³C NMR spectra.

Full text of DOI:10.1135/cccc19980813

Mitsunobu Reaction
813
PREPARATION OF 2,3-DIDEOXY-2,3-EPIMINO AND 3,4-DIDEOXY-3,4-EPIMINO
DERIVATIVES OF 1,6-ANHYDRO-β-D-HEXOPYRANOSES BY MITSUNOBU
REACTION
a1
a2
b
a3,
Jiri KROUTIL , Tomas TRNKA , Milos BUDESINSKY and Miloslav CERNY
*
a Department of Organic Chemistry, Charles University, 128 40 Prague 2, Czech Republic;
e-mail: 1 kroutil@mail.natur.cuni.cz, 2 trnka@mail.natur.cuni.cz, 3 mila@mail.natur.cuni.cz
b Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
166 10 Prague 6, Czech Republic; e-mail: milos.budesinsky@uochb.cas.cz
Received November 27, 1997
Accepted May 5, 1998
A series of new 2-, 3- and 4-benzylamino-2-, 3- and 4-deoxy derivatives of 1,6-anhydro-β-D-hexo-
pyranoses were prepared from 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses by treatment with
benzylamine and converted into 2,3-(N-benzylepimino)-2,3-dideoxy- and 3,4-(N-benzylepimino)-3,4-
dideoxy-β-D-hexopyranoses of the D-allo, D-galacto and D-talo configuration by Mitsunobu reaction.
The structures of benzylamino and benzylimino derivatives were confirmed by 1H and 13C NMR
spectra.
Key words: Anhydrosugars; Oxiranes; Aziridines; Epimino derivatives; Aminosugars; Carbohy-
drates; NMR spectroscopy.
Whereas 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses and their derivatives are
versatile starting compounds in the synthesis of sugars and non-sugar compounds1–3
,
there has been only a little known on the chemistry of 1,6-anhydro-2,3-dideoxy-2,3-
epimino- and 1,6-anhydro-3,4-dideoxy-3,4-epimino-β-D-hexopyranoses in the lit-
erature2,4–8. First epimino derivatives of hexoses, namely methyl 4,6-O-benzylidene-
2,3-dideoxy-2,3-epimino-β-D-hexopyranoses, were synthesized9 not earlier than in
1960. In contrast, aliphatic aziridines have been widely investigated10,11 and used for
the preparation of 2-substituted ethylamines12–14 and amino acids15–17
.
Though the reactivity of the aziridine rings is lower than that of oxirane rings,
nucleophilic reagents are effective in cleaving them to give amino compounds with
trans-oriented nucleophiles. If necessary, the reactivity of the aziridine rings can be
enhanced by protonation18–20, by interaction with Lewis acids21,22, and also by N-alkyl-
ation and N-acylation18,23,24. We assumed that the epimino derivatives of 1,6-anhydro-
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

814
Kroutil, Trnka, Budesinsky, Cerny:
hexoses could be used as chiral synthons in a similar way as the corresponding oxirane
derivatives, and hence we concentrated on their preparation.
The most frequent method used for the preparation of aziridines is the intramolecular
SN2 substitution of sulfonyloxy groups or halogen atoms by nitrogen-containing
groups, such as the amino, azido, acylamino or thioureido group4,18,25–31, and genera-
ting an amide ion under reaction conditions. In the less common Staudinger reaction32–35
,
the azido group is cleaved by triphenylphosphine to give the iminophosphorane group
which reacts in a similar way as described above. The Mitsunobu reaction36–38 was used
for the preparation of aliphatic aziridines from N-alkyl and N-acyl 2-amino alcohols39–41
but in sugar chemistry, only the preparation of a phenylimino derivative of uracil from
1-(2-deoxy-2-phenylamino-β-D-arabinofuranosyl)uracil was described42.
In this study we applied the Mitsunobu reaction for the preparation of new epimino
derivatives of 1,6-anhydro-β-D-hexopyranoses from starting 1,6:2,3- and 1,6:3,4-dian-
hydro-β-D-hexopyranoses according to Scheme 1. We made use of benzylamine as a
reactive agent for the cleavage of oxirane rings, exploiting the temporary protective
function of the benzyl group.
RO
O
RO OH
RO
(i)
(ii)
Bn = benzyl
NHBn
NBn
o
(i) benzylamine, 140-150 C;
(ii) diisopropyl azodicarboxylate, triphenylphosphine, toluene
SCHEME 1
EXPERIMENTAL
The melting points were determined with a Boëtius melting-point microapparatus and were uncor-
rected. The optical rotation was measured with a Bendix–Ericsson ETL-143A polarimeter at 21 °C.
1
The H and 13C NMR spectra were measured with a Varian UNITY-500 apparatus (1H at 500 MHz;
13C at 125 MHz) in CDCl3 or CD3SOCD3 solutions. The proton 2D-COSY spectra and 1H-13C 2D-
HMQC spectra were used for the structural assignment of proton and carbon signals. Mass spectra
were recorded on a Finnigan MAT INCOS 50 spectrometer using EI ionization (70 eV). Thin layer
chromatography was performed on DC Alufolien plates (Merck) with Kieselgel 60 F254 with detec-
tion by spraying with 50% sulfuric acid in methanol or with a solution of anisaldehyde in sulfuric
acid and heating. UV detection was also employed when appropriate. Preparative column chromato-
graphy was carried out on Kieselgel 60 (Merck, 60–230 mesh). Solutions were evaporated at a re-
duced pressure at temperatures below 40 °C. Triphenylphosphine was purchased from Fluka Chemie
AG, diisopropyl and diethyl azodicarboxylates from Sigma–Aldrich, Czech Republic. Light petro-
leum was a 40–60 °C fraction. Toluene was dried by reflux with sodium, and methanol with magne-
sium; all solvents were distilled before use.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Mitsunobu Reaction
815
General Procedure for Preparation of (Benzylamino)hexopyranoses 2a–2e
Dianhydro derivatives 1a–1e and benzylamine were mixed and heated under argon atmosphere at
140–150 °C for a given time. After cooling to room temperature, the reaction mixture was worked up
1
as described below for individual compounds. H and 13C NMR data for compounds 2a–2e are given
in Tables I and II.
1,6-Anhydro-4-O-benzyl-2-benzylamino-2-deoxy-β-D-glucopyranose (2a)
1,6:2,3-Dianhydro-4-O-benzyl-β-D-mannopyranose43 1a (117 mg, 0.5 mmol) and benzylamine (0.6 ml,
5.4 mmol) were heated for 2 h and the reaction mixture was left at room temperature overnight.
Thereafter light petroleum (about 10 ml) was added to the solidified reaction mixture, the crude pro-
duct 2a was filtered off and crystallized from ethanol. Yield 130 mg (76%), m.p. 187–188 °C, [α]D
–33 (c 0.6, chloroform). For C20H23NO4 (341.2) calculated: 70.33% C, 6.81% H, 4.10% N; found:
70.40% C, 6.70% H, 4.06% N.
1,6-Anhydro-2-O-benzyl-4-benzylamino-4-deoxy-β-D-glucopyranose (2b)
1,6:3,4-Dianhydro-2-O-benzyl-β-D-galactopyranose44 1b (500 mg, 2.135 mmol) and benzylamine (1.4 ml,
12.8 mmol) were heated for 2 h. The reaction mixture was worked up as described for compound 2a.
Yield 635 mg (87%), m.p. 172–173 °C, [α]D –41 (c 1.0, chloroform). For C20H23NO4 (341.2) calcu-
lated: 70.33% C, 6.81% H, 4.10% N; found: 70.45% C, 6.68% H, 4.11% N.
1,6-Anhydro-4-benzylamino-4-deoxy-2-O-(4-methylbenzenesulfonyl)-β-D-glucopyranose (2c)
1,6:3,4-Dianhydro-2-O-(4-methylbenzenesulfonyl)-β-D-galactopyranose45 1c (10.48 g, 38 mmol) and
benzylamine (8.7 ml, 79.6 mmol) in toluene (50 ml) were heated under reflux for 3 h. After cooling
to room temperature, light petroleum (125 ml) was added, the resulting solid was separated and
treated with 5% HCl (100 ml). The undissolved 1c was recovered and the solution was adjusted to
pH ca 9 with concentrated ammonia; the precipitated 2c was crystallized from ethanol. Yield 8.4 g
(59%), m.p. 153–154 °C, [α]D –33 (c 0.75, chloroform). For C20H23NO6S (405.3) calculated: 59.21% C,
5.73% H, 3.45% N, 7.92% S; found: 58.98% C, 5.81% H, 3.58% N, 8.03% S.
1,6-Anhydro-3-benzylamino-3-deoxy-β-D-glucopyranose (2d)
1,6:3,4-Dianhydro-β-D-allopyranose46 1d (390 mg, 2.71 mmol) and benzylamine (1.4 ml, 12.8 mmol)
were heated for 70 h. After cooling to room temperature, chloroform (20 ml) was added to the reac-
tion mixture, and the product 2d was extracted with water (total volume 100 ml). Combined aqueous
extracts were evaporated to dryness, and the residue was crystallized from an ethanol–ether–light pe-
troleum mixture. Yield 490 mg (72%), m.p. 132–134 °C, [α]D –47 (c 0.8, chloroform). For
C13H17NO4 (251.2) calculated: 62.11% C, 6.84% H, 5.58% N; found: 61.87% C, 7.00% H, 5.50% N.
1,6-Anhydro-2-O-benzyl-3-benzylamino-3-deoxy-β-D-mannopyranose (2e)
1,6:3,4-Dianhydro-2-O-benzyl-β-D-altropyranose47 1e (300 mg, 1.28 mmol) and benzylamine (0.7 ml,
6.4 mmol) were heated for 70 h. After cooling to room temperature, the reaction mixture was evapo-
rated under reduced pressure at 90 °C to give a light yellow syrup which did not crystallize. Analysis
of its NMR spectra proved small contamination with traces of benzylamine, but the product is suffi-
ciently pure to be used for further reactions. Yield 219 mg (50%). For C20H23NO4 (341.2) found
mass spectrum: m/z 341 (M+).
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Kroutil, Trnka, Budesinsky, Cerny:
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Kroutil, Trnka, Budesinsky, Cerny:
2-Amino-1,6-anhydro-4-O-benzyl-β-D-glucopyranose (2f)
To a well-stirred solution of compound 2a (340 mg, 1 mmol) and triphenylphosphine (293 mg, 1.12 mmol)
in chloroform (10 ml, acidified with gaseous HCl to pH ca 1), diethyl azodicarboxylate (0.2 ml, 1.27 mmol)
was added dropwise at room temperature during 1 h, and the reaction mixture was allowed to stand
for 24 h. The 5% KOH solution (25 ml) and chloroform (20 ml) were added and the reaction mixture
was stirred for 3 days at room temperature in order to hydrolyse the present hydrazodicarboxylate.
Then the organic layer was separated and extracted with diluted HCl (50 ml, 5%), aqeous extract
neutralized with concentrated ammonia and reextracted with chloroform (5 × 15 ml). The chloroform
solution was dried (CaCl2) and evaporated. Resulting oil was crystallized from an ethanol–chloroform
mixture to yield 176 mg (70%) of 2f, m.p. 148–152 °C, [α]D –47 (c 1.0, chloroform) (ref.6 gives m.p.
1
151–152 °C, [α]D –46). H and 13C NMR data were the same as described in ref.6.
General Procedure for Preparation of Epiminohexopyranoses 3a–3e
Compound 2a–2e (1 mmol) was mixed with a solution of triphenylphosphine (1.1–1.15 mmol) in
toluene (10 ml). Diisopropyl azodicarboxylate (1.1–1.15 mmol) in toluene (5 ml) was added drop-
wise within 1 h with stirring and cooling at 0–5 °C in an ice-water bath. The reaction was monitored
by TLC with toluene–acetone 5 : 1 (for dibenzyl derivatives) or with ethyl acetate (for monobenzyl
derivatives), in these systems the RF of epimines are in the range 0.4–0.5. When the reaction ceased
(total reaction time was 2 h for 3a–3c and 2–3 days for 3d–3e), the solvent was removed in vacuo
and the resulting oil was chromatographed on silica gel (25 g, Merck 60–230 mesh, TLC solvent
mixture). The combined fractions containing a mixture of epimine and diisopropyl hydrazodicarboxylate
were concentrated and the residue was hydrolyzed with 5% NaOH in aqueous ethanol at 45 °C for
24 h and extracted several times with dichloromethane (100 ml). After drying (Na2SO4) and evapora-
tion of the solvent, the residue was crystallized from an ethanol–ether–light petroleum mixture. 1H
and 13C NMR data for compounds 3a–3e are given in Tables III and IV.
1,6-Anhydro-4-O-benzyl-2,3-(N-benzylepimino)-2,3-dideoxy-β-D-allopyranose (3a)
The epimine 3a was prepared according to general procedure from 2a. Yield 75%, m.p. 85–88 °C,
[α]D +113 (c 0.88, chloroform). For C20H21NO3 (323.2) calculated: 74.25% C, 6.60% H, 4.33% N;
found: 74.05% C, 6.59% H, 4.38% N.
1,6-Anhydro-2-O-benzyl-3,4-(N-benzylepimino)-3,4-dideoxy-β-D-allopyranose (3b)
The epimine 3b was prepared according to general procedure from 2b. Yield 73%, m.p. 94–96 °C,
[α]D –137 (c 0.79, chloroform). For C20H21NO3 (323.2) calculated: 74.25% C, 6.60% H, 4.33% N;
found: 74.18% C, 6.56% H, 4.36% N.
1,6-Anhydro-3,4-(N-benzylepimino)-3,4-dideoxy-2-O-(4-methylbenzenesulfonyl)-β-D-allopyranose (3c)
The epimine 3c was prepared according to general procedure from 2c. Yield 37%, m.p. 123–124 °C,
[α]D –68 (c 0.84, chloroform). For C20H21NO5S (387.3) calculated: 61.96% C, 5.47% H, 3.61% N,
8.28% S; found: 62.24% C, 5.32% H, 3.72% N, 8.10% S.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Mitsunobu Reaction
819
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Kroutil, Trnka, Budesinsky, Cerny:
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Mitsunobu Reaction
821
1,6-Anhydro-3,4-(N-benzylepimino)-3,4-dideoxy-β-D-galactopyranose (3d)
The epimine 3d was prepared according to general procedure from 2d. Yield 67%, m.p. 103.5–104.5 °C,
[α]D –55 (c 0.72, chloroform). For C13H15NO3 (233.2) calculated: 66.90% C, 6.50% H, 6.00% N;
found: 66.50% C, 6.57% H, 5.80% N.
1,6-Anhydro-2-O-benzyl-3,4-(N-benzylepimino)-3,4-dideoxy-β-D-talopyranose (3e)
The epimine 3e was prepared according to general procedure from 2e. Yield 76%, syrup, [α]D +15 (c 0.9,
chloroform). For C20H21NO3 (323.2) found mass spectrum: m/z 323 (M+).
1,6-Anhydro-2,3-dideoxy-2,3-epimino-β-D-allopyranose (4)
A well-stirred solution of benzylepimine 3a (122 mg, 0.4 mmol) and about 20 mg of 10% Pd on
charcoal (Fluka) in dry methanol (15 ml) was hydrogenated under atmospheric pressure at room tem-
perature. The reaction course was monitored by TLC using propan-2-ol–chloroform–concentrated am-
monia–water system (10 : 10 : 1 : 1). After disappearing of the starting epimine (≈ 5 h), the catalyst was
filtered off with suction and the solution was evaporated to dryness. Yield 45 mg (78%) of 4, syrup,
[α]D +92 (c 0.65, chloroform). Physical constants and 1H and 13C NMR data are in agreement with
those of the authentic sample48
.
RESULTS AND DISCUSSION
Free or substituted 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses 1a–1e were
heated with neat benzylamine or with a solution of benzylamine in boiling toluene at
140–150 °C to give N-benzylamino derivatives 2a–2e. The oxirane ring cleavage pro-
O
O
O
O
O
O
O
O
O
O
O
BnO
O
O
O
BnO
RO
OR
OH
O
1a
1b, R = Bn
1c, R = Ts
1d
1e
1f, R = Bn
1g, R = H
O
O
O
BnO
O
R
2
R
R
3
HO
R
1
1
2
3
R
R
R
2e, R = NHBn
NHBn OH
OBn
2a
2b
2c
2d
2f
OBn
OTs
OH
OH
OH
NHBn
NHBn
NHBn OH
OH OBn
NH
2
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

822
Kroutil, Trnka, Budesinsky, Cerny:
ceeded diaxially with high regioselectivity, in good yields and without formation of
by-products. Dianhydrides 1a–1c with the oxirane ring endo-oriented toward the 1,6-
anhydro bridge react more rapidly than those 1d–1f with exo-orientation. Thus, the
steric hindrance caused by presence of the 1,6-anhydro bridge might play an important
role in controlling the reaction rate. The failure of the reaction in the case of dianhy-
dride 1f, which gradually decomposed on prolonged heating, could be explained by
analogous reactions of dianhydrides 1f and 1g with sodium hydroxide2 and with potas-
sium tert-butoxide43, respectively.
1
The structure of amino derivatives 2a–2e was determined from H and 13C NMR
spectra (Tables I and II). All non-protonated benzylamines 2a–2d adopt the chair con-
1
formation C4 in chloroform solution as indicated by low values of coupling constants
J(2,3) and J(3,4) (J(2,3) = 1.8–2.6 Hz and J(3,4) = 1.4–1.8 Hz) and characteristic long-
range couplings J(1,3), J(2,4) and J(3,5) (see Table I). The increase of coupling con-
stants J(2,3) and J(3,4) of benzylamine 2d in CD3SOCD3 (from 1.8 to 3.3 Hz) indicates
certain population of the boat form BO,3, which becomes the predominant conformer of
protonated 2d in CD3SOCD3 as follows from large values J(2,3) = J(3,4) = 7.6 Hz and
the absence of long-range couplings J(1,3), J(2,4) and J(3,5) (see Table I). A compari-
son with reference J-values of 2d observed in CDCl3 (chair-form) and of protonated 2d
(boat-form) gives for 2d in CD3SOCD3 ca 25% of the boat-form. This corresponds with
the known behaviour of 3-amino-1,6-anhydro-3-deoxy-β-D-glucopyranose and its N-methyl
derivatives49,50. A significant increase in population of the boat form on protonation
was deduced for benzylamine 2e of D-manno configuration from coupling constants
J(1,2), J(3,4) and J(4,5). While the values J(3,4) = 1.9 Hz and J(4,5) = 2.2 Hz observed
in CDCl3 solution of 2e are very similar to those of 2d in the same solvent and clearly
1
indicate chair conformation C4 in CDCl3 (and also in CD3SOCD3), then the changed
values (J(3,4) = 4.5 Hz and J(4,5) < 1 Hz) observed for the protonated form of 2e in
CD3SOCD3 indicate a conformational equilibrium with a significant population of the
1
boat conformation (the ratio C4 : BO,3 ≈ 54 : 46 was calculated from J(3,4) values).
These conformational changes (Scheme 2) induced by protonation of the benzylamino
group may be explained by effective solvation of the corresponding ammonium salts
and consequent unfavourable steric interaction with the 1,6-anhydro bond.
O
O
1
2
O
R
R
H
+ HCl
- HCl
O
2
NHBn
R
2
OH
H
2d
2e
R
1
HO
R
OBn
1
HO
R
NHBn
1
C
B
O,3
4
SCHEME 2
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

Mitsunobu Reaction
823
Compounds 2a–2d described above were converted into epimines 3a–3d by treat-
ment with triphenylphosphine and diisopropyl azodicarboxylate in dry toluene at re-
duced temperature; the yields in dry ether or tetrahydrofuran were only a few per cent
lower. Inert atmosphere37,38 can be avoided and does not influence the yields. The reac-
tion time at the optimum temperature of 0–5 °C was strongly dependent on the structure
of the starting amino compound. Diisopropyl azodicarboxylate was chosen as a more
convenient reagent than diethyl azodicarboxylate because it made possible to perform
the reaction at 0 °C and thus to minimize the formation of by-products. However, some
N-debenzylation (up to 5%) of starting compound during the cyclization was observed.
In the case of compound 2a, when chloroform was used as solvent instead of toluene,
the free amine 2f was isolated from the reaction mixture in 70% yield. Probably, this
results from the change of the acidity of the reaction mixture. Another experiment, in
which amine 2a was treated with diisopropyl azodicarboxylate–triphenylphosphine
mixture (in the presence of HCl, pH ca 1), gave the same yield of amine 2f. Thus, the
presence of HCl in the reaction mixture might play the key role.
O
O
O
O
O
O
O
O
NBn
X BnO
BnN
RO
OR
OH
NR
3a, R = Bn
4, R = H
3b, R = Bn
3c, R = Ts
3d
3e, X = NBn
The course of the Mitsunobu reaction was not negatively affected by the presence of
an additional free or substituted hydroxyl group in the starting amines 2. Epimines
3a–3e were easily obtained from compound 2d (free OH group) as well as from com-
pounds 2a, 2b, 2e (O-benzyl group) and 2c (O-tosyl group). Axial hydroxyl group
activated by diisopropyl azodicarboxylate–triphenylphosphine adduct exhibited good
leaving capability, nevertheless with the reactivity decreasing in the order C(4)–OH >
C(3)–OH > C(2)–OH. Therefore, as expected, epimine 3d was formed from 2d with
high regioselectivity due to a higher reactivity of the OH group at C(4) than that at C(2)
(cf. a similar reactivity of tosyl groups at C(4) and C(2), refs45,51). A rather unexpected,
relatively high reactivity of the OH group at C(3) indicates that the potentially unfa-
vourable steric interaction between the 1,6-anhydro bond and the diisopropyl azodicar-
boxylate–triphenylphosphine adduct does not play a dominant role. A free amino group
exhibited a markedly lower reactivity than a benzylamino group as we could show in
the reaction of free amine 2f under the conditions used for the preparation of epimines.
Tetrahydrofuran was used as a solvent instead of toluene; unreacted amine 2f was iso-
lated as a sole product.
As usual with Mitsunobu reaction, it is difficult to separate the reaction product(s)
from triphenylphosphine oxide and/or diisopropyl hydrazodicarboxylate. In our case,
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

824
Kroutil, Trnka, Budesinsky, Cerny:
the reaction mixture was first chromatographed on silica gel to separate a mixture of
epimine and hydrazodicarboxylate. Then, after hydrolysis of hydrazodicarboxylate by
sodium hydroxide in aqueous ethanol, the epimine was extracted with dichloromethane.
The structure of epimines was determined from 1H and 13C NMR spectra (Tables III and IV)
and by comparison with the data for 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses3.
5
The 2,3-epimines adopt a half-chair conformation HO whereas the 3,4-epimines adopt
1
the HO conformation, similar to the corresponding 2,3- and 3,4-epoxides1,3. The coup-
ling constant values of aziridine ring protons are J(2,3) = 6.3 Hz for 2,3-epimine 3a and
J(3,4) = 6.2–6.9 Hz for 3,4-epimines 3b–3e, the chemical shifts of corresponding hy-
drogens H-2, H-3 and H-3, H-4, respectively, appear in the narrow range δ 1.80–2.33.
Epimine carbon atoms of 3b–3e give characteristic signals in the upfield region of 13C NMR
spectra (δ ≈ 34–44).
The free epimine 4 was obtained with a good yield (78%) after hydrogenolysis of N-benzyl
epimine 3a on Pd on charcoal under the conditions described in ref.4.
This work was supported by the Grant Agency of the Czech Republic (grant No. 203/94/0702).
REFERENCES
1. Cerny M. in: Levoglucosenone and Levoglucosans, Chemistry and Applications (Z. J. Witczak,
Ed.), p. 121. ATL Press, New York 1994; and references therein.
2. Cerny M., Stanek J.: Adv. Carbohydr. Chem. Biochem. 1977, 34, 23.
3. Budesinsky M., Cerny M., Cerny I., Samek S., Trnka T. : Collect. Czech. Chem. Commun. 1995,
60, 311.
4. Cerny M., Elbert T., Pacak J.: Collect. Czech. Chem. Commun. 1974, 39, 1752.
5. Cerny M., Cerny I., Pacak J.: Collect. Czech. Chem. Commun. 1976, 41, 2942.
6. Cerny M., Julakova O., Pacak J., Budesinsky M.: Collect. Czech. Chem. Commun. 1975, 40,
2116.
7. Cerny M., Cerny I., Trnka T.: Carbohydr. Res. 1978, 67, 33.
8. Elbert T., Cerny M.: Collect. Czech. Chem. Commun. 1985, 50, 2000.
9. Christensen J. E., Goodman L.: J. Am. Chem. Soc. 1960, 82, 4738.
10. Bestian H. in: Houben–Weyl. Methoden der Organischen Chemie (E. Muller, Ed.), Vol. XI, Part
2, p. 223. Thieme, Stuttgart 1958.
11. Fanta P. E. in: Heterocyclic Compounds with Three and Four Membered Rings (A. Weissberger,
Ed.), Part 1, p. 524. Interscience, New York 1964.
12. Dureault A., Tranchepain I., Greck C., Depezay J.: Tetrahedron Lett. 1987, 28, 3341.
13. Stamm H., Weiss R.: Synthesis 1986, 392.
14. Baldwin J. E., Adlington R. M., Robinson N. G.: J. Chem. Soc., Chem. Commun. 1987, 153.
15. Parry R. J., Naidu M. V.: Tetrahedron Lett. 1983, 24, 1133.
16. Bernstein Z., Ben-Ishai D.: Tetrahedron 1977, 33, 881.
17. Hata Y., Watanabe M.: Tetrahedron 1987, 43, 3881.
18. Ali Y., Richardson A. C.: Carbohydr. Res. 1968, 7, 255.
19. Buss D. H., Hough L., Richardson A. C.: J. Chem. Soc. 1965, 2736.
20. Gibbs C. F., Hough L.: Carbohydr. Res. 1971, 18, 363.
Collect. Czech. Chem. Commun. (Vol. 63) (1998)

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21. Shao H., Zhu Q., Goodman M.: J. Org. Chem. 1995, 60, 790.
22. Crotti P., Favero L., Gardelli C., Macchia F., Pineschi M.: J. Org. Chem. 1995, 60, 2514.
23. Guthrie R. D., Murphy D.: J. Chem. Soc. 1965, 3828.
24. Tsuchiya T., Ajito K., Umezawa S., Ikeda A.: Carbohydr. Res. 1984, 126, 45.
25. Guthrie R. D., Murphy D.: J. Chem. Soc. 1963, 5288.
26. Guthrie R. D., Liebmann J. A.: J. Chem. Soc., Perkin Trans. 1 1974, 650.
27. Buss D. H., Hough L., Richardson A. C.: J. Chem. Soc. 1963, 5295.
28. Gibbs C. F., Hough L., Richardson A. C.: Carbohydr. Res. 1965, 1, 290.
29. Rhoads W. D., Gross P. H.: Carbohydr. Res. 1969, 11, 561.
30. Meyer zu Reckendorf W., Lenzen H. J.: Liebigs Ann. Chem. 1982, 265.
31. Meyer zu Reckendorf W., Lenzen H. J.: Tetrahedron Lett. 1979, 3657.
32. Staudinger R., Meyer J.: Helv. Chim. Acta 1919, 2, 635.
33. Golobov Y. G., Zhmurova I. N., Kasukhin L. F.: Tetrahedron 1981, 37, 437.
34. Ittah Y., Sasson Y., Shahah I., Tsaroom S., Blum J.: J. Org. Chem. 1978, 43, 4271.
35. Pinter I., Kovacs J., Messmer A., Kalman A., Toth G., Lindberg B. K.: Carbohydr. Res. 1979,
72, 289.
36. Mitsunobu O.: Synthesis 1981, 1.
37. Hughes D. L.: Org. React. 1992, 42, 335.
38. Camp D., Hanson G. R., Jenkins I. D.: J. Org. Chem. 1995, 60, 2977.
39. Carlock J. T., Mack M. P.: Tetrahedron Lett. 1978, 5153.
40. Pfister J. R.: Synthesis 1984, 969.
41. Thomson R., von Itzstein M.: Carbohydr. Res. 1995, 274, 29.
42. Minamoto K., Azuma K., Tanaka T., Iwasaki H., Eguchi S., Kadoya S., Moroi R.: J. Chem. Soc.,
Perkin Trans. 1 1988, 2955.
43. Trnka T., Cerny M.: Collect. Czech. Chem. Commun. 1971, 36, 2216.
44. Prystas M., Kalvoda L., Sorm F.: Collect. Czech. Chem. Commun. 1976, 41, 1426.
45. Cerny M., Gut V., Pacak J.: Collect. Czech. Chem. Commun. 1961, 26, 2542.
46. Cerny M., Trnka T., Beran P., Pacak J.: Collect. Czech. Chem. Commun. 1969, 34, 3377.
47. a) Dolezalova J., Trnka T., Cerny M.: Collect. Czech. Chem. Commun. 1982, 47, 2415; b)
Baladova E.: M.S. Thesis. Charles University, Prague 1989.
48. Karban J.: Unpublished results.
49. Trnka T., Cerny M., Budesinsky M., Pacak J.: Collect. Czech. Chem. Commun. 1975, 40, 3038.
50. Grindley T. B., Cude A., Kralovic J., Thangarasar R.: Ref.1, p. 147.
51. Cerny M., Buben I., Pacak J.: Collect. Czech. Chem. Commun. 1963, 28, 1569.
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