A new method for the synthesis of 2,3-Aziridino-2,3-Didoxyhexonamides and their conversion into 3-Amino-2,3-Dideoxyhexonic acids

Article abstract of DOI:10.1055/s-1998-4485

Two new 2,3-aziridino-2,3-dideoxyhexonamides 3 and 11 were prepared by a three-step procedure from commercially available D-glucono-1,5-1actone and D- gulono-1,4-1actone, respectively. The lactones were converted into methyl 3,4:5,6-diO-isopropylidene-2-O

Full text of DOI:10.1055/s-1998-4485

March 1998
SYNTHESIS
325
A New Method for the Synthesis of 2,3-Aziridino-2,3-dideoxyhexonamides
and Their Conversion into 3-Amino-2,3-dideoxyhexonic Acids
Christel Jørgensen,a Christian Pedersen,a Inger Søtofteb
a Department of Organic Chemistry, Technical University of Denmark, Building 201, DK-2800, Lyngby, Denmark
Fax +45(45)933968. E-mail: okcp@pop.dtu.dk
b Chemistry Department, Technical University of Denmark, Building 206, DK-2800 Lyngby, Denmark
E-mail: is@kemi.dtu.dk.
Received 4 July 1997; 13 October 1997
Abstract: Two new 2,3-aziridino-2,3-dideoxyhexonamides 3 and
11 were prepared by a three-step procedure from commercially
available D-glucono-1,5-lactone and D-gulono-1,4-lactone,
respectively. The lactones were converted into methyl 3,4:5,6-di-
O-isopropylidene-2-O-mesyl esters 2 and 10, which upon treat-
ment with ammonia formed the title aziridino compounds. These
were reductively cleaved by hydrazine to give 3-amino-2,3-
dideoxyhexonic hydrazides 13 and 15, which were easily con-
verted into the corresponding lactone 14 and acid 16, respectively.
Key words: sugar lactones, aziridines, amino acids
Enantiopure aziridine-2-carboxylic acids are an important
class of compounds as they can be used as intermediates
in the synthesis of a- and b-amino acids. An aziridine ring
can be opened by nucleophiles with complete stereochem-
ical inversion.1 Optically active aziridine-2-carboxylic
acid derivatives have previously been prepared from start-
ing materials such as oxiranes,2 the naturally occurring
hydroxy acids,3 L-amino acids4 and carbohydrates.5,6
Asymmetric aziridination, with and without the use of
chiral auxiliaries, has also been reported.7 – 9 We describe
here a novel and easy three-step procedure for the prepa-
ration of 2,3-aziridino-2,3-dideoxyhexonamides using
readily available sugar lactones. The applicability of these
new products is illustrated by a simple transformation into
Scheme 1
3-amino-2,3-dideoxyhexonolactones. The latter may be
reduced to aminodeoxy-hexoses, which constitute the
sugar part of a large number of antibiotics.10 The aziridi-
nohexonamides allow a simultaneous generation of the C-
3 amino and C-2 deoxy functions. In contrast, 3-aminode-
oxyhexoses are usually prepared by introducing the C-3
amino function into mono- and dideoxyhexoses.10
It has been previously reported that the acid-catalyzed
isopropylidenation of D-glucono-1,5-lactone with 2,2-
dimethoxypropane (2,2-DMP) and methanol gives the di-
acetal methyl ester 1 in good yield.11 Different derivatives
of this ester have been synthesized by modification of the
C-2 position (halogenation and deoxygenation,12 O-acyla-
tion and O-alkylation13,14). In the present work, the 2-O-
mesyl ester 214 was treated with concentrated aqueous am-
Scheme 2
monia to give the 2,3-aziridino-2,3-dideoxyhexonamide 3 as
themainproduct(Scheme1).Thereactionisbelievedtopro-
ceedviaelimination12,13 to4followedbyadditionofammo-
nia to give 5, which subsequently yields the trans-aziridine 3
(Scheme 2). The addition of ammonia appeared to be diaste-
reoselective as predicted from the work of Chittenden and
Regeling,12 but the 1H NMR spectrum of the crude product
showedseveralminorbyproducts,noneofwhichhavebeen
isolated and identified. The observed selectivity is in analogy
with similar additions to a-bromoacrylates.6 Compound 3
couldbeeasilyisolatedin46%yieldbycrystallizationafter
treatment with a basic ion-exchange resin.
The structure of 3 was established by X-ray analysis of the
N-tosylated derivative 6, which also proved to be more
suitable for NMR spectroscopic characterization. The un-
1
protected aziridine 3 gave broad signals in both H and
13C NMR spectra due to slow exchange of the NH proton
and/or slow inversion at the nitrogen atom. N-Tosylation
is known to lower the energy barrier for inversion15 and,
1
in agreement with this, H NMR spectrum of 6 showed
sharp lines revealing the expected low value (4.3 Hz) of
the J2,3 coupling constant.16

326
Papers
SYNTHESIS
Starting with D-mannono-1,4-lactone, obtained from
isoascorbic acid,17 the crystalline diacetal methyl ester 8
was prepared analogously to 2 in 52% overall yield
(Scheme 3). The assigned structure was established by
1
comparison of the H NMR data of 7 and 8. As the only
notable change, the doublet at d = 4.35 (J2,3 = 3.0 Hz) in 7
was moved downfield to d = 5.35 (J2,3 = 2.2 Hz) in 8 indi-
cating O-mesylation at C-2. The manno-configurated
compound 7 had previously been prepared from 1 by
epimerization of the OH-group, but no physical data were
reported.13 Treatment of 8 with concentrated aqueous am-
monia gave 3 in accordance with the suggested mecha-
nism.
Scheme 4
Scheme 3
As the original stereochemistry at C-2 and C-3 is assumed
to be lost during the reaction, only C-4 or C-5 isomeric
products could lead to other isomers. Using commercially
available D-gulono-1,4-lactone and applying the same re-
action conditions as described above, a similar regioselec-
tive di-O-isopropylidenation took place to give 9.
Mesylation of crude 9 gave the crystalline gulo-derivative
10 in 56% overall yield. Treatment of 10 with concentrat-
ed aqueous ammonia yielded the crystalline 2,3-aziridino-
2,3-dideoxy hexonamide 11 in 40% yield (Scheme 4). Un-
identified byproducts were also formed in this case. The
ido-configuration was proven by X-ray analysis of the N-
tosylate 12.
Scheme 5
drazide 15 could be obtained quantitatively from 11, and
subsequent cleavage of the hydrazide gave the acid 16 in
91% yield (Scheme 6).
Reductive cleavage of aziridine-2-carboxylic acids pro-
vides a route to a- and b-amino acids. Hydrogenolysis can
be used, but substitution patterns, catalyst and solvent ef-
fect the direction of the reduction. With N-tosylated aziri-
dine-2-carboxylates high yields of both a-amino and b-
amino esters have been obtained.8,18 Recently a highly re-
gioselective reduction with samarium(II) iodide was re-
ported, leading exclusively to b-amino esters.19 In the
present work it was found that boiling 3 with aqueous hy-
drazine gave the 3-amino-2,3-dideoxyhydrazide 13 in
quantitative yield. The reaction is believed to proceed via
a ketene intermediate.20 A similar cleavage of the aziri-
dine ring has been observed for N-alkylated aziridines.21
Treatment of the hydrazide 13 with bromine gave the
crystalline 3-amino-2,3-dideoxylactone 14 as the hydro-
bromide in 74% yield (Scheme 5). Analogously, the hy-
Scheme 6
In summary, we have described a three-step synthesis of
two 2,3-aziridino-2,3-dideoxyhexonamides with D-gluco
and D-ido configuration. Although the yields are moder-
ate, the method is convenient as the starting materials are
readily available and the experimental procedures are
simple (no chromatography). These diastereomerically
pure aziridine-2-carboxyamides 3 and 11 proved to be
useful precursors for 3-amino-2,3-dideoxyhexonic acids.
Melting points are uncorrected. Optical rotations were measured on a
Perkin Elmer 241 polarimeter. NMR spectra were recorded on Bruker
AC-250 or AM-500 instruments. CHCl3 (d = 7.27 and 76.9) was used

March 1998
SYNTHESIS
327
Compound 7:
as an internal reference for CDCl3 solutions and dioxane (d = 67.4)
for 13C NMR spectra measured in D2O. H2O (d = 4.60) was used as
13C NMR (CDCl3): d = 171.9 (C-1), 109.8 (2 C, isoprop-C), 82.0,
77.0, 76.9, 71.0 (C-2, C-3, C-4 and C-5), 67.6 (C-6), 52.3 (OCH3),
26.8, 26.6, 26.2, 25.1 (isoprop-CH3).
1
internal reference for H NMR spectra measured in D2O solutions.
Column chromatography was performed on silica gel using the flash
technique. Microanalyses were performed by Research Institute for
Ph armacy and Biochemistry, Prague, and Chemistry Department II,
University of Copenhagen.
The product 7 was treated with MeSO2Cl (4.3 g, 38 mmol) in pyridine
(15 mL) for 1 h at 0 °C and 1 h at r.t. When the mixture was poured
into ice water (100 mL) the product precipitated immediately. Filtra-
tion and washing with MeOH/H2O gave 8 (4.86 g, 52%); mp 67–
68°C. Recrystallization from MeOH/H2O gave colorless needles; mp
68–69°C; [a]D –4.8 (c = 1.8, CHCl3).
Methyl 3,4;5,6-Di-O-isopropylidene-2-O-mesyl-D-gluconate (2):
D-Glucono-1,5-lactone (10.6 g, 59.6 mmol) was stirred for 48 h at r.t.
in a mixture of 2,2-dimethoxypropane (20 mL), anhyd acetone
(6 mL), MeOH (2 mL) and MeSO3H (0.1 mL). The mixture was then
neutralized with NaHCO3, filtered and concentrated to give crude 1
(~17 g), which was dissolved in pyridine (40 mL) and cooled in an ice
bath. MeSO2Cl (10.0 g, 89.4 mmol) was added and the mixture was
stirred for 1 h at 0 °C and then 1 h at r.t. When the mixture was poured
into a large volume of ice water (250 mL), the product precipitated as
a white solid. Filtration and recrystallization from MeOH/H2O gave 2
(12.7 g, 58%); mp 82–84°C. Further recrystallization of a sample
from MeOH/H2O gave a product with mp. 84–85°C (Lit.12 mp 86–
88°C); [a]D +42.6 (c = 1.8, CHCl3) (Lit.12 [a]D +19.4). The NMR data
are in accordance with the literature.14
Compound 8:
13C NMR (CDCl3): d = 166.4 (C-1), 110.4, 110.0 (isoprop-C), 80.1,
76.8 (2 C), 76.6 (C-2, C-3, C-4 and C-5), 67.6 (C-6), 52.6 (OCH3),
39.1 (OMs), 27.1, 26.6, 26.3, 25.2 (isoprop-CH3).
1H NMR (CDCl3): d = 5.37 (d, J = 2.2 Hz, 1 H, H-2), 4.42 (dd, J =
2.2; 7.0 Hz, 1 H, H-3), 4.14 (dd, J = 5.6; 8.5 Hz, 1 H, H-6a), 4.05 (dd,
J = 7.0; 8.5 Hz, 1 H, H-4), 4.01 (m, 1 H, H-5), 3.96 (dd, J = 4.5; 8.5
Hz, 1 H, H-6b), 3.80 (s, 3 H, OCH3), 3.19 (s, 3 H, OSO2CH3), 1.40 (s,
3 H, CH3), 1.39 (s, 6 H, CH3), 1.32 (s, 3 H, CH3).
C14H24O9S (368.4): calc. C 45.64 H 6.57; found C 45.75 H 6.38.
Preparation of 3 from 8:
The methyl ester 8 (1.05 g, 2.9 mmol) was suspended in 25% aq am-
monia (15 mL) and the mixture was stirred for 5 d and then worked
up as described above. Crystallization from EtOAc afforded 3
(0.16 g, 26%); mp 106–108°C; [a]D –42.8(c = 1.0, H2O).
2,3-Aziridino-2,3-dideoxy-5,6-O-isopropylidene-D-gluconamide (3):
The methyl ester 2 (13 g, 35 mmol) was suspended in 25% aq ammo-
nia (200 mL) and stirred for 5 d. The ammonia was then evaporated
and the crude product was passed through a column of ion exchange
resin (IRA 420 OH–, 100 mL) in order to remove mesylate ions. The
resin was washed with H2O (500 mL) and the eluate concentrated to
give about 6 g (80 %) of a crude syrup, which was coevaporated twice
with EtOAc. The syrup could then be crystallized from EtOAc to give
3 (3.5 g, 46 %) as colorless crystals; mp 106–108 °C. Recrystalliza-
tion from EtOAc gave a product with mp 110–111 °C. [a]D –44. 1 (c
= 1 .0, H2O).
Methyl 3,4;5,6-Di-O-isopropylidene-2-O-mesyl-D-gulonate (10):
D-Gulono-1,4-lactone (10.9 g, 61.2 mmol) was stirred for 48 h in 2,2-
dimethoxypropane (20 mL), anhyd acetone (6 mL), MeOH (2 mL)
and MeSO3H (0. 1 mL) and worked up as described above to give
crude methyl 3,4:5,6-di-O-isopropylidene-D-gulonate (9, ~17 g) as a
syrup.
13C NMR (D2O): d = 174.8 (C-1), 11 1.0 (isoprop-C), 77.8 (C-5), 72.3
(C-4), 66.2 (C-6), 39.4, 34.4 (C-2 and C-3), 26.2, 24.8 (isoprop- CH3).
C9H16N2O4 (216.2): calc. C 49.99 H 7.46 N 12.95 ; found C 49.79 H
7.46 N 12.95.
Compound 9:
3C NMR (CDCl3): d = 171.9 (C-1), 109.7, 109.2 (isoprop-C), 78.1,
76.5, 74.6, 70.9 (C-2, C-3, C-4 and C-5), 65.3 (C-6), 52.1 (OCH3),
26.6 (2C), 25.6, 25.1 (isoprop- CH3).
The product 9 was then mesylated with MeSO2Cl (10 g, 87.7 mmol)
as described above. When poured into ice water (250 mL) a syrup was
obtained. The H2O was decanted and the syrup dissolved in a mixture
of MeOH and H2O (2:1) by gentle heating. The product then crystal-
lized to give 10 (12.5 g, 56%); mp 73–75°C. Recrystallization from
MeOH/H2O gave a product with mp 78–79°C; [a]D –8.7 (c = 2.0,
CHCl3).
2,3-Aziridino-2,3-dideoxy-5,6-O-isopropylidine-N-tosyl-D-glu-
conamide (6):
The aziridine 3 (1.6 g, 7.4 mmol) was dissolved in pyridine (6 mL)
and cooled in an ice bath. p-Toluenesulfonyl chloride (1.6 g, 8.4
mmol) was added and the mixture was stirred for 2 h at 0°C. Crystal-
lization of the product took place upon addition of ice water (15 mL)
to give 6 (1.0 g, 37%); mp 157–158 °C. No attempts were made to op-
timize the yield. Recrystallization from EtOAc did not alter the mp;
[a]D –27.3 (c = 1.3, CHCl3).
Compound 10:
13C NMR (CDCl3): d = 166.8 (C-l), 110.6, 109.7 (isoprop-C), 76.4,
76.2, 75.6, 74.0 (C-2, C-3, C-4 and C-5), 65.5 (C-6), 52.8 (OCH3),
39.0 (OSO2CH3), 26.9, 26.8, 25.9, 25.4 (isoprop-CH3).
1H NMR (CDCl3): d = 5.20 (d, J = 3.8 Hz, 1 H, H-2), 4.45 (dd, J =
3.8; 8.0 Hz, 1 H, H-3), 4.21 (dd, J = 2.9; 8.0 Hz, 1 H, H-4), 4.05 (m,
2 H, H-5 and H-6a), 3.89 (dd, J = 6.0; 6.5 Hz, 1 H, H-6b), 3.83 (s, 3
H, OCH3), 3.14 (s, 3 H, OSO2CH3), 1.43 (s, 3 H, CH3), 1.41 (s, 3 H,
CH3), 1.39 (s, 3 H, CH3), 1.35 (s, 3 H, CH3).
13C NMR (CDCl3): d = 167.5 (C-l), 145.2, 129.9, 127.3 (Carom),
110.0 (isoprop-C), 76.6 (C-5), 71. 1 (C-4), 66.8 (C-6), 52.3, 44.2 (C-2
and C-3), 26.7, 25.0 (isoprop-CH3), 21.5 (Ar-CH3).
1H NMR (CDCl3): d = 7.85 (d, J = 8.2 Hz, 2 Harom), 7.40 (d, J =
8.2 Hz, 2 Harom), 5.9–6.0 (2 br s, 2 H, CONH2), 4.05–4.16 (m, 3 H, H-
4, H-5, H-6a), 3.95 (br t, J = 8.0 Hz, 1 H, H-6b), 3.54 (d, J = 4.3 Hz,
1 H, H-2), 3.53 (br s, 1H, OH), 3.09 (dd, J = 4.3 ; 8.8 Hz, 1 H, H-3),
2.45 (s, 3H, Ar-CH3), 1.46 (s, 3H, CH3), 1.35 (s, 3H, CH3).
C6H22N2O6S (370.4): calc. C 51.88 H 5.99 N 7.56; found C 51.95 H
5.97 N 7.52.
C14H24O9S (368.4): calc. C 45.64 H 6.57; found C 45.84 H 6.73.
2,3-Aziridino-2,3-dideoxy-5,6-O-isopropylidene-D-idonamide
(11):
The methyl ester 10 (6.7 g, 18 mmol) was suspended in 25% aq am-
monia (90 mL) and treated as described above. The major product
crystallized on addition of EtOAc to give 11 (1.6 g, 40 %); mp 138–
141 °C. Recrystallization from EtOH gave a product with mp 148–
149 °C; [a]D +18.4 (c = 1.0, H2O).
Selected Crystal Structure Data for 6:23
C16H22N2O6S = 370.42; crystal system orthorhombic; space group
P212121; Z = 4; cell parameters a = 6.760(4) Å, b = 12.248(4) Å, c
= 21.732(4) Å; radiation (CuKa) l = 1.5418 Å; 315 parameters for
2716 reflections (I > 2s(I)); final R = 0.065.
C9H11N2O4 (216.2): calc. C 49.99 H 7.46 N 12.95 : found C 50.19 H
7.30 N 12.92.
Methyl 3,4;5,6-Di-O-isopropylidene-2-O-mesyl-D-mannonate (8):
D-Mannono-1,4-lactone (4.5 g, 25 mmol) was stirred for 48 h in a
mixture of 2,2-dimethoxypropane (10 mL), anhyd acetone (2.5 mL),
MeOH (1 mL) and a drop of MeSO3H. The mixture was worked up
as described above to give the crude methyl 3,4:5,6-di-O-isopro-
pylidene-D-mannonate (7, ~ 5.8 g) as a syrup.
2,3-Aziridino-2,3-dideoxy-5,6-O-isopropylidene-N-tosyl-D-idona-
mide (12):
The aziridine 11 (1.0 g, 4.6 mmol) was tosylated as described above.
Crystallization of the product took place by addition of ice water to
give 12 (0.60 g, 35%); mp 164–166 °C. Recrystallization from EtOAc

328
Papers
SYNTHESIS
6.9; 8.2 Hz, 1 H, H-6a), 3.60 (dd, J = 6.9; 8.2 Hz, 1 H, H-6b), 3.28
(dd, J = 4.5; 5.0 Hz, 1 H, H-4), 3.00 (m, 1 H, H-3), 2.27 (dd, J = 5.3;
14.5 Hz, 1 H, H-2a), 2.10 (dd, J = 8.5; 14.5 Hz, 1 H, H-2b), 1.22 (s,
3 H, CH3), 1.18 (s, 3 H, CH3).
gave a product with mp 171 °C; [a]D –1.8 (c = 1.0, CHCl3). [a]D
–24.0 (c = 1.1, pyridine). No attempts were made to optimize the yield.
13C NMR (CDCl3): d = 167.4 (C-1), 129.9, 127.5 (Carom), 110.0 (iso-
prop-C), 76.4 (C-5), 69.0 (C-4), 65.3 (C-6), 52.1, 42.8 (C-2 and C-3),
26.0, 24.9 (isoprop-CH3), 21.6 (Ar- CH3).
Compound 16:
1H NMR (CDCl3): d = 7.88 (d, J = 8.2 Hz, 2 Harom), 7.37 (d, J =
8.2 Hz, 2 Harom), 5.85 and 5.58 (2 br s, 2 H, CONH2), 4.28 (ddd, J =
4.0; 6.8, 7.0 Hz, 1 H, H-5), 4.13 (m, 1 H, H-4, shows dd with J = 4.0
and 9.0 Hz after exchange with D2O), 4.10 (dd, J = 7.0; 8.5 Hz, 1 H,
H-6a), 4.01 (dd, J = 6.8; 8.5 Hz, 1 H, H-6b), 3.47 (d, J = 4.1 Hz, 1 H,
H-2), 3.23 (br d, J = 5.0 Hz, 1 H, OH, exchangeable with D2O), 3.17
(dd, J = 4.1, 9.0 Hz, 1 H, H-3), 2.47 (s, 3 H, Ar-CH3), 1.42 (s, 3 H,
CH3), 1.35 (s, 3 H, CH3).
Hydrolysis with 10% aq CF3CO2H (4 mL) followed by treatment with
Br2 as described above gave a solution, which was neutralized with
IRA-67 OH– and concentrated to give the title compound 16 (0.33 g,
91%) as a syrup (containing some lactone). Crystallization from
MeOH/H2O gave colorless crystals, which started to decompose from
~180°C; [a]D –24.5 (c = 0.8, H2O).
13C NMR (D2O): d = 178.1 (C-1), 72.5, 69.9 (C-4 and C-5), 63.4 (C-
6), 52.7 (C-3), 36.9 (C-2).
1H NMR (D2O): d = 3.78 (ddd, J = 2.0; 5.5; 6.2 Hz, 1 H, H-5), 3.75
(dd, J = 2.0; 6.0 Hz, 1 H, H-4), 3.59–3.65 (m, 3 H, H-6a, H-6b and H-
3), 2.58 (dd, J = 5.2; 16.8 Hz, 1 H, H-2a), 2.48 (dd, J = 8.0; 16.8 Hz,
1 H, H-2b).
C16H22NO6S (370.4): calc. C 51.88 H 5.99 N 7.56; found C 51.94 H
6.09 N 7.54.
Selected Crystal Structure Data for 12:22
C16H22N2O6S = 370.42; crystal system monoclinic; space group P21;
Z = 2; cell parameters a = 5.918(3) Å, b = 26.801(2) A, c = 5.908(2)
Å; radiation (MoKa) l = 0.71073 Å; 233 parameters for 1297 reflec-
tions [I > 2s(I)]; final R = 0.059.
C6H13NO5 (179.2): calc. C 40.22 H 7.31 N 7.82; found C 40.08 H
7.01 N 7.66.
(1) Tanner, D. Angew. Chem. 1994, 106, 625; Angew. Chem., Int.
Ed. Engl. 1994, 33, 599.
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(4) Kuyl-Yeheskiely, E.; Lodder, M.; van der Marel, G. A.; van
Boom, J. H. Tetrahedron Lett. 1992, 33, 3013.
3-Amino-2,3-dideoxy-D-arabino-hexono-1,4-lactone Hydrogen
Bromide (14):
The aziridine 3 (2.0 g, 9.3 mmol) was dissolved in a mixture of H2O
(10 mL) and hydrazine hydrate (10 mL) and refluxed for 2 h. The so-
lution was evaporated 4 times with H2O in order to remove the hydra-
zine and then concentrated to give 3-amino-2,3-dideoxy-5,6-di-O-
isopropylidene-D-arabino-hexonohydrazide (13; 2.1 g, 100%) as a
partly crystalline solid; mp ~ 215°C (dec.).
Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 6267.
(5) Dubois, L.; Dodd, R. H. Tetrahedron 1993, 49, 901.
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609.
Compound 13:
13C NMR (D2O): d = 176.8 (C-1), 110.0 (isoprop-C), 75.0 (C-5), 69.7
(C-4), 65.3 (C-6), 50. 1 (C-3), 35.5 (C-2), 24.9, 23.4 (isoprop- CH3).
1H NMR (D2O): d = 4.10 (m, 1 H, H-5), 4.06 (dd, J = 6.8; 8.5 Hz, 1 H,
H-6a), 3.84 (dd, J = 5.0; 8.5 Hz, 1 H, H-6b), 3.63 (dd, J = 4.5; 6.5 Hz,
1 H, H-4), 3.48 (ddd, J = 4.5; 5.5; 8.0 Hz, 1 H, H-3), 2.49 (dd, J = 5.5;
17.0 Hz, 1 H, H-2a), 2.43 (dd, J = 8.0; 17.0 Hz, 1 H, H-2b), 1.24 (s, 3
H, CH3), 1.25 (s, 3 H, CH3).
The crude solid product 13 was dissolved in 10% aq CF3CO2H
(10 mL) and stirred for 1 h at r.t. The mixture was then concentrated
and the residue dissolved in H2O (20 mL). Br2 was added (dropwise)
until no more N2 evolved and the solution was taken to almost dry-
ness. The remaining crude product crystallized upon addition of
EtOH to give 14 (1.65 g, 74%); mp ~225°C (dec.). Recrystallization
from 90% EtOH gave a product with mp 226–227°C (dec); [a]D
+16.5 (c = 1.0, H2O).
Compound 14:
13C NMR (D2O): d = 176.9 (C-1), 80.4 (C-4), 69.4 (C-5), 62.8 (C-6),
50.5 (C-3), 35.1 (C-2).
1H NMR (D2O): d = 4.69 (t, J = 6.2 Hz, 1 H, H-4), 4.27 (ddd, J = 0.7;
6.2; 8.0 Hz, 1 H, H-3), 3.99 (dt, J = 3.0, 6.2 Hz, 1 H, H-5), 3.72 (dt, J
= 3.0; 12.5 Hz, 1 H, H-6a), 3.61 (dd, J = 3.0; 12.5 Hz, 1 H, H-6b), 3.17
(dd, J = 8.0; 18.5 Hz, 1 H, H-2a), 2.65 (dd, J = 0.7; 18.5 Hz, 1 H, H-
2b).
(15) Lambert, J. B.; Takeuchi, Y. Cyclic Organonitrogen Stereody-
namics, VCH Publishers: Weinheim, 1992.
(16) Backes, J, In Houben-Weyl; Methoden der Organischen Che-
mie, Vol. E 16 c; Klamann, D., Thieme: Stuttgart, 1992, p 370.
(17) Vekemans, J. A. J. M.; Boerekamp, J.: Godefroi, E. F.; Chitten-
den, G. J. F. Recl. Trav. Chim. Pays-Bas 1985, 104, 266.
(18) Lim, Y.; Lee. W. K. Tetrahedron Lett 1995, 36, 8431.
(19) Molander, G. A.; Stengel P. J. J. Org. Chem. 1995, 60, 6660.
(20) Paulsen, H.: Stoye, D. Chem. Ber. 1966, 99, 908.
(21) Deyrup, J. A.; Clough, S. C. J. Am. Chem. Soc. 1968, 90, 3592.
(22) Atomic coordinates have been deposited at the Cambridge
Crystallographic Data Centre, 12 Union Road, Cambridge,
CB21EZ, UK, and are available on request. Requests should be
accompanied by a full citation of this paper
C6H12BrNO4 (242.1): calc. C 29.77 H 5.00 N 5.79 Br 33.01; found C
29.80 H 4.93 N 5.80 Br 33.70.
3-Amino-2,3-dideoxy-D-xylo-hexonic Acid (16):
The aziridine 11 (0.44 g) was refluxed for 2 h with a mixture of hy-
drazine hydrate (2 mL) and H2O (2 mL) and then worked up as de-
scribed above to give 3-amino-2,3-dideoxy-5,6-di-O-isopropylidene-
D-xylo-hexonohydrazide (15; 0.47 g, 100%) as a colorless syrup.
Compound 15:
13C NMR (D2O): d = 173.2 (C-1), 110.9 (isoprop-C), 77.1 (C-5), 73.3
(C-4), 66.3 (C-6), 51.2 (C-3), 38.6 (C-2), 26.1, 25.0 (isoprop- CH3).
1H NMR (D2O): d = 4.12 (dt, J = 5.0; 6.9 Hz, 1 H, H-5), 3.92 (dd, J =