Notes
J . Org. Chem., Vol. 63, No. 11, 1998 3791
Sch em e 2
In summary, by use of mildly removable TCP or pent-
4-enoyl amino-protecting groups, followed by diazotrans-
fer, 2-azido-2-deoxy derivatives could be prepared in good
yields. Common carbohydrate protecting groups are
compatible with the methods, allowing advanced differ-
entially protected derivatives to be transformed into their
azido analogues. The late introduction of the azido group
is of special preparative value, allowing relatively large
amounts of building blocks to be synthesized conve-
niently.19 Further exploration of this methodology and
use of the 2-azido-2-deoxy building blocks in the synthesis
of R-linked glucosamine glycosides is currently under
way.
Exp er im en ta l Section
Gen er a l Rem a r k s. Solvents of commercial anhydrous grade
have been used without further purification. TLC plates (Riedel-
de Haen, coated with silica gel 60 F 254) were detected by UV
and by charring with 8% sulfuric acid. Silica gel (Spectrum SIL
58, 230-400 mesh, grade 60) was used for column chromatog-
raphy. All NMR spectra were recorded at 25 °C at 400 MHz
(1H) or 100 MHz (13C), and chemical shifts are reported relative
to internal TMS. Accurate mass measurements were made
using FAB at 10K resolution, and elemental analyses were
conducted by Atlantic Microlab, Norcross, GA. Procedures for
preparation of compounds 1, 2, 4, and 5 can be found in ref 11.
P en t-4-en yl 3,4-Di-O-ben zoyl-6-O-(ter t-bu tyld im eth ylsi-
lyl)-2-d eoxy-2-t et r a ch lor op h t h a lim id o-â-D-glu cop yr a n o-
sid e (3). Pent-4-enyl 2-deoxy-2-tetrachlorophthalimido-â-D-
glucopyranoside (1) (951 mg, 1.84 mmol), tert-butyldimethylsilyl
chloride (305 mg, 2.03 mmol), and a catalytic amount of DMAP
were dissolved in pyridine (15 mL) and stirred overnight at room
temperature. TLC indicated that silylation was complete, and
benzoyl chloride (534 µL, 4.60 mmol) was added to the reaction
mixture. Stirring continued, and further additions of benzoyl
chloride were made 2 and 4 h after the first (200 µL, 1.72 mmol,
each time). After 6 h of benzoylation, the reaction was com-
pleted, and water (2 mL) was added. Five minutes later, the
reaction mixture was partitioned between 5% HCl (aqueous) and
toluene. The organic phase was washed with 5% HCl (aqueous)
and NaHCO3 (saturated, aqueous), dried (MgSO4), and evapo-
rated. Flash chromatography (petroleum ether/EtOAc 12:1)
gave product 3 as a white crispy foam in 77% yield (1168 mg,
1.41 mmol). NMR data: 13C δ -5.4 (two signals), 18.3, 25.8,
28.5, 29.9, 55.8, 62.8, 69.0, 70.0, 71.7, 75.2, 97.7, 114.9, 128.3-
129.8 (several signals), 133.3, 133.4, 137.7, 165.1, 166.1; 1H
(selected data) δ 5.47 (d, 1H, J ) 8.4 Hz), 5.53 (t, 1H, J ) 9.2
Hz), 5.68 (m, 1H), 6.12 (t, 1H, J ) 9.0 Hz). Anal. Calcd for
C39H41NO9SiCl4: C, 55.92; H, 4.93; N, 1.67. Found: C, 56.03;
H, 4.95; N, 1.61.
P en t-4-en yl 3,6-Di-O-ben zyl-2-deoxy-2-tetr ach lor oph th al-
im id o-â-D-glu cop yr a n osid e (6). Pent-4-enyl 3-O-benzyl-4,6-
O-benzylidene-2-deoxy-2-tetrachlorophthalimido-â-D-glucopyr-
anoside (5) (1133 mg, 1.63 mmol) was dissolved in a mixture of
THF/diethyl ether (2:1, 75 mL). NaBH3CN (1000 mg, 15.9
mmol) was added in one portion and the mixture stirred for 5
min. HCl (g) was bubbled into the mixture for 2 min, and 15
min later, all starting material was consumed. Water (25 mL)
and toluene (100 mL) were added, and the resulting phases were
separated. The organic layer was washed with brine, NaHCO3
(saturated aqueous) twice, dried (MgSO4), and evaporated.
Gradient flash chromatography (petroleum ether/EtOAc 8:1-
4:1) gave product 6 (890 mg, 1.28 mmol, 78%). NMR data: 13C
δ 28.4, 29.8, 56.0, 68.8, 70.6, 73.4, 73.8, 74.7, 75.0, 79.4, 97.8,
114.8, 126.9, 127.8-128.5 (several signals), 137.4, 137.7, 138.6;
1H (selected data) δ 5.09 (d, 1H, J ) 8.0 Hz), 5.61 (m, 1H). This
compound (6) has previously been synthesized and fully char-
acterized using a different procedure and starting material. See
ref 11.
products from the TCP-deprotecting step was necessary
for formation of the final product in acceptable and re-
producible overall yields. And so, rough purification of
the intermediate amine followed. Overnight reaction
with TfN3 (CAUTION!)18 in acetonitrile then gave the
2-azido derivative 7. The results with substrates 3, 5
and 6 indicate that commonly applied protecting groups
such as benzylidene acetals and benzyl and tert-bu-
tyldimethylsilyl ethers survive the conversion well. Over-
night treatment with ethylenediamine was allowed rou-
tinely for substrates 5 and 6, and clean deprotection was
achieved with no breakdown detected.
Ester protecting groups required special consideration.
Yields were lower when benzoates were present (2 and
3) owing to some ester cleavage during the ethylenedi-
amine treatment. The primary 6-O-benzoate was espe-
cially labile, as a comparison of the obtained yields of 9
and 10 shows. In these cases, careful monitoring by TLC,
allowing as short reaction time as possible, was impor-
tant to obtain best yields.
Acetate groups are not as sturdy,11 but for such cases
use of the pent-4-enoyl group seemed advantageous,
since its deprotection by iodine occurs under nonbasic
conditions. Indeed, transformation of substrate 11 into
to 2-azido product 12 shows that this is a promising
approach.
The diazotransfer step caused no concern. Reactions
proceeded excellently in all cases in a spot-to-spot fashion.
Preparation of compounds 7-10 followed the general proce-
dure: The TCP-protected compound (1 equiv) was dissolved in
(18) Considering the hazardous nature of TfN3, it should be prepared
in situ and used in solution only according to refs 6 and 8.
(19) Gram amount single preparations of advanced compound 7 have
been carried out.