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B. M. Syed et al. / Tetrahedron 60 (2004) 5571–5575
Potassium carbonate (0.80 g, 5.85 mmol), CuSO4 mono-
hydrate (6 mg, 0.024 mmol), and triflyl azide solution
prepared as above were added to a solution of crude borane
complex 1 (1.1 g, 3.89 mmol) in methanol (25 mL). The
reaction mixture was stirred for 18 h at rt and concentrated.
The residue was extracted by ethyl acetate (20 mL) from
water (15 mL) and the organic phase was dried (Na2SO4)
and concentrated. The residue was purified by flash column
chromatography using CHCl3–MeOH (19:1) as eluent to
afford azido derivative 3 (0.67 g, 56%) as a yellow
amorphous solid: [a]2D0¼210.2 (c 1.7, MeOH); IR (neat,
cm21): 840, 960, 1214, 1261, 1357, 1450, 1697, 2098, 2842,
2919, 3114, 3222; 1H NMR (CDCl3þMeOH-d4, 400 MHz):
d 0.56 (br s, 2H, B-(CH)2), 1.35–1.88 (m, 15H, B-(CH2)6,
H-b, H-g, H-g0), 2.03–2.17 (m, 2H, H-b0, –OH), 3.26 (dd,
1H, J¼7.6, 12.2 Hz, H-1), 3.38 (dd, 1H, J¼3.6, 12.4 Hz,
H-10), 3.77–3.84 (m, 1H, H-d), 3.85–3.93 (m, 1H, H-a),
5.23 (dd, 1H, J¼8.0, 12.4 Hz, –NH), 5.56 (dd, 1H, J¼8.2,
12.4 Hz, –NH); 13C NMR (CDCl3þMeOH-d4, 100 MHz):
d 23.6, 24.1, 26.4, 29.2, 30.8, 30.8, 31.0, 31.1, 54.7, 56.5,
69.7, 127.8, 128.7, 175.3; HR-MS (FAB): calcd for
C14H27BN4O3 309.2092 [MþH]þ, found 309.2103.
dioxane (2 mL) was added dropwise to a solution of crude
7 (0.36 g) in dioxane–10% Na2CO3 (6 mL, 1:2) at 0 8C. The
solution was stirred for 4 h at room temperature and the
dioxane was evaporated. Chloroform (15 mL) was added
and the mixture was acidified to pH 2 with a 1 M solution of
KHSO4 at 0 8C. The organic phase was separated, and the
aqueous phase extracted with an additional amount of
chloroform (2£10 mL). The combined organic layers were
dried (Na2SO4) and concentrated to afford crude acid 8
(0.58 g). Trimethylsilyl chloride (0.38 mL, 3.0 mmol) was
added dropwise to an ice cold solution of crude 8 (0.58 g) in
allyl alcohol (5 mL) under nitrogen. After stirring for 10 h at
rt the solvent was evaporated and the residue was purified by
flash column chromatography using hexane–ethyl acetate
as eluent to afford the ester 9 (0.45 g, 45% over three steps).
[a]2D0¼þ0.58 (c¼2.0, CHCl3); 1H NMR (CDCl3,
400 MHz): d 1.48–1.61 (m, 2H, H-g, g0), 1.70–1.83 (m,
1H, H-b), 1.99–2.11 (m, 1H, H-b0), 2.16–2.56 (br s, 1H,
–OH), 3.18–3.37 (2 m, 2H, H-1, 10), 3.71–3.82 (m, 1H,
H-d), 4.21 (t, 1H, J¼7.0 Hz, Fmoc-CH), 4.35–4.50 (m, 3H,
Fmoc-CH2, H-a), 4.64 (d, 2H, J¼5.3 Hz, allylic CH2), 5.29
(ddd, 2H, J¼17.8, 10.6, 30.2 Hz, vCH2), 5.55 (d, 1H,
J¼7.6 Hz, N–H), 5.82–5.95 (m, 1H, –CHv), 7.30 (t, 2H,
J¼7.5 Hz, Fmoc), 7.39 (t, 2H, J¼7.3 Hz, Fmoc), 7.58 (d,
2H, J¼7.1 Hz, Fmoc), 7.75 (d, 2H, J¼7.4 Hz, Fmoc); 13C
NMR (CDCl3, 100 MHz): d 20.5, 20.5, 20.8, 21.4, 23.1,
23.9, 24.3, 26.5, 29.0, 31.0, 31.3, 31.3, 31.8, 44.1, 55.5,
61.7, 66.9, 67.0, 69.0, 70.5, 71.0, 81.4, 101.4, 125.2, 128.0,
128.2, 128.2, 128.4, 128.6, 129.0, 129.0, 136.2, 137.8,
157.1, 170.2, 170.2, 170.4, 173.5; IR (neat, cm21): 742,
1267, 1450, 1525, 1710, 2100, 2927, 3330; MS: HR-MS
(FAB): calcd for C24H26N4O5 450.1903 [MþH]þ, found
450.1898.
4.1.3. (5R)-N a-(Fluoren-9-ylmethoxycarbonyl)-N 1-
benzyloxycarbonyl-5-hydroxy-L-lysine allyl ester (6).
Excess ethylenediamine (1 mL, 16 mmol) was added to a
solution of 2 (1.51 g, 3.62 mmol) in THF (5 mL) at room
temperature and heated for 1 min. The suspension was
cooled and filtered. The precipitate was washed with an
additional amount of THF (15 mL) and dried in vacuo to
afford crude 4 (0.95 g) which was used as such for the next
step. A solution of 9-fluorenylmethyl chloroformate (1.25 g,
4.84 mmol) in dioxane (5 mL) was added dropwise to a
solution of 4 in dioxane–10% Na2CO3 (15 mL, 1:2) at 0 8C.
The solution was stirred for 5 h at rt and the dioxane was
evaporated. Chloroform (20 mL) was added and the mixture
was acidified to pH 2 with a 1 M solution of KHSO4 at 0 8C.
The organic phase was separated and the aqueous phase was
extracted with an additional amount of chloroform
(2£10 mL). The combined organic layers were dried
(Na2SO4) and concentrated to afford acid 5 (1.53 g).
Aqueous Cs2CO3 was added to a solution of 5 in aqueous
ethanol (80%) so that the pH was adjusted to 7. The solution
was concentrated after stirring for 2 h. Allyl bromide
(0.73 g, 5.43 mmol) was added to a solution of the resulting
cesium salt in DMF (5 mL) and stirred for 12 h under
nitrogen. The mixture was diluted with water and extracted
with diethyl ether. The organic phase was dried (Na2SO4),
concentrated and the residue was purified by column
chromatography over silica gel using heptane–ethyl acetate
as eluent to afford allyl ester 6 (1.45 g, 72% for three steps).
4.1.5. (5R)-N 1-Benzyloxycarbonyl-5-O-(2,3,4,6-tetra-O-
acetyl-b-D-galactopyranosyl)-5-hydroxy-L-lysinato-
bicyclononylboron (11). A solution of acetobromo galac-
tose (10, 1.45 g, 3.53 mmol) in dichloromethane (5 mL) was
added dropwise to a stirred solution of 2 (1.02 g.
2.35 mmol) in dichloromethane (10 mL) containing silver
˚
silicate (3.2 g) and powdered molecular sieves (3 A, 0.5 g)
in the absence of light at 0 8C. The reaction mixture was
stirred overnight under nitrogen at 0 8C. It was filtered and
the filterate was concentrated. The residue was purified by
flash column chromatography using toluene-acetonitrile as
eluent to yield 11 (1.24 g, 68%) as a white amorphous solid.
[a]2D0¼þ4.9 (c 1.9, CHCl3); 1H NMR (CDCl3, 400 MHz): d
0.55 (br s, 2H, (B-(CH)2), 1.37–1.92 (m, 16H, B-(CH2)6,
H-b, b0, H-g, g0), 1.95 (s, 3H, COCH3), 1.97 (s, 3H,
COCH3), 2.09 (s, 3H, COCH3), 2.12 (s, 3H, COCH3), 3.30
(m, 2H, H-1, H-10), 3.56–3.71 (m, 2H, H-d, H-a), 3.82 (t,
J¼6.1 Hz, 1H, H-5), 4.03 (dd, 1H, J¼7.5, 11.4 Hz, H-6),
4.14 (dd, 1H, J¼5.4, 11.5 Hz, H-60), 4.45 (d, 1H, J¼8.0 Hz,
H-1), 4.75–4.92 (m, 1H, NH-a), 4.97 (dd, 1H, J¼3.3,
10.5 Hz, H-3), 5.07–5.14 (m, 4H, PhCH2, H-2, NH-a0),
5.35 (d, 1H, J¼3.0 Hz, H-4), 5.61 (t, 1H, J¼6.1 Hz, N–H1),
7.28–7.39 (m, 5H, Ph); 13C NMR (CDCl3, 100 MHz): d
20.4, 20.7, 21.3, 23.0, 23.8, 24.3, 26.4, 28.9, 31.0, 31.2,
31.3, 31.7, 44.1, 55.5, 61.7, 66.9, 67.0, 68.9, 70.4, 71.0,
81.3, 101.4, 125.2, 128.0, 128.1, 128.3, 128.6, 128.9, 136.1,
137.8, 157.1, 169.9, 170.0, 170.2, 173.5; HR-MS (FAB):
calcd for C36H51BN2NaO14 769.3326 [MþNa]þ, found
769.3347.
1
Compound 6 had H and 13C NMR data identical to those
reported previously.8
4.1.4. (5R)-N a-(Fluoren-9-yl-methoxycarbonyl)-6-azido-
5-hydroxy-L-lysine allyl ester (9). Concentrated aqueous
HCl (2 mL) was added to a solution of 3 (0.67 g,
2.14 mmol) in methanol (5 mL) at 0 8C. The solution was
stirred for 10 min at rt and then concentrated. The residue
was triturated with hot hexanes and finally with ether. It was
dried under high vacuum to afford crude 7 (0.36 g) which
was used as such in the next step. A solution of 9-
fluorenylmethyl chloroformate (0.631 g, 2.44 mmol) in