T. Tanaka et al. / Carbohydrate Research 346 (2011) 340–342
341
O
O
OH
2.5 mol % Cu(CH3CN)4PF6
3 mol % chiral ligand
R
PhCO3-t-Bu
O
+
O
O
acetone
R = H; 84% ee
R = NO2; >99% ee
>99% ee
2
ligand:
Me
after recrystallization
N
H
N
Me
Scheme 1.
the MeOH was removed by an evaporator. The aqueous solution
was extracted with EtOAc (50 mL ꢁ 3). The combined organic layer
was washed with brine (20 mL ꢁ 3) and dried (Na2SO4). After evap-
oration of the solvent, the residue was purified by chromatography
(5:1 hexane–EtOAc) to give compound 4 as a colorless liquid
OH
OMOM
OMOM
NaN3
HO
N3
MOMCl
NH4Cl
O
O
MeOH
80%
CH2Cl2
94%
(1.04 g, 82%). Rf 0.26 (3:1 hexane–EtOAc); ½a D18
ꢀ
+165 (c 0.5, CHCl3);
>99% ee
3
4
1H NMR (400 MHz, CDCl3): d 5.71–5.66 (m, 1H), 5.60–5.55 (m, 1H),
4.79 (s, 2H), 4.4 (br s, 1H), 4.0 (br s, 1H), 3.66–3.57 (m, 2H), 3.47 (s,
3H), 2.50–2.43 (m, 1H), 2.13–2.06 (m, 1H); 13C NMR (100.6 MHz,
CDCl3): d 127.2, 125.9, 97.6, 83.3, 75.6, 60.6, 55.8, 30.7; ESIMS:
m/z 222.3 (M+Na)+. Anal. Calcd for C8H13N3O3: C, 48.23; H, 6.58;
N, 21.09. Found: C, 48.55; H, 6.61; N, 20.95.
2
OMOM
OH
BnBr
NaH
BnO
N3
BnO
N3
CF3CO2H
DMF
91%
CH2Cl2
94%
5
1
1.5. (1S,5R,6S)-5-Azido-6-benzyloxy-1-methoxymethoxycy-
clohex-2-ene (5)
Scheme 2.
liquid (0.89 g, 99%). Rf 0.18 (1:1 hexane–EtOAc); ½a D20
ꢀ
+119 (c 0.5,
To a suspension of NaH (60% dispersion in oil, 40 mg, 1.0 mmol)
in DMF (1 mL) was added 4 (100 mg, 0.5 mmol) in DMF (0.5 mL).
The mixture was stirred for 30 min. Then, BnBr (120 lL, 1.0 mmol)
CHCl3); 99% ee (determined by GC: b-DEX-225 (SupelcoÒ), oven
temp.150 °C,tR ofmajorisomer = 7.17 min(1S,5S,6R), tR ofminoriso-
mer = 8.57 min (1R, 5R, 6S)); 1H NMR (400 MHz, CDCl3): d 5.71–5.67
(m, 1 H), 5.62–5.58 (m, 1H), 4.5 (br s, 1H), 3.3 (br s, 1H), 3.3 (br s, 1H),
2.59–2.50 (m, 2H), 2.0 (br s, 1H); 13C NMR (100.6 MHz, CDCl3): d
124.7, 124.6, 62.8, 53.6, 50.2, 25.0; ESIMS: m/z 113.0 (M+H)+.
was added. The mixture was stirred for 3 h and brine (10 mL) was
added to quench the reaction. The aqueous solution was extracted
with EtOAc (50 mL ꢁ 3). The combined organic layer was washed
with brine (20 mL) and dried (Na2SO4). After evaporation of the
solvent, the residue was purified by chromatography (20:1 hex-
ane–EtOAc) to give compound 5 (130 mg, 90%). Rf 0.55 (2:1 hex-
1.3. (1S,5S,6S)-1-Methoxymethoxy-5,6-epoxycyclohex-2-ene (3)
ane–EtOAc); ½a 2D1
ꢀ
+78.4 (c 1.0, CHCl3); 1H NMR (CDCl3, 400 MHz):
d 7.41 (d, J = 7.0 Hz, 2H), 7.36 (t, J = 7.0 Hz, 2H), 7.31 (d, J = 7.0 Hz,
1H), 4.89 (d, J = 10.8 Hz, 1H), 4.82 (d, J = 10.8 Hz, 1H), 4.80 (d,
J = 7.0 Hz, 1H), 4.71 (d, J = 7.0 Hz, 1H), 4.24–4.27 (m, 1H), 3.68
(ddd, J = 6.0, 10.4, 10.4 Hz, 1H), 3.54 (dd, J = 7.2, 10.4 Hz, 1H),
3.38 (s, 3H), 2.43–2.50 (m, 1H), 2.05–2.13 (m, 1H); 13C NMR (CDCl3,
100.6 MHz): d 138.1, 128.4, 128.2, 128.0, 127.8, 125.2, 96.9, 83.3,
78.8, 75.3, 60.8, 55.6, 31.3; ESIMS: m/z 312 (M+Na)+.
To a solution of the deprotected compound 2 (0.64 g, 5.7 mmol) in
CH2Cl2 (30 mL) was added diisopropylethylamine (DIPEA, 2.9 mL,
17.3 mmol), followed by the additionofMOMCl(1.3 mL, 17.3 mmol).
The mixture was stirred for 10 h and H2O (30 lL) was added to
quench the reaction. The aqueous layer was extracted with EtOAc
(30 mL ꢁ 3). The combined organic layer was washed with brine
(20 mL) and dried over Na2SO4. After evaporation of the solvent,
the residue was purified by chromatography (5:1 hexane–EtOAc)
to give the MOM-protected compound 3 as a colorless oil (0.88 g,
1.6. Preparation of (1S,5R,6S)-5-azido-6-benzyloxycyclohex-2-
ene-1-ol (1)
99%). Rf 0.28 (3:1 hexane–EtOAc); ½a D17
ꢀ
+118.3 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3): d 5.6 (br s, 2H), 4.78 (d, J = 7.2 Hz, 1H), 4.75
(d, J = 7.2 Hz, 1H), 4.4 (br s, 1H), 3.40 (s, 3H), 3.2 (br s, 1H), 3.3 (br s,
1H), 2.63–2.51 (m, 2H); 13C NMR (100.6 MHz, CDCl3): d 125.3,
122.8, 95.9, 68.7, 55.5, 52.4, 50.3, 25.1; ESIMS: m/z 157 (M+H)+. Anal.
Calcd for C8H12O3: C, 61.52; H, 7.74. Found: C, 61.25; H, 7.81.
To a solution of 5 (90 mg, 0.3 mmol) in CH2Cl2 (1 mL) was added
TFA (0.5 mL, 3.0 mmol). The mixture was stirred at 18 °C for 1.5 h,
and the TFA and CH2Cl2 were evaporated. EtOAc (40 mL) was
added to dilute the mixture. The solution was washed with satd
aq NaHCO3 (10 mL ꢁ 2) and the organic layer was dried (Na2SO4).
After evaporation of the solvent, the residue was purified by chro-
matography (10:1 hexane–EtOAc) to give compound 1 (65 mg,
1.4. (1S,5R,6S)-5-Azido-1-methoxymethoxy-cyclohex-2-ene-6-ol
(4)
86%). Rf 0.40 (2:1 hexane–EtOAc); ½a D22
ꢀ
+110.5 (c 1.0, CHCl3) (lit.5
[a]
+106.2 (c 1.16, CHCl3)); 1H NMR (CDCl3, 400 MHz): d 7.41 (d,
D
To a solution of 3 (1.0 g, 6.4 mmol) in MeOH (48 mL) and H2O
(6 mL) were added NH4Cl (0.68 g, 12.8 mmol) and NaN3 (1.25 g,
19.2 mmol). The mixture was heated at 80 °C for 16 h. After cooling
to rt, additional H2O (30 mL) was added to dissolve the solid, and
J = 7.4 Hz, 2H), 7.37 (t, J = 7.4 Hz, 2H), 7.33 (d, J = 7.4 Hz, 1H),
5.55–5.65 (m, 2H), 4.97 (d, J = 11.4 Hz, 1H), 4.76 (d, J = 11.4 Hz,
1H), 4.26 (br s, 1H), 3.69 (ddd, J = 5.6, 9.6, 9.6 Hz, 1H), 3.42 (dd,