378
R. F. Martínez, G. W. J. Fleet / Tetrahedron: Asymmetry 25 (2014) 373–380
CH2), 1.88 (m, 4H, CH2 and CH3), 2.98 (m, 1H, NCH2), 3.24 (m, 1H,
4.11. Methyl N-benzyl-2,4-dideoxy-2,4-imino-6-O-trityl-b-D-lyxo-
0
NCH2), 3.96 (bs, 1H, 4-H), 4.20 (dd, J5,5 = 12.0 Hz, J5,4 = 6.5 Hz, 1H,
hexopyranoside-3-ulose 13
5-H), 4.32–4.34 (m, 1H, 50-H), 4.48 (s, 1H, 2-H), 4.94 (d, Jgem = 11.5 -
Hz, 1H, OCH2Ph), 5.02 (d, Jgem = 11.5 Hz, 1H, OCH2Ph), 7.31–7.41
(m, 5H, ArH) ppm; 13C NMR (125 MHz, C5D5N): d = 15.9, 16.9
(CH3), 22.6 (CH2), 32.5 (CH2), 60.6 (NCH2), 62.5 (C-5), 68.2 (OCH2-
Ph), 76.8, 77.2 (C-2 and C-4), 80.2 (C-3), 130.2–141.4 (Ph), 173.9
(C-1) ppm; m/z (ESI+ve): 308 ([M+H]+, 100%; 330 ([M+Na]+, 65%);
HRMS m/z (ESI+ve): found 330.1671 ([M+Na]+); C17H25NNaO4 re-
quires 330.1676.
Dess-Martin periodinane (284 mg, 0.66 mmol) was added to a
solution of 11 (170 mg, 0.33 mmol) in dichloromethane (6 mL) at
0 °C. After 20 h at rt, the mixture was diluted with dichlorometh-
ane (10 mL) and saturated aqueous sodium hydrogen carbonate
(10 mL) containing sodium thiosulfate (0.12 g mLꢀ1), and the mix-
ture was stirred vigorously until both phases had cleared. The lay-
ers were separated, and the organic layer washed with more of the
sodium hydrogen carbonate/sodium thiosulfate solution (10 mL).
The aqueous layers were back extracted with dichloromethane
(10 mL), and the combined organic layers dried (MgSO4) and con-
centrated in vacuo. This residue was purified by flash column chro-
matography on silica gel (5:1 cyclohexane/ethyl acetate) to afford
4.9. N-Butyl-2,4-dideoxy-2,4-imino-3-methyl-D-ribonic acid 16
At first, 10% Pd on carbon (6 mg) was added to a degassed solu-
tion of 23 (14 mg, 0.05 mmol) in 1,4-dioxane (1 mL) and aqueous
HCl (2 m, 1 mL) and the resulting solution was stirred at room tem-
perature under hydrogen. After 3 h, the reaction mixture was fil-
tered (GF/A glass microfibre) and the solvents were removed in
13 as a colorless oil (172 mg, quant). ½a D20
ꢂ
¼ ꢀ55:4 (c 0.26, CH2Cl2);
Vmax (thin film, cmꢀ1): 3086, 3060, 3031 (Ar), 1786 (CO); 1H NMR
e
0
(400 MHz, CD3CN): d = 3.21 (s, 3H, OCH3), 3.33 (dd, J6,6 = 8.8 Hz,
J6,5 = 5.4 Hz, 1H, 6-H), 3.61 (d, Jgem = 13.6 Hz, 1H, NCH2), 3.66 (dd,
vacuo to afford 16 as a colorless oil (10 mg, quant). ½a D20
ꢂ
¼ þ7:0
(c 0.60, methanol); Vmax (thin film, cmꢀ1): 3291 (OH), 1733 (CO);
1H NMR (400 MHz, D2O): d = 0.90 (t, J = 7.2 Hz, 3H, CH3), 1.24–
1.37 (m, 2H, CH2), 1.41 (s, 3H, CH3), 1.57–1.64 (m, 2H, CH2),
3.25–3.32 (m, 1H, NCH2), 3.40–3.48 (m, 1H, NCH2), 3.99 (d,
J6 ,6 = 8.8 Hz, J6 ,5 = 8.0 Hz, 1H, 60-H), 3.70 (d, Jgem = 13.6 Hz, 1H,
NCH2), 3.89 (dd, J2,4 = 6.4 Hz, J2,1 = 2.8 Hz, 1H, 2-H), 4.18 (dd,
J4,2 = 6.4 Hz, J4,5 = 2.8 Hz, 1H, 4-H), 4.22–4.26 (m, 1H, 5-H), 4.82
(d, J1,2 = 2.8 Hz, 1H, 1-H), 7.24–7.38 (m, 20H, ArH) ppm; 13C NMR
(100 MHz, CD3CN): d = 55.9 (OCH3), 59.1 (NCH2), 63.8 (C-6), 77.9
(C-5), 85.5 (C-4), 86.7 (C-2), 87.6 (CPh3), 101.3 (C-1), 128.1–145.1
(Ph), 187.4 (C-3) ppm; m/z (ESI+ve): 538 ([M+H+CH3OH]+, 100%);
HRMS m/z (ESI+ve): found 538.2566 ([M+H+CH3OH]+);
e
0
0
J5,4 = 6.4 Hz, 2H, 5-H and 50-H), 4.25 (t, J4,5 = J4,5 = 6.4 Hz, 1H,
0
4-H), 4.74 (s, 1H, 2-H) ppm; 13C NMR (100 MHz, D2O): d = 13.3,
16.8 (CH3), 19.7 (CH2), 26.8 (CH2), 57.1 (NCH2 and C-5), 71.9 (C-
3), 76.1 (C-2), 77.0 (C-4), 168.9 (C-1) ppm; m/z (ESI+ve): 218
([M+H]+, 100%; HRMS m/z (ESI+ve): found 240.1208 ([M+Na]+);
C34H36NO5 requires 538.2588.
C10H19NNaO4 requires 240.1206.
4.12. Methyl N-benzyl-2,4-dideoxy-2,4-imino-3-methyl-6-O-tri-
tyl-b- -talopyranoside 24
4.10. Methyl N-benzyl-2,4-dideoxy-2,4-imino-6-O-trityl-b-
D-talo-
D
pyranoside 11
Methyl lithium (1.6 M in Et2O, 0.42 mL, 0.67 mmol) was added
dropwise to a stirred solution of 13 (170 mg, 0.33 mmol) in diethyl
ether (6 mL) under an atmosphere of argon. After 18 h, TLC analysis
(1:1 cyclohexane/ethyl acetate) showed the complete consump-
tion of the starting material (Rf 0.79) and the formation of a single
product (Rf 0.61). The reaction was quenched with water (10 mL)
and extracted with ethyl acetate (3 ꢁ 10 mL). The combined organ-
ic extracts were dried (MgSO4), filtered, and concentrated in vacuo.
The resulting residue was purified by flash column chromatogra-
phy on silica gel (5:1 to 1:1, cyclohexane/ethyl acetate) to afford
Compound
4 (277 mg, 0.46 mmol), 10% Pd on carbon
(148 mg), and ammonium formate (146 mg, 2.32 mmol) were
suspended in anhydrous methanol (20 mL) and the mixture
was heated at reflux under argon. After 2 h, TLC analysis (2:1
cyclohexane/ethyl acetate) showed no remaining starting mate-
rial (Rf 0.65) and the formation of a single product (Rf 0.16).
The mixture was filtered through Celite and the path was
washed with more methanol. The solvent was concentrated in
vacuo to afford 18 as a colorless oil (194 mg, quant.). The crude
azetidine 18 (177 mg, 0.42 mmol) was dissolved in 1,4-dioxane
(4 mL) and benzaldehyde (0.22 mL, 2.11 mmol) was added. A
solution of NaBH3CN (133 mg, 2.11 mmol) in methanol (4 mL)
was added, and the mixture stirred at rt. After 15 h, mass spec-
trometry showed the formation of a single product (m/z 508).
Solvents were removed in vacuo and the resulting residue was
partitioned between ethyl acetate (10 mL) and 50% brine
(10 mL). The aqueous layer was extracted with ethyl acetate
(2 ꢁ 10 mL), and the combined organics were dried (MgSO4), fil-
tered, and concentrated in vacuo. Purification by flash column
chromatography on silica gel (10:1 to 1:2, cyclohexane/ethyl
24 as a colorless oil (161 mg, 92%). ½a D20
ꢂ
¼ ꢀ48:5 (c 0.70, CH2Cl2);
Vmax (thin film, cmꢀ1): 3086, 3059, 3029, 1492, 1449 (Ar); 1H
e
NMR (500 MHz, CD3CN): d = 1.20 (s, 3H, CH3), 2.69 (dd,
J6,6 = 9.5 Hz, J6,5 = 4.5 Hz, 1H, 6-H), 3.14 (d, J4,2 = 4.5 Hz, 1H, 4-H),
0
3.19 (d, J2,4 = 4.5 Hz, 1H, 2-H), 3.50 (s, 3H, OCH3), 3.52 (dd,
J6 ,6 = 9.5 Hz, J6 ,5 = 7.5 Hz, 1H, 60-H), 3.91 (d, Jgem = 14.5 Hz, 1H,
NCH2), 3.97–4.02 (m, 2H, 5-H and NCH2), 4.15 (s, 1H, OH), 4.84
(s, 1H, 1-H), 7.04–7.43 (m, 20H, ArH) ppm; 13C NMR (125 MHz,
CD3CN): d = 16.9 (CH3), 53.7 (NCH2), 56.5 (OCH3), 67.0 (C-6), 70.4
(C-4), 72.5 (C-2), 73.4 (C-5), 77.9 (C-3), 87.4 (CPh3), 100.6 (C-1),
127.4–145.1 (Ph) ppm; m/z (ESI+ve): 522 ([M+H]+, 100%); HRMS
m/z (ESI+ve): found 522.2622 ([M+H]+); C34H36NO4 requires
522.2639.
0
0
acetate) afforded 11 as a colorless oil (177 mg, 82% after 2
steps). ½a 2D0
ꢂ
¼ ꢀ29:8 (c 0.40, methanol); Vmax (thin film, cmꢀ1):
e
3060, 3026, 1599, 1492, 1448 (Ar); 1H NMR (400 MHz, CD3CN):
0
d = 2.83 (dd, J6,6 = 9.2 Hz, J6,5 = 5.2 Hz, 1H, 6-H), 3.22 (d,
4.13. Methyl N-benzyl-3-O-benzyl-2,4-dideoxy-2,4-imino-3-
J2,4 = 4.6 Hz, 1H, 2-H), 3.26 (d, J4,2 = 4.6 Hz, 1H, 4-H), 3.44 (dd,
methyl-6-O-trityl-b-D-talopyranoside 25
J6 ,6 = 9.6 Hz, J6 ,5 = 8.0 Hz, 1H, 60-H), 3.46 (s, 3H, OCH3), 3.79
(bs, 1H, OH), 3.93–4.02 (m, 4H, 5-H, 3-H and NCH2), 4.79 (s,
1H, 1-H), 7.07–7.42 (m, 20H, ArH) ppm; 13C NMR (100 MHz, CD3-
CN): d = 56.4 (OCH3), 61.0 (NCH2), 66.6 (C-6), 68.1 (C-4), 70.5 (C-
2), 75.3 (C-5), 76.9 (C-3), 87.4 (CPh3), 101.6 (C-1), 127.3–145.1
(Ph) ppm; m/z (ESI+ve): 508 ([M+H]+, 100%); HRMS m/z (ESI+ve):
found 508.2474 ([M+H]+); C33H34NO4 requires 508.2482.
0
0
Sodium hydride (60% in mineral oil, 10 mg, 0.41 mmol) was
added to a stirred solution of 24 (107 mg, 0.21 mmol) in anhydrous
N,N-dimethylformamide (3 mL) at 0 °C under an argon atmo-
sphere. Benzyl bromide (0.05 mL, 0.41 mmol) was added dropwise,
and the resulting suspension stirred at rt. After 15 h, TLC analysis
(3:1 cyclohexane/ethyl acetate) showed no remaining starting