E
S. Ajay et al.
Letter
Synlett
(13) Petakamsetty, R.; Jain, V. K.; Majhi, P. K.; Ramapanicker, R. Org.
Biomol. Chem. 2015, 13, 8512.
(14) Li, W.; Niu, Y.; Xiong, D.-C.; Cao, X.; Ye, X.-S. J. Med. Chem. 2015,
58, 7972.
(15) Sletten, E. M.; Liotta, L. J. J. Org. Chem. 2006, 71, 1335.
(16) Seetharamsingh, B.; Rajamohanan, P. R.; Reddy, D. S. Org. Lett.
2015, 17, 1652.
(17) Gupta, P.; Vankar, Y. D. Eur. J. Org. Chem. 2009, 1925.
(18) Ajay, S.; Saidhareddy, P.; Shaw, A. K. Synthesis 2016, 48, 1191.
(19) Synthesis of (3S,4R)-Piperidine-3,4-diol (6)
reaction mixture was filtered and washed with MeOH. The fil-
trate was evaporated to dryness to give a solid compound which
was washed with Et2O to provide compound 8 as a white solid
(54 mg, 92%). Rf = 0.62 (MeOH–CH2Cl2, 1:9); mp 142–144 °C;
25
[α]D +1.4 (c 0.21, MeOH). 1H NMR (400 MHz, CD3OD): δ =
4.11–4.12 (m, 1 H), 3.80–3.84 (m, 1 H), 3.18–3.36 (m, 4 H),
1.98–2.02 (m, 1 H), 1.78–1.94 (m, 3 H). 13C NMR (100 MHz,
CD3OD): δ = 74.3, 69.7, 46.9, 46.0, 30.0, 20.5. IR (KBr): 3393,
1386, 1219, 1061, 771 cm–1. ESI-HRMS: m/z [M + H]+ calcd for
C6H14NO2+: 132.1019; found: 132.1014.
To a solution of compound 15 (112 mg, 0.45 mmol) in 6 N meth-
anolic HCl (3 mL) was added a catalytic amount of 10% Pd/C (10
mg). The reaction mixture was stirred under the H2 (balloon)
atmosphere at room temperature for 6 h. After completion of
the reaction, Pd/C was removed by filtering through a short pad
of Celite, and the filtrate was evaporated under vacuum to give a
residue. It was washed again with Et2O to get the pure com-
pound 6 (48 mg, 91 %) as a white solid. Rf = 0.61 (MeOH–CH2Cl2,
(24) Calder, E. D. D.; Zaed, A. M.; Sutherland, A. J. Org. Chem. 2013,
78, 7223.
(25) Ghosal, P.; Kumar, V.; Shaw, A. K. Tetrahedron 2010, 66, 7504.
(26) Llaveria, J.; Díaz, Y.; Matheu, M. I.; Castillón, S. Eur. J. Org. Chem.
2011, 1514.
(27) Synthesis of (3S,4R,Z)-1,2,3,4,7,8-Hexahydroazocine-3,4-diol
(9)
Compound 21 (105 mg, 0.37 mmol) was dissolved in 6 N meth-
anolic HCl (3 mL), and the reaction mixture was allowed to stir
at room temperature for 2 h. After completion of the reaction,
the organic solvent was evaporated under reduced pressure,
and the resulting residue was washed with Et2O to afford the
azocine 9 (48 mg, 95%) as a white solid. Rf = 0.61 (MeOH–
27
1:9); mp 129–131 °C; [α]D +10.0 (c 0.11, H2O). 1H NMR (400
MHz, D2O): δ = 4.13 (brm, 1 H), 4.00–4.02 (m, 1 H), 3.34–3.39
(m, 2 H), 3.21–3.24 (m, 1 H), 3.10–3.16 (m, 1 H), 1.94–2.12 (m, 2
H). 13C NMR (100 MHz, D2O): δ = 66.3, 65.2, 46.5, 41.4, 25.1. IR
(KBr): 3400, 3020, 2926, 1403, 1216 cm–1. ESI-HRMS: m/z [M +
H]+ calcd for C5H12NO2+: 118.0863; found: 118.0875.
(20) Smith, A. B. III.; Cho, Y. S.; Zawacki, L. E.; Hirschmann, R.; Pettit,
G. R. Org. Lett. 2001, 3, 4063.
(21) Takahata, H.; Banba, Y.; Ouchi, H.; Nemoto, H. Org. Lett. 2003, 5,
2527.
(22) Synthesis of (3S,4R)-2,3,4,7-Tetrahydro-1H-azepine-3,4-diol
(7)
26
CH2Cl2, 1:9); mp 143–145 °C; [α]D –8.6 (c 0.32, MeOH). 1H
NMR (400 MHz, CD3OD): δ = 5.84–5.88 (m, 1 H), 5.66–5.72 (m, 1
H), 4.57 (d, 1 H, J = 4.09 Hz), 4.16 (d, 1 H, J = 4.33 Hz), 3.27–3.41
(m, 3 H), 3.16 (td, 1 H, J1 = 13.16 Hz, J2 = 2.75 Hz), 2.59–2.70 (m,
1 H), 2.37–2.40 (m, 1 H). 13C NMR (100 MHz, CD3OD): δ = 138.4,
124.8, 71.9, 71.8, 48.2, 47.9, 23.6. IR (KBr): 3392, 3020, 1650,
1385, 1216, 1068, 771 cm–1. ESI-HRMS: m/z [M + H]+ calcd for
C7H14NO2+: 144.1019; found: 144.1018.
Compound 17 (89 mg, 0.33 mmol) was dissolved in 6 N metha-
nolic HCl (3 mL) and stirred at room temperature for 2 h. After
completion of the reaction, the solvent was removed under
reduced pressure to obtain a solid residue, which was washed
with Et2O to get the pure compound 7 (43 mg, 96%) as a white
(28) Synthesis of (3S,4R)-Azocane-3,4-diol (10)
To a solution of compound 21 (130 mg, 0.46 mmol) in 6 N meth-
anolic HCl was added a catalytic amount of 10% Pd/C (20 mg),
and the resulting reaction mixture was stirred under hydrogen
atmosphere at room temperature for 3 h. After completion of
the reaction, the catalyst was filtered, and the filtrate was con-
centrated under vacuum to obtain a residue, which was washed
with Et2O to attain pure azocane 10 (60 mg, 90%) as a white
solid. Rf = 0.64 (MeOH–CH2Cl2, 1:9); mp 160–163 °C; [α]D26 +5.4
(c 0.81, MeOH). 1H NMR (400 MHz, CD3OD): δ = 4.09–4.11 (m, 1
H), 3.91–3.94 (m, 1 H), 3.38–3.48 (m, 1 H), 3.22–3.30 (m, 2 H),
3.09–3.13 (m, 1 H), 2.00–2.08 (m, 1 H), 1.80–1.90 (m, 3 H),
1.69–1.72 (m, 2 H). 13C NMR (100 MHz, CD3OD): δ = 74.2, 69.2,
48.2, 47.7, 31.0, 24.5, 21.8. IR (KBr): 3392, 2924, 1650, 1385,
1216, 1068, 770 cm–1. ESI-HRMS: m/z [M + H]+ calcd for
C7H16NO2+: 146.1176, found: 146.1175.
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solid. Rf = 0.59 (MeOH–CH2Cl2, 1:9); mp 135–139 °C; [α]D –37.0
(c 0.21, MeOH). 1H NMR (400 MHz, CD3OD): δ = 5.98–6.01 (m, 1
H), 5.77–5.84 (m, 1 H), 4.58–4.59 (m, 1 H), 4.10–4.12 (m, 1 H),
3.71–3.84 (m, 2 H), 3.50–3.55 (m, 1 H), 3.41–3.44 (m, 1 H). 13C
NMR (100 MHz, CD3OD): δ = 140.2, 121.7, 73.2, 69.1, 51.7, 46.1.
IR (KBr): 3683, 3399, 2927, 1476, 1216 cm–1. ESI-HRMS: m/z [M
+ H]+ calcd for C6H12NO2+: 130.0863; found: 130.0861.
(23) Synthesis of (3S,4R)-Azepane-3,4-diol (8)
Catalytic amount of Pd (10% on carbon, 15 mg) was added to a
solution of 17 (121 mg, 0.45 mmol) in 6 N methanolic HCl (4
mL). The reaction mixture was degassed and left for stirring
under a positive pressure of H2 (balloon) for 3 h at room tem-
perature. After completion of the reaction (TLC control), the
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E