LETTER
Novel Oxidation Reaction of Tertiary Amines with Osmium Tetroxide
2345
(19) (a) Sheehan, J. C.; Tulis, R. W. J. Org. Chem. 1974, 39,
2264. (b) Bettoni, G.; Franchini, C.; Morlacchi, F.; Tangari,
N.; Tortorella, V. J. Org. Chem. 1976, 41, 2780.
Ketolactam 3
1H NMR (300 MHz, CDCl3): d = 1.31–1.58 (m, 2 H), 1.66–
1.82 (m, 2 H), 2.63–2.73 (m, 1 H), 2.78–2.96 (m, 2 H), 3.71–
4.03 (m, 4 H), 3.87 (s, 3 H), 4.20–4.29 (m, 1 H), 5.42 (s, 1
H), 6.67 (d, J = 8.1 Hz, 1 H), 6.86 (d, J = 8.4 Hz, 1 H), 7.74
(br s, 1 H). IR (film): 1736, 1694 cm–1. HRMS–FAB: m/z
calcd for C19H20NO6 [M + H]+: 358.1291; found: 358.1300.
Ketolactam 4a
(c) Yoshifuji, S.; Tanaka, K.; Nitta, Y. Chem. Pharm. Bull.
1985, 33, 1749. (d) Yoshifuji, S.; Arakawa, Y.; Nitta, Y.
Chem. Pharm. Bull. 1985, 33, 5042. (e) Yoshifuji, S.;
Tanaka, K.; Kawai, T.; Nitta, Y. Chem. Pharm. Bull. 1985,
33, 5515. (f) Yoshifuji, S.; Tanaka, K.; Kawai, T.; Nitta, Y.
Chem. Pharm. Bull. 1986, 34, 3873. (g) Kaname, M.;
Yoshifuji, S.; Sashida, H. Tetrahedron Lett. 2008, 49, 2786.
(20) Compound 1f: Horikiri, H.; Kawamura, K. Heterocycles
2004, 63, 865.
1H NMR (300 MHz, CDCl3): d = 0.28–0.40 (m, 2 H), 0.49–
0.69 (m, 2 H), 1.03–1.18 (m, 1 H), 1.35–1.61 (m, 2 H), 1.66–
1.86 (m, 2 H), 2.67–2.76 (m, 1 H), 2.78 (dd, J = 4.2, 17.7 Hz,
1 H), 2.93 (dd, J = 6.9, 14.1 Hz, 1 H), 3.04 (dd, J = 1.2, 17.7
Hz, 1 H), 3.75–4.10 (m, 5 H), 3.86 (s, 3 H), 4.21–4.29 (m, 1
H), 5.40 (s, 1 H), 6.65 (d, J = 8.1 Hz, 1 H), 6.84 (d, J = 8.1
Hz, 1 H). IR (film): 2923, 1733, 1670 cm–1. HRMS–FAB:
m/z calcd for C23H26NO6 [M + H]+: 412.1760; found:
412.1776.
(21) Oxidation of Amine with OsO4
Stoichiometric Reaction Conditions: Conditions I
To the solution of amine in pyridine was added OsO4 (3 mol
equiv) and stirred at r.t. for the time indicated in Tables 1
and 2. The aqueous solution of Na2SO3 was added to the
reaction mixture and stirred vigorously at r.t. for several
hours. The resulting mixture was evaporated under reduced
pressure and extracted with CHCl3. The organic layer was
washed with brine and dried over Na2SO4. After removing
the solvent under reduced pressure, the residue was purified
by silica gel column chromatography and/or preparative
TLC.
Hydroxylactam 5a
1H NMR (300 MHz, CDCl3): d = 0.21–0.36 (m, 2 H), 0.45–
0.65 (m, 2 H), 0.99–1.13 (m, 1 H), 1.17–1.35 (m, 1 H), 1.51–
1.77 (m, 3 H), 2.60–2.71 (m, 2 H), 2.76 (dd, J = 7.1, 14.0 Hz,
1 H), 2.89 (br d, J = 17.4 Hz, 1 H), 3.71–4.00 (m, 6 H), 3.87
(s, 3 H), 4.17–4.25 (m, 1 H), 5.17 (s, 1 H), 6.59 (d, J = 8.1
Hz, 1 H), 6.79 (d, J = 8.1 Hz, 1 H). One proton of the OH
group was not observed. IR (film): 3294, 2928, 1623, 1503,
1439, 1276, 1194, 1055 cm–1. HRMS–FAB: m/z calcd for
C23H28NO6 [M + H]+: 414.1917; found: 414.1896.
Lactam 6a
Catalytic Reaction Conditions: Conditions II
Amine was added to the solution of K3Fe(CN)6 (9 mol equiv),
K2CO3 (9 mol equiv), and OsO4 (0.1 mol equiv) in t-BuOH
and distilled H2O (1:1) and stirred at r.t. for the time
indicated in Tables 1 and 2. To the reaction mixture was
added the aqueous solution of Na2SO3 and stirred at r.t. for
several hours. The resulting mixture was poured into
distillated H2O and extracted with CHCl3. The organic layer
was dried over Na2SO4 and concentrated under reduced
pressure. The residue was purified by silica gel column
chromatography and/or preparative TLC.
1H NMR (300 MHz, CDCl3): d = 0.21–0.34 (m, 2 H), 0.45–
0.63 (m, 2 H), 0.98–1.12 (m, 1 H), 1.18–1.35 (m, 1 H), 1.52–
1.77 (m, 3 H), 2.35 (dt, J = 12.7, 3.7 Hz, 1 H), 2.61 (d,
J = 17.1 Hz, 1 H), 2.60–2.77 (m, 2 H), 2.72 (d, J = 17.4 Hz,
1 H), 2.93 (dd, J = 1.2, 17.4 Hz, 1 H), 3.73–3.81 (m, 1 H),
3.84–4.02 (m, 4 H), 3.87 (s, 3 H), 4.20 (dt, J = 5.2, 6.8 Hz, 1
H), 4.49 (s, 1 H), 6.60 (d, J = 8.4 Hz, 1 H), 6.77 (d, J = 8.1
Hz, 1 H). IR (film): 2923, 1635, 1504, 1440 cm–1. HRMS–
FAB: m/z calcd for C23H28NO5 [M + H]+: 398.1967; found:
398.1962.
(22) Amide 2a
1H NMR (300 MHz, CDCl3): d = 0.67–1.25 (m, 5 H), 1.44–
1.86 (m, 6 H), 1.93–2.02 (m, 0.7 H), 2.07–2.15 (m, 0.3 H),
2.54–2.63 (m, 0.3 H), 2.62 (d, J = 18.3 Hz, 0.7 H), 2.76 (d,
J = 18.0 Hz, 0.3 H), 2.90 (dd, J = 5.9, 18.3 Hz, 0.7 H), 3.00
(dd, J = 5.4, 18.0 Hz, 0.3 H), 3.05–3.18 (m, 0.7 H), 3.76–
3.93 (m, 2 H), 3.89 (s, 3 H), 3.96–4.09 (m, 1.7 H), 4.14–4.24
(m, 1 H), 4.38–4.47 (m, 0.3 H), 4.49 (s, 1 H), 4.65 (br s, 0.3
H), 5.10–5.16 (m, 0.7 H), 6.64 (br d, J = 8.4 Hz, 1 H), 6.78
(d, J = 8.1 Hz, 1 H). IR (film): 3467, 2947, 1632, 1502,
1437, 1261, 1168, 1017 cm–1. HRMS–FAB: m/z calcd for
C23H28NO5 [M + H]+: 398.1962; found: 398.1976.
Iminoketone 7
1H NMR (400 MHz, CDCl3): d = 1.28–1.41 (m, 1 H), 1.44–
1.54 (m, 1 H), 1.68–1.78 (m, 2 H), 2.45 (ddd, J = 3.2, 4.3,
12.3 Hz, 1 H), 2.91 (ddd, J = 0.8, 5.4, 17.9 Hz, 1 H), 2.96
(ddd, J = 0.7, 2.0, 17.8 Hz, 1 H), 3.77–3.82 (m, 1 H), 3.86 (s,
3 H), 3.91 (dt, J = 7.3, 6.5 Hz, 1 H), 4.00 (q, J = 6.6 Hz, 1 H),
4.24 (ddd, J = 5.4, 6.8, 7.1 Hz, 1 H), 4.54 (ddd, J = 1.8, 3.3,
6.7 Hz, 1 H), 5.32 (s, 1 H), 6.66 (d, J = 8.2 Hz, 1 H), 6.84 (d,
J = 8.2 Hz, 1 H), 7.70 (d, J = 1.5 Hz, 1 H). IR (film): 2928,
1710, 1606, 1503, 1440, 1279, 1187, 1061 cm–1. HRMS–
FAB: m/z calcd for C19H20NO5 [M + H]+: 342.1341; found:
342.1335.
Synlett 2009, No. 14, 2341–2345 © Thieme Stuttgart · New York