1072
B. Balagam et al. / Tetrahedron Letters 49 (2008) 1071–1075
Table 1
formation of NMO from NMM via a clean, economical cata-
lyst/oxidant combination (CO2/H2O2).
Cis-dihydroxylation of trans-5-decene employing CO2 and H2O2 as
terminal oxidanta
Our studies on amine oxidation reactions have shown
that the tertiary amines are efficiently oxidized to their
corresponding N-oxides by H2O2 with CO2 catalysis (under
1 atm pressure) at room temperature. The proposed mech-
anism is shown as Eqs. 1–5, with the net reaction as the
CO2-catalyzed peroxide oxidation of the substrate.
b
Entry
Amineb
(equiv)
CO2/pressure
(atm)
H2O2
TEAAb
(equiv)
% Yieldc
(equiv)
1d
2d
3.0
3.0
3.0
3.0
2.0
4.0
5.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
23
40
36
95
55
90
20
85
75
60
35
94
93
93
85
2.0
3d
1
1
1
1
1
1
1
1
1
1
1
1
1
4d
2.0
2.0
2.0
2.0
1.5
1.3
1.1
1.0
1.5
1.3
1.1
1.0
À
5d
The HCO4 ion is formed via the reversible addition of
6d
OOHÀ to CO2 under the mildly basic conditions set by the
amine substrate. Furthermore, the relatively high rate con-
stant for oxidationÀof NMM to NMO by the catalytic
intermediate HCO4 (Eq. 3, 0.016 MÀ1 sÀ1) compared to
slow oxidation by H2O2 alone reduces the oxidation time
to <1 h under our conditions.
7d
8e
9e
10e
11e
12f
13f
14f
15f
a
2.0
2.0
2.0
2.0
-
+
2
2
-
-
2
4
Solvent: acetone and water 3:1, T = 25 °C.
Equivalents relative to alkene.
Isolated yield.
b
c
-
-
3
4
3
3
+
-
d
Experimental conditions: (Method A) trans-5-decene (1 mmol), NMM
(2 mmol), H2O2 (2–5 mmol), OsO4 (0.014 mmol) in water (1 mL) and
acetone (3 mL).
(Method B) trans-5-decene (1 mmol), NMM (1–1.5 mmol), H2O2
(3 mmol), OsO4 (0.014 mmol) in water (1 mL) and acetone (3 mL).
(Method C) trans-5-decene (1 mmol), NMM (1–1.5 mmol), H2O2
(3 mmol), OsO4 (0.014 mmol), TEAA (2 mmol) in water (1 mL) and ace-
tone (3 mL).
3
2
2
2
2
2
3
3
e
In the Upjohn procedure,11 NMO is employed as the
terminal oxidant in the dihydroxylation of olefins. The
re-oxidation of Os(VI) to Os(VIII) by NMO leads to
formation of NMM. In our present one-pot, two-step
method, instead of NMO we use NMM directly in stoichio-
metric amounts. In the initial step the NMM is oxidized
to NMO by the CO2/H2O2 catalytic system. The resulting
NMO then re-oxidizes Os(VI) to Os(VIII) in the usual
dihydroxylation cycle. This process is economical given
the replacement of isolated and purified NMO by NMM,
CO2 gas, and H2O2.
f
the yields of diol are reduced, and at higher peroxide (Table
1, entries 6 and 7) significantly lowers the yields due to over-
oxidation by excess peroxide. When the amount of NMM
was decreased from 2 equiv (based on substrate) to 1.5, 1.3,
1.1, or 1 equiv, lower yields of diol 2 were observed (Table
1, entries 8–11).
Oxidation of trans-5-decene (1) was studied under differ-
ent reaction conditions employing H2O2 as the terminal
oxidant (Scheme 1, Table 1). The control reaction using
NMO in stoichiometric amounts gave a 95% yield of diol
The slow step in the osmium cycle is the most likely
hydrolysis of the intermediate osmate ester.10,18,19 The
hydrolysis step is facilitated by addition of salts such as tetra-
ethylammonium acetate (TEAA).10,15,22,20 We therefore
studied the influence of this salt on the NMM-catalyzed
dihydroxylation of trans-5-decene based on CO2 and
H2O2 as the terminal oxidant. Addition of TEAA to the
reaction mixture did indeed result in a major improvement
of the yield of diol 2 (Table 1, entries 12–15) with yields in
excess of 90% using as little as 10% excess of NMM (entry
14).
Several other olefins were oxidized to their correspond-
ing cis-diols in good to excellent isolated yields by our pres-
ent method (Table 2). Control reactions using NMO in
place of NMM, CO2 gas, and H2O2 gave comparable yields
of cis-diols (Table 2, entries 1, 7, and 13).
4
2. Direct re-oxidation of osmium(VI) by H2O2 without
using NMM results in a nonselective reaction, with 23%
yield of diol 2 (Table 1, entry 1). In the presence of
NMM the reaction with unactivated H2O2 gave 40% yield
of diol 2 (Table 1, entry 2). In the absence of NMM, the
reaction using CO2 and H2O2 gave a similar 36% yield of
2 (Table 1, entry 3). The re-oxidation of Os(VI) using
CO2 and H2O2 (3 equiv based on substrate) in the presence
of NMM gave the highest yield of diol (Table 1, entry 4,
yield 95%). At higher and lower concentrations of H2O2
We have also investigated the enantioselectivity of vari-
ous oxidations (1 atm CO2 and 3 equiv H2O2) using the
Sharpless chiral ligand hydroquinidine 1,4-phthalazinediyl-
diether ((DHQD)2PHAL), 0.03 equiv, with 0.014 equiv
OsO4 in 3:1 acetone/water (Table 3). With slow addition
of olefin, ee values of 80–90% were obtained. Enantiomeric
excesses and absolute configurations of diols were
Scheme 1. Osmium-catalyzed cis-dihydroxylation of trans-5-decene by
in situ formation of NMO employing CO2 and H2O2.