the catalyst. One potential application of this methodology would
be to use the labeled dioxiranes as a means of investigating oxygen
transfer to some less-than-optimal substrates, with the extent of
label transfer providing an efficient marker of avs. bface approach.
In terms of labeling efficiency in the preparation of non-racemic
18O-epoxides, the synthetic methodology described in this work is
a very efficient one, as it ensures full isotopic labeling from the
oxidizing agent to the alkene (89.4 0.4% experimental vs. 90.0
0.3% theoretical).
(6 mL, 1 : 2 v/v). A pH = 6 buffer§ solution (1.3 mL) and
tetrabutylammonium hydrogen sulfate (5 mg, 0.015 mmol) were
added slowly with stirring and the mixture was cooled to 0 ◦C.
The flask was equipped with two syringe pumps; one filled with
a solution of KSO218O18OH (0.60 mmol theoretical amount,
reaction mixture from the previous step) in the pH = 6 buffer
(2.3 mL) and the other one with a solution of K2CO3 (0.11 g,
0.83 mmol) in water (2.3 mL). The two solutions were added
dropwise over a 2h period (syringe pump). The solution was stirred
at 0 ◦C for 18 h. The reaction mixture was extracted with hexanes
(4 × 6 mL), the combined organic fractions were washed with
saturated NaCl(aq) (10 mL) and then dried over Na2SO4. 18O-(R,R)-
trans-stilbene oxide was obtained, together with starting material,
after filtration and removal of the hexanes in vacuo. No isolation of
18O-(R,R)-trans-stilbene oxide was attempted: chiral HPLC of the
raw material (Chiralpak AD, see general procedure) indicated a
94% ee; 1H-NMR and MS-CI analysis of the raw material provided
the yield of the epoxidation (7 lmol, 2% yield) and the relative
abundance of the 16O : 18O isotopologues.
Experimental
General procedure for the epoxidation of alkenes
The alkene (2.22 mmol) and the catalyst 3 (10–30 mol%) were
dissolved in 1 : 2 v/v acetonitrile–dimethoxymethane (44 mL).
A solution of pH = 6 buffer§ (8 mL) and tetrabutylammonium
hydrogen sulfate (35 mg, 0.10 mmol) were then slowly added with
stirring, and the mixture was cooled to the desired temperature.
The flask was equipped with two syringe pumps: one was filled
with K2CO3 (5.33–15.10 mmol) in water (14 mL), and the other
Mass spectrometric determination of the relative abundance of
16O : 18O isotopologues from the epoxidation of trans-stilbene with
KSO218O18OH
R
with the required amount of Oxoneꢀ (3.55–7.10 mmol) in the pH =
6 buffer (14 mL). The two solutions were added dropwise over a
2 h period by syringe pump. The reaction mixture was stirred at
0 ◦C for the corresponding time. The crude reaction mixture was
quenched by the addition of water (40 mL) and pentane (10 mL),
then extracted with an organic solvent (5a hexane, 4 × 40 mL;
5b–c: 4 × 40 mL DCM). The combined organic extracts were
washed with brine (50 mL), dried over sodium sulfate, filtered,
and concentrated under reduced pressure. The crude material was
purified by flash chromatography on silica gel. Enantioselectivity
was determined by chiralchromatographyand the configuration of
epoxides 5 was established by comparison with either the reported
elution order or optical rotation if reported data was available.
For 5a, HPLC, Chiralpak AD, (R,R)-5a elutes first.15 For 5b, GC,
gamma dex, (S,S)-5b elutes first.5 For 5c, GC, gamma dex, (S,S)-5c
elutes first.16
A time-of-flight mass (TOF) mass spectrometer (Waters GCT)
coupled to a gas chromatograph (Agilent 6890 N) was used to
determine the relative abundance of 16O : 18O labeled 18O-(R,R)-
trans-stilbene oxide. The GC conditions were as follows: a DB-
XLB (Agilent) column, 30 m × 0.18 mm × 0.18 lm; GC analysis
time 30 min (18O-(R,R)-trans-stilbene oxide retention time 21 min);
inlet temperature 250 ◦C (1 ng of sample injected, split ratio
100◦: 1); oven temperature program, 40 ◦C held for 3 min, then a
(10 C min−1) ramp to 340 ◦C; GC carrier gas He; constant flow
0.6 mL min−1. The mass spectrometer was operated in positive
ion mode, using CH4 as the chemical ionization reagent gas at a
source pressure of 2 × 10−4 mbar. The ion source temperature was
165 ◦C with an electron energy of 70 eV and an emission current of
100 lA. Spectra were acquired at 25 000 Hz using an integration
time of 0.45 s and a delay of 0.05 s (2 integrated spectra s−1).
The 16O : 18O isotopologues were not separated using the GC
method applied in this work. Rather the GC sample introduction
provided an accurate means of background ion subtraction,
facilitating subsequent 16O : 18O determination by comparison with
a simulated mixed isotopologue mass spectrum. The simulation is
generated by convolution of the respective 16O : 18O isotopologue
m/z channel intensities, as determined experimentally using a
pure, unlabeled standard (Sigma Aldrich). The relative intensities
in each m/z channel are assumed to be identical for the two
isotopologues. The 16O : 18O proportion, the only free parameter
in the simulation, is obtained from a least squares fit of the
observed intensities as a function of the intensities in the calculated
spectrum.
Asymmetric epoxidation of trans-stilbene with 18O-labeled tracers
Preparation of KSO218O18OH
18O2-Hydrogen peroxide (Cambridge Isotope Laboratories, 0.93 g,
2.5% H2O2 content in water, 23 mg, 0.60 mmol, 90 0.3% 18O-
content) was carefully concentrated in vacuo (70 ◦C, 90 mbar) by
eliminating 0.84 g of distillate through a 5 cm Vigreux column. The
residue was cooled to −5 ◦C and fuming sulfuric acid (20% as free
SO3, 0.49 g, 1.22 mmol of SO3) was added carefully (10 min). The
mixture was allowed to reach 0 ◦C and was stirred for a further 2 h.
K2CO3 (0.65 g) in 1 mL water was added dropwise (10 min) to the
solution, which was stirred for a further 15 min. The suspension,
which contained KSO218O18OH (0.60 mmol theoretical amount),
was stored at 4 ◦C and used in the next step without any further
work-up.
After the epoxidation the catalyst 3 was analyzed for 16O :
18O content using a time-of-flight (TOF) mass spectrometer
equipped with an electrospray ionization (ESI) source (Waters
LCT premier) applying the following conditions: capillary voltage
Epoxidation of trans-stilbene with KSO218O18OH.13
trans-Stilbene (65 mg, 0.35 mmol) and hydrate 3 (34 mg,
0.10 mmol) were dissolved in acetonitrile–dimethoxymethane
§ The pH = 6 buffer consisted of 6.8 g of KH2PO4 and 5 mL of 1M
KOH L−1
.
This journal is
The Royal Society of Chemistry 2008
Org. Biomol. Chem., 2008, 6, 2276–2281 | 2279
©