2948
G. Carrea et al. / Tetrahedron: Asymmetry 15 (2004) 2945–2949
complexity of the steady-state velocity equation (Eq. 1)
for this system (Scheme 2), the substrate response curves
can be visualized in a qualitative way.18,19 Considering
the data of Figure 4, at zero HOOꢀ concentration the
catalyst will be present only as PLL and PLL:chalcone.
By increasing HOOꢀ starting from very low concentra-
tions, PLL:HOOꢀ:chalcone will form faster via the
PLL:chalcone intermediate than via PLL:HOOꢀ. As
the HOOꢀ concentration is increased, the faster se-
quence gradually takes over and the slope of the initial
rates increases sharply (sigmoid). By increasing further
the HOOꢀ concentration, the PLL ! PLL:HOOꢀ !
PLL:HOOꢀ:chalcone route becomes predominant and
the sloping off of the curve is observed as the rate ap-
proaches Vmax. Considering the data of Figure 3, at
the beginning the rate curves will rise in the usual way
as the ternary complex is formed via the kinetically fa-
voured intermediate PLL:HOOꢀ. However, when the
concentration of chalcone becomes high enough to over-
come the kinetic factors, a greater proportion of the
reaction flux will proceed via the PLL:chalcone interme-
diate. As a consequence, the initial rate will pass through
a maximum and then will decrease. We believe that the
information obtained on the optimal conditions to be
used and on the kinetics and mechanism of PLL-cata-
lysed asymmetric epoxidation reaction will be helpful
in broadening the applications of this interesting cata-
lyst in organic synthesis.
4.4. Chiral HPLC
The ee values of the (2R,3S)-epoxychalcone formed by
PLL catalysis were determined by chiral HPLC using
a ChiralPack (Daicel) column, eluted with a 9/1 hex-
ane/ethanol mixture, at a flow rate of 1mL/min and with
reading at 254nm. The retention times for chalcone,
(2S,3R)-epoxychalcone, and (2S,3R)-epoxychalcone
were 12, 14, and 21min, respectively.
Acknowledgements
We thank AstraZeneca for a research studentship
(A.D.M.).
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4.Experimental
4.1. Materials
The PEG bound polyleucine (PLL) was bought from
Lancaster (Eastgate, England). DBU, BEMP and the
phosphazene base P2-t-Bu were obtained from Fluka.
All other reagents and compounds were of analytical
grade.
8. Baars, S.; Drauz, K.; Krimmer, H.-P.; Roberts, S. M.;
Sander, J.; Skidmore, J.; Zanardi, G. Org. Process Res.
Development 2003, 7, 509–513.
9. Flood, R. W.; Geller, T. P.; Petty, S. A.; Roberts, S. M.;
Skidmore, J.; Volk, M. Org. Lett. 2001, 3, 683–686;
Tsogoeva, S. B.; Wo¨ltinger, J.; Jost, C.; Reichert, D.;
4.2. Preparation of the urea hydrogen peroxide adduct
Kuhnle, A.; Krimmer, H.-P.; Drauz, K. Synlett 2002,
¨
707–710.
To avoid water addition to the reaction medium, the
urea hydrogen peroxide adduct was utilised. The adduct
(1g) was added to THF (10mL) and stirred overnight.
The suspension was centrifuged and the precipitate
(urea and remaining adduct) discarded. The supernatant
was titrated and stored in the freezer. Hydrogen perox-
ide concentration was around 1M and remained con-
stant over time.
10. The polymer contains different lengths of polyamino acid
chains, averaging 15 see: Bentley, P. A.; Kroutil, W.;
Littlechild, J. A.; Roberts, S. M. Chirality 1997, 9,
198–202.
11. Berkessel, A.; Gasch, N.; Glaubitz, K.; Koch, C. Org.
Lett. 2001, 3, 3839–3842; Bentley, P. A.; Flood, R. W.;
Roberts, S. M.; Skidmore, J.; Smith, C. B.; Smith, J. A.
Chem. Commun. 2001, 1616–1617.
12. Bui, T. T. T.; Caroff, E.; Drake, A. F.; Kelly, D. R.;
Roberts, S. M. Tetrahedron Lett. 2004, 45, 3885–3888.
13. The catalyst solution in THF was slightly turbid and was
clarified by centrifugation. The pellet, which represented
1.7% of the total catalyst, was unable to catalyse the
epoxidation of chalcone.
14. The bases tested were 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU), 2-tert-butylimino-2-diethylamino-1,3-dimethyl-
perhydro-1,3,2-diazaphosphorine (BEMP) and the phos-
phazene base P2-t-Bu. The latter two are 2 · 103 and 109
more basic than DBU, whose basicity is comparable to
that of H2O2 (pKa in water 11.75 for H2O2 and 11.9 for
DBU). The use of the very strong phosphazene base P2-t-
4.3. Kinetics
The PLL catalysed oxidation of chalcone by hydrogen
peroxide was spectrophotometrically monitored by
measuring the disappearance of chalcone at 420nm in
a cuvette with a 0.5-cm path length at 25ꢁC. For calcu-
lations,
a
molar extinction coefficient of 36.7
Lmolꢀ1 cmꢀ1 was utilised. The reported rates were
corrected for the spontaneous chalcone oxidation by
H2O2 and therefore represent only the PLL catalysed
reaction.