Asymmetric Organocatalysis on a Technical Scale
151
needed. In addition, the catalyst has to be preactivated and the duration
of this process is more than 6 h. Another drawback are the long reaction
times of 1–5 days, which limits technical applicability significantly.
Researchers at Bayer AG addressed the critical issues with respect to
technical application and developed successful solutions towards a technically applicable Julia–Colonna-type epoxidation (Bosch 2004; Geller
et al. 2003, 2004a,b). Catalyst preparation has been improved by
a straightforward synthesis of the poly-Leu-catalyst. Key features are
cheap reagents and a shorter reaction time (Bosch 2004; Geller et al.
2003, 2004a). In particular the reaction time for the new polymerization process is only 3 h when the the process is carried out at 80 °C in
toluene, compared with 5 days under classic reaction conditions (THF,
room temperature). The catalyst prepared by the ‘Bayer route’ is also
much more active, and does not require preactivation (Bosch 2004;
Geller et al. 2003, 2004a). In parallel, the triphasic reaction system has
been improved: A strongly enhanced reaction rate occurs in the presence of an achiral PTC as an additive (Bosch 2004; Geller et al. 2003,
2004a,b). Carrying out the epoxidation of chalcone 27 with 10 mol%
of TBAB as an achiral PTC catalyst on a 100-g scale in the presence
of a catalytic amount of 10%–20%(w/w) of the poly-l-Leu organocatalyst, equivalent to 0.25–0.7 mol%, led to a complete conversion within
12 h (Bosch 2004). The desired product 29 was obtained in 75% yield
and with an enantiomeric excess of 97.6% ee (Scheme 8). Notably, on
a smaller scale, a conversion of more than 99% was reached within only
7 min, whereas in the absence of TBAB the asymmetric poly-l-leucine
catalyzed epoxidation gave only 2% conversion after 1.5 h. Furthermore, it was found that efficient stirring was essential for a complete
conversion. Notably, the catalyst can be re-used without loss of reactivity and enantioselectivity (Bosch 2004).
Researchers at Degussa AG focused on an alternative solution with
respect to a technical application of the Julia–Colonna epoxidation (Tsogoeva et al. 2002). Successful process development is based on the design of a continuously operated process in a chemzyme membrane reactor (CMR reactor). Therein, the epoxide and unconverted chalcone pass
through the membrane whereas the polymer-enlarged organocatalyst is
retained in the reactor by means of a nanofiltration membrane. The setup
for this type of continuous epoxidation reaction is shown in Scheme 9.
151
needed. In addition, the catalyst has to be preactivated and the duration
of this process is more than 6 h. Another drawback are the long reaction
times of 1–5 days, which limits technical applicability significantly.
Researchers at Bayer AG addressed the critical issues with respect to
technical application and developed successful solutions towards a technically applicable Julia–Colonna-type epoxidation (Bosch 2004; Geller
et al. 2003, 2004a,b). Catalyst preparation has been improved by
a straightforward synthesis of the poly-Leu-catalyst. Key features are
cheap reagents and a shorter reaction time (Bosch 2004; Geller et al.
2003, 2004a). In particular the reaction time for the new polymerization process is only 3 h when the the process is carried out at 80 °C in
toluene, compared with 5 days under classic reaction conditions (THF,
room temperature). The catalyst prepared by the ‘Bayer route’ is also
much more active, and does not require preactivation (Bosch 2004;
Geller et al. 2003, 2004a). In parallel, the triphasic reaction system has
been improved: A strongly enhanced reaction rate occurs in the presence of an achiral PTC as an additive (Bosch 2004; Geller et al. 2003,
2004a,b). Carrying out the epoxidation of chalcone 27 with 10 mol%
of TBAB as an achiral PTC catalyst on a 100-g scale in the presence
of a catalytic amount of 10%–20%(w/w) of the poly-l-Leu organocatalyst, equivalent to 0.25–0.7 mol%, led to a complete conversion within
12 h (Bosch 2004). The desired product 29 was obtained in 75% yield
and with an enantiomeric excess of 97.6% ee (Scheme 8). Notably, on
a smaller scale, a conversion of more than 99% was reached within only
7 min, whereas in the absence of TBAB the asymmetric poly-l-leucine
catalyzed epoxidation gave only 2% conversion after 1.5 h. Furthermore, it was found that efficient stirring was essential for a complete
conversion. Notably, the catalyst can be re-used without loss of reactivity and enantioselectivity (Bosch 2004).
Researchers at Degussa AG focused on an alternative solution with
respect to a technical application of the Julia–Colonna epoxidation (Tsogoeva et al. 2002). Successful process development is based on the design of a continuously operated process in a chemzyme membrane reactor (CMR reactor). Therein, the epoxide and unconverted chalcone pass
through the membrane whereas the polymer-enlarged organocatalyst is
retained in the reactor by means of a nanofiltration membrane. The setup
for this type of continuous epoxidation reaction is shown in Scheme 9.