Cross-Coupling Chemistry in Continuous Flow - New Trends in Cross-Coupling: Theory and Applications - page 619

I

O OMe

membrane

catalyst

+

O

OMe

Nanof iltration

Figure 13.7 Continuous nanofiltration for catalyst retention in palladium-catalyzed
Mizoroki-Heck coupling.

aqueous phase. A micro packed-bed reactor was utilized to ensure high
mixing eciency between the two phases. Upon exiting the microreactor, the
two layers were separated in a micro extraction device. In this fashion, the
catalyst was recycled a total of five times without a decrease in activity.
The examples given above involve biphasic reaction conditions in which
the product and catalyst are separated based on a different solubility for one
phase. The main drawback of this method is that the chemistry has to be
compatible with the chosen biphasic reaction conditions. Recently, organic
solvent nanofiltration has emerged as a new separation technique making
use of a polymeric membranes to separate organic solvents from high mo-
lecular weight species, which is based on molecular weight cutoff, i.e. a
membrane property. This technique allows the use of a single solvent phase
and separates the catalyst from the solvent and reaction products. This
technique was used in a continuous flow Heck-type coupling (Figure 13.7). 26
The experiment could be performed for 1000 h and allowed 1081 mol of
product to be produced utilizing only 0.61 mmol of catalyst [turnover
number (TON) = 1772]. Nevertheless, a significant amount of leaching was
still observed (317 mg Pd per kg product). In comparison, there was 20-fold
lower product contamination than was observed in a batch experiment
without nanofiltration.

13.3.4 Homogeneous Catalysts in a Stationary Liquid Phase
A homogeneous catalyst can also be retained by dissolving it in a stationary
liquid phase. 27 A porous support, e.g. mesoporous silica, is impregnated
with a catalyst solution. Consequently, the catalyst is immobilized and can
be retained after reaction, while the advantageous properties of high catalyst
activity of homogeneous systems can be kept. The catalyst coating can be
easily regenerated after deactivation by simply replacing the liquid film. As
such, these catalyst systems are easier to produce and therefore more cost-
ecient than methods that rely on a chemical bonding immobilization
technique.
A supported aqueous phase catalyst was used for the Mizoroki-Heck re-
action in flow. 28 A fused silica-coated capillary was impregnated with an
aqueous solution of Pd(OAc) 2 and tris(2,4-dimethyl-5-sulfophenyl)phosphine
(TXPTS). The reagents were introduced into the capillary microreactor and a