Cross-Coupling Chemistry in Continuous Flow - New Trends in Cross-Coupling: Theory and Applications - page 626

1) Tf 2 O, DIPEA, CH 2 Cl 2
2) 2M HCl (microextraction)
3) DMF (microdistillation)
4) Pd(OAc) 2 (3.4 mol %), dppp (5 mol %)
n -butyl vinyl ether, Et 3 N, 125 °C

O n -Bu

OH

t -Bu t -Bu

79 %

Figure 13.14 Microfluidic assembly for the synthesis of n-butyl vinyl ethers. 41
Copyright Wiley-VCH Verlag GmbH & Co. KGaA 2010.
Reproduced with permission.

13.4.3 Palladium-Catalyzed Carbonylative
Cross-Coupling in Flow
Despite the use of toxic carbon monoxide as a reagent, the palladium-
catalyzed carbonylation reaction (Heck carbonylation) has become the
method of choice for synthesizing carbonyl-containing compounds in a
regioselective fashion. The large gas-liquid interfacial area encountered in
microreactors allows for significant acceleration of this process. Such fast
reactions are particularly advantageous for labeling of organic compounds
with radioisotopes. Short reaction times are crucial to obtain high radio-
chemical purities, which are required for molecular imaging applications.
An example of a microreactor capable of performing fast carbonylations for
radiolabeling is shown in Figure 13.15. 42 Carbon-11 (t 2 = 20.4 min) was
utilized as the carbonyl source for the palladium-catalyzed aminocarbony-
lation reaction of aryl iodides. 43 11 CO was first preconcentrated and sub-
sequently brought in contact with the reagents in a microreactor. An annular
flow regime was used to maximize the interfacial area, which allowed the
reaction rate to be increased. A total of 15 min was required to finish the
entire process, i.e. from generation of 11 CO to the collection of the product.
Microreactors have also been used to optimize rapidly and reliably re-
action parameters such as reaction temperature, CO pressure and residence