Topics in Current Chemistry (2018) 376:46
1 3
to be faced [11–14]. The breakthrough of continuous flow processing is mainly
due to the features of flow devices over batch processing, and in particular to: (a)
large surface-to-volume ratios, (b) efficient mass and heat transfer, (c) precise mixing, (d) intrinsic safety, (e) reduced use of solvent and improved stoichiometry, (f)
scalability, and last but not least, (g) reduced footprint and capital investment. All
this makes flow chemistry appealing for industrial production. In addition, flow
chemistry might be considered a green technology, as the use of flow processing
also allows complying with sustainability and environmental protection [15]. Heterogenous catalysis plays a pivotal role in chemical synthesis at both academic and
industrial levels, as witnessed by the still vigorous research activity in this field, and
also justified by the intrinsic environmental compliance of catalytic methodologies
[16–20]. Both flow chemistry and heterogenous catalysis hold incredible potential
from a sustainability point of view and from a green perspective. In fact, if heterogenous catalysts are required by the chemical industry for their efficiency, on the
other hand, heterogenous flow catalysis would allow performing greener and more
efficient chemistry at an industrial level. As proof of this fruitful “green” combination between flow and heterogenous catalysis, a seminal work recently reported
by Kobayashi can be mentioned on the multistep continuous-flow synthesis of the
industrial-relevant molecule rolipram [21]. In this chapter, we wish to describe some
recent advancements in the field of heterogeneous flow catalysis, with reference to
the use of supported catalysts (mainly organic and organometallic) employed in flow
devices. The field has grown quickly in the last decade, as witnessed by the reviews
on this topic published in recent years [22–28]. Thus, while an exhaustive report
would be difficult in this context, selected examples and tactics on the use of supported catalysts in continuous flow synthesis, including some recent examples not
reviewed elsewhere, will be reported herein. After a short description of the main
features of supported catalysts used in flow devices, the use of organo- and organometallic-catalysts in chemo- and stereoselective synthesis will be described.
2 Heterogenous Catalysis in Flow
As reported in the Introduction section, the combination of flow chemistry and heterogeneous catalysis holds the potential to perform cleaner, safer, and scalable flow
reactions in a sustainable way. In fact, heterogeneous catalysis in flow brings about
several advantages such as safety, high efficiency, less waste production, no accumulation of hazardous chemicals, continuous product formation, and easy recovery
and reuse of the catalyst. Three general approaches can be utilized to perform heterogeneous flow catalysis using (micro)fluidic devices (Fig. 1); namely, (1) by using
packed-bed flow reactors; (2) by using monolithic flow reactors; and (3) by using
wall-coated flow reactors. In packed-bed flow reactors, the catalyst is, covalently or
non-covalently, grafted on an insoluble solid material [29]. Using either organic or
inorganic polymeric materials, various types of catalysts (organic, organometallic,
metallic, enzymatic) can be supported. High catalyst loading and the relative ease
of characterization and quantification of the catalyst makes this kind of heterogenous catalyst suitable for filling the columns used as flow reactors [30]. However,
30
Reprinted from the journal
1 3
to be faced [11–14]. The breakthrough of continuous flow processing is mainly
due to the features of flow devices over batch processing, and in particular to: (a)
large surface-to-volume ratios, (b) efficient mass and heat transfer, (c) precise mixing, (d) intrinsic safety, (e) reduced use of solvent and improved stoichiometry, (f)
scalability, and last but not least, (g) reduced footprint and capital investment. All
this makes flow chemistry appealing for industrial production. In addition, flow
chemistry might be considered a green technology, as the use of flow processing
also allows complying with sustainability and environmental protection [15]. Heterogenous catalysis plays a pivotal role in chemical synthesis at both academic and
industrial levels, as witnessed by the still vigorous research activity in this field, and
also justified by the intrinsic environmental compliance of catalytic methodologies
[16–20]. Both flow chemistry and heterogenous catalysis hold incredible potential
from a sustainability point of view and from a green perspective. In fact, if heterogenous catalysts are required by the chemical industry for their efficiency, on the
other hand, heterogenous flow catalysis would allow performing greener and more
efficient chemistry at an industrial level. As proof of this fruitful “green” combination between flow and heterogenous catalysis, a seminal work recently reported
by Kobayashi can be mentioned on the multistep continuous-flow synthesis of the
industrial-relevant molecule rolipram [21]. In this chapter, we wish to describe some
recent advancements in the field of heterogeneous flow catalysis, with reference to
the use of supported catalysts (mainly organic and organometallic) employed in flow
devices. The field has grown quickly in the last decade, as witnessed by the reviews
on this topic published in recent years [22–28]. Thus, while an exhaustive report
would be difficult in this context, selected examples and tactics on the use of supported catalysts in continuous flow synthesis, including some recent examples not
reviewed elsewhere, will be reported herein. After a short description of the main
features of supported catalysts used in flow devices, the use of organo- and organometallic-catalysts in chemo- and stereoselective synthesis will be described.
2 Heterogenous Catalysis in Flow
As reported in the Introduction section, the combination of flow chemistry and heterogeneous catalysis holds the potential to perform cleaner, safer, and scalable flow
reactions in a sustainable way. In fact, heterogeneous catalysis in flow brings about
several advantages such as safety, high efficiency, less waste production, no accumulation of hazardous chemicals, continuous product formation, and easy recovery
and reuse of the catalyst. Three general approaches can be utilized to perform heterogeneous flow catalysis using (micro)fluidic devices (Fig. 1); namely, (1) by using
packed-bed flow reactors; (2) by using monolithic flow reactors; and (3) by using
wall-coated flow reactors. In packed-bed flow reactors, the catalyst is, covalently or
non-covalently, grafted on an insoluble solid material [29]. Using either organic or
inorganic polymeric materials, various types of catalysts (organic, organometallic,
metallic, enzymatic) can be supported. High catalyst loading and the relative ease
of characterization and quantification of the catalyst makes this kind of heterogenous catalyst suitable for filling the columns used as flow reactors [30]. However,
30
Reprinted from the journal