(79g) Chemical Reaction Engineering Principles of Continuous Flow Photoredox Catalysis

Authors: 
Chemical
Reaction Engineering Principles of Continuous Flow Photoredox Catalysis

 

Eric
G. Moschetta,* Kaid Harper,* Steven M. Richter, Steve J.
Wittenberger

 

AbbVie,
Inc. Process R&D, 1401 Sheridan Road North Chicago, IL 60064

 

*co-corresponding
authors: eric.moschetta@abbvie.com, kaid.harper@abbvie.com

 

            Scaling
up complex organic syntheses via flow chemistry is becoming common in the
pharmaceutical industry. Careful reaction engineering of continuous flow
chemistries allows for increased throughputs of desired chemical products and
clever solutions to common problems observed in large scale batch reactors,
such as improved heat transfer in highly exothermic reactions. One area of
recent interest in organic synthesis is photoredox catalysis, reactions that
involve species being excited to high energy states by visible light to undergo
single electron transfer events that lead to the desired product(s). These
reactions frequently use ruthenium and iridium polypyridyl complexes as the
catalysts because they have long-lived excited states and high redox
potentials, allowing access to many reaction pathways.[1] However, these
precious metal catalysts would incur a large expense if such reactions are to
be used at scale. As an alternative, various organic photocatalysts, such as
Eosin Y and acridinium-based species, also possess high redox potentials and
can facilitate other single electron transfer events that their transition metal
counterparts cannot.[2] The main
disadvantage of these organic photocatalysts is their shorter excited state
lifetimes. Organic photocatalysts have excited state lifetimes on the order of
nanoseconds while transition metal photocatalysts often have observed excited
state lifetimes on the order of microseconds. While synthetic organic chemists
have made, and continue to make, significant advances in the synthetic utility
of transition metal and organic photocatalysts alike, the universal challenge
in applying photoredox catalysis in the pharmaceutical industry is scaling up
such reactions for kilogram-level production.

Photoredox
catalysis, and photochemistry in general, is not a part of the traditional
chemical reaction engineering paradigm. For example, chemical engineers have
many tools and solutions available for reactions where heat and mass transfer
limitations, mixing limitations, multi-phase chemistry, and chemoselectivity
all present problems in scale up of continuous flow reactors. Over the last
decade, the enormous increase in the interest and study of photoredox catalysis
has led to a broad and diverse array of chemical transformations. As such, a
platform for scalable photoredox chemistry should be as versatile as possible
to accommodate the many types of photocatalysts, reactants, and chemistries
that are already developed. Additionally, such reactors should include high
intensity light sources to supply the reactor with high photon fluxes to allow
operation under the intrinsic kinetics of the reaction. Most importantly, the
ideal reactor should operate in continuous flow to maximize production. This
study implements a new continuous flow reactor for several photoredox chemistries
and compares the observed rates of reactions to those obtained from other known
reactor configurations, in both batch and flow. The discussion emphasizes how
and why this reactor configuration outperforms the other reactors using
fundamental principles of chemical reaction engineering and physical chemistry.
The discussion concludes with a demonstration of the scale-up potential of the
continuous flow reactor and how this new reactor configuration may be used
across the entire discipline of photoredox catalysis in organic synthesis.

 

References

[1]        C. K.
Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113,
5322-5363.

[2]        N. A.
Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075-10166.

 

This
abstract presentation was sponsored by AbbVie. AbbVie contributed to the
design, research, and interpretation of data, writing, reviewing, and approving
the publication. All authors are AbbVie employees.