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Review
. 2024 Feb 28;15(13):4618-4630.
doi: 10.1039/d3sc06808k. eCollection 2024 Mar 27.

Continuous flow synthesis enabling reaction discovery

Antonella Ilenia Alfano  1 , Jorge García-Lacuna  1 , Oliver M Griffiths  2 , Steven V Ley  2 , Marcus Baumann  1
Affiliations
Review

Continuous flow synthesis enabling reaction discovery

Antonella Ilenia Alfano et al. Chem Sci. .

Abstract

This article defines the role that continuous flow chemistry can have in new reaction discovery, thereby creating molecular assembly opportunities beyond our current capabilities. Most notably the focus is based upon photochemical, electrochemical and temperature sensitive processes where continuous flow methods and machine assisted processing can have significant impact on chemical reactivity patterns. These flow chemical platforms are ideally placed to exploit future innovation in data acquisition, feed-back and control through artificial intelligence (AI) and machine learning (ML) techniques.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Photocarboxylation reactions in flow mode.
Scheme 2
Scheme 2. Flow intensification activating light alkanes via photocatalysis.
Scheme 3
Scheme 3. Carbonylative hydroacylation of styrenes exploiting photochemical flow conditions.
Scheme 4
Scheme 4. Photochemical reaction cascade discovered in flow.
Scheme 5
Scheme 5. Skeletal rearrangements of isoxazoles discovered in flow mode.
Scheme 6
Scheme 6. Photochemical benzyne formation as a starting point for discovering a new route to triazines.
Scheme 7
Scheme 7. Ni-catalysed photochemical Negishi cross coupling reactions in flow mode.
Scheme 8
Scheme 8. Photochemical C(sp2)–C(sp3) cross-coupling reactions in flow.
Scheme 9
Scheme 9. Electrochemical flow synthesis of 1,4-benzoxathiins.
Scheme 10
Scheme 10. Electrochemical flow synthesis via Rh-catalysis.
Scheme 11
Scheme 11. Flow-based C–H phosphorylation and hydroxylation reactions exploiting electrochemistry.
Scheme 12
Scheme 12. Development of a flow-based C–H alkynylation reaction.
Scheme 13
Scheme 13. Synthesis of homoallyl alcohols in flow mode.
Scheme 14
Scheme 14. Discovery of new reactivities under thermal conditions.
Scheme 15
Scheme 15. Flow synthesis of benzothiazines from (E)-β-vinyl ketones.
Scheme 16
Scheme 16. Thermal rearrangement of peroxides in flow.
Scheme 17
Scheme 17. Generation and use of lithiated dibromomethyl species in flow.
Scheme 18
Scheme 18. Lithiation of m- and p-iodophenyl isothiocyanate with phenyllithium.
Scheme 19
Scheme 19. Flow protocols exploiting ortho-lithiated aryl benzyl ethers.
Scheme 20
Scheme 20. Regioselective flow synthesis of α-functionalised stilbenes via precise residence time control.
Scheme 21
Scheme 21. Exploration of new chemical space via lithiated azabicyclo[1.1.0]butanes.
Scheme 22
Scheme 22. Product divergency in flow-based lithiations of dihalogenated pyridine scaffolds.
Scheme 23
Scheme 23. Flow-based formation of unsaturated nitriles via in situ generated chloramine.
Scheme 24
Scheme 24. Deuterio difluoromethylation of aldehydes exploiting in situ generated difluorocarbene.
See this image and copyright information in PMC

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