Flow microreactor synthesis in organo-fluorine chemistry

Abstract

Organo-fluorine compounds are the substances of considerable interest in various industrial fields due to their unique physical and chemical properties. Despite increased demand in wide fields of science, synthesis of fluoro-organic compounds is still often faced with problems such as the difficulties in handling of fluorinating reagents and in controlling of chemical reactions. Recently, flow microreactor synthesis has emerged as a new methodology for producing chemical substances with high efficiency. This review outlines the successful examples of synthesis and reactions of fluorine-containing molecules by the use of flow microreactor systems to overcome long-standing problems in fluorine chemistry.

Keywords: defluorination; flow microreactor; fluorination; fluorine; organo-fluorine; perfluoroalkylation.

Scheme 1

Direct fluorination using microreactor systems.

Scheme 2

Use of DAST in continuous-flow reactors.

Scheme 3

Flow microreactor synthesis of fluorinated epoxides.

Scheme 4

Highly controlled isomerization of gem-difluoroalkenes.

Scheme 5

Flow system for catalytic aromatic fluorination.

Scheme 6

Continuous-flow reactor for electrophilic aromatic fluorination.

Scheme 7

Examples of [¹⁸F]-radiolabeled molecular imaging probes.

Scheme 8

Flow microreactor synthesis of dipeptides.

Scheme 9

Flow synthesis involving S_NAr reactions.

Scheme 10

Flow synthesis of fluoroquinolone antibiotics.

Scheme 11

Highly controlled formation of PFPMgBr.

Scheme 12

Selective flow synthesis of photochromic diarylethenes.

Scheme 13

Flow microreactor system for perfluoroalkylation by generation of perfluoroalkyllithiums in the presence of electrophiles.

Scheme 14

Integrated flow microreactor system for perfluoroalkylation by generation of perfluoroalkyllithiums in the absence of electrophiles.