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Review
. 2014 Apr 18;18(4):474-480.
doi: 10.1021/op400349g. Epub 2014 Mar 11.

Late-Stage Fluorination: From Fundamentals to Application

Michael G Campbell  1 , Tobias Ritter  1
Affiliations
Review

Late-Stage Fluorination: From Fundamentals to Application

Michael G Campbell et al. Org Process Res Dev. .

Abstract

In this brief account, we review work from our lab with a focus on late-stage introduction of fluorine and fluorinated functional groups into small molecules. We attempt to highlight practical developments, which we believe may have potential for industrial applications, and critically reflect on developments that may not yet meet the bar for practical use.

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Figures

Figure 1
Figure 1
(a) Deoxyfluorination of phenols with PhenoFluor. (b) Late-stage deoxyfluorination of complex aliphatic alcohols with PhenoFluor. (c) Intermediate 2 observed upon treatment of phenols with PhenoFluor, with hydrogen-bonding interaction observed via X-ray crystallography and 1H NMR spectroscopy.
Figure 2
Figure 2
Pd-mediated electrophilic fluorination of arenes, and well-defined C–F reductive elimination from Pd(IV) fluoride 5 featuring a hemilabile pyridyl-sulfonamide ligand to promote reductive elimination via a five-coordinate transition state.
Figure 3
Figure 3
(a) Palladium-catalyzed fluorination of aryl trifluoroborates. (b) Proposed mechanism for palladium-catalyzed fluorination, involving a single-electron-transfer (SET) pathway and isolated Pd(III) intermediate C.
Figure 4
Figure 4
Silver-catalyzed late-stage fluorination of complex small molecules.
Figure 5
Figure 5
(a) Silver-mediated fluorination of arylboronic acids and aryl silanes. (b) Proposed bimetallic mechanism for Ag-mediated C–F bond formation ([M] = SnBu3, B(OH)2, Si(OEt)3).
Figure 6
Figure 6
C–18F bond formation for 18F-PET tracer synthesis via two-step 18F– capture/transfer sequence.
Figure 7
Figure 7
One-step Ni-mediated C–18F bond formation using aqueous 18F– and oxidant 10.
Figure 8
Figure 8
Silver-mediated trifluoromethoxylation of aryl stannanes.
See this image and copyright information in PMC

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