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. 2017 Jul 12;139(27):9152-9155.
doi: 10.1021/jacs.7b05160. Epub 2017 Jun 29.

Catalytic 1,3-Difunctionalization via Oxidative C-C Bond Activation

Steven M Banik  1 , Katrina M Mennie  1 , Eric N Jacobsen  1
Affiliations

Catalytic 1,3-Difunctionalization via Oxidative C-C Bond Activation

Steven M Banik et al. J Am Chem Soc. .

Abstract

Electronegative substituents arrayed in 1,3-relationships along saturated carbon frameworks can exert strong influence over molecular conformation due to dipole minimization effects. Simple and general methods for incorporation of such functional group relationships could thus provide a valuable tool for modulating molecular shape. Here, we describe a general strategy for the 1,3-oxidation of cyclopropanes using aryl iodine(I-III) catalysis, with emphasis on 1,3-difluorination reactions. These reactions make use of practical, commercially available reagents and can engage a variety of substituted cyclopropane substrates. Analysis of crystal and solution structures of several of the products reveal the consistent effect of 1,3-difluorides in dictating molecular conformation. The generality of the 1,3-oxidation strategy is demonstrated through the catalytic oxidative ring-opening of cyclopropanes for the synthesis of 1,3-fluoroacetoxylated products, 1,3-diols, 1,3-amino alcohols, and 1,3-diamines.

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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
1,3-Difluorination of cyclopropanes. a. Conformational properties of 1,3-difluorides. b. Aryl iodide-catalyzed oxidation of alkenes and cyclopropanes. c. Catalyst optimization studies.
Figure 2
Figure 2
Evaluation of substrate scope for 1,3-difluorination. a. Substrate scope evaluation for aryl cyclopropanes. b. Substrate scope evaluation for aliphatic and vinyl cyclopropanes. Isolated yields are indicated below each product (2 and 4); experimental details are provided in the Supporting Information.
Figure 3
Figure 3
Stereospecificity in the generation of 1,3-difluorination products. a, 1,3-Difluorination of chiral highly substituted cyclopropanes. b. Evaluation of the stereospecificity of both C–F bond forming steps. c. Mechanistic proposals for the divergent stereochemical outcomes observed between substrates 5 and 6. Isolated yields are indicated for all products (6, 8); experimental details are provided in the Supporting Information.
Figure 4
Figure 4
X-ray crystal structures of 1,3-difluorides
Figure 5
Figure 5
1,3-Difluorination of 1,1-difluorocyclopropanes.
Figure 6
Figure 6
General 1,3-catalytic oxidative difunctionalization of cyclopropanes. a. Synthesis of fluoroacetoxylated products using acetic acid as a cosolvent. b. Synthesis of 1,3-diols using trifluoroacetic acid as a cosolvent followed by hydrolysis. c. Synthesis of 1,3-amino alcohols using trifluoroacetic acid and acetonitrile as cosolvents. d. Synthesis of 1,3-diamines using p-tolylmethanesulfonamide and BF3•OEt2. Isolated yields are indicated below each product (11, 12, 13, 14); for experimental details, see the Supporting Information.
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