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. 2018 Jun 27;140(25):8037-8047.
doi: 10.1021/jacs.8b05243. Epub 2018 Jun 19.

Redox-Neutral Photocatalytic Cyclopropanation via Radical/Polar Crossover

James P Phelan  1 , Simon B Lang  1 , Jordan S Compton  1 , Christopher B Kelly  1 , Ryan Dykstra  2 , Osvaldo Gutierrez  2 , Gary A Molander  1
Affiliations

Redox-Neutral Photocatalytic Cyclopropanation via Radical/Polar Crossover

James P Phelan et al. J Am Chem Soc. .

Abstract

A benchtop stable, bifunctional reagent for the redox-neutral cyclopropanation of olefins has been developed. Triethylammonium bis(catecholato)iodomethylsilicate can be readily prepared on multigram scale. Using this reagent in combination with an organic photocatalyst and visible light, cyclopropanation of an array of olefins, including trifluoromethyl- and pinacolatoboryl-substituted alkenes, can be accomplished in a matter of hours. The reaction is highly tolerant of traditionally reactive functional groups (carboxylic acids, basic heterocycles, alkyl halides, etc.) and permits the chemoselective cyclopropanation of polyolefinated compounds. Mechanistic interrogation revealed that the reaction proceeds via a rapid anionic 3- exo- tet ring closure, a pathway consistent with experimental and computational data.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Cyclopropane-containing pharmacons and trifluoromethyl cyclopropanes.
Figure 2.
Figure 2.
Synthesis of trifluoromethyl-substituted cyclopropanes.
Figure 3.
Figure 3.
Convergent strategies to TFCps from commercial materials.
Figure 4.
Figure 4.
Plausible Mechanism for Cyclopropanation.
Scheme 1.
Scheme 1.
Synthesis and Optimization of the Bifunctional Silicate Reagent
Scheme 2.
Scheme 2.
Zero Precaution Reaction
Scheme 3.
Scheme 3.
Stereoconvergent Cyclopropanation
Scheme 4.
Scheme 4.
Insensitivity of Cyclopropanation to Electronicsa
Scheme 5.
Scheme 5.
Influence of Halogen Substituent on the Barriers for the SH2-type 3-exo-tet Cyclization Pathway.a
Scheme 6.
Scheme 6.
Energetics of Anionic 3-exo-tet Cyclization Versus E1cb-type Fluoride Eliminationa
Scheme 7.
Scheme 7.
Energetics of Anionic Versus Radical 3-exo-tet Cyclization in a Non-α-Trifluoromethyl Systema
Scheme 8.
Scheme 8.
Bracketing Experiment.
Scheme 9.
Scheme 9.
Energetics of Ring Opening Versus Anionic Cyclizationa
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