Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

Radical Trifluoroacetylation of Alkenes Triggered by a Visible-Light-Promoted C−O Bond Fragmentation of Trifluoroacetic Anhydride

Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules. Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of a,b-unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo- and regioselective functionalization of small-molecule drugs and common pharmacophores.

One-Pot Sequential Multistep Transformation of α,β-Unsaturated Trifluoromethyl Ketones: Facile Synthesis of Trifluoromethylated 2-Pyridones

A one-pot transformation of α,β-unsaturated trifluoromethyl ketones with 2-(phenylsulfinyl)acetamide to give trifluoromethylated 2-pyridones is realized. The reaction proceeds under mild conditions and involves multiple steps in an expeditious and controlled sequence to provide efficient access to a broad range of trifluoromethylated 2-pyridones in moderate to high yields. Moreover, further synthetic manipulations permit the routine synthesis of a diverse array of trifluoromethylated pyridines with good efficiency.

Highly enantioselective copper(i)-catalyzed conjugate addition of 1,3-diynes to α,β-unsaturated trifluoromethyl ketones

The conjugate diynylation of α,β-unsaturated trifluoromethyl ketones with terminal diynes is carried out. Pre-metalation of the terminal 1,3-diyne is not required. Diynes bearing a propargylic stereogenic center are obtained with good yields and ee's.