Photocatalytic Reductive Olefin Hydrodifluoroalkylation Enabled by Tertiary Amine Reductants Compatible with Complex Systems

Noncanonical amino acids (NCAAs) are imperative to many
facets
of chemistry and biology. Herein, we report a method for the reductive
hydrodifluoroalkylation of olefins that utilizes triethylamine base
as the terminal reductant. The alkene acceptors include a range of
electronically diverse alkenes, chief among them, dehydroalanine in
variously protected forms, which provides access to synthetically
relevant NCAA scaffolds under mild and general reaction conditions.
We have demonstrated that a chiral auxiliary may be incorporated to
provide diastereocontrol for pro-stereogenic substrates. Mechanistically
motivated experiments provide some insight into the reaction mechanism,
which supports a terminal step involving proton transfer for electron-poor
olefins, while H atom transfer assisted by a thiol cocatalyst may
complete the catalytic cycle for electron-rich olefins. The protocol
is found to be compatible with additions to complex molecules, including
the natural product thiostrepton.