Photoinduced Hydrodifluoromethylation and Hydromethylation of Alkenes Enabled by Ligand-to-Iron Charge Transfer Mediated Decarboxylation

Directly
utilizing abundant and inexpensive sources of aliphatic
carboxylic acids is highly attractive for the synthesis of CF2H- and CH3-containing compounds. Herein, we report
a versatile photoinduced iron-catalyzed platform for hydrodifluoromethylation
and hydromethylation of alkenes without the need of additional stoichiometric
oxidants. These two transformations are accomplished by a visible-light-induced
ligand-to-iron charge transfer open-shell activation system by using
industrial chemical difluoroacetic and acetic acids as precursors
and postulated to operate via a difluoromethyl and methyl radical-mediated
decarboxylation mechanism. Experimental results show that the strategy
is also applicable to the difunctionalization of unactivated alkenes.
Meanwhile, this strategy provides a viable route for the synthesis
of pharmaceutically active molecules containing deuterated methyl
units. The protocol exhibits several features, including mild reaction
conditions, divergent radical precursors, operational simplicity and
scalability, good chemo- and regioselectivity, scalability supported
by continuous flow technology, and the ability to provide high-value
building blocks for applications in one step.