Iridium-Catalyzed Borylation of Primary Benzylic C–H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity

Primary
benzylic boronate esters are useful intermediates in organic
synthesis, but these reagents cannot be prepared by hydroboration.
The benzylic C–H boryl­ation of methyl­arenes would
be a method to form these products, but such reactions without neat
methyl­arene or a directing group are unknown. We report an approach
to divert the boryl­ation of methyl­arenes from aromatic
positions to benzylic positions with a silylborane as reagent and
a new iridium catalyst containing an electron-deficient phenanthroline
as ligand. This system forms benzylic boronate esters selectively
over the corresponding aryl boronate esters. An Ir diboryl monosilyl
complex ligated by the phenanthroline was isolated and determined
to be the resting state of the catalyst. Mechanistic studies show
that this complex is kinetically competent to be an intermediate in
the catalytic process. Kinetic studies of benzylic and aryl C–H
boryl­ation catalyzed by various Ir complexes show that the rate
of aryl C–H boryl­ation decreases with decreasing electron
density at the metal center of the Ir catalyst, but that the rate
of benzylic C–H boryl­ation is less sensitive to the degree
of electron density at the metal center of the Ir catalyst. Kinetic
and computational studies suggest that the two boryl­ation reactions
respond differently to the degree of electron density at the metal
center because they occur with different turnover-limiting steps.
The turnover-limiting step in the boryl­ation of aryl C–H
bonds is known to be C–H oxidative addition, but the turnover-limiting
step of the boryl­ation of benzylic C–H bonds appears
to be an isomerization prior to C–B reductive elimination.