Iron–bisphosphines
have attracted broad interest as highly
effective and versatile catalytic systems for two- and three-component
cross-coupling strategies. While recent mechanistic studies have defined
the role of organoiron(II)–bisphosphine species as key intermediates
for selective cross-coupled product formation in these systems, mechanistic
features that are essential for catalytic performance remain undefined.
Specifically, key questions include the following: what is the generality
of iron(II) intermediates for radical initiation in cross-couplings?
What factors control reactivity toward homocoupled biaryl side-products
in these systems? Finally, what are the solvent effects in these reactions
that enable high catalytic performance? Herein, we address these key
questions by examining the mechanism of enantioselective coupling
between α-chloro- and α-bromoalkanoates and aryl Grignard
reagents catalyzed by chiral bisphosphine–iron complexes. By
employing freeze-trapped57Fe Mössbauer and EPR
studies combined with inorganic synthesis, X-ray crystallography,
reactivity studies, and quantum mechanical calculations, we define
the key in situ iron speciation as well as their catalytic roles.
In contrast to iron–SciOPP aryl–alkyl couplings, where
monophenylated species were found to be the predominant reactive intermediate
or prior proposals of reduced iron species to initiate catalysis,
the enantioselective system utilizes an iron(II)-(R,R)-BenzP* bisphenylated intermediate to initiate
the catalytic cycle. A profound consequence of this radical initiation
process is that halogen abstraction and subsequent reductive elimination
result in considerable amounts of biphenyl side products, limiting
the efficiency of this method. Overall, this study offers key insights
into the broader role of iron(II)–bisphosphine species for
radical initiation, factors contributing to biphenyl side product
generation, and protocol effects (solvent, Grignard reagent addition
rate) that are critical to minimizing biphenyl generation to obtain
more selective cross-coupling methods.