Intermediates and Reactivity in Iron-Catalyzed Cross-Couplings of Alkynyl Grignards with Alkyl Halides

Iron-catalyzed
cross-coupling reactions using alkynyl nucleophiles
represent an attractive approach for the incorporation of alkynyl
moieties into organic molecules. In the present study, a multitechnique
approach combining inorganic spectroscopic methods, inorganic synthesis,
and reaction studies is applied to iron-SciOPP catalyzed alkynyl-alkyl
cross-couplings, providing the first detailed insight into the effects
of variation from sp2- to sp-hybridized nucleophiles on iron speciation and reactivity. Reaction
studies demonstrate that reaction of FeBr2(SciOPP) with
1 equiv (triisopropyl­silyl)­ethynyl­magnesium bromide (TIPS-CC-MgBr)
leads to a distribution of mono-, bis-, and tris-alkynylated iron­(II)-SciOPP
species due to rapid alkynyl ligand redistribution. While solvents
such as THF promote these complex redistribution pathways, nonpolar
solvents such as toluene enable increased stabilization of these iron
species and further enabled assessment of their reactivity with electrophile.
While the tris-alkynylated iron­(II)-SciOPP species was found to be
unreactive with the cycloheptyl bromide electrophile over the average
turnover time of catalysis, the in situ formed neutral mono- and bis-alkynylated
iron­(II)-SciOPP complexes are consumed upon reaction with the electrophile
with concomitant generation of cross-coupled product at catalytically
relevant rates, indicating the ability of one or both of these species
to react selectively with the electrophile. The nature of the reaction
solvent and Grignard reagent addition rate were found to have broader
implications in overall reaction selectivity, reaction rate, and accessibility
of off-cycle iron­(I)-SciOPP species. Additionally, the effects of
steric substitution of the alkynyl Grignard reagent on catalytic performance
were investigated. Fundamental insight into iron speciation and reactivity
with alkynyl nucleophiles reported herein provides an essential foundation
for the continued development of this important class of reactions.