On the Radical Nature of Iron-Catalyzed Cross-Coupling Reactions

The radical nature of iron‐catalyzed cross‐coupling between Grignard reagents and alkyl halides has been studied by using a combination of competitive kinetic experiments and DFT calculations. In contrast to the corresponding coupling with aryl halides, which commences through a classical two‐electron oxidative addition/reductive elimination sequence, the presented data suggest that alkyl halides react through an atom‐transfer‐initiated radical pathway. Furthermore, a general iodine‐based quenching methodology was developed to enable the determination of highly accurate concentrations of Grignard reagents, a capability that facilitates and increases the information output of kinetic investigations based on these substrates. Iron cross: The iron‐catalyzed cross‐coupling reaction between alkyl halides and Grignard reagents has been investigated by competitive Hammett studies and DFT calculations. The results support the presence of radical intermediates in an FeI–FeIII cycle with an atom‐transfer (AT) mechanism as the rate‐limiting step (see figure; TM=transmetalation, RE=reductive elimination).