This article discusses advancements in radical cross-coupling chemistry, focusing on the challenges of achieving enantiospecific reactions with free radicals. While traditional methods have limitations, the authors present a novel solution using non-chiral catalysts and accessible sulfonylhydrazides. This method allows for the coupling of enantioenriched alkyl fragments to (hetero)aryl halides under mild conditions, overcoming prior hurdles associated with stereochemical control. The study introduces a unique Ni-diazene transition state mechanism that facilitates CC bond formation by eliminating N2, showcasing a significant milestone in organic synthesis.
In contrast to widely employed polar cross-coupling chemistry, radical cross-coupling is advantageous when applied to coupling saturated systems due to the mild conditions employed.
Despite advantages, enantiospecific coupling reactions involving free radicals are unknown and are believed to be challenging due to their near-instantaneous racemization.
We show how readily accessible enantioenriched sulfonylhydrazides can be enlisted to enable enantiospecific, stereoretentive radical cross-coupling without the use of chiral ligands.
Calculations support the intermediacy of a unique Ni-bound diazene-containing transition state, with CC bond formation driven by loss of N2.
#homogeneous-catalysis #organic-chemistry #radical-cross-coupling #enantiospecific-synthesis #nickel-catalysis
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