Iron/NHC‐Catalyzed Regio‐ and Stereoselective 1,6‐Additions of Aliphatic Grignard Reagents to α,β,γ,δ‐Unsaturated Carbonyl Compounds: Asymmetric Variants with Chiral NHCs

Abstract Although conjugate addition to an α,β‐unsaturated carbonyl compound is a well‐established method in synthetic organic chemistry, controlling regioselectivity, olefin geometry, and positional isomerism in analogous 1,6‐addition chemistry, which provides a powerful approach for constructing molecular complexity, remains a key challenge. Herein, we report the iron‐catalyzed regio‐, stereo‐, and enantioselective 1,6‐additions of aliphatic Grignard reagents to α,β,γ,δ‐unsaturated carbonyl compounds. The incorporation of an N ‐heterocyclic carbene (NHC) ligand effectively suppresses undesired β‐hydride elimination, thereby enabling the highly cis ‐selective installation of the aliphatic group. Remarkably, the use of a rigid tetracyclic chiral NHC ligand afforded the corresponding adducts with enantioselectivities of up to 99%. The developed reaction shows broad substrate scope, accommodating various aliphatic Grignard reagents and unsaturated carbonyl compounds, thereby providing direct access to optically active 1,6‐adducts bearing cis ‐configured olefins. Mechanistic investigations, including deuterium‐labeling experiments, support the involvement of magnesium enolates and an iron–NHC catalytic cycle. The developed transformation provides a powerful strategy for the remote functionalization of extended conjugated carbonyl frameworks.