Ni-Catalyzed Enantioselective Arylboration of 1,3-Cyclohexadiene

Abstract

The development of straightforward and efficient methodologies for synthesizing compounds featuring chiral six-membered ring scaffolds represents a crucial pursuit within the realm of synthetic chemistry. Herein, we report a Ni-catalyzed regio-, enantio-, and diastereoselective arylboration of 1,3-cyclohexadienes employing readily available bis(pinacolato)diboron (B₂pin₂) and aryl iodides, providing convenient access to synthetically valuable chiral boronated 1,4-cis-cyclohexenes with high levels of regio-, enantio-, and diastereoselectivity. Notably, the mild reaction conditions ensure broad functional group compatibility. This has been demonstrated by the broad substrate scope and late-stage functionalizations of bioactive compounds or drug molecules within the reaction system. Moreover, the functionally diverse chiral boronated 1,4-cis-cyclohexene derivatives demonstrate high reactivity in a range of downstream transformations, allowing for the efficient preparation of various enantio-enriched, multisubstituted six-membered ring compounds, thereby underscoring the importance of preserving both the boron moiety and the double bond. Preliminary mechanistic investigations, supported by density functional theory (DFT) calculations, provide insights into the origins of the observed regio- and enantioselectivity.