Copper- and Palladium-Cocatalyzed Chemo-, Regio-, Stereo-, and Atroposelective Arylboration of 1,3-Enynes

Abstract

Catalytic enantioselective borylation reactions of unsaturated bonds as powerful tools for the synthesis of diverse chiral organoboron compounds have gained much attention and have wide applications in various fields. However, the atroposelective arylboration reaction with carbon−carbon triple bonds of 1,3-enynes to obtain axially chiral 1,3-dienylboronates remains an elusive and significant challenge. Hence, we develop a cooperative copper-and palladium-catalyzed arylboration reaction to assemble plentiful function enriched axially chiral 1,3-dienylboronates in a single step from easily available 1,3-enynes, B 2 pin 2 , and aryl bromides with high levels of chemo-, regio-, stereo-, and atroposelectivity. The mild reaction conditions lead to good functional group tolerance, which is proven by the broad substrate scope and late-stage functionalizations of bioactive compounds or drug molecules. Moreover, the reaction can be easily scaled up, and a series of further transformations can be achieved. It is worth emphasizing that several olefin catalysts and ligands with axial chirality can also be synthesized through the corresponding elaborations of such products, which further explains the powerful transformative ability and application potential of such axially chiral 1,3-dienylboronates. The mechanism experiment and density functional theory (DFT) calculations revealed the cooperative process of copper and palladium catalysis, indicating that the chemoselectivity and regioselectivity of boration are determined by the enyne insertion step on copper, and the atroposelectivity is controlled by the further reductive elimination on the palladium center. Meanwhile, the calculation also demonstrated that the distinct interactions between the P�O and C�O groups with the Pd or Bpin center in the key transition state lead to the formation of products with varying configurations while employing identical configuration ligands.