An asymmetric 1,2-dicarbofunctionalization of unactivated
alkenes
with aryl iodides and aryl/alkenylboronic esters under nickel/bioxazoline
catalysis is disclosed. A wide array of aryl and alkenyl nucleophiles
are tolerated, furnishing the products in good yield and with high
enantioselectivity. In addition to terminal alkenes, 1,2-disubstituted
internal alkenes participate in the reaction, establishing two contiguous
stereocenters with high diastereoselectivity and moderate enantioselectivity.
A combination of experimental and computational techniques shed light
on the mechanism of the catalytic transformation, pointing to a closed-shell
pathway with an enantiodetermining migratory insertion step, where
stereoinduction arises from synergistic interactions between the sterically
bulky achiral sulfonamide directing group and the hemilabile bidentate
ligand.
We report a redox-neutral catalytic coupling of nitroalkanes and unactivated alkenes that proceeds by a directed carbopalladation mechanism. The reaction is uniquely enabled by the combination of PdI 2 as the precatalyst and HFIP solvent. Structurally complex nitroalkane products, including nitro-containing carbo-and heterocycles, are prepared under operationally convenient conditions without the need for toxic or corrosive reagents. Deuterium labeling experiments and isolation of a catalytically relevant intermediate shed light on the reaction mechanism. By taking advantage of different catalytic activation modes, we demonstrate orthogonal methods for site-selective functionalization of a polyfunctional nitroalkyl ketone. Density functional theory (DFT) calculations show that the carbopalladation transition state is stabilized by a Na•••I interaction and H•••I hydrogen bond with HFIP.
The catalytic enantioselective synthesis of αchiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group (TDG) strategy to facilitate site-selective palladium-catalyzed reductive Heck-type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ-position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L-tert-leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.
The catalytic enantioselective synthesis of α‐chiral alkenes and alkynes represents a powerful strategy for rapid generation of molecular complexity. Herein, we report a transient directing group (TDG) strategy to facilitate site‐selective palladium‐catalyzed reductive Heck‐type hydroalkenylation and hydroalkynylation of alkenylaldehyes using alkenyl and alkynyl bromides, respectively, allowing for construction of a stereocenter at the δ‐position with respect to the aldehyde. Computational studies reveal the dual beneficial roles of rigid TDGs, such as L‐tert‐leucine, in promoting TDG binding and inducing high levels of enantioselectivity in alkene insertion with a variety of migrating groups.
An asymmetric 1,2-dicarbofunctionalization of unactivated alkenes with aryl iodides and aryl/alkenylboronic esters under nickel/bioxazoline catalysis is disclosed. A wide array of aryl and alkenyl nucleophiles are tolerated, furnishing the products in good yield and with high enantioselectivity. In addition to terminal alkenes, 1,2-disubstituted internal alkenes participate in the reaction, establishing two contiguous stereocenters with high diastereoselectivity and moderate enantioselectivity. A combination of experimental and computational techniques shed light on the mechanism of the catalytic transformation, pointing to a closed-shell pathway with an enantiodetermining migratory insertion step, where stereoinduction arises from synergistic interactions between the sterically bulky achiral sulfonamide directing group and the hemilabile bidentate ligand.
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