Atom Transfer Radical Coupling Enables Highly Enantioselective Carbo-Oxygenation of Alkenes with Hydrocarbons.

The selective functionalization of C(sp3)-H bonds has emerged as a transformative approach for streamlining synthetic routes, offering remarkable efficiency in the preparation and modification of complex organic molecules. However, the direct enantioselective transformation of hydrocarbons to medicinally valuable chiral molecules remains a significant challenge that has yet to be addressed. In this study, we adopt an atom transfer radical coupling (ATRC) strategy to achieve the asymmetric functionalization of C(sp3)-H bonds in hydrocarbons. This approach involves intermolecular H atom transfer (HAT) between a hydrocarbon and an alkoxy radical, leading to the formation of a carbon-centered radical. The resulting radical adds to alkenes, generating a new radical species that is intercepted by a chiral copper-mediated C-O bond coupling. By employing this method, we can directly access valuable chiral lactones bearing a quaternary stereocenter with high efficiency and excellent enantioselectivity. Importantly, ATRC exhibits great potential as a versatile platform for achieving stereoselective transformations of hydrocarbons.

Redox-Neutral 1,4-Dicarbonfunctionalization of 1,3-Butadiene by Merging Photoredox and Nickel Catalysis.

The diverse functionalization of 1,3-butadiene provides wide applicability toward the synthesis of abundant and useful allylic compounds. Here, we describe a three-component and redox-neutral assembly of readily available C═X compounds, 1,3-butadiene, and various nucleophiles by merging photoredox and nickel catalysis, enabling the rapid synthesis of structurally diverse homoallyl amines and homoallylic alcohols.

Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

Nucleophile Coordination Enabled Regioselectivity in Palladium-Catalyzed Asymmetric Allylic C-H Alkylation.

Branched selectivity in asymmetric allylic C-H alkylation is enabled by using 2-acylimidazoles as nucleophiles in the presence of a chiral phosphoramidite-palladium catalyst. A wide range of terminal alkenes, including 1,4-dienes and allylarenes, are nicely tolerated and provide chiral 2-acylimidazoles in moderate to high yields and with high levels of regio-, and enantio-, and E/Z-selectivities. Mechanistic studies using density-functional theory calculations suggest a nucleophile-coordination-enabled inner-sphere attack mode for the enantioselective carbon-carbon bond-forming event.

Monodentate Phosphorus Ligand-Enabled General Palladium-Catalyzed Allylic C-H Alkylation of Terminal Alkenes.

Monodentate phosphorus ligands have been found to enable the palladium-catalyzed allylic C-H alkylation reaction of terminal alkenes with a wide variety of carbon nucleophiles. Moreover, an asymmetric allylic C-H alkylation of terminal alkenes with pyrazol-5-ones has been established in the presence of chiral phosphoramidite ligand and chiral phosphoric acid as co-catalyst. Mechanistic studies suggest that a ternary Pd(0) complex, coordinated with a monodentate phosphorus ligand, benzoquinone, and alkene, is most likely to be an active species.

Asymmetric Allylic C-H Alkylation of Allyl Ethers with 2-Acylimidazoles.

An asymmetric allylic C-H alkylation of allyl ethers has been established by chiral phosphoramidite-palladium catalysis, affording a wide variety of functionalized chiral 2-acylimidazoles in moderate to high yields and with high levels of enantioselectivity. Moreover, this protocol could be applied to a concise asymmetric synthesis of a tachykinin receptor antagonist.

Enantioselective Decarboxylative Propargylation/Hydroamination Enabled by Organo/Metal Cooperative Catalysis.

The first catalytic enantioselective decarboxylative propargylation/hydroamination reaction of ethynyl benzoxazinanones with malononitriles enabled by organo/copper cooperative catalysis was established. Various 3-indolin-malononitrile derivatives, displaying a high tolerance for functional groups, could be obtained in good yields with high levels of enantioselectivity (up to 85% yield, 96:4 er). More importantly, this organo/metal cooperative catalytic system will provide a powerful synthetic strategy for new reaction development.

Palladium-Catalyzed Asymmetric Aminohydroxylation of 1,3-Dienes.

A PdII -catalyzed asymmetric aminohydroxylation of 1,3-dienes with N-tosyl-2-aminophenols was developed by making use of a chiral pyridinebis(oxazoline) ligand. The highly regioselective reaction provides direct and efficient access to chiral 3,4-dihydro-2H-1,4-benzoxazines in high yield and enantioselectivity (up to 96:4 e.r.). The reaction employs readily available N-tosyl-2-aminophenols as a unique aminohydroxylation reagent and is complementary to known asymmetric aminohydroxylation methods.