PdII -Catalyzed C(alkenyl)-H Activation Facilitated by a Transient Directing Group.

Palladium(II)-catalyzed C(alkenyl)-H alkenylation enabled by a transient directing group (TDG) strategy is described. The dual catalytic process takes advantage of reversible condensation between an alkenyl aldehyde substrate and an amino acid TDG to facilitate coordination of the metal catalyst and subsequent C(alkenyl)-H activation by a tailored carboxylate base. The resulting palladacycle then engages an acceptor alkene, furnishing a 1,3-diene with high regio- and E/Z-selectivity. The reaction enables the synthesis of enantioenriched atropoisomeric 2-aryl-substituted 1,3-dienes, which have seldom been examined in previous literature. Catalytically relevant alkenyl palladacycles were synthesized and characterized by X-ray crystallography, and the energy profiles of the C(alkenyl)-H activation step and the stereoinduction model were elucidated by density functional theory (DFT) calculations.

Regio- and Stereoselective 1,2-Oxyhalogenation of Non-Conjugated Alkynes via Directed Nucleopalladation: Catalytic Access to Tetrasubstituted Alkenes.

A catalytic 1,2-oxyhalogenation method that converts non-conjugated internal alkynes into tetrasubstituted alkenes with high regio- and stereoselectivity is described. Mechanistically, the reaction involves a PdII /PdIV catalytic cycle that begins with a directed oxypalladation step. The origin of regioselectivity is the preference for formation of a six-membered palladacycle intermediate, which is facilitated by an N,N-bidentate 2-(pyridin-2-yl)isopropyl (PIP) amide directing group. Selectivity for C(alkenyl)-X versus -N (X=halide) reductive elimination from the PdIV center depends on the identity of the halide anion; bromide and iodide engage in C(alkenyl)-X formation, while intramolecular C(alkenyl)-N reductive elimination occurs with chloride to furnish a lactam product. DFT calculations shed light on the origins of this phenomenon.

Low-Valent Tungsten Catalysis Enables Site-Selective Isomerization-Hydroboration of Unactivated Alkenes.

A tungsten-catalyzed hydroboration of unactivated alkenes at distal C(sp3)-H bonds aided by native directing groups is described herein. The method is characterized by its simplicity, exquisite regio- and chemoselectivity, and wide substrate scope, offering a complementary site-selectivity pattern to other metal-catalyzed borylation reactions and chain-walking protocols.

Site-Selective Ni-Catalyzed Reductive Coupling of α-Haloboranes with Unactivated Olefins.

A mild, chemo- and site-selective catalytic protocol that allows for incorporating an alkylboron fragment into unactivated olefins is described. The use of internal olefins enables C-C bond-formation at remote sp3 C-H sites, constituting a complementary and conceptually different approach to existing borylation techniques that are currently available at sp3 centers.

Intermolecular Pummerer Coupling with Carbon Nucleophiles in Non-Electrophilic Media.

A new Pummerer-type C-C coupling protocol is introduced based on turbo-organomagnesium amides, which unlike traditional Pummerer reactions, does not require strong electrophilic activators, engages a broad range of C(sp3 )-, C(sp2 )-, and C(sp)-nucleophiles, and seamlessly integrates with C-H and C-X magnesiation. Given the central character of sulfur compounds in organic chemistry, this protocol allows access to unrelated carbonyls, olefins, organometallics, halides, and boronic esters through a single strategy.

Ni-catalyzed Reductive Deaminative Arylation at sp3 Carbon Centers.

A Ni-catalyzed reductive deaminative arylation at unactivated sp3 carbon centers is described. This operationally simple and user-friendly protocol exhibits excellent chemoselectivity profile and broad substrate scope, thus complementing existing metal-catalyzed cross-coupling reactions to forge sp3 C-C linkages. These virtues have been assessed in the context of late-stage functionalization, hence providing a strategic advantage to reliably generate structure diversity with amine-containing drugs.