A Modular Dual-Catalytic Aryl-Chlorination of Alkenes.

Alkyl chlorides are a class of versatile building blocks widely used to generate C(sp)-rich scaffolds through transformation such as nucleophilic substitution, radical addition reactions and metal-catalyzed cross-coupling processes. Despite their utility in the synthesis of high-value functional molecules, distinct methods for the preparation of alkyl chlorides are underrepresented. Here, we report a visible-light-mediated dual catalysis strategy for the modular synthesis of highly functionalized and structurally diverse arylated chloroalkanes via the coupling of diaryliodonium salts, alkenes and potassium chloride.

A General Iron-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids.

We report an iron-catalyzed decarboxylative C(sp)-O bond-forming reaction under mild, base-free conditions with visible light irradiation. The transformation uses readily available and structurally diverse carboxylic acids, iron photocatalyst, and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives as oxygenation reagents. The process exhibits a broad scope in acids possessing a wide range of stereoelectronic properties and functional groups.

Multicomponent alkene azidoarylation by anion-mediated dual catalysis.

Molecules that contain the β-arylethylamine motif have applications in the modulation of pain, treatment of neurological disorders and management of opioid addiction, among others, making it a privileged scaffold in drug discovery. De novo methods for their assembly are reliant on transformations that convert a small class of feedstocks into the target compounds via time-consuming multistep syntheses. Synthetic invention can drive the investigation of the chemical space around this scaffold to further expand its capabilities in biology.

Palladium-Catalyzed Oxidation of β-C(sp)-H Bonds of Primary Alkylamines through a Rare Four-Membered Palladacycle Intermediate.

Site-selective functionalizations of C-H bonds are often achieved with a directing group that leads to five- or six-membered metallacyclic intermediates. Analogous reactions that occur through four-membered metallacycles are rare. We report a challenging palladium-catalyzed oxidation of primary C-H bonds β to nitrogen in an imine of an aliphatic amine, a process that occurs through a four-membered palladacyclc intermediate.

Traceless Silylation of β-C(sp)-H Bonds of Alcohols via Perfluorinated Acetals.

We report the silylation of primary C-H bonds located β to secondary and tertiary alcohols by exploiting perfluorinated esters as traceless directing groups. The conversion of a secondary or tertiary alcohol to a perfluoroalkyl ester and conversion of the ester to the corresponding silyl acetals by hydrosilylation allows for selective β-C(sp)-H silylation catalyzed by the combination of [Ir(cod)OMe] and MePhen (3,4,7,8-tetramethyl-1,10-phenanthroline) to form 6-membered dioxasilinane. Tamao-Fleming oxidation of these dioxasilinane leads to 1,2 diols.

Catalytic Hydroxylation of Polyethylenes.

Polyolefins account for 60% of global plastic consumption, but many potential applications of polyolefins require that their properties, such as compatibility with polar polymers, adhesion, gas permeability, and surface wetting, be improved. A strategy to overcome these deficiencies would involve the introduction of polar functionalities onto the polymer chain. Here, we describe the Ni-catalyzed hydroxylation of polyethylenes (LDPE, HDPE, and LLDPE) in the presence of CPBA as an oxidant.

Copper-Catalyzed Three-Component Carboazidation of Alkenes with Acetonitrile and Sodium Azide.

A copper-catalyzed three-component reaction of alkenes, acetonitrile, and sodium azide afforded γ-azido alkyl nitriles by formation of one C(sp )-C(sp ) bond and one C(sp )-N bond. The transformation allows concomitant introduction of two highly versatile groups (CN and N ) across the double bond. A sequence involving the copper-mediated generation of a cyanomethyl radical and its subsequent addition to an alkene, and a C(sp )-N bond formation accounted for the reaction outcome.

Synthesis of functionalized epoxides by copper-catalyzed alkylative epoxidation of allylic alcohols with alkyl nitriles.

A copper-catalyzed oxyalkylation of allylic alcohols using nonactivated alkyl nitriles as reaction partners was developed. A sequence involving generation of an alkyl nitrile radical followed by its addition to a double bond and a copper-mediated formation of C(sp(3))-O bond was proposed to account for the reaction outcome. The protocol provided an efficient route to functionalized tri- and tetrasubstituted epoxides via formation of a C(sp(3))-C(sp(3)) and a C(sp(3))-O bond with moderate to excellent diastereoselectivity.

Copper-catalyzed cyanomethylation of allylic alcohols with concomitant 1,2-aryl migration: efficient synthesis of functionalized ketones containing an α-quaternary center.

A copper-catalyzed alkylation of allylic alcohols by alkyl nitriles with concomitant 1,2-aryl migration was developed. Formation of the alkyl nitrile radical was followed by its intermolecular addition to alkenes and the migration of a vicinal aryl group with the concomitant generation of a carbonyl functionality to complete the domino sequence. Mechanistic studies suggested that 1,2-aryl migration proceeded through a radical pathway (neophyl rearrangement).

Pd-catalyzed dehydrogenative aryl-aryl bond formation via double C(sp(2))-H bond activation: efficient synthesis of [3,4]-fused oxindoles.

A Pd(0)-catalyzed double cyclization of easily available o-bromoanilides leading to strained [3,4]-fused oxindoles was developed. The reaction proceeded through a highly ordered sequence involving key carbopalladation, 1,4-Pd migration, and C(sp(2))-H functionalization steps.

Copper-mediated/catalyzed oxyalkylation of alkenes with alkylnitriles.

A copper-promoted oxyalkylation of alkenes with alkylnitriles has been developed. The protocol provides rapid access to phthalides (γ-lactones) or isochromanones (δ-lactones) via the formation of a C(sp(3) )C(sp(3) ) and a C(sp(3) )O bond with the generation of up to two quaternary carbon atoms. Mechanistic studies suggest that this reaction is initiated by the formation of the C(sp(3) )C(sp(3) ) bond rather than the C(sp(3) )O bond.

Three-component Povarov reaction-heteroannulation with arynes: synthesis of 5,6-dihydroindolo[1,2-a]quinolines.

A reaction of 2-acyl substituted tetrahydroquinolines, prepared by Lewis acid-catalyzed three-component reaction of α-oxo aldehydes, anilines, and dienophiles, with in situ generated arynes afforded 5,6-dihydroindolo[1,2-a]quinolines in good to excellent yields.

Heteroannulation of arynes with N-aryl-α-aminoketones for the synthesis of unsymmetrical N-aryl-2,3-disubstituted indoles: an aryne twist of Bischler-Möhlau indole synthesis.

Reaction of 2-(trimethylsilyl)aryl triflates 1 with N-aryl-α-amino ketones 2 afforded N-aryl-2,3-disubstituted indoles in good to excellent yields with complete control of the substitution patterns. This methodology allowed for the first time a one-step synthesis of unsymmetrical 2,3-dialkyl substituted indoles in a regiospecific manner.