Site-Selective Distal C(sp)-H Bromination of Aliphatic Amines as a Gateway for Forging Nitrogen-Containing sp Architectures.

Herein, we disclose a new strategy that rapidly and reliably incorporates bromine atoms at distal, secondary C(sp)-H sites in aliphatic amines with an excellent and predictable site-selectivity pattern. The resulting halogenated building blocks serve as versatile linchpins to enable a series of carbon-carbon and carbon-heteroatom bond-formations at remote C(sp) sites, thus offering a new modular and unified platform that expediates the access to advanced sp architectures possessing valuable nitrogen-containing saturated heterocycles of interest in medicinal chemistry settings.

Regiodivergent C-H Functionalization via Ni-Catalyzed Chain-Walking Reactions.

The catalytic translocation of a metal catalyst along a saturated hydrocarbon side chain constitutes a powerful strategy for enabling bond-forming reactions at remote, yet previously unfunctionalized, C-H sites. In recent years, Ni-catalyzed chain-walking reactions have offered counterintuitive strategies for forging architectures that would be difficult to accomplish otherwise. Although these strategies have evolved into mature tools for advanced organic synthesis, it was only recently that chemists showed the ability to control the motion at which the catalyst "walks" throughout the alkyl chain.

C(sp)-H Hydroxylation via Catalytic 1,4-Ni Migration with NO.

Herein, we report a Ni-catalyzed C(sp)-H hydroxylation of aryl bromides with NO as an oxygen-atom donor. The reaction is enabled by a 1,4-Ni translocation that results in difunctionalized products. Regioselectivity and stereocontrol are dictated by a judicious choice of the ligand backbone, thus giving access to either carbonyl or phenol derivatives and offering an opportunity to repurpose hazardous substances en route to valuable oxygen-containing building blocks.

Native Amides as Enabling Vehicles for Forging spsp Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking.

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges spsp architectures at remote, yet previously unfunctionalized, methylene sp C-H sites enabled by the presence of native amides. This protocol is characterized by its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated by a judicious choice of the ligand, thus offering an opportunity to enable spsp bond formations that are otherwise inaccessible in conventional chain-walking events.

Pd(II)-Catalyzed Enantioselective C(sp)-H Arylation of Cyclopropanes and Cyclobutanes Guided by Tertiary Alkylamines.

Strained aminomethyl-cycloalkanes are a recurrent scaffold in medicinal chemistry due to their unique structural features that give rise to a range of biological properties. Here, we report a palladium-catalyzed enantioselective C(sp)-H arylation of aminomethyl-cyclopropanes and -cyclobutanes with aryl boronic acids. A range of native tertiary alkylamine groups are able to direct C-H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios.

Catalytic C(sp)-H bond activation in tertiary alkylamines.

The development of robust catalytic methods to assemble tertiary alkylamines provides a continual challenge to chemical synthesis. In this regard, transformation of a traditionally unreactive C-H bond, proximal to the nitrogen atom, into a versatile chemical entity would be a powerful strategy for introducing functional complexity to tertiary alkylamines. A practical and selective metal-catalysed C(sp)-H activation facilitated by the tertiary alkylamine functionality, however, remains an unsolved problem.

Direct and Asymmetric Nickel(II)-Catalyzed Construction of Carbon-Carbon Bonds from N-Acyl Thiazinanethiones.

A wide array of new N-acyl thiazinanethiones are employed in a number of direct and enantioselective carbon-carbon-bond-forming reactions catalyzed by nickel(II) complexes. The electrophilic species are mostly prepared in situ from ortho esters, methyl ethers, acetals, and ketals, which makes the overall process highly efficient and experimentally straightforward. Theoretical calculations indicate that the reactions proceed through an open transition state in a S1-like mechanism.