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-catalyzed C(sp 3)-H activation facilitated by the tertiary alkylamine functionality, however, remains an unsolved problem. Here, we report a Pd(II)-catalyzed protocol that appends arene feedstocks to tertiary alkylamines via C(sp 3)-H functionalization. A simple ligand for Pd(II) orchestrates the C-H activation step in favor of deleterious pathways. The reaction can utilize both simple and complex starting materials to produce a range of multi-faceted g-aryl tertiary alkylamines and can

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 S N 1-like mechanism. The utility of this novel procedure has been demonstrated by the asymmetric preparation of synthetically useful intermediates and the total synthesis of peperomin D.

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp 3 −sp 3 architectures at remote, yet previously unfunctionalized, methylene sp 3 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 sp 3 −sp 3 bond formations that are otherwise inaccessible in conventional chain-walking events.

Herein, we report a Ni-catalyzed C(sp 2 )−H hydroxylation of aryl bromides with N 2 O as an oxygen-atom donor. The reaction is enabled by a 1,4-Ni translocation that results in ipso/ortho 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.

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 3 )–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. Central to the success of this strategy is the use of a simple N -acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes γ-C–H activation of over other pathways. Computational analysis of the cyclopalladation step provides an understanding of how enantioselective C–H cleavage occurs and revealed distinct transition structures to our previous work on enantioselective desymmetrization of N -isobutyl tertiary alkylamines. This straightforward and operationally simple method simplifies the construction of functionalized aminomethyl-strained cycloalkanes, which we believe will find widespread use in academic and industrial settings relating to the synthesis of biologically active small molecules.