Heterocyclic compounds are the fundamental structural motifs distributed in natural products, pharmaceuticals and biologically active compounds. Thus, there is increasing interest in the development of novel synthetic strategies for the...

Recent advances in transition metal-catalyzed heteroannulative difunctionalization of alkenes via C-H activation for the synthesis of heterocycles

Regiodivergent alkene functionalization that produces either regioisomer starting from the same raw materials is desirable. Herein, we report a nickel-catalyzed switchable site-selective alkene hydroalkylation. The selection of reaction temperatures leads to protocols that provide regiodivergent hydroalkylated products starting from a single alkene substrate. This protocol allows the convenient synthesis of α- and β-branched protected amines, both of which are important to the fields of pharmaceutical chemistry and biochemistry. In addition, enantioenriched β-branched alkylamines can be accessed in a catalytic asymmetric variant. Preliminary mechanistic studies indicate that the formation of a more stable nickelacycle provides the driving force of migration. The thermodynamic and kinetic properties of different reduction elimination intermediates are responsible for the switchable site-selectivity.

Nickel-Catalyzed Switchable Site-Selective Alkene Hydroalkylation by Temperature Regulation.

Catalytic carbon-nitrogen bond formation in hydrocarbons is an appealing synthetic tool to access valuable nitrogen-containing compounds. Although a number of synthetic approaches have been developed to construct a bifunctional α-amino carbonyl scaffold in this realm, installation of an amino functionality at the remote and unfunctionalized aliphatic sites remains underdeveloped. Here we present a tandem iridium catalysis that enables the redox-relay amidation of alkenyl alcohols via chain walking and metal-nitrenoid transfer, which eventually offers a new route to various α-amino ketones with excellent regioselectivity. The virtue of this transformation is that an unrefined isomeric mixture of alkenyl alcohols can be utilized as the readily available starting materials to lead to the regioconvergent amidation. Mechanistic investigations revealed that the reaction proceeds via a tandem process involving two key components of redox-relay chain walking and intermolecular nitrenoid transfer with the assistance of hydrogen bonding, thus representing the competence of Ir catalysis for the olefin migratory C-N coupling with high efficiency and exquisite selectivity.

Chain Walking as a Strategy for Iridium-Catalyzed Migratory Amidation of Alkenyl Alcohols to Access α-Amino Ketones.

Linear, α-branched, and β-branched aliphatic amines are widespread in pharmaceuticals, agrochemicals, and fine chemicals. Thus, the development of direct and efficient methods to these structures in a tunable manner is highly desirable yet challenging. Herein, a catalyst-controlled synthesis of α-branched, β-branched and linear aliphatic amines from Ni/Co-catalyzed regio- and site-selective hydroalkylations of alkenyl amines with alkyl halides is developed. This catalytic protocol features the reliable prediction and control of the coupling position of alkylation to provide orthogonal access to α-branched, β-branched and linear alkyl amines from identical starting materials. This platform unlocks orthogonal reactivity and selectivity of nickel hydride and cobalt hydride chemistry to catalytically repurpose three types of alkyl amines under mild conditions.

Orthogonal Access to α-/β-Branched/Linear Aliphatic Amines by Catalyst-Tuned Regiodivergent Hydroalkylations.

The structural diversity of sp 3 -triorganometallic reagents enhances their potentiality in the modular construction of molecular complexity in chemical synthesis. Despite significant achievements on the preparation of sp 3 1,1,1- and 1,1,2-triorganometallic B,B,B-reagents, catalytic approaches that enable the installation of multiple boryl groups at skipped carbons of unactivated alkenes still remain elusive. Herein, we report a cobalt-catalyzed selective triborylation reaction of unactivated alkenes to access synthetically versatile 1,1,3-triborylalkanes. This triborylation protocol provides a general platform for regioselective trifunctionalization of unactivated alkenes, and its utility is highlighted by the synthesis of various value-added chemicals from readily accessible unactivated alkenes. Mechanistic studies, including deuterium-labelling experiments and evaluation of potential reactive intermediates, provide insight into the experimentally observed chemo- and regioselectivity.

Synergistic Hydrocobaltation and Borylcobaltation Enable Regioselective Migratory Triborylation 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.

Phillippa Cooper

Papers

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

Recent advances in palladium-catalyzed (hetero)annulation of CC bonds with ambiphilic organo(pseudo)halides