Photocatalyzed Direct α-Alkylation of Esters Using Styrenes.

A mild photocatalyzed approach to achieve the α-alkylation of esters via formation of an α -radical is disclosed here. Cesium enolates of esters were generated using CsCO as a base. A subsequent photocatalyzed oxidation at the α-carbon of these enolates produced an α-radical that was added into activated alkenes.

Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.

An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp -carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules.

Single-electron Carbene Catalysis in Redox Processes.

Inspired by the role of -heterocyclic carbenes (NHCs) in natural enzymatic processes, chemists have harnessed the umpolung (polarity reversal) reactivity of these reactive, Lewis basic species over the past few decades to construct key chemical bonds. While NHCs continue to play a role in two-electron transformations, their unique redox properties enable a variety of useful, stabilized radical species to be accessed via single-electron oxidation or reduction. As a result, their utility in synthesis has grown rapidly concurrent with the revival of radical chemistry, highlighted by their extensive use as reactive single-electron species in recent years.

Synthesis of Cyclohexanones by a Tandem Photocatalyzed Annulation.

The rapid synthesis of cyclic scaffolds is of high importance to the chemistry community. Strategies for the convergent synthesis of substituted carbocycles and heterocycles remain underexplored despite the plethora of applications that these cyclic motifs have in the pharmaceutical and materials industries. Reported herein is a tandem carbene and photoredox-catalyzed process for the convergent synthesis of substituted cycloalkanones via a formal [5 + 1] cycloaddition.

Light-Driven Carbene Catalysis for the Synthesis of Aliphatic and α-Amino Ketones.

Single-electron N-heterocyclic carbene (NHC) catalysis has gained attention recently for the synthesis of C-C bonds. Guided by density functional theory and mechanistic analyses, we report the light-driven synthesis of aliphatic and α-amino ketones using single-electron NHC operators. Computational and experimental results reveal that the reactivity of the key radical intermediate is substrate-dependent and can be modulated through steric and electronic parameters of the NHC.

Combined Photoredox and Carbene Catalysis for the Synthesis of Ketones from Carboxylic Acids.

As a key element in the construction of complex organic scaffolds, the formation of C-C bonds remains a challenge in the field of synthetic organic chemistry. Recent advancements in single-electron chemistry have enabled new methods for the formation of various C-C bonds. Disclosed herein is the development of a novel single-electron reduction of acyl azoliums for the formation of ketones from carboxylic acids.

A Cooperative Hydrogen Bond Donor-Brønsted Acid System for the Enantioselective Synthesis of Tetrahydropyrans.

Carbocations stabilized by adjacent oxygen atoms are useful reactive intermediates involved in fundamental chemical transformations. These oxocarbenium ions typically lack sufficient electron density to engage established chiral Brønsted or Lewis acid catalysts, presenting a major challenge to their widespread application in asymmetric catalysis. Leading methods for selectivity operate primarily through electrostatic pairing between the oxocarbenium ion and a chiral counterion.