Amine α-heteroarylation via photoredox catalysis: a homolytic aromatic substitution pathway

First published on 4th August 2014.The direct α-heteroarylation of tertiary amines has been accomplished via photoredox catalysis to generate valuable benzylic amine pharmacophores. A variety of five- and six-membered chloroheteroarenes are shown to function as viable coupling partners for the α-arylation of a diverse range of cyclic and acyclic amines. Evidence is provided for a homolytic aromatic substitution mechanism, in which a catalytically-generated α-amino radical undergoes direct addition to an electrophilic chloroarene

Synergistic catalysis: A powerful synthetic strategy for new reaction development

First published on 25th January 2012.ynergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature

Chemical Science editorial

Professor David W. C. MacMillan, Editor-in-Chief. Dr Robert D. Eagling, Managing Editor. Miss Jane Hordern, Deputy Editor. Miss Philippa Ross, Senior Publishing Editor.In this Editorial, we look back at a successful 2013 and forward to a landmark 5th year for the journal

Development of a generic activation mode: nucleophilic α-substitution of ketones via oxy-allyl cations

Oxy-allyl cations have been known as transient electrophilic species since they were first proposed as intermediates in the Favorskii rearrangement in 1894. Since that time, they also have been used as a mode of activation for [4 + 3] cycloadditions in a variety of natural product syntheses. In this manuscript, we describe a method for the interception of oxy-allyl cations with a diverse range of common nucleophiles, thereby demonstrating the value of this intermediate as a generic mode of activation. This simple, mild, room temperature protocol allows for the formation of a variety of high value carbon–carbon and carbon–heteroatom bonds that are readily incorporated within a series of cyclic and acyclic ketone systems. Initial efforts into the development of an enantioselective catalytic variant are also described

Erratum: Development of a generic activation mode: nucleophilic a-substitution of ketones via oxy-allyl cations

Erratum.Oxy-allyl cations have been known as transient electrophilic species since they were first proposed as intermediates in the Favorskii rearrangement in 1894. Since that time, they also have been used as a mode of activation for [4 + 3] cycloadditions in a variety of natural product syntheses. In this manuscript, we describe a method for the interception of oxy-allyl cations with a diverse range of common nucleophiles, thereby demonstrating the value of this intermediate as a generic mode of activation. This simple, mild, room temperature protocol allows for the formation of a variety of high value carbon–carbon and carbon–heteroatom bonds that are readily incorporated within a series of cyclic and acyclic ketone systems. Initial efforts into the development of an enantioselective catalytic variant are also described

Accelerating visible-light photoredox catalysis in continuous-flow reactors

This chapter gives an overview of the most important examples of visible-light photoredox catalysis in continuous-flow reactors based on the heterogeneity of the reaction mixture (homogeneous, gas-liquid, and solid-liquid). Photocatalysis in a homogeneous single phase can be straightforwardly converted to a continuous-flow protocol. In a continuous-flow system, the mixing efficiency is well controlled by the large and well-defined surface-to-volume ratios and the reaction times are defined by the flow rates. The efficient generation of reactive radical species in a gas-liquid continuous-flow system was demonstrated by Noel et al. for the trifluoromethylation of five-membered heterocycles. For gas-liquid reactions, it is important to maximize the interfacial area to avoid mass transfer limitations. Immobilization of photocatalysts in continuous-flow reactors provides a number of advantages with regard to catalyst recuperation and reuse. Transferring the chemistry to continuous flow resulted in a substantial acceleration of photocatalytic oxidation protocol

Reactive intermediates for interactome mapping

The interactions of biomolecules underpin all cellular processes, and the understanding of their dynamic interplay can lead to significant advances in the treatment of disease through the identification of novel therapeutic strategies. Protein-protein interactions (PPIs) in particular play a vital role within this arena, providing the basis for the majority of cellular signalling pathways. Despite their great importance, the elucidation of weak or transient PPIs that cannot be identified by immunoprecipitation remains a significant challenge, particularly in a disease relevant cellular environment. Recent approaches towards this goal have utilized the in situ generation of high energy intermediates that cross-link with neighboring proteins, providing a snapshot of the biomolecular makeup of the local area or microenvironment, termed the interactome. In this tutorial review, we discuss these reactive intermediates, how they are generated, and the impact they have had on the discovery of new biology. Broadly, we believe this strategy has the potential to significantly accelerate our understanding of PPIs and how they affect cellular physiology

Native functionality in triple catalytic cross-coupling: sp3 C-H bonds as latent nucleophiles

The use of sp3 C–H bonds—which are ubiquitous in organic molecules—as latent nucleophile equivalents for transition metal–catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C–H arylation protocol that activates a wide array of C–H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp3 C–H bonds in both cyclic and acyclic systems