Light-assisted functionalization of aryl radicals towards metal-free cross-coupling.

The many synthetic possibilities that arise when using radical intermediates, in place of their polar counterparts, make contemporary radical chemistry research an exhilarating field. The introduction of photocatalysis has helped tame aryl radicals, leading to a resurgence of interest in their chemistry, and an expansion of viable coupling partners and attainable transformations. These methods are more selective and safer than classical approaches, and they utilize new radical precursors.

Alkyl Cyclopropyl Ketones in Catalytic Formal [3 + 2] Cycloadditions: The Role of SmI Catalyst Stabilization.

Alkyl cyclopropyl ketones are introduced as versatile substrates for catalytic formal [3 + 2] cycloadditions with alkenes and alkynes and previously unexplored enyne partners, efficiently delivering complex, sp-rich products. The key to effectively engaging this relatively unreactive new substrate class is the use of SmI as a catalyst in combination with substoichiometric amounts of Sm; the latter likely acting to prevent catalyst deactivation by returning Sm to the catalytic cycle. In the absence of Sm, background degradation of the SmI catalyst can outrun product formation.

Flavin-Mediated Photocatalysis Provides a General Platform for Sulfide C-H Functionalization.

Functionalized sulfides are important in many areas of science, ranging from chemical biology through drug discovery to organic materials chemistry. Sulfides bearing pendant reactive groups in the α-position are particularly useful; however, methods for the selective valorization of simple sulfides or the late-stage functionalization of complex sulfides by the convenient addition of valuable functionality are underexplored. Here we exemplify a general reaction platform for sulfide functionalization by showcasing three modes of α-sulfur C-H functionalization; cyanation, alkenylation, and alkynylation.

Metal-Free Arylation of Benzothiophenes at C4 by Activation as their Benzothiophene S-Oxides.

Benzothiophenes, activated by oxidation to the corresponding S-oxides, undergo C-H/C-H-type coupling with phenols to give C4 arylation products. While an electron-withdrawing group at C3 of the benzothiophene is important, the process operates without a directing group and a metal catalyst, thus rendering it compatible with sensitive functionalities-e.g.

Sulfonium Salts as Acceptors in Electron Donor-Acceptor Complexes.

The photoactivation of electron donor-acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation of radical species. Electron donor-acceptor (EDA) complexation, however, imposes electronic constraints on the donor and acceptor components and this can limit the range of radicals that can be generated using the approach. New EDA complexation strategies exploiting sulfonium salts allow radicals to be generated from native functionality.

A catalytic alkene insertion approach to bicyclo[2.1.1]hexane bioisosteres.

C(sp)-rich bicyclic hydrocarbon scaffolds, as exemplified by bicyclo[1.1.1]pentanes, play an increasingly high-profile role as saturated bioisosteres of benzenoids in medicinal chemistry and crop science.

A Vitamin B-Photocatalysed Approach to Methionine Analogues.

Access to new non-canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the amino acid methionine have been far less explored-despite their use in biochemistry, pharmacology and peptide bioconjugation. This is largely due to limited synthetic access.

A general arene C-H functionalization strategy via electron donor-acceptor complex photoactivation.

The photoactivation of electron donor-acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation of radical species. However, when it comes to aryl radical formation, this strategy remains hamstrung by the electronic properties of the aromatic radical precursors, and electron-deficient aryl halide acceptors are required. This has prevented the implementation of a general synthetic platform for aryl radical formation.

A Vitamin B -Photocatalysed Approach to Methionine Analogues.

Access to new non-canonical amino acid residues is crucial for medicinal chemistry and chemical biology. Analogues of the amino acid methionine have been far less explored-despite their use in biochemistry, pharmacology and peptide bioconjugation. This is largely due to limited synthetic access.

Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI.

Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI, Kagan's reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI. In contrast, acyclic esters are considered to be unreactive to SmI and their participation in reductive cyclizations is unprecedented.

Asymmetric Total Synthesis of (-)-Phaeocaulisin A.

The therapeutic properties of (ginger and turmeric's family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework.

Modular synthesis of unsymmetrical [1]benzothieno[3,2-][1]benzothiophene molecular semiconductors for organic transistors.

A modular approach to underexplored, unsymmetrical [1]benzothieno[3,2-][1]benzothiophene (BTBT) scaffolds delivers a library of BTBT materials from readily available coupling partners by combining a transition-metal free Pummerer CH-CH-type cross-coupling and a Newman-Kwart reaction. This effective approach to unsymmetrical BTBT materials has allowed their properties to be studied. In particular, tuning the functional groups on the BTBT scaffold allows the solid-state assembly and molecular orbital energy levels to be modulated.

Inhibitors of the Bub1 spindle assembly checkpoint kinase: synthesis of BAY-320 and comparison with 2OH-BNPP1.

Bub1 is a serine/threonine kinase proposed to function centrally in mitotic chromosome alignment and the spindle assembly checkpoint (SAC); however, its role remains controversial. Although it is well documented that Bub1 phosphorylation of Histone 2A at T120 (H2ApT120) recruits Sgo1/2 to kinetochores, the requirement of its kinase activity for chromosome alignment and the SAC is debated. As small-molecule inhibitors are invaluable tools for investigating kinase function, we evaluated two potential Bub1 inhibitors: 2OH-BNPPI and BAY-320.

Copper-catalyzed functionalization of enynes.

The copper-catalyzed functionalization of enyne derivatives has recently emerged as a powerful approach in contemporary synthesis. Enynes are versatile and readily accessible substrates that can undergo a variety of reactions to yield densely functionalized, enantioenriched products. In this perspective, we review copper-catalyzed transformations of enynes, such as boro- and hydrofunctionalizations, copper-mediated radical difunctionalizations, and cyclizations.

Recent advances in the chemistry of ketyl radicals.

Ketyl radicals are valuable reactive intermediates for synthesis and are used extensively to construct complex, functionalized products from carbonyl substrates. Single electron transfer (SET) reduction of the C[double bond, length as m-dash]O bond of aldehydes and ketones is the classical approach for the formation of ketyl radicals and metal reductants are the archetypal reagents employed. The past decade has, however, witnessed significant advances in the generation and harnessing of ketyl radicals.

Enantioselective Copper-Catalyzed Borylative Cyclization for the Synthesis of Quinazolinones.

Quinazolinones are common substructures in molecules of medicinal importance. We report an enantioselective copper-catalyzed borylative cyclization for the assembly of privileged pyrroloquinazolinone motifs. The reaction proceeds with high enantio- and diastereocontrol, and can deliver products containing quaternary stereocenters.

SmI-Catalyzed Intermolecular Coupling of Cyclopropyl Ketones and Alkynes: A Link between Ketone Conformation and Reactivity.

The archetypal single electron transfer reductant, samarium(II) diiodide (SmI, Kagan's reagent), remains one of the most important reducing agents and mediators of radical chemistry after four decades of widespread use in synthesis. While the chemistry of SmI is very often unique, and thus the reagent is indispensable, it is almost invariably used in superstoichiometric amounts, thus raising issues of cost and waste. Of the few reports of the use of catalytic SmI, all require the use of superstoichiometric amounts of a metal coreductant to regenerate Sm(II).

Single-Scan Selective Excitation of Individual NMR Signals in Overlapping Multiplets.

2D NMR is an immensely powerful structural tool but it is time-consuming. Targeting individual chemical groups by selective excitation in a 1D experiment can give the information required far more quickly. A major problem, however, is that proton NMR spectra are often extensively overlapped, so that in practice only a minority of sites can be selectively excited.

Cytoplasmic control of intranuclear polarity by human cytomegalovirus.

Despite its size and rigidity, the cell nucleus can be moved or reorganized by cytoskeletal filaments under various conditions (for example, during viral infection). Moreover, whereas chromatin organizes into non-random domains, extensive heterogeneity at the single-cell level means that precisely how and why nuclei reorganize remains an area of intense investigation. Here we describe convolutional neural network-based automated cell classification and analysis pipelines, which revealed the extent to which human cytomegalovirus generates nuclear polarity through a virus-assembled microtubule-organizing centre.

Weekend and weekday associations between the residential built environment and physical activity: Findings from the ENABLE London study.

Background: We assessed whether the residential built environment was associated with physical activity (PA) differently on weekdays and weekends, and contributed to socio-economic differences in PA.

Methods: Measures of PA and walkability, park proximity and public transport accessibility were derived for baseline participants (n = 1,064) of the Examining Neighbourhood Activities in Built Living Environments in London (ENABLE London) Study. Multilevel-linear-regressions examined associations between weekend and weekday steps and Moderate to Vigorous PA (MVPA), residential built environment factors, and housing tenure status as a proxy for socio-economic position.

Copper-Catalyzed Borylative Couplings with C-N Electrophiles.

Copper-catalyzed borylative multicomponent reactions (MCRs) involving olefins and C-N electrophiles are a powerful tool to rapidly build up molecular complexity. The products from these reactions contain multiple functionalities, such as amino, cyano and boronate groups, that are ubiquitous in medicinal and process chemistry programs. Copper-catalyzed MCRs are particularly attractive because they use a relatively abundant and non-toxic catalyst to selectively deliver high-value products from simple feedstocks such as olefins.

Trifluoromethyl Sulfoxides: Reagents for Metal-Free C-H Trifluoromethylthiolation.

Trifluoromethyl sulfoxides are a new class of trifluoromethylthiolating reagent. The sulfoxides engage in metal-free C-H trifluoromethylthiolation with a range of (hetero)arenes. The method is also applicable to the functionalization of important compound classes, such as ligand derivatives and polyaromatics, and in the late-stage trifluoromethylthiolation of medicines and agrochemicals.