High Site Selectivity in Electrophilic Aromatic Substitutions: Mechanism of C-H Thianthrenation.

The introduction of thianthrene as a linchpin has proven to be a versatile strategy for the C-H functionalization of aromatic compounds, featuring a broad scope and fast diversification. The synthesis of aryl thianthrenium salts has displayed an unusually high regioselectivity, notably superior to those observed in halogenation or borylation reactions for various substrates. We report an experimental and computational study on the mechanism of aromatic C-H thianthrenation reactions, with an emphasis on the elucidation of the reactive species and the nature of the exquisite site selectivity.

Site-Selective C-H Functionalization-Sulfination Sequence to Access Aryl Sulfonamides.

Aryl sulfinates are precursors to a diverse number of sulfonyl-derived arenes, which are common motifs in pharmaceuticals and agrochemicals. Here, we report a site-selective two-step C-H sulfination sequence via aryl sulfonium salts to access aryl sulfonamides. Combined with site-selective aromatic thianthrenation, an operationally simple one-pot palladium-catalyzed protocol introduces the sulfonyl group using sodium hydroxymethylsulfinate (Rongalite) as a source of SO.

Regio- and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles.

Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C-H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse-electron-demand hetero-Diels-Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium- and ruthenium-catalyzed cross-coupling reactions to make alkenyl C-C, C-Cl, C-Br, and C-SCF bonds with stereoretention.

Photoredox catalysis with aryl sulfonium salts enables site-selective late-stage fluorination.

Photoredox catalysis, especially in combination with transition metal catalysis, can produce redox states of transition metal catalysts to facilitate challenging bond formations that are not readily accessible in conventional redox catalysis. For arene functionalization, metallophotoredox catalysis has successfully made use of the same leaving groups as those valuable in conventional cross-coupling catalysis, such as bromide. Yet the redox potentials of common photoredox catalysts are not sufficient to reduce most aryl bromides, so synthetically useful aryl radicals are often not directly available.

Site-selective and versatile aromatic C-H functionalization by thianthrenation.

Direct C-H functionalization can quickly increase useful structural and functional molecular complexity. Site selectivity can sometimes be achieved through appropriate directing groups or substitution patterns-in the absence of such functionality, most aromatic C-H functionalization reactions provide more than one product isomer for most substrates. Development of a C-H functionalization reaction that proceeds with high positional selectivity and installs a functional group that can serve as a synthetic linchpin for further functionalization would provide access to a large variety of well-defined arene derivatives.

The Hitchhiker's Guide to Flow Chemistry ∥.

Flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask. Flow equipment provides chemists with unique control over reaction parameters enhancing reactivity or in some cases enabling new reactions. This relatively young technology has received a remarkable amount of attention in the past decade with many reports on what can be done in flow.

Visible-Light-Mediated Achmatowicz Rearrangement.

Visible-light-mediated photoredox catalysis is a viable method to access highly reactive intermediates from cheap, readily available, and shelf-stable reagents to perform clean chemical transformations. Here, we report the first photoredox-catalyzed Achmatowicz reaction of furfuryl alcohol derivatives to produce functionalized dihydropyranones while only forming easily separable NaHSO as a byproduct. The water solubility of the byproduct facilitates direct Boc-protection of the resulting hemiacetal without the need for column purification.

Factors influencing the regioselectivity of the oxidation of asymmetric secondary amines with singlet oxygen.

Aerobic amine oxidation is an attractive and elegant process for the α functionalization of amines. However, there are still several mechanistic uncertainties, particularly the factors governing the regioselectivity of the oxidation of asymmetric secondary amines and the oxidation rates of mixed primary amines. Herein, it is reported that singlet-oxygen-mediated oxidation of 1° and 2° amines is sensitive to the strength of the α-C-H bond and steric factors.

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe.

We describe the synthesis of 1-amino-2,5-anhydro-D-mannose ("mannitolamine"), a key intermediate to the 7-nitro-1,2,3-benzadiazole conjugate (NBDM), using commercially available fluidic devices to increase the throughput. The approach is the first example of a flow-based Tiffeneau-Demjanov rearrangement. Performing this step in flow enables a ~64-fold throughput enhancement relative to batch.

Fluorescent THF-based fructose analogue exhibits fructose-dependent uptake.

Recent publications suggest that high dietary fructose might play a significant role in cancer metabolism and can exacerbate a number of aspects of metabolic syndrome. Addressing the role that fructose plays in human health is a controversial question and requires a detailed understanding of many factors including the mechanism of fructose transport into healthy and diseased cells. Fructose transport into cells is thought to be largely mediated by the passive hexose transporters Glut2 and Glut5.

Passive fructose transporters in disease: a molecular overview of their structural specificity.

The SLC2 family of facilitative Glucose transporters (Gluts) contains 14 isoforms divided into three classes based on amino acid sequence. While the majority of these proteins transport glucose, a subset can transport fructose. Recently, fructose and the Gluts responsible for fructose uptake have received increased interest due to the correlation between high fructose consumption and early onset of metabolic syndrome.