We describe a new catalytic strategy to transcend the energetic limitations of visible light by electrochemically priming photocatalyst prior excitation. This system is able productively engage aryl chlorides with reduction potentials hundreds millivolts beyond potential Na0 in productive radical coupling reactions. The radicals produced via this can be leveraged for both carbon–carbon and carbon–heteroatom bond-forming Through direct comparison, we illustrate reactivity selectivity...

We describe a photocatalytic system that elicits potent photoreductant activity from conventional photocatalysts by leveraging radical anion intermediates generated in situ. The combination of an isophthalonitrile photocatalyst and sodium formate promotes diverse aryl coupling reactions abundant but difficult to reduce chloride substrates. Mechanistic studies reveal two parallel pathways for substrate reduction both enabled key terminal reductant byproduct, carbon dioxide anion.

Herein we disclose a new photochemical process to prepare carboxylic acids from formate salts and alkenes. This redox-neutral hydrocarboxylation proceeds in high yields across diverse functionalized alkene substrates with excellent regioselectivity. operationally simple procedure can be readily scaled batch at low photocatalyst loading (0.01% photocatalyst). Furthermore, this reaction leverage commercially available carbon isotologues enable the direct synthesis of isotopically labeled...

Herein we disclose a strategy to promote the hydrocarboxylation of unactivated alkenes using photochemical activation formate salts. We illustrate that an alternative initiation mechanism circumvents limitations prior approaches and enables this challenging substrate class. Specifically, found accessing requisite thiyl radical initiator without exogenous chromophore eliminates major byproducts have plagued attempts exploit similar reactivity for alkene substrates. This redox-neutral method...

Three catalysts create alcohols by guiding water to attack carbon-carbon bonds in the opposite sense than it normally would.

A method for efficient and aldehyde-selective Wacker oxidation of aryl-substituted olefins using PdCl2(MeCN)2, 1,4-benzoquinone, t-BuOH in air is described. Up to a 96% yield aldehyde can be obtained, up 99% selectivity achieved with styrene-related substrates.

Breaking the rules: Reversal of high Markovnikov selectivity Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with yield and aldehyde selectivity, several functional groups are tolerated. 18O-labeling experiments indicate that aldehydic O atom is derived from salt. As service to our authors readers, this journal provides supporting information supplied by authors. Such materials peer reviewed may re-organized for online delivery,...

The aldehyde-selective oxidation of alkenes bearing diverse oxygen groups in the allylic and homoallylic position was accomplished with a nitrite-modified Wacker oxidation. Readily available oxygenated were oxidized up to 88% aldehyde yield as high 97% selectivity. enabled rapid, enantioselective synthesis an important pharmaceutical agent, atomoxetine. Finally, influence proximal functional on this anti-Markovnikov reaction explored, providing preliminary mechanistic insight.

Make it simple! A convenient and general palladium-catalyzed oxidation of internal olefins to ketones is reported. The transformation occurs at room temperature shows wide substrate scope. Applications the seed-oil derivatives a bioactive natural product (see scheme) are described, as well intriguing mechanistic features. As service our authors readers, this journal provides supporting information supplied by authors. Such materials peer reviewed may be re-organized for online delivery, but...

Allylic amines are valuable synthetic targets en route to diverse biologically active amine products. Current allylic C–H amination strategies remain limited with respect the viable N-substituents. Herein, we disclose a new electrochemical process prepare aliphatic by coupling two abundant starting materials: secondary and unactivated alkenes. This oxidative transformation proceeds via generation of an electrophilic adduct between thianthrene alkene substrates. Treatment these adducts...

Herein, we disclose that electrochemical stimulation induces new photocatalytic activity from a range of structurally diverse conventional photocatalysts. These studies uncover electron-primed photoredox catalyst capable promoting the reductive cleavage strong C(sp2 )-N and )-O bonds. We illustrate several examples synthetic utility these deeply reducing but otherwise safe mild catalytic conditions. Finally, employ current measurements to perform reaction progress kinetic analysis. This...

We describe a photocatalytic system that reveals latent photooxidant behavior from one of the most reducing conventional photoredox catalysts, N-phenylphenothiazine (PTH). This aerobic photochemical reaction engages difficult to oxidize feedstocks, such as benzene, in C(sp2)–N coupling reactions through direct oxidation. Mechanistic studies are consistent with activation PTH via photooxidation and Lewis acid cocatalysts scavenging inhibitors inextricably formed this process.

Herein, we describe a practical protocol for the removal of alcohol functional groups through reductive cleavage their benzoate ester analogs. This transformation requires strong single electron transfer (SET) reductant and means to accelerate slow fragmentation following substrate reduction. To accomplish this, developed photocatalytic system that generates potent from formate salts alongside Brønsted or Lewis acids promote reduced intermediate. deoxygenation procedure is effective across...

The rapid preparation of complex three-dimensional (3D) heterocyclic scaffolds is a key challenge in modern medicinal chemistry. Despite the increased probability clinical success for small molecule therapeutic candidates with 3D complexity, new drug targets remain dominated by flat molecules due to abundance coupling reactions available their construction. In principle, heteroarene hydrofunctionalization offer an opportunity transform readily accessible planar into more three-dimensionally...

Modular strategies to rapidly increase molecular complexity have proven immensely synthetically valuable. In principle, transformation of an alkene into a dielectrophile presents opportunity deliver two unique nucleophiles across alkene. Unfortunately, the selectivity profiles known dielectrophiles largely precluded this deceptively simple synthetic approach. Herein, we demonstrate that dicationic adducts generated through electrolysis alkenes and thianthrene possess profile relative more...

Herein, we report a new class of electrophotocatalysts, polycyclic aromatic hydrocarbons, that promote the reduction unactivated carbonyl compounds to generate versatile ketyl radical intermediates. This catalytic platform enables previously challenging intermolecular coupling reactions, including those classic reductants (e.g., SmI2/HMPA) have failed promote. More broadly, this study outlines an approach fundamentally expand array reactive intermediates can be generated via...

Abstract Cyclopropanes are desirable structural motifs with valuable applications in drug discovery and beyond. Established alkene cyclopropanation methods give rise to cyclopropanes a limited array of substituents, difficult scale, or both. Herein, we disclose new cyclopropane synthesis through the formal coupling abundant carbon pronucleophiles unactivated alkenes. This strategy exploits dicationic adducts derived from electrolysis thianthrene presence substrates. We find that these...

A precisely designed chiral squaramide derivative is shown to promote the highly enantioselective addition of trimethylsilyl bromide (TMSBr) a broad variety 3-substituted and 3,3-disubstituted oxetanes. The reaction provides direct general access synthetically valuable 1,3-bromohydrin building blocks from easily accessed achiral precursors. products are readily elaborated both by nucleophilic substitution through transition-metal-catalyzed cross-coupling reactions. catalytic oxetane ring...

A detailed mechanistic study of the Z-selective allylic functionalization via thianthrenium salts is presented. Kinetic analyses, deuterium labeling experiments, and computational methods are used to rationalize observed reactivity selectivity. We find that reaction proceeds a rate-determining stereodetermining deprotonation an alkenylthianthrenium species. The Z-configuration resultant ylide translated into Z-allylic amine product through sequence subsequent fast irreversible steps:...

Wacka wacka: The title reaction makes use of a wide range directing groups (DG) to enable the highly regioselective oxidation alkenes, and occurs predictably at distal position. Both E Z alkenes afford valuable functionalized ketones cross-metathesis was shown facilitate preparation starting materials. BQ=benzoquinone.

Generality in asymmetric catalysis can be manifested dramatic and valuable ways, such as high enantioselectivity across a wide assortment of substrates given reaction (broad substrate scope) or applicability chiral framework variety mechanistically distinct reactions (privileged catalysts). Reactions catalysts that display generality hold special utility, because they applied broadly sometimes even predictably new applications. Despite the great value systems, factors underlie are not well...

Abstract Catalytic nitrite was found to enable carbon–oxygen bond‐forming reductive elimination from unstable alkyl palladium intermediates, providing dioxygenated products alkenes. A variety of functional groups were tolerated, and high yields (up 94 %) observed with many substrates, also for a multigram‐scale reaction. Nitrogen dioxide, which could form under the reaction conditions, demonstrated be potential intermediate in catalytic cycle. Furthermore, event probed 18 O‐labeling...