A straightforward and simple method of electrochemical desaturative β-C(sp3)−H acylation of cyclic N-aryl amines has been developed to access the desired β-substituted enamines with excellent levels of chemo- and regioselectivity under mild conditions. This procedure proved to be a powerful route to the late-stage modification of natural products and derivatives.
Herein, we disclose a straightforward, robust, and simple route to access β-substituted desaturated cyclic amines via an electrochemically driven desaturative β-functionalization of cyclic amines. This transformation is based on multiple single-electron oxidation processes using catalytic amounts of ferrocene. The reaction proceeds in the absence of stoichiometric amounts of electrolyte under mild conditions, affording the desired products with high chemo- and regioselectivity. The reaction was tolerant of a broad range of substrates and also enables late-stage β-C(sp3)−H acylation of potentially valuable products. Preliminary mechanistic studies using cyclic voltammetry reveal the key role of ferrocene as a redox mediator in the reaction.
Fumarate to maleate (E→Z) isomerization was investigated to validate nO→ πC=O* interactions as a driving force for contra-thermodynamic isomerization. A general protocol based on selective energy transfer catalysis was developed with inexpensive thioxanthone as a sensitizer for the conversion of diverse fumarate derivatives, including tetrasubstituted alkenes. The involvement of nO→πC=O* interactions was confirmed by X-ray crystallography.
Examples of geometric alkene isomerization in nature are often limited to the net exergonic direction (ΔG°<0), with the antipodal net endergonic processes (ΔG°>0) comparatively under-represented. Inspired by the expansiveness of the maleate to fumarate (Z→E) isomerization in biochemistry, we investigated the inverse E→Z variant to validate nO→πC=O* interactions as a driving force for contra-thermodynamic isomerization. A general protocol involving selective energy transfer catalysis with inexpensive thioxanthone as a sensitizer (λ max=402 nm) is disclosed. Whilst in the enzymatic process nO→πC=O* interactions commonly manifest themselves in the substrate, these same interactions are shown to underpin directionality in the antipodal reaction by shortening the product alkene chromophore. The process was validated with diverse fumarate derivatives (>30 examples, up to Z:E>99:1), including the first examples of tetrasubstituted alkenes, and the involvement of nO→πC=O* interactions was confirmed by X-ray crystallography.
Nature Chemistry, Published online: 02 August 2021; doi:10.1038/s41557-021-00744-9
Manganese(i) is isoelectronic to iron(ii) but has typically been overlooked as a cheap Earth-abundant metal for the development of 3d6 metal-to-ligand charge transfer (MLCT) emitters and photosensitizers. Now, using chelating isocyanide ligands, air-stable manganese(i) complexes have been obtained that exhibit MLCT luminescence, as well as energy- and electron-transfer photoreactivity.
The complexity of the Pd-catalyzed Suzuki-Miyaura C−C bond formation reaction lies in the indivdual steps of the cycle, as well as in the generation of the catalytically active species. An overview of the topic is provided from a historical perspective.
The story of C−C bond formation includes several reactions, and surely Suzuki-Miyaura is among the most outstanding ones. Herein, a brief historical overview of insights regarding the reaction mechanism is provided. In particular, the formation of the catalytically active species is probably the main concern, thus the preactivation is in competition with, or even assumes the role of the rate determining step (rds) of the overall reaction. Computational chemistry is key in identifying the rds and thus leading to milder conditions on an experimental level by means of predictive catalysis.
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A new family of carbon-bound boron enolates, in cooperation with a Pd complex supported by an 1,4-azaborine-derived phosphine ligand, transforms enynes into highly substituted dienyl boronates in exquisite site-, regio-, and cis-diastereoselectivity.
A new family of carbon-bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These C−boron enolates are demonstrated to activate 1,3-enyne substrates in the presence of a Pd0/Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate-equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site-, regio-, and diastereoselectivity by the described catalytic cis-carboboration reaction.
Hydroxamic acids were electrochemically oxidised to initiate acyl nitroso Diels–Alder reactions with 1,3-dienes. By using alternating current, their often encountered electrochemically induced decomposition could be suppressed to generate the desired cycloaddition products in up to 96 % yield. The optimisation of this reaction was performed using the Design of Experiments approach.
The acyl nitroso Diels–Alder reaction of 1,3-dienes with electrochemically oxidised hydroxamic acids is described. By using alternating current electrolysis, their typical electro-induced decomposition could be suppressed in favour of the 1,2-oxazine cycloaddition products. The reaction was optimised using Design of Experiments (DoE) and a sensitivity test was conducted. A mixture of triethylamine/hexafluoroisopropanol served as supporting electrolyte in dichloromethane, thus giving products of high purity after evaporation of the volatiles without further purification. The optimised reaction conditions were applied to various 1,3-dienes and hydroxamic acids, giving up to 96 % isolated yield.
Beyond C(sp2)–X cleavage: We report reductive cleavages of C(sp3)−O bonds of phosphinated alcohols to alkyl carbanions by electro-mediated photoredox catalysis. Deoxygenations as well as E- or Z-selective olefinations are reported. Surprisingly, reactions tolerate C(sp2)–X cleavages such as aryl halides. Radical ion catalyst-substrate preassembly is key in enabling reactivity and overturning conventional redox chemoselectivity.
We report a novel example of electro-mediated photoredox catalysis (e-PRC) in the reductive cleavage of C(sp3)−O bonds of phosphinated alcohols to alkyl carbanions. As well as deoxygenations, olefinations are reported which are E-selective and can be made Z-selective in a tandem reduction/photosensitization process where both steps are photoelectrochemically promoted. Spectroscopy, computation, and catalyst structural variations reveal that our new naphthalene monoimide-type catalyst allows for an intimate dispersive precomplexation of its radical anion form with the phosphinate substrate, facilitating a reactivity-determining C(sp3)−O cleavage. Surprisingly and in contrast to previously reported photoexcited radical anion chemistries, our conditions tolerate aryl chlorides/bromides and do not give rise to Birch-type reductions.
Nature Communications, Published online: 22 June 2021; doi:10.1038/s41467-021-24144-2
Use of aryl halides as coupling precursors typically occurs through transition metal catalysis and/or photoredox chemistry, which requires some combination of light, metals, and oxidants or reductants. Here, the authors show a method to generate aryl radicals from halides using only an NHC organocatalyst.
A direct γ-oxidation of β,γ-unsaturated amides is reported. This regioselective reaction with TEMPO proceeds under mild conditions, tolerant of other carbonyl functionality. A rare example of regioselective amide activation of unsaturated substrates; it results in products carrying oxyaminated substitution ripe for remarkably selective radical cyclisation reactions.
A chemoselective and robust protocol for the γ-oxidation of β,γ-unsaturated amides is reported. In this method, electrophilic amide activation, in a rare application to unsaturated amides, enables a regioselective reaction with TEMPO resulting in the title products. Radical cyclisation reactions and oxidation of the synthesised products highlight the synthetic utility of the products obtained.
