Asymmetric Paired Electrocatalysis: Enantioselective Olefin-Sulfonylimine Coupling.

Asymmetric electrocatalysis offers exciting new strategies for the synthesis of chiral molecules through novel reaction pathways. However, simultaneous activation of reactants on both electrodes via asymmetric paired electrolysis, which is more energy efficient and economic than single half-electrode synthesis, remains a formidable challenge. Herein, an asymmetric olefin-sulfonylimine coupling via paired electrocatalysis is presented for the first time. In this protocol, Co-catalyzed hydrogen atom transfer on the anode and Ni-catalyzed sulfonylimine reduction on the cathode were seamlessly cross-coupled. The new catalytic system enables the formation of chiral amine products bearing a tetrasubstituted carbon stereocenter with a high enantioselectivity (up to 96% ee).

Selective C(sp3)-H arylation/alkylation of alkanes enabled by paired electrocatalysis.

We report a combination of electrocatalysis and photoredox catalysis to perform selective C(sp3)-H arylation/alkylation of alkanes, in which a binary catalytic system based on earth-abundant iron and nickel is applied. Reaction selectivity between two-component C(sp3)-H arylation and three-component C(sp3)-H alkylation is tuned by modulating the applied current and light source. Importantly, an ultra-low anodic potential (~0.23 V vs. Ag/AgCl) is applied in this protocol, thus enabling compatibility with a variety of functional groups (>70 examples). The robustness of the method is further demonstrated on a preparative scale and applied to late-stage diversification of natural products and pharmaceutical derivatives.

Rape straw biochar enhanced Cd immobilization in flooded paddy soil by promoting Fe and sulfur transformation.

Cd is normally associated with sulfide and Fe oxides in flooded paddy soil. The mechanisms of biochar enhanced Cd immobilization by promoting Fe transformation and sulfide formation are unclear. Rape straw biochar (RSB) pyrolyzed at 450 °C (LB) and 800 °C (HB) was added to Cd-contaminated paddy soil at 1% (LB1, HB1) and 2% (LB2, HB2) doses. The results showed that Fe/Mn oxide-Cd (Fe/Mn-Cd) and free Fe oxide (Fed) concentrations decreased in the first 12 days and then rose, while Fe2+ in pore water (W-Fe2+) tended to rise first and then fall. The electron transfer rate of soil in the HB2 treatment was 4.9-fold higher than that in the treatment without biochar (CK). Fe oxide reduction was enhanced by RSB, with a maximum increase in W-Fe2+ by 62.1% in HB2 on Day 12. The negative correlation between W-Fe2+ and Fed showed that Fe2+ promoted the reformatted of seconded Fe minerals after Day 12, and the Fed in the HB2 treatments increased by 31.5% in this period. RSB addition also promoted the reformation of poorly crystallized Fe oxide (Feo) by increasing soil pH, which increased by 17.2% and 15.1% on average in the LB2 and HB2 treatments, respectively, compared to CK. Compared to Day 7, the increased rate of Fe/Mn-Cd on Day 30 in RSB was approximately twice that of CK. Compared to the molybdate group, the maximum decrease in CaCl2-Cd was 29.1% in LB2 on Day 12. LB2 increased SO42- and acid-volatile sulfide concentrations by 6.9- and 4.1-fold, respectively, compared to CK. These results suggested that RSB, particularly HB, promoted more Cd adsorption in Fe minerals by increasing Fe hydroxylation and recrystallization processes. LB increased the contribution of sulfide to Cd immobility.

Unlocking the Nucleophilicity of Strong Alkyl C-H Bonds via Cu/Cr Catalysis.

Direct functionalization of inert C-H bonds is one of the most attractive yet challenging strategies for constructing molecules in organic chemistry. Herein, we disclose an unprecedented and Earth abundant Cu/Cr catalytic system in which unreactive alkyl C-H bonds are transformed into nucleophilic alkyl-Cr(III) species at room temperature, enabling carbonyl addition reactions with strong alkyl C-H bonds. Various aryl alkyl alcohols are furnished under mild reaction conditions even on a gram scale. Moreover, this new radical-to-polar crossover approach is further applied to the 1,1-difunctionalization of aldehydes with alkanes and different nucleophiles. Mechanistic investigations reveal that the aldehyde not only acts as a reactant but also serves as a photosensitizer to recycle the Cu and Cr catalysts.

Paired Oxidative and Reductive Catalysis: Breaking the Potential Barrier of Electrochemical C(sp3 )-H Alkenylation.

Due to the intrinsic inertness of alkanes, strong oxidative conditions are typically required to enable their C(sp3 )-H functionalization. Herein, a paired electrocatalysis strategy was developed by integrating oxidative catalysis with reductive catalysis in one cell without interference, in which earth-abundant iron and nickel are employed as the anodic and cathodic catalysts, respectively. This approach lowers the previously high oxidation potential required for alkane activation, enabling electrochemical alkane functionalization at the ultra-low oxidation potential of ≈0.25 V vs. Ag/AgCl under mild conditions. Structurally diverse alkenes, including challenging all-carbon tetrasubstituted olefins, can be accessed using readily available alkenyl electrophiles.

Electrooxidative Activation of B-B Bond in B2 cat2 : Access to gem-Diborylalkanes via Paired Electrolysis.

This report describes the unprecedented electrooxidation of a solvent (e.g., DMF)-ligated B2 cat2 complex, whereby a solvent-stabilized boryl radical is formed via quasi-homolytic cleavage of the B-B bond in a DMF-ligated B2 cat2 radical cation. Cyclic voltammetry and density functional theory provide evidence to support this novel B-B bond activation strategy. Furthermore, a strategy for the electrochemical gem-diborylation of gem-bromides via paired electrolysis is developed for the first time, affording a range of versatile gem-diborylalkanes, which are widely used in synthetic society. Notably, this reaction approach is scalable, transition-metal-free, and requires no external activator.

Epoxide Electroreduction.

Selective hydrogenation of epoxides would be a direct and powerful approach for alcohol synthesis, but it has proven to be elusive. Here, electrochemically epoxide hydrogenation using electrons and protons as reductants is reported. A wide range of primary, secondary, and tertiary alcohols can be achieved through selective Markovnikov or anti-Markovnikov ring opening in the absence of transition metals. Mechanistic investigations revealed that the regioselectivity is controlled by the thermodynamic stabilities of the in situ generated benzyl radicals for aryl-substituted epoxides and the kinetic tendency for Markovnikov selective ring opening for alkyl-substituted epoxides.

Electrochemical Borylation of Alkyl Halides: Fast, Scalable Access to Alkyl Boronic Esters.

Herein, a fast, scalable, and transition-metal-free borylation of alkyl halides (X = I, Br, Cl) enabled by electroreduction is reported. This process provides an efficient and practical access to primary, secondary, and tertiary boronic esters at a high current. More than 70 examples, including the late-stage borylation of natural products and drug derivatives, are furnished at room temperature, thereby demonstrating the broad utility and functional-group tolerance of this protocol. Mechanistic studies disclosed that B2cat2 serves as both a reagent and a cathodic mediator, enabling electroreduction of difficult-to-reduce alkyl bromides or chlorides at a low potential.

Site-selective C-H activation and regiospecific annulation using propargylic carbonates.

Herein we describe an unprecedented RuII-catalyzed site-selective and regiospecific annulation of benzoic acids with propargylic carbonates. The weakly coordinating carboxylic acid moiety outperformed other typically used directing groups in C-H activation, including ketone, nitrile, sulfonamide, amide and strongly coordinating nitrogen heterocycles. This is an important step towards the application of C-H activation reactions in complex (functional) real-world molecules.

MnI /AgI Relay Catalysis: Traceless Diazo-Assisted C(sp2 )-H/C(sp3 )-H Coupling to ß-(Hetero)Aryl/Alkenyl Ketones.

An unprecedented MnI /AgI -relay-catalyzed C(sp2 )-H/C(sp3 )-H coupling of (vinyl)arenes with α-diazoketones is reported, wherein the diazo group was exploited as a traceless auxiliary for control of regioselectivity. Challenging ß-(hetero)aryl/alkenyl ketones were obtained through this operationally simple approach. The cascade process merges denitrogenation, carbene rearrangement, C-H activation, and hydroarylation/hydroalkenylation. The robustness of this method was demonstrated at preparative scale and applied to late-stage diversification of natural products.

Manganese(I)-Catalyzed C-H (2-Indolyl)methylation: Expedient Access to Diheteroarylmethanes.

An unprecedented MnI -catalyzed (2-indolyl)methylation of heteroarenes is reported. This method makes use of an aromatizing cascade strategy to install a (2-indolyl)methyl group into target molecules, thereby leading to the expedient synthesis of previously challenging and important unsymmetrical diheteroarylmethanes, in particular bis(2-indolyl)methanes. The proposed cascade process comprises the reorganization of multiple bonds with controlled regioselectivity and high atom economy and can be performed on a gram-scale. Furthermore, a metal-free C-H propargylation is observed. The diverse application of this method is also demonstrated.

Redox-Neutral Manganese(I)-Catalyzed C-H Activation: Traceless Directing Group Enabled Regioselective Annulation.

A strategy is reported in which traceless directing groups (TDGs) are used to promote the redox-neutral MnI -catalyzed regioselective synthesis of N-heterocycles. Alkyne coupling partners bearing a traceless directing group, which serves as both the chelator and internal oxidant, were used to control the regioselectivity of the annulation reactions. This operationally simple approach is highly effective with previously challenging unsymmetrical alkyne systems, including unbiased dialkyl alkynes, with perfect regioselectivity. The simple conditions and the ability to carry out synthesis on a gram scale underscore the usefulness of this method. The application of this strategy in the concise synthesis of the bioactive compound PK11209 and the pharmaceutical moxaverine is also described.

Manganese(I)-Catalyzed Regioselective C-H Allenylation: Direct Access to 2-Allenylindoles.

A MnI -catalyzed regioselective C-H allenylation is reported that allows a broad range of 2-allenylindoles to be synthesized regioselectively on a gram scale under simple conditions. Notably, a highly efficient chirality transfer was observed (up to 93 % ee) in this transformation. This procedure was further found to allow, for the first time, the direct preparation of ketones by MnI -catalyzed C-H activation. Mechanistic investigations revealed that the precoordination of the oxygen atom to the manganese center as well as the congested tertiary carbon atom in the propargylic carbonates play a crucial role.

Manganese-catalyzed allylation via sequential C-H and C-C/C-Het bond activation.

Manganese-catalyzed sequential C-H and C-C/C-Het bond activation to synthesize allylic alcohols, allylated arenes, functionalized cyclopentenes and skipped dienes is reported. This protocol can be readily scaled up and various coupling partners are applied in manganese catalysis for the first time. Moreover, manganese-catalyzed alkenyl C(sp2)-H activation is also shown. Complimentary to the standard solution-based protocols, these reactions also proceed efficiently under neat conditions, which is unprecedented for abundant metal catalyzed C-H activation reactions.

Markovnikov-Selective Radical Addition of S-Nucleophiles to Terminal Alkynes through a Photoredox Process.

Direct radical additions to terminal alkynes have been widely employed in organic synthesis, providing credible access to the anti-Markovnikov products. Because of the Kharasch effect, regioselective control for the formation of Markovnikov products still remains a great challenge. Herein, we develop a transition-metal-free, visible light-mediated radical addition of S-nucleophiles to terminal alkynes, furnishing a wide array of α-substituted vinyl sulfones with exclusive Markovnikov regioselectivity. Mechanistic investigations demonstrated that radical/radical cross-coupling might be the key step in this transformation. This radical Markovnikov addition protocol also provides an opportunity to facilitate the synthesis of other valuable α-substituted vinyl compounds.

Radical Enantioselective C(sp3 )-H Functionalization.

Radical style: Several breakthroughs have recently been achieved in enantioselective C(sp3 )-H functionalization through radical activation. These new strategies show how radical chemistry can be used to convert alkanes into functionalized chiral molecules (see scheme; HAT=hydrogen atom transfer).

Dioxygen-induced oxidative activation of a P-H bond: radical oxyphosphorylation of alkenes and alkynes toward ß-oxy phosphonates.

The dioxygen-induced radical oxyphosphorylation of alkenes and alkynes is presented, wherein a P-H bond was activated by molecular oxygen. Various ß-oxy phosphonates could be facilely synthesized without the assistance of any transition metals or extra organic initiators. Mechanistic studies showed that HP(O)Ph2 acts as a reductant to accelerate oxyphosphorylation.

Regio- and Stereoselective Oxysulfonylation of Allenes.

A highly regio- and stereoselective oxysulfonylation of allenes was developed that provided direct access to 2-sulfonyl allylic alcohols in good yields. By means of dioxygen activation, selective difunctionlization of allenes could be successfully achieved under mild metal-free conditions. Preliminary mechanistic investigation disclosed that this transformation probably goes through a radical process.

Catalyst-Free Difunctionalization of Activated Alkenes in Water: Efficient Synthesis of ß-Keto Sulfides and Sulfones.

Difunctionalization of activated alkenes, a powerful strategy in chemical synthesis, has been accomplished for direct synthesis of a series of ß-keto sulfides and ß-keto sulfones. The transformation, mediated by O2 , proceeds smoothly in water and without any catalyst. Prominent advantages of this method include mild reaction conditions, purification simplicity, and gram-scale synthesis, underlining the practical utility of this methodology.

Solvent-Enabled Radical Selectivities: Controlled Syntheses of Sulfoxides and Sulfides.

Controlling selectivity is of central importance to radical chemistry. However, the highly reactive and unstable radical intermediates make this task especially challenging. Herein, a strategy for taming radical redox reactions has been developed, in which solvent-bonding can alter the reactivity of the generated radical intermediates and thereby drastically alter the reaction selectivity at room temperature. Various ß-oxy sulfoxides and ß-hydroxy sulfides can be facilely obtained, some of which are difficult to synthesize by existing methods. Notably, neither a metal catalyst nor any further additives are necessary in these processes.