Electrochemical Benzylic C-H Amination via N-Aminopyridinium.

An electrochemical protocol for benzylic C(sp3)-H aminopyridylation via direct C-H/N-H cross-coupling of alkylarenes with N-aminopyridinium triflate has been developed. This method features excellent site-selectivity, broad substrate scope, redox reagent-free and facile scalability. The generated benzylaminopyridiniums can be readily converted to benzylamines via electroreductive N-N bond cleavage.

Electrochemical chemoselective hydrogenation of 1,4-enediones with HFIP as the hydrogen donor: scalable access to 1,4-diketones.

A straightforward electrochemical protocol for efficient hydrogenation of unsaturated CC bonds has been reported in an undivided cell. A series of versatile 1,4-diketones are smoothly generated under metal-free and external-reductant-free electrolytic conditions. Moreover, the tolerance of various functional groups and decagram-scale experiments have shown the practicability and potential applications of this methodology. Moreover, a range of heterocyclic compounds were easily prepared through follow-up procedures of 1,4-diketones.

SO42- ions as a nucleophilic reagent: straightforward electrochemical access to organosulfates.

An electrooxidation direct difunctionalization of alkynes with sulfonyl hydrazides has been developed for the construction of sulfonyl alkenyl sulfates in the absence of metal catalysts and a stoichiometric amount of oxidants. Notably, it is the first example to verify that SO42- ions can act as a nucleophilic reagent for the preparation of organosulfates.

Selective Electrochemical Synthesis of 9-Aryl-10-sulfonyl Substituted Phenanthrene from Alkynes and Sulfonyl Hydrazides.

An efficient electrochemical synthesis of sulfonated phenanthrenes via the reaction of internal alkynes with sulfonyl hydrazides has been established. The protocol does not require a metal catalyst or external oxidants, providing a green and mild route to functionalized phenanthrenes. Moreover, the compatibility of various functional groups and decagram-scale experimental conditions demonstrate the practicality of the electrochemical strategy.

Electrochemically-promoted synthesis of benzo[b]thiophene-1,1-dioxides via strained quaternary spirocyclization.

We report an approach for the synthesis of benzothiophene motifs under electrochemical conditions by the reaction of sulfonhydrazides with internal alkynes. Upon the formation of a quaternary spirocyclization intermediate by the selective ipso-addition instead of an ortho-attack, the S-migration process was rationalized to lead to the products. Computational studies revealed the selectivity and the compatibility of drug molecules showcased the potential application of the protocols.

Electrochemically Promoted [3 + 2] Annulation of Imidazo[1,2-a]pyridine with Alkynes.

The efficient electrochemically promoted [3 + 2] annulation of imidazo[1,2-a]pyridines with alkynes using traceless electrons as green reagents has been developed, leading to the synthesis of a large class of polycyclic heteroaromatics in good yields with a broad substrate scope under mild and green conditions. The scaled-up experiment, follow-up procedures, and potential biological applications show the practicability and feasibility of the electrochemical method.

Iridium-Catalyzed Selective B(4)-H Amination of o-Carboranes with Anthranils.

We report here a catalytic selective cage B4-H amination of o-carboranes employing an Ir(III) complex as a catalyst and anthranils as aminating agents, leading to a large class of B4-aminated o-carboranes with very high yields and a broad substrate scope under mild conditions without any oxidants. In these reactions, the carboxyl group serves as a traceless directing unit to determine the site selectivity and degree of substitution.

Hypervalent iodine promoted the synthesis of cycloheptatrienes and cyclopropanes.

A new strategy is reported for intramolecular Buchner-type reactions using PIDA as a promotor. Traditionally, the Buchner reaction is achieved via Rh-carbenoids derived from RhII catalysts with diazo compounds. Herein, the first metal-free Buchner-type reaction to construct highly strained cycloheptatriene- and cyclopropane-fused lactams is presented. The advantage of these transformations is in their mild reaction conditions, simple operation, broad functional group compatibility and rapid synthetic protocol. In addition, scaled-up experiments and a series of follow-up synthetic procedures were performed to clarify the flexibility and practicability of this method. DFT calculations were carried out to clarify the mechanism.

Iridium-Catalyzed Selective B(4)-H Acylmethylation of o-Carboranes with Sulfoxonium Ylides.

A highly efficient Ir-catalyzed regioselective cage B(4)-H acylmethylation of o-carboranyl acids using sulfoxonium ylides as alkylating regents has been developed, leading to the preparation of a large class of B(4)-acylmethylated o-carboranes in good to excellent yields with a broad substrate scope under redox neutral conditions. The -COOH moiety serves as the traceless directing group and controls the regioselectivity and monoselectivity.

Contamination and ecological risks of steroid metabolites require more attention in the environment: Evidence from the fishing ports.

Due to strong endocrine disrupting effects, steroids in the environment have attracted substantial attention, with studies mostly focusing on the parent steroids. Here, we conducted the first investigation on the contamination profiles, possible sources, mass inventories, and ecological risks of 27 steroids and their metabolites in 15 typical fishing ports in Southeast China. Twelve steroids were detectable in the sediment samples with the total mean concentrations of 4.6-35 ng/g. High proportions of steroid metabolites were measured in the sediments and five metabolites were newly observed. Untreated municipal sewage and aquaculture wastes constitute the possible steroid sources in the studied fishing ports. The total inventories of steroids in fishing ports ranged from 2.1-16 mg/m2, with their metabolites being important contributors. The ecological risk analysis indicated high risks across all sampling sites mainly due to the contributions of parent steroids. Furthermore, our results found that progesterone is an acceptable chemical indicator for various steroids in sediments. This study provides the first evidence of steroid metabolites in the marine environment, calling for more studies in environmental behavior and ecotoxicology of steroid metabolites.

Nickel-promoted oxidative domino Csp3-H/N-H bond double-isocyanide insertion reaction to construct pyrrolin-2-ones.

The first nickel-catalyzed oxidative domino Csp3-H/N-H double isocyanide insertion reaction of acetamides with isocyanides has been developed for the synthesis of pyrrolin-2-one derivatives. A wide range of acetamides bearing various functional groups are compatible with this reaction system by utilizing Ni(acac)2 as a catalyst. In this transformation, isocyanide could serve as a C1 connector and insert into the inactive Csp3-H bond, representing an effective way to construct heterocycles.

The ruthenium(ii)-catalyzed C-H olefination of indoles with alkynes: the facile construction of tetrasubstituted alkenes under aqueous conditions.

An environmentally-friendly and facile protocol for the construction of tetrasubstituted alkenes has been established with Ru(ii)-catalyzed C-H bond functionalizations under mild conditions. The method features the usage of readily available substrates, without external oxidants and additives, 100% atom economy, and excellent regioselectivity, thus enhancing the practicability of this protocol. Moreover, this transformation proceeded smoothly under aqueous conditions and could be extended to the gram scale. N-Methoxyamide, as a directing group (DG), played a vital role in the transformation.

Fast construction of isoquinolin-1(2H)-ones by direct intramolecular C-H/N-H functionalization under metal-free conditions.

The general protocol for the synthesis of isoxazolidine-fused isoquinolin-1(2H)-ones was established with the help of bench stable hypervalent iodine reagent PIDA. Polycyclic six-, seven- and eight-membered N-heterocycles can be rapidly synthesized from available amides under metal-free conditions within 1 min at room temperature through C-H/N-H functionalization. Moreover, the protocol has the merits of broad substrate scope, atom economy and operational simplicity.

Silver-promoted regioselective [4+2] annulation reaction of indoles with alkenes to construct dihydropyrimidoindolone scaffolds.

An AgI-promoted regioselective [4+2] annulation reaction of indoles with alkenes has been established. During the transformation, N-centered radicals are generated by the oxidation of the N-H bond of N-alkoxyamides. Control experiments and DFT calculations reveal a plausible mechanism. This synergistic process achieves the direct construction of new C-C and C-N bonds under relatively mild conditions with broad substrate scope, high atom economy, and easy-to-handle nature.

N-Phenoxyamides as Multitasking Reagents: Base-Controlled Selective Construction of Benzofurans or Dihydrobenzofuro[2,3- d]oxazoles.

An efficient method to selectively construct benzofuran and dihydrobenzofuro[2,3- d]oxazole derivatives has been successfully established by means of base-controlled cyclization of N-phenoxyamides with 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1 H)-one (TIPS-EBX). N-phenoxyamides as multitasking reagents have triggered two different cascade reaction sequences. This is the first example of using TIPS-EBX for the transformation of C(sp) to either C(sp2) or C(sp3) under metal-free conditions.

Construction of Benzofuran-3(2 H)-one Scaffolds with a Quaternary Center via Rh/Co Relay Catalyzed C-H Functionalization/Annulation of N-Aryloxyacetamides and Propiolic Acids.

An unprecedented synthesis of valuable benzofuran-3(2 H)-one scaffolds with a quaternary center was developed via Rh/Co relay catalyzed C-H functionalization/annulation of N-aryloxyacetamides with propiolic acids in moderate to good yields. The reaction features the simultaneous construction of the benzofuran motif containing a C2 quaternary center and a C3 carbonyl group. The preliminary mechanism study verified that the O atom of C3 carbonyl group originates from molecular oxygen.

Cobalt(II)-Catalyzed C-H Amination of Arenes with Simple Alkylamines.

A new method of cobalt-catalyzed amination of arylamides with simple alkylamines is reported through C(sp(2))-H bond functionalization. For the first time, inexpensive cobalt is exploited as the catalyst in the amination of C(sp(2))-H bond using simple alkylamines.

Cobalt(II)-Catalyzed C(sp2)-H Alkynylation/Annulation with Terminal Alkynes: Selective Access to 3-Methyleneisoindolin-1-one.

A highly efficient cobalt(II)-catalyzed alkynylation/annulation of terminal alkynes assisted by an N,O-bidentate directing group is described. This protocol is characterized by wide substrate scope utilizing cheap cobalt catalysts, and offers a new approach to 3-methyleneisoindolin-1-one, which can be converted into an oxadiazine salt in one step. Moreover, the directing group could be removed in three steps.

Mechanistic insights into cobalt(ii/iii)-catalyzed C-H oxidation: a combined theoretical and experimental study.

Cobalt-mediated C-H functionalization has been the subject of extensive interest in synthetic chemistry, but the mechanisms of many of these reactions (such as the cobalt-catalyzed C-H oxidation) are poorly understood. In this paper, possible mechanisms including single electron transfer (SET) and the concerted metalation-deprotonation (CMD) pathways of the CoII/CoIII-catalyzed alkoxylation of C(sp2)-H bonds have been investigated for the first time using the DFT method. CoII(OAc)2 has been employed as an efficient catalyst in our previous experimental study, but the calculated results unexpectedly indicated that the intermolecular SET pathway with CoIII as the actual catalyst might be the most favorable pathway. To support this theoretical prediction, we have explored a series of Cp*CoIII(CO)I2 catalyzed C(sp2)-H bond alkoxylations, extending the application of cobalt-catalyzed functionalization of C-H bonds. Furthermore, kinetic isotope effect (KIE) data, electron paramagnetic resonance (EPR) data, and TEMPO inhibition experiments also support the SET mechanism in both the Co-catalyzed alkoxylation reactions. Thus, this work should support an understanding of the possible mechanisms of the CoII/CoIII-catalyzed C(sp2)-H functionalization, and also provide an example of the rational design of novel catalytic reactions guided by theoretical calculations.

Cobalt-catalyzed C(sp(2))-H alkoxylation of aromatic and olefinic carboxamides.

The cobalt-catalyzed alkoxylation of C(sp(2) )H bonds in aromatic and olefinic carboxamides has been developed. The reaction proceeded under mild conditions in the presence of Co(OAc)2 ⋅4H2 O as the catalyst and tolerates a wide range of both alcohols and benzamide substrates, including even olefinic carboxamides. In addition, this reaction is the first example of the direct alkoxylation of alkenes through CH bond activation.