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α-Alkyl and α-aryl vinyl azides were found to be able to couple with cysteine-derived alkyl thiols chemoselectively under mild conditions, providing the corresponding β-ketosulfides with simultaneous extrusion of N2 and ammonia.

An electrochemical oxidative thio(seleno)cyanation of enamides to synthesize various (E)-β-thio(seleno)cyanated enamide compounds is reported herein.

A new cobalt-catalyzed hydroazidation of 1-aryl-1,3-dienes by using TMSN3 as a nucleophilic azide source under mild conditions has been reported, leading to the synthesis of a wide range of allylic azides with moderate to good yields.

When treated with an alkoxide base like t-BuOK in aprotic solvent, N-diphenylmethyl imino oxindoles, made conveniently through condensation of corresponding isatins with N-diphenylmethyl amine, are deprotonated to form azaallyl anions. Allylation and alkylation of this type of intermediates proceed smoothly with diverse C-electrophiles. Acidic work up finishes 3-amino-3-allyl/alkyl oxindoles. The overall transformation equals to an umpolung process at the C3 of isatins.

Cyclopropenes carrying an alkene moiety undergo a stereoselective Alder-ene cycloisomerization under thermal conditions. Diverse functionalized (hetero)spiro[2.4]heptanes are obtained with excellent trans diastereoselectivity. According to computational studies, this thermal process takes place via transition state TS(E-exo) or TS(Z-endo) if the former is not available.

A ruthenium based catalytic system ([Ru(p-cymene)Cl2]2/XantPhos with substoichiometric Cs2CO3) has been established to effectively achieve the first direct amination cyclization of 1,2,4-butanetriol with primary aromatic amines. The product of this sustainable hydrogen autotransfer process is valuable N-aryl-3-pyrrolidinol.

Promoted by a silver catalyst, 1,6-enynamides with a cyclic ene moiety can undergo cycloisomerization to fused N-heterobicycles. This transformation presents an unusual type II Alder-ene reaction and is believed to proceed through a catalytic cycle of formation of a keteneiminium silver intermediate, subsequent 6-endo-trig cyclization and protodemetalation.

Although vinyl azide is an important class of functional group that possesses diverse reactivities and is a convenient synthon for N-heterocycles, cyclic vinyl azide remains underdeveloped due to difficult preparation. This work discloses a rhodium catalyzed intramolecular [4 + 2] cycloaddition reaction that can afford challenging fused bicyclic vinyl azides efficiently in ambient conditions and paves a facile route for the research in the chemistry of cyclic vinyl azides.

Intramolecular imino-ene reaction of 2 H-aziridine has been studied experimentally and computationally, demonstrating that (1) the concerted process takes place regioselectively on the alkene E-CH group; (2) the geometry of the N-linker impacts the reaction activation energy and diastereoselectivity significantly, with pyramidal alkyl amine as the linkage, an exclusive cis-product is achieved; (3) when the reaction has to occur with the Z-CH group, the cis-diastereoselectivity is solely observed regardless of the nature of the N-linkage.

A copper catalyzed intramolecular 1,2-carboboration of o-aldiminyl cinnamate has been realized in both regio- and stereoselective fashions. This reaction provides a convenient entry to highly valuable and otherwise challenging cis-2,3,4-trisubstituted tetrahydroquinolines carrying a 4-boryl group. An unusual non-Michael addition intermediate or alternatively, a cyclic enolate is proposed to account for the intriguing all-cis configuration in the final products.

The addition reaction of thiol to vinyl azide has been extensively studied. Variously substituted aryl thiols are all viable for this coupling process. The scope of the other partner is successfully expanded from α-aryl vinyl azide to α-alkyl vinyl azide. A thiol–vinyl azide coupling/cyclization cascade is realized with substituted aryl vinyl azides carrying a 2-methoxycarbonyl group. The value of β-ketosulfide products was demonstrated by its application in S-heterocycle synthesis.

A t-BuOCu-initiated reaction sequence of styrene borometalation and intramolecular imine addition has been achieved using a Cu(OTf)2/dppf combination as catalyst. The product of this reaction cascade is a useful 2,3-disubstituted indoline bearing a versatile boryl moiety and is formed with sole cis-selectivity. To account for the observation of the exclusive formation of cis-stereoisomers, a transition state featuring copper–imine coordination is suggested. The application to the synthesis of antioxidant tetrahydroindenoindoles is described.

A unique protocol for the synthesis of substituted and fused pyrroles has been developed through the iridium catalyzed fragmentation/cyclization of related N-butynyl 4,4-dimethylisoxazolidine-3,5-diones in hot ethanol. Both the substitution pattern and electronic properties can affect the reaction rate and yield.

A CuSO4 catalyzed ynamide formation/[4 + 2] cycloaddition relay reaction was achieved in one-pot. Various 4,7-cis-dihydroindolines were produced in good to high yields. The one-pot operation in conjunction with the cheap and benign copper catalysis renders this reaction highly sustainable.

A convenient rhodium catalyzed oxidative arene homologation of aniline derivatives with symmetrical or unsymmetrical alkynes using Cu(OAc)2 as oxidant is described. Urea group is shown to be effective as a directing group for initial ortho C–H activation. Two migratory insertion events of alkyne into Rh–C bond occur successively, both with complete regioselectivity. This method is particularly useful for synthesis of polyarenes with different substituents, which has not been reported with conventional protocol. A mechanism has been proposed to explain the observed data.

A copper catalyzed intramolecular 1,2-carboboration of o-aldiminyl cinnamate has been realized in both regio- and stereoselective fashions. This reaction provides a convenient entry to highly valuable and otherwise challenging cis-2,3,4-trisubstituted tetrahydroquinolines carrying a 4-boryl group. An unusual non-Michael addition intermediate or alternatively, a cyclic enolate is proposed to account for the intriguing all-cis configuration in the final products.

The aza-Diels–Alder reaction of 2H-azirines with 1,3-dienes provides facile access to the structurally intriguing and difficult to access 1-azabicyclo[4.1.0]hept-3-ene scaffold. Its application in organic synthesis and medicinal chemistry is heavily hampered by the narrow substrate scope for both reacting partners. Herein, the discovery and exploration of this reaction are summarized and discussed. A recent breakthrough is an intramolecular version that overcomes the limitations of conventional methods.

Vinyl azide with a pendent diene can undergo thermal decomposition to a related azirine intermediate, which was used immediately in an intramolecular aza-Diels-Alder reaction to furnish an aziridine-containing trans-fused tricyclic core structure with excellent stereoselectivity. The method provides a facile entry to complex polycyclic alkaliods which can be further elaborated by ring-opening reactions and ring expansion of the aziridine moiety, as well as by dihydroxylation of the alkene group.

Most genetically modified crops are engineered for herbicide tolerance, among them, glyphosate tolerant crops have the greatest share. Glyphosate is one of the most extensively used herbicides worldwide. The popularity of glyphosate stems from its low cost, low environmental impact, and effectiveness while being safe for animals. The toxicity of glyphosate to untargeted organisms was studied using goldfish (Carassius auratus) after exposure to different concentrations of glyphosate isopropylamine salt, a glyphosate based herbicide for 96 hours. Tissues of brain, kidney and liver were collected and subjected to NMR-based metabolomics analysis and histopathological inspection. Plasma was collected and the hematological parameters of glutamic-oxaloacetic transaminase (GOT), glutamate-pyruvate transaminase (GPT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and creatinine (CRE) were quantified. Glyphosate produced an increase in the hematological parameters of BUN and CRE and dose-dependent injuries. Metabolomics analysis revealed significant perturbations in neurotransmitter equilibrium, energy metabolism and amino acid metabolism in glyphosate dosed fish, which are associated with the toxicity of glyphosate. The results highlight the vulnerability of glutaminergic neurons to glyphosate and enlighten the potential of glutamine as an early marker of glyphosate induced neurotoxicity.

A rhodium catalyzed regioselective coupling of thiirane with 1-sulfonyl-1,2,3-triazole has been realized to give a formal [3 + 3] cycloaddition product 3,4-dihydro-2H-1,4-thiazine via the 1,3-insertion model of azavinyl carbene. An acetic acid additive is used to improve the reaction in terms of both yield and rate.

A one-pot synthesis of N -alkyl acridone via rhodium catalyzed decomposition of N -phenyl-2-(1-sulfonyl-1 H -1,2,3-triazol-4-yl)aniline and subsequent oxidative C–C bond fragmentation has been developed. 14 examples are presented and the yields range from 30% to 80%.

A range of novel (poly)cyclic alkaloids incorporating an unprecedented 1,5-diazaspiro[2.4]heptane core that carry a spiro NH aziridine moiety and a 7-vinyl group are constructed from the thermal reaction of vinyl azides with tethered alkenes. Vinyl azides are converted to 2H-azirines in situ, which serve as enophiles for intramolecular imino-ene reactions with suitable alkenes. High stereoselectivity and specificity have been achieved for this novel intramolecular imino-ene reaction of azirines.

Three types of aza-bicycles, 3-azabicylo[4.1.0]heptane-6-carbaldehyde, 3-azabicylo[4.1.0]heptane-1-carbaldehyde, and 3-azabicyclo[5.1.0]octane-7-carbaldehyde, are constructed conveniently from corresponding carbene progenitors of N-allyl or N-homoallyl triazoles. Yields are modest to high. These transformations feature a key rhodium catalyzed intramolecular cyclopropanation of the pendent C–C double bond and show complete stereo specificity.

The toxic effects of AVM were investigated using a teleost experimental model, the juvenile goldfish (Carassius auratus). Goldfish were consecutively exposed to AVM for 7 days and then the tissues of brains, kidneys and livers and plasma were collected and subjected to a NMR based metabolomics study. AVM changed the metabolomic profiles of goldfish dose-dependently and significantly changed the levels of metabolites in dosed goldfish, such as the branch-chain amino acids (BCAAs), aromatic amino acids (AAAs), betaine, taurine, lactate, etc. These metabolite changes affect energy metabolism, amino acid metabolism, nucleic acids metabolism, osmotic equilibrium as well as redox equilibrium, and are related with the toxicity of AVM. 1H NMR-based metabolomics approach promises to be an advantageous tool for the systematic and holistic view of the response of aquatic organisms to pesticides and is thus suitable for the assessment of the environmental risk of pesticides and the understanding of the underlying mechanism.

A method for convenient synthesis of N-alkyl-2-aryl-indole-3-carbaldehyde has been described. A variety of highly valuable indolyl aldehydes have been prepared through this method. Electron donating groups on both aromatic rings (anilinyl and benzyl) facilitate the formation of the desired products. A benzylic C-H insertion by rhodium carbene is the key step for this transformation.

A copper(II) acetate catalyzed ring-opening cross-coupling of cyclopropanol with sulfonyl azide has been developed. By this method, various β-amino ketones have been made efficiently in medium to high yields and venerable functional groups such as benzylic C–H, alkyl and aryl bromides, alkyl sulfonate, silyl ether and alkene are compatible with these reaction conditions. Control experiments have precluded the involvement of both radical and simple copper nitrene intermediates and a possible mechanism featuring key steps of ring-opening metalation and alkyl group migratory insertion into copper nitrene has been proposed.

4-N-allylarylpropylamino-1-sulfonyl triazoles are converted to structurally unique benzopyrrolizidinyl sulfonamides in a one-pot operation. Intramolecular capture of rhodium carbene with arylamino nitrogen gives rise to the formation of an ammonium ylide immediate. A [2,3]- or [1,2]-rearrangement occurs to give a 2-allylpyrrolidinyl-2-carbimine intermediate which undergoes Cu(OTf)2 catalyzed aza-Friedel-Crafts cyclization to finish a highly functionalized tricyclic system decorated with a synthetically difficult quaternary carbon center, a sulfonamide group, and an allyl segment.

A practical method for a facile entry to structurally unique ring-fused dihydroazepine has been developed using 1-sulfonyl-1,3-dienyltriazole as starting materials. Driven by ring strain release of cyclopropyl group, a rhodium-catalyzed α-imino carbenoid formation–cyclopropanation–aza-Cope rearrangement cascade takes place efficiently in a single operation. Substitution effects on yield and diastereoselectivity are also explored.

An intramolecular ketene aza-Claisen rearrangement is developed for the first time to enable the stereoselective synthesis of α-ally-α-cyano-lactams from N-allyl amino esters. This reaction also exhibits outstanding chemoselectivity when an unsymmetrical bis-N-allyl group is present in the starting molecule. The usefulness of this method is demonstrated by a short synthesis of optically active bicyclolactam from l-proline.

There exist three possible patterns for the reaction of cyclic 2-oxazolidinethione and 2-benzoxazolidinethione with arynes, namely (a) S-arylation, (b) N-arylation, and (c) aryne insertion into the thiocarbonyl group (C[double bond, length as m-dash]S). Our studies demonstrate that S-arylation wins out affording S-aryl dihydrooxazoles. In contrast, for related reactions of cyclic 2-benzoxazolinone and 2-benzimidazolinone with arynes, it is found that N-arylation outcompetes O-arylation and aryne insertion into the C[double bond, length as m-dash]O group to give N-aryl 2-benzoxazolinones and N-aryl 2-benzimidazolinones.

N-Aryl-N-allyl-bis-functionalized amino-1-sulfonyl-1,2,3-trizoles undergo rhodium-catalyzed cyclization reactions and subsequent hydrolytic cleavage of the sulfonyl imine to give two structurally distinct N-heterocycles, 3-indolyl aldehydes and 3-azabicyclo[3,1,0]hexyl aldehydes. The product ratio can be tuned by varying the electronic properties of the two functional groups attached to the N atom. Based on these findings, two efficient and general methods for the synthesis of highly valuable 3-indolyl aldehydes and 3-azabicyclo[3,1,0]hexyl aldehydes have been developed.

An efficient and convenient synthesis of α-allyl cyclic amidines has been achieved by applying a novel cascade reaction. Copper(I)-mediated in situ N-sulfonyl ketenimine formation from the reaction of a terminal alkyne with sulfonyl azide is followed by an intramolecular nucleophilic attack on the central carbon atom by an allylic tertiary amine, and then an aza-Claisen rearrangement takes place through a chair transition state to furnish the titled amidines with complete stereocontrol.

Reactive benzyne generated from o-(trimethylsilyl)phenyl triflate under the action of CsF has been trapped in situ by thioethers to give sulfonium ylides, which in turn have been intercepted by isatins to give rise to corresponding spiroepoxy oxindoles in moderate to high yields. This reaction provides a facile and efficient synthesis of spiroepoxy oxindoles.