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A convenient, transition-metal-free access to a series of unprecedented saccharin substituted 2,5-dihydropyrroles is reported. This approach employs a post-Ugi–Smiles 5-endo-dig Conia–ene cyclization sequence under mild conditions while incorporating a series of readily available precursors and sodium azide substrate as a catalyst for the cyclization step. The method provides a broad scope of 2,5-dihydropyrrole derivatives in good yields.

Designing antibody-powered DNA nanodevice switches is crucial and fascinating to perform a variety of functions in response to specific antibodies as regulatory inputs, achieving highly sensitive detection by integration with simple amplified methods. In this work, we report a unique DNA-based conformational switch, powered by a targeted anti-digoxin mouse monoclonal antibody (anti-Dig) as a model, to rationally initiate the hybridization chain reaction (HCR) for enzyme-free signal amplification. As a proof-of-concept, both a fluorophore Cy3-labeled reporter hairpin (RH) in the 3' terminus and a single-stranded helper DNA (HS) were individually hybridized with a recognition single-stranded DNA (RS) modified with Dig hapten, while the unpaired loop of RH was hybridized with the exposed 3'-toehold of HS, isothermally self-assembling an intermediate metastable DNA structure. The introduction of target anti-Dig drove the concurrent conjugation with two tethered Dig haptens, powering the directional switch of this DNA structure into a stable conformation. In this case, the unlocked 3'-stem of RH was implemented to unfold the 5'-stem of the BHQ-2-labeled quench hairpin (QH), rationally initiating the HCR between them by the overlapping complementary hybridization. As a result, numerous pairs of Cy3 and BHQ-2 in the formed long double helix were located in spatial proximity. In response to this, the significant quenching of the fluorescence intensity of Cy3 by BHQ-2 was dependent on the variable concentration of anti-Dig, achieving a highly sensitive quantification down to the picomolar level based on a simplified protocol integrated with enzyme-free amplification.

An InCl3-catalyzed atom-economic intramolecular 5-exo-dig cyclization/1,6-conjugate addition/aromatization of N-propargylamides with p-QMs to produce oxazoles tethering diarylmethane has been successfully developed. InCl3 not only served as Lewis acid to catalyze the cyclization of propargylic amides but also activated the carbonyl of p-QMs to achieve the 1,6-addition process in a one-pot manner. The reaction has attractive features, including mild reaction conditions, broad scope of substrates, good yields, and scalability.

An efficient approach for the synthesis of immobilized copper (triazole-5-yl)methanamine complexes onto MCM-41 (Cu@TZMA@MCM-41), as a novel recyclable nanocatalyst, is described. This nanocatalyst was used for the synthesis of pyridine-containing pseudopeptides through a sequential Ugi/nucleophilic addition/1,5-enyne cyclization reaction and elicited good-to-excellent yields. The nanocatalyst was fully characterized by SEM, EDS, TEM, BET, ICP-OES, TGA, and XRD techniques. Furthermore, the catalyst was recovered by simple filtration and could be used for at least 5 cycles without significant loss of activity.

The development of simple, flexible, cost-effective and sensitive electrochemical biosensing strategies is highly desirable to advance their applications in disease diagnostics and clinical biomedicine. Herein, we fabricated a new enzyme-based electrochemical aptasensor with the use of adenosine triphosphate (ATP) and thrombin as model targets on the basis of a responsive surface bioaffinity binding strategy. It took full advantage of an immobilized complex duplex probe (hybrids of a hairpin-like aptamer probe with a digoxigenin (Dig)-labeled immobilization strand) to effectively inhibit the approach of the bulky horseradish peroxidase linked-anti-Dig antibody (anti-Dig-HRP) to the Dig on the electrode due to the steric effect. The target recognition dissociated the aptamer strand from the duplex probe and exposed the Dig for its effective binding with anti-Dig-HRP. The successive electrocatalysis offered a significantly amplified electrochemical signal correlated with the target recognition event. Sensitive detection toward ATP and thrombin was achieved with detection limits of 0.87 nM and 6.3 pM, respectively. The proposed strategy is simple and sensitive without any complex operations that hinder many amplified aptasensors. Also, the target recognition and signal reporting units are relatively isolated, making the biosensor fabrication more flexible. It thus provided a new and versatile pathway for sensitive biosensor fabrication.

An efficient method was developed for the synthesis of substituted aryl-fused pyrazolooxazepines from ortho-O-propargyl aryl pyrazoles by gold catalysis. In this organic transformation a new C-N bond was formed regioselectively via 7-exo-dig cyclization. Moderate to good yields of aryl-fused pyrazolooxazepine derivatives were obtained with significant molecular complexity in one-pot.

The first examples of highly diastereoselective tandem 8/9-endo-dig and 8-exo-dig hydroalkoxylation-formal-[4 + 2] cycloaddition are described for the synthesis of medium ring heterocycle-fused chromenes. TMS-alkynols preferred the exo-dig mode of hydroalkoxylation over the endo-dig mode leading to spiro-cyclic chromenes. The method could be used for the synthesis of linearly-fused ladder-like polyethers. A thia-heterocycle-fused chromene could be transformed into a complex bridged tricyclic ketal by a tandem carbene-insertion-[2,3]-sigmatropic shift.

A palladium and iodine-cocatalyzed 5-exo-dig aza-thiocyclization of 8-alkynylnaphthalen-1-amines for the synthesis of (E)-2-alkylene-1,2-dihydrobenzo[cd]indole thioethers is reported. As a result of broad reaction scope, simple operation, mild conditions, and high stereoselectivity and regioselectivity, this reaction should have potential utility in organic synthesis.

Pyrazoles are important heterocyclic compounds with a broad range of biological activities. A new procedure toward tri- or tetrasubstituted pyrazoles has been developed, via a one-pot gold catalyzed synthesis from hydrazines with alkynyl aldehydes or ketones. The reaction proceeds through consecutive hydrazone formation, 5-endo-dig cyclization and an aza-Claisen rearrangement resulting in the desired polysubstitued pyrazoles.

A TBAB-mediated brominative 5-exo-dig oxy-cyclization of 2-alkynylbenzamide is described here for the synthesis of isobenzofuran-1-imines and isobenzofuran derivatives at room temperature with a high efficiency and a broad reaction scope. The resulting isobenzofuran derivatives are also applied for synthesising various substituted isobenzofuran derivatives.

An efficient and concise procedure has been developed for the synthesis of functionalized 2-aryl-4H-chromenes based on a tandem reaction of propargylamines and benzoylacetonitriles/malononitriles in the presence of FeCl3 as an environmentally friendly promoter. This reaction involves a highly efficient tandem sequence consisting of 1,4-conjugate addition, 6-endo-dig cyclization, and oxidation. This protocol tolerates a variety of functional groups, thereby providing a practical and efficient method for the fabrication of 2-aryl-4H-chromene skeletons.

A di-tert-butyl peroxide-promoted radical rearrangement of N-sulfonyl-N-aryl propynamides has been developed. This procedure proceeds with sequential homolytic N–SO2 bond cleavage and 6-endo-dig radical cyclization to access a variety of 2-sulfonyl-3-aryl-2(1H)-quinolinones with high atom economy. The cross experiment confirmed the involvement of an intermolecular rearrangement, which was triggered by the thermo-induced homolytic cleavage of the N–SO2 bond.

New S-doped yttrium oxide ultrathin nanosheets (NSs) were synthesized which had good electrochemiluminescence (ECL) properties. Through combining these NSs with small molecule linked DNA as the substrate, a novel ECL biosensor was constructed for the detection of protein biomarkers with an acceptable performance.

A convenient method for the facile synthesis of 1-trifluoromethyl-3-alkylidene-1,3-dihydrofuro[3,4-b]quinolines was developed from the TBAB-catalyzed nucleophilic addition/cyclization reaction of o-arylalkynylquinoline aldehydes with trimethyl trifluoromethyl silane, cesium fluoride, and water; the product was obtained in good to excellent yields. The reaction proceeded smoothly via 5-exo-dig selectivity and anti co-planarity addition, affording Z-selective products in an aerobic atmosphere at room temperature. The dihydrofuroquinoline derivatives formed are structurally related to the well-known furoquinoline alkaloids of the rutaceae family.

A new silver-mediated 5-exo-dig cyclization of 2-alkynylbenzonitriles with disubstituted phosphine oxide and H2O has been developed. The reaction enables multiple bond-forming events including C–P, C–C and C–O bonds under atmospheric conditions, leading to the concise and direct formation of 28 examples of phosphorus-containing 1-indenones with generally good yields.

An efficient synthesis of nitrogen ring junction pyrimido-indazoles has been developed. This is a metal catalyzed transformation that proceeds via A3 coupling reaction between 1H-indazol-3-amine, aromatic aldehydes and alkynes, which undergoes 6-endo-dig cyclization leading to the highly functionalized pyrimido[1,2-b]indazoles. Response surface methodology (RSM) was used to investigate the effect of catalyst (A1), reaction temperature (B1) and time (C1). The fluorescence quantum yields of the pyrimido[1,2-b]indazoles were calculated.

This manuscript describes a study on relatively unexplored halogen mediated 7-exo-dig/trig cyclization reactions of 2-(2-amino-aryl)-3-prop-2-ynyl/allyl-thiazolidin-4-ones for the formation of thiazole condensed 1,4-benzodiazepines in good yields. The reactions are facile, chemoselective and involve the use of simple substrates leading to synthesis of diversely functionalized 1,4-benzodiazepines. The synthesis of such condensed 1,4-benzodiazepines is important in terms of their usefulness as biological active agents.

An efficient and highly regio-selective synthesis of fused & substituted furans has been described using Ca(OTf)2 as the catalyst. This tandem process involves alkylation, 5-exo dig cyclisation and isomerization to furnish densely substituted furans under solvent free conditions. A case study of regioselectivity has been demonstrated.

A concise synthesis of functionalized indene derivatives via the gold(i)-catalysed cascade C-H functionalization/conia-ene type reaction of electron-rich aromatics with o-alkynylaryl α-diazoesters has been developed. In this transformation, the gold catalyst not only catalysed the formation of the zwitterionic intermediate via intermolecular C-H functionalization but promoted the subsequent intramolecular 5-endo-dig cyclization via activation of alkynes. The reaction is characterized by high chemo- and site-selectivity, readily available starting materials, nice functional-group tolerance and mild reaction conditions.

A highly effective 6-endo dig cyclisation of o-alkynylaldimines to 1,2-dihydroisoquinolines has been described via direct and nitro Mannich condensation using inexpensive and readily available cobalt chloride as catalyst. This strategy provides an effective procedure for the synthesis of substituted 1,2-dihydroisoquinolines derivatives in moderate to high yields. An addition of pronucleophiles, such as nitromethane, acetone and α-hydroxyacetone, to o-alkynylarylaldimines has been achieved via isoquinolinium intermediate.

α-Amino allenylphosphonates were treated with cerium(iv) ammonium nitrate under various conditions to form spirodienones in good to excellent yields. The 5-endo-dig cyclization proceeds through the formation of a key iminium intermediate. A comprehensive study on the nature of the solvent used for this reaction was undertaken resulting in the formation of three types of spirodienone scaffolds.

Phthalides have been synthesized exclusively in one pot via Pd-free Sonogashira coupling. A Cu-catalyzed domino Sonogashira coupling and 5-exo-dig cyclization between suitable substituted ortho-bromobenzoic acids and terminal alkynes afforded phthalides in good yields under mild reaction conditions.

A metal-free facile and efficient two-step synthetic protocol for the preparation of 1,4-benzoxazepine-5(2H)-one derivatives has been developed. The protocol involves Ugi reaction followed by K2CO3 mediated highly regioselective 7-exo-dig intramolecular cyclization of less-nucleophilic oxygen with the pendant alkyne moiety of an Ugi-propargyl precursor to afford the 1,4-benzoxazepine-5(2H)-one derivatives in good to excellent yields.

Double-tagged DNA coming from PCR amplification of a Salmonella spp. sample was detected by an electrochemical impedimetric genosensor based on avidin bulk-modified graphite-epoxy biocomposite (Av-GEB). The double-tagging PCR strategy provided the amplicon with both biotin and digoxigenin (DIG) moieties. The immobilization of the double-tagged DNA was based on its biotin moiety, while the DIG label was used for signal amplification. Impedance spectra were recorded to detect the change in interfacial charge transfer resistance (R(ct)), experimented by the redox marker ferri-/ferro-cyanide after the avidin-biotin fixation of the sample DNA onto the electrode surface. A further step in the genosensing strategy was the amplification of impedimetric signal by the use of an enhancing procedure. The latter was based on the reaction of the DIG moiety belonging to the amplicon with an anti-DIG antibody from mouse. Two different secondary enhancing steps based both on gold nanoparticle-labelled anti-mouse IgG or on Protein G were performed and compared for improving assay sensitivity.

A representative series of homopropargylic sulfonamides 19 and 22b have been found to undergo smooth 5-endo-dig cyclisation upon exposure to excess iodine in acetonitrile containing potassium carbonate. The resulting 4-iodo-2,3-dihydropyrroles 23 readily react with two equivalents of DBU in DMF at 20 °C to give the corresponding β-iodopyrroles 24 and 26 in excellent yields by the elimination of toluene-p-sulfinic acid. Use of less than two equivalents of base results in some loss of iodine. The iodo-2,3-dihydropyrroles 23 can be used in palladium-catalysed coupling reactions as shown by the efficient formation of the Sonogashira product 29 under mild conditions.

The synthesis of acetylenic amides from 2-bromoaniline and propiolic acids followed by their cyclisation via the derived aryl radical is presented. Silylation of the terminal end of the triple bond is shown to be required for successful cyclisation to 3-methyleneindol-2(3H)-ones. The exocyclic double bond can be epoxidised using m-chloroperoxybenzoic acid (MCPBA).

The Pd(II)-SDP-catalyzed first enantioselective intramolecular cyclization of α,α-disubstituted γ-alkynoic acids is described. This 5-exo-dig cyclization afforded dihydrofuran-2(3H)-ones bearing a chiral quaternary carbon center in excellent yields with enantioselectivities up to 71%. A mechanism involving palladium(II) species is proposed to rationalize the outcome of the reaction.

5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.

A new entry for the synthesis of functionalized arylidene cyclopentenes under metal-free reaction conditions is disclosed via the base-promoted [4 + 1]-annulation of Morita-Baylis-Hillman acetates of acetylenic aldehydes with active methylene derivatives involving tandem allylic substitution followed by 5-exo-dig-carbocyclization.

A novel method was developed for the preparation of N-fused heterocycles via a Csp–S coupling reaction and a sequence of 5-endo-dig cyclization. This method involves the reaction of –NHC(S)NH-containing compounds and alkynes in the presence of CuCl and N,N′-dicyclohexylimidazolium chloride.

Intramolecular radical hydrosilylations using allyloxy- and propargyloxycyclohexadienylsilanes comprising 5-endo-trig as well as 5-endo-dig processes are presented.

Serial radical cyclisation on sugar-furanose templates to create angularly fused oxa- and dioxa-triquinane skeletons has been described, the salient feature of this approach being to incipiently generate a tertiary radical from cyclopropylmethyl bromide with simultaneous release of allyl group and to subsequently incorporate it in the triquinane system.

The tin-mediated tandem 5-exo-dig-5-exo-trig radical cyclization of dibromoacetal 4a stereoselectively gives the angular 6,5,5-ring fused tricycle 6via spirocyclic acetal 5 in 93% yield.

Reaction of [Yb(CpPh5)(C[triple bond]CPh)(thf)]2 (CpPh5 = pentaphenylcyclopentadienyl), prepared from Yb(C triple bond CPh)2 and HCpPh5 or Yb metal, HgPh(C[triple bond]CPh) and HCpPh5, with a controlled amount of diglyme (dig), and of Eu(C triple bond CPh)2, P triple bond CBut and dig, yield the unusual organolanthanoid(II) dicationic complexes [Yb(C[triple bond]CPh)(dig)(thf)2]2[CpPh5]2.4thf and [Eu(C triple bond CPh)(dig)2]2[P2C3But3]2 respectively.