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Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.

An operationally simple, one-pot multicomponent reaction has been developed for the assembly of 9H-benzo[f]imidazo[1,2-d][1,2,3]triazolo[1,5-a][1,4] diazepines adorned with three diversification points via an atom-economical transformation incorporating α-diketones, o-azidobenzaldehydes, propargylic amines, and ammonium acetate. This process involves tandem InCl 3-catalyzed cyclocondensation and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions; optimization data, substrate scope, and mechanistic insights are discussed. © 2013 American Chemical Society.

The first synthesis of the protected chain specific to the enacyloxin antibiotic family is reported. The noticeable features are (a) the construction of the chlorinated undecapentaenoic moiety implementing the sequence Tsuji's alkyne syn allyl-chlorination, E -selective Pd/Cu-catalyzed allene-alkyne coupling, Horner-Wadsworth-Emmons olefination, dehydration; (b) control of the C18 chlorinated stereogenic center by organo-catalyzed aldehyde α-chlorination; and (c) the assemblage of this aldehyde with the C1-C16 ketone using a highly diastereoselective Mukaiyama aldol.

A multicomponent synthesis of tetrahydroisoquinolines from carboxylic acids, alkynyl ethers, and dihydroisoquinolines is described. This process features readily available starting materials, simple experimental procedures for achievement of molecule complexity, and structural diversity. The preliminary control experiment and crossover reaction provide important insight into the reaction mechanism. The formed tetrahydroisoquinolines could be transformed to an array of compounds. [ABSTRACT FROM AUTHOR]

Enamides equipped with N-acyliminium ion precursors were obtained through reduction of ynamides tethered to N-imides. Intramolecular TMSOTf-mediated trapping of N-acyliminium ions provided a variety of polyfunctionalized medium-sized diaza-heterocycles of putative pharmacological interest. [ABSTRACT FROM AUTHOR]

An interesting selectivity-controlled palladium-catalyzed oxidative carbonylation procedure for the synthesis of propiolates and chromenones has been developed. Starting from phenols and alkynes, under slightly different conditions, various propiolates and chromenones can be isolated in moderate to good yields. Additionally, this also presents the first example of direct carbonylative annulation of nonpreactivated phenols and terminal alkynes to produce chromenones. [ABSTRACT FROM AUTHOR]

A novel decarbonylative coupling of α-keto acids and ynamides with extrusion of CO for synthesis of β-keto imides is reported. This process features mild reaction conditions, a broad substrate scope, and high efficiency. An isotope-labeling reaction and GC analysis were conducted to elucidate a plausible reaction mechanism. [ABSTRACT FROM AUTHOR]

The first intermolecular ring-expansion cascade of azirines with alkynes for the synthesis of pyridines, enabled by a copper/triethylamine catalytic system via simultaneous generation and utilization of yne-enamine and skipped-yne-imine intermediates, is reported. Experimental as well as computational mechanistic studies revealed that the role of triethylamine is crucial in deciding the reaction pathway toward the pyridine products. This process offers a novel, one-step, direct, and practical strategy for the rapid construction of highly substituted pyridines under exceedingly mild conditions, and an installed alkyne functionality. [ABSTRACT FROM AUTHOR]

A scalable and operationally simple synthesis of trisubstituted alkenyl boronic esters has been achieved using a Zr-catalyzed carboalumination of terminal alkynes followed by in situ transmetalation with i-PrOBpin. The products are formed in good yields and with excellent regioselectivity and perfect stereoselectivity. The new procedure provides a significant improvement over the previously reported syntheses. [ABSTRACT FROM AUTHOR]

A novel and efficient oxygenation approach to trisubstituted oxazoles via a copper-catalyzed aerobic oxidative dehydrogenative annulation of amines, alkynes, and O2 has been developed. This transformation combines dioxygen activation and oxidative C-H bond functionalization and provides a practical protocol for the preparation of oxazole derivatives, which are privileged units found in various bioactive compounds or other natural products. 18O-labeling experiments were conducted to reveal that oxygenation was involved in this chemistry. [ABSTRACT FROM AUTHOR]

An unprecedented gold-catalyzed bicyclization reaction of diaryl alkynes has been developed for the synthesis of indoles in good to high yields. Mechanistically, this alkyne bifunctionalization transformation was terminated by a stepwise formal X-H insertion reaction to furnish the corresponding polycyclic-frameworks with structural diversity, and the key intermediate 3H-indole was isolated and characterized for the first time. In addition, further transformation of these generated tetracyclic-indoles with PCC as the oxidant provided straightforward access to the spirooxindoles in high yields. [ABSTRACT FROM AUTHOR]

A dearomative coupling of β-naphthols with alkynes via Pd hydride catalysis has been developed. This redox-neutral strategy provides a straightforward platform to access diverse naphthalenones bearing congested quarternary stereocenters with excellent atom and step economy since no leaving groups are needed to preinstall on the allylic reagents. The overall utility of this protocol is exemplified by broad functional group compatibility and gram-scale capacity. [ABSTRACT FROM AUTHOR]

Azolopyrimidines are efficiently prepared by direct imidoyl C-H bond activation. Annulations of N-azolo imines with sulfoxonium ylides and diazoketones under redox-neutral conditions and alkynes under oxidizing conditions provide products with various arrangements of nitrogen atoms and carbon substituents. We have also probed the mechanism of this first example of Rh(III)-catalyzed direct imidoyl C-H activation by structural characterization of a catalytically competent rhodacycle obtained after C-H activation and by kinetic isotope effects. [ABSTRACT FROM AUTHOR]

A copper(I)-mediated cross-coupling of stereodefined secondary alkyllithiums with bromoalkynes provided stereodefined alkynes with high diastereoselectivity (dr up to 98:2). This cross-coupling was extended to various secondary alkyllithiums bearing a remote oxygen functionality, and the alkyne synthesis was also performed with optically enriched alkyl iodides (up to 99% ee) providing, after cross-coupling, alkynes bearing two stereocenters (dr = 93:7; up to 99% ee). [ABSTRACT FROM AUTHOR]

An unprecedented Ru(II)-catalyzed C-H activation and annulation reaction, which proceeds via C-C triple bond cleavage, is reported. This reaction of 2-phenyldihydrophthalazinediones with alkynes, which works most efficiently in the presence of bidented ligand 1,3-bis(diphenylphosphino)propane, affords good yields of substituted quinazolines. [ABSTRACT FROM AUTHOR]

A protocol for synthesis of chalcone derivatives with a 2-pyridone subunit from N-(2-furanylmethyl) alkynamides is reported. This synthesis involves Pd/Cu-catalyzed oxidative furan-yne cyclization at room temperature in air and may proceed via nucleopalladation of the alkyne to form a vinylpalladium intermediate, with a furan ring acting as the nucleophile. [ABSTRACT FROM AUTHOR]

A convenient and practical synthetic route to α-ketoamides from bromoalkynes and anilines through phototriggered organic transformations via a C-N cross-coupling and an oxidation of C≡C was developed. The reaction could be furnished without an external photocatalyst at ambient conditions, and a wide range of α-ketoamides were obtained in good yields. [ABSTRACT FROM AUTHOR]

The unprecedented use of CF3SO2Cl for direct bifunctional chloro-trifluoromethylthiolation of alkenes and alkynes is reported. CF3SCl, which is generated by the reduction of PPh3, undergoes electrophilic addition and then chlorination to give the bifunctionalized products without using an additional chlorine source. The method is also applicable for chloro-difluoromethylthiolation using CF2HSO2Cl. [ABSTRACT FROM AUTHOR]

A novel transition-metal-free cleavage reaction of C-C triple bonds in aromatic alkynes with S8 and amides furnishes aryl thioamides in moderate to excellent yields. The remarkable features of this thioamidation include the metal-free cleavage of C-C triple bond, mild reaction conditions, as well as wide substrate scope that is particularly compatible with some internal aromatic alkynes and acetamides. [ABSTRACT FROM AUTHOR]

A tin-free strategy for the successful cyclization of a variety of internal alkyne-containing N-chloroamine precursors to the ABC core via cyclization of a neutral aminyl radical is established. Deuterium labeling experiments confirm that the solvent is the primary source of the final H atom in the cyclization cascade. These conditions enabled a streamlined route to a β-ketoester intermediate poised for intramolecular Knoevenagel condensation to construct the seven-membered D-ring of calyciphylline A alkaloids. However, exposure to CsF in t-BuOH at elevated temperatures led to an unexpected decarboxylation to form a D-ring-contracted tetracyclic core. [ABSTRACT FROM AUTHOR]

We here describe a new Cu-catalyzed annulation cascade of alkyne-tethered α-bromocarbonyls with common alkynes for the synthesis of various heteropolycycle frameworks, including 1H-benzo[de]quinolin-2(3H)-ones, 4H-dibenzo[de,g]quinolin-5(6H)-one, and benzo[de]chromen-2(3H)-one, which were constructed with high selectivity. This was achieved by two-component annulation cascades, rather than atom-transfer radical cyclization (ATRC), with alkyne-tethered α-bromocarbonyls for one-step accessing heteropolycycles via C-Br bond split, intramolecular cyclization, intermolecular [4 + 2] annulation, and aryl C(sp²)-H functionalization cascades. [ABSTRACT FROM AUTHOR]

A nontrivial Ru-catalyzed one-pot sequential oxidative coupling of a (hetero)arene/vinylic/chromene system with alkyne and quinone is presented; the methyl phenyl sulfoximine (MPS) directing group is vital. This cyclization forms four (two C–C and two C–N) bonds in a single operation and produces unusual spiro-fused-isoquinolones with a broad scope. The release of phenyl methyl sulfoxide makes the MPS group transformable. A deuterium scrambling study sheds light on the reaction path. [ABSTRACT FROM AUTHOR]

A unique and efficient method for one-pot synthesis of diverse 4-quinolones from simple and readily available primary anilines and alkynes via Cu(I)-catalyzed direct cyclization has been developed. The (thio)phenols were also found to visible substrates for this reaction. Moreover, an unprecedented synthesis of dihydroepindolidiones has been demonstrated by using secondary anilines as the versatile substrates. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed intermolecular direct C–H allylation of polyfluoroarenes with alkynes is reported. Unlike classic hydroarylation reactions, alkynes are used as allylic electrophile surrogates in this direct aromatic C–H allylation. As an atom-economic and efficient method, various linear allylated fluoroarenes were synthesized from two simple and easy-to-access feedstocks in good to excellent yields, as well as regio- and stereoselectivity. [ABSTRACT FROM AUTHOR]

The direct oxidative addition of CF3 and H2O to alkynes was achieved with photoredox catalysis to obtain α-trifluoromethyl ketones via rapid enol-keto tautomerization. The reaction exhibits high functional group tolerance and regioselectivity. Heterocycles of various sizes containing CF3 were synthesized from the α-CF3-substituted diketones obtained through the protocol, thereby demonstrating the versatile applicability of the method. Mechanistic studies of the reaction with isotopes provided insight into the reaction pathway. [ABSTRACT FROM AUTHOR]

A novel protocol for the regio- and stereoselective iodofluorination of internal and terminal alkynes using 1,3-diiodo-5,5,-dimethylhydantoin and HF-based reagents is disclosed. This approach is used to prepare a fluorinated tamoxifen derivative in two steps from commercially available starting materials. A facile method enabling controlled regioselective double iodofluorination of terminal alkynes is also presented. [ABSTRACT FROM AUTHOR]

A reductive nickel-catalyzed bis-allylation of alkynes with allyl acetates has been developed, leading to 1,4,7-triene skeletons. This reductive bis-allylation proceeds under mild conditions and exhibits good functional group tolerance in both the allyl acetates and the alkynes. [ABSTRACT FROM AUTHOR]

Active pyrylium intermediates are in situ generated by a Rh-catalyzed vinylic C-H annulation reaction between exocyclic α,β-enones and alkynes, which undergo a base-promoted rearrangement via 1,5-H shift to form 1H-benzo[f]chromene derivatives. [ABSTRACT FROM AUTHOR]

A novel full atom-economic process for the transformation of alkynes into chiral alcohols by TfOH-catalyzed hydration coupled with Ru-catalyzed tandem asymmetric hydrogenation in TFE under simple conditions has been developed. A range of chiral alcohols was obtained with broad functional group tolerance, good yields, and excellent stereoselectivities. [ABSTRACT FROM AUTHOR]

A one-pot protocol for the construction of fluoroalkylated isoxazoles directly from commercially available amines and alkynes is described. The reaction is scalable, operationally simple, regioselective, mild, and tolerant of a broad range of functional groups. As such, it could be viewed as a “click synthesis” of fluoroalkylated isoxazoles. Preliminary mechanistic investigations reveal that the transformation involves an unprecedented Cu-catalyzed cascade sequence involving RfCHN2. [ABSTRACT FROM AUTHOR]

The rhodium-catalyzed asymmetric N1-selective and regioselective coupling of triazole derivatives with internal alkynes and terminal allenes gives access to secondary and tertiary allylic triazoles in very good enantioselectivities. For this process, three new members of the JosPOphos ligand family have been prepared and employed in catalysis. The optimized reaction conditions enable the coupling of triazoles with internal alkynes as well as with allenes, displaying a high tolerance for functional groups. A gram scale reaction provided N1-allyltriazole, which was subjected to various transformations highlighting synthetic utility. [ABSTRACT FROM AUTHOR]

A unique Co(III)-catalyzed and DMSO-involved C–H activation/cyclization of simple, cheap, and easily available anilines with alkynes for direct and highly efficient synthesis of privileged quinolines with exclusive regioselectivity and broad substrate/functional group tolerance and in good to excellent yields, where DMSO was employed as both the solvent and the C1 building block of quinoline products, is reported. Mechanistic experiments revealed that the versatile reaction might employ the 2-vinylbenzenamine species as the active intermediate. [ABSTRACT FROM AUTHOR]

A Rh(III)-catalyzed C-H activation reaction has been developed for the preparation of pyridinium salts from secondary allylamines and internal alkynes. The pyridinium salts formed by this N-annulation reaction have interesting fluorescence properties. This protocol has been applied to the surface modification of mesoporous silica materials to generate functionalized silica that can be used for the detection of nitrobenzene. [ABSTRACT FROM AUTHOR]