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Macroscopic ‘click’ covalent assembly using azide/alkyne functionalized polymer hydrogels was studied. It is achieved by amplifying chemoselective alkyne-azide click reaction through interfacial multisite interactions. The underlying LEGO-like building process could be generalized with the help of click chemistry. Macroscopic assembly of hydrogels via host–guest chemistry or non-covalent interactions such as electrostatic interactions has been reported. Unlike macroscopic supramolecular assembly, here we report visible ‘click’ covalent assembly of hydrogels at macroscale. PAAm hydrogels modified with alkyne and azide groups, respectively, can click together via formation of covalent bonds. Monomer concentration-dependent assembly and selective covalent assembly have been conducted. Notably, macroscopic gel assembly clearly elucidates the substrate selectivity not observed in the solution reactions of competing monomers.

ipso-Hydroxylation of arylboronic acids with Hantzsch ester has been developed. The by-product Hantzsch pyridine was found to promote the reaction in the presence of oxygen under ambient conditions.

Efficient and metal-free cross-coupling of arenes has been developed. Inexpensive hypervalent iodine reagents (HIRs) diacetoxyl iodobenzene and BBr3 were used to in situ generate a non-symmetrical HIR as the active species.

Non-symmetrical bromoiodanes are useful for bromination reactions, and some protocols were found to be suitable for specific substrates. Herein, we report the use of a DIB/BBr

1,2-Diols are extremely useful building blocks in organic synthesis. Hypervalent iodine reagents are useful for the vicinal dihydroxylation of olefins to give 1,2-diols under metal-free conditions, but strongly acidic promoters are often required. Herein, we report a catalytic vicinal dioxygenation of olefins with hypervalent iodine reagents using Lewis bases as catalysts. The conditions are mild and compatible with various functional groups.

A mechanochemical and solvent/catalyst-free functionalization of olefins with hypervalent iodine reagents has been developed, enabling the synthesis of 1,3-dioxygenated compounds. Under similar reaction conditions with the addition of molecular iodine, 1,4-iodoalcohols can be synthesized. These valuable products are non-trivial to achieve via standard solution-phase methods. Mechanistic study reveals that the hypervalent iodine reagent might dimerize at solid state with the help of mechanical force. The active monomeric form of hypervalent iodine reagent might trigger the 1,3- and 1,4-difunctionalization reactions in an intermolecular cascade manner.

A proof-of-concept study of hypervalent chalcogenonium⋅⋅⋅π bonding catalysis was performed. A new catalytic strategy using 1,2-oxaselenolium salts as chalcogen bond donors and alkenes as chalcogen bond acceptors is described. The feasibility of this concept is demonstrated by the use of trisubstituted selenonium salts in the metal-free catalytic hydrofunctionalization and polymerization of alkenes via unconventional seleniranium ion-like intermediates. The results indicate that counter anions have a significant effect on the catalysis based on hypervalent chalcogenonium⋅⋅⋅π bonding interactions.

Brominated compounds are important, but they are usually prepared in organic solvents. Here, efficient amphiphilic indole-based phase-transfer organocatalysts were developed for environmentally benign bromination reactions in water. As test reactions, hydroxybromination of olefins and aromatic bromination could be conducted in a greener and more sustainable manner compared with methods using organic solvents, producing the corresponding bromides in good yields. Some pure products could be obtained without column chromatography.

Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water or tert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3., Anti-Markovnikov hydrobromination of cyclopropanes was achieved using boron tribromide and water as the bromine and proton sources, respectively.

α,α-Dihalo-N-arylacetamides are commonly used as intermediates in various organic reactions. In the study described here, a catalytic synthesis of α,α-dihalo-N-arylacetamides from β-oxo amides was developed using zwitterionic catalysts and N-halosuccinimides as the halogen sources. The corresponding α,α-dihalo-N-arylacetamides were obtained in good to excellent yields, and no aromatic halogenated side products were detected. The reaction conditions were mild, and no strong base or acid was required.

Umpolung amide synthesis (UmAS) is a new strategy for the construction of amide bonds and is complementary to conventional amide synthesis. However, its mechanistic understanding remains very limited. In this issue of Chem, Johnston and co-workers report the preparation and study of analogs of the tetrahedral intermediates in UmAS.

Selenofunctionalization is used for the introduction of aryl- or alkylseleno moieties, which can then be transformed into other functional groups (such as alkenes and carbonyls). However, asymmetric selenofunctionalization of unactivated olefins is often difficult to realize, as aryl- and alkylseleno cations rapidly interchange between olefinic partners. Recently, it has been demonstrated that Lewis bases, assisted by Bronsted acids, induce high levels of enantioselectivity in selenocyclization reactions. The Bronsted acid serves as an activator for the reaction. In this work, we demonstrate an asymmetric selenoetherification and desymmetrization of olefinic 1,3-diols, driven by a unique chiral pairing between a C2-symmetric cyclic selenide catalyst and a chiral Bronsted acid. The resulting substituted tetrahydrofurans contain a phenylselenoether handle and can be transformed into synthetically useful building blocks. A series of experimental and computational investigations suggest that the reaction proc...

Halogenated aromatic compounds are the cores of many pharmaceutical, agricultural and chemical products but they are commonly prepared using electrophilic halogenation reactions in non-green chlorinated solvents under harsh conditions. A separate problem happens in the aromatic halogenation of thioarenes because they readily undergo oxidative side-reactions. Herein we report an environmentally benign electrophilic bromination of aromatics using an indole-catalytic protocol, which is suitable for a wide range of substrates including thioarenes.

How can high enantioselectivity be achieved when the racemic background reaction proceeds at a rate comparable to that of the catalytic asymmetric reaction? We attempted to rationalize this counterintuitive observation by studying the effect of (1) catalyst structure, (2) temperature and addition sequence of components, (3) catalyst loading, and (4) Bronsted acid additives. In the course of our investigation, it was found that increasing the amount of catalyst used led to inhibition of the stoichiometric reaction. Olefinic 1,3-diol 1 , 5 mol % of catalyst 3a , 1 equiv of MsOH, and NBS were added at low temperature in a specific sequence to provide the best performance for the enantioselective bromoetherification.

A highly facile and efficient electrophilic bromolactonization of cyclopropylcarboxylic acids could be effected by a Lewis basic sulfide catalyst. Mechanistic studies performed revealed that the cyclopropane substrates could undergo radical bromination upon exposure to light, yielding a mixture of regioisomers. In stark contrast, the Lewis basic sulfide catalyst could promote the electrophilic bromolactonization and yield the Markovnikov product exclusively.

A mild and efficient mono-selective bromination of 1,3-dicarbonyl compounds has been developed using lipophilic indole catalysts. Inexpensive and commercially available N-bromosuccinimide (NBS) was used as the brominating reagent. The selectivity was further enhanced when using stoichiometric amount of 3-bromoindole species. Mechanistic studies reveal that the indole catalyst has dual functions in the mono-bromination process.

This review covers work published in the calendar year 2012. References to new, naturally occurring furans, dihydrofurans, and tetrahydrofurans are given. New methods for the ring synthesis of furans, dihydrofurans, and tetrahydrofurans, and benzofurans are discussed. Novel reaction chemistry of furans, dihydrofurans, and tetrahydrofurans, and benzofurans is covered.

An enantioselective and highly diastereoselective bromoetherification and desymmetrization of olefinic 1,3-diols has been developed using a C2-symmetric cyclic sulfide catalyst. This methodology has been successfully applied to the synthesis of the key intermediate of an orally active antifungal drug posaconazole (Noxafil).

A series of platinum(II) terpyridine complexes with L-valine-modified alkynyl ligands has been synthesized. A complex with an unsubstituted terpyridine and one valine unit on the alkynyl is shown to be capable of gel formation, which is in sharp contrast to the gelation properties of the corresponding organic counterparts. Upon sol-gel transition, a drastic color change from yellow to red is observed, which is indicative of the involvement of Pt⋅⋅⋅Pt interactions. Through the concentration- and temperature-dependent UV/Vis absorption, emission, circular dichroism, and (1) H NMR studies, the contribution of hydrogen bonding, Pt⋅⋅⋅Pt and π-π stacking interactions as driving forces for gelation have been established, and the importance of maintaining a delicate balance between different intermolecular forces has also been illustrated.

Coronaviral infection is associated with up to 5% of respiratory tract diseases. The 3C-like protease (3CLpro) of coronaviruses is required for proteolytic processing of polyproteins and viral replication, and is a promising target for the development of drugs against coronaviral infection. We designed and synthesized four nitrile-based peptidomimetic inhibitors with different N-terminal protective groups and different peptide length, and examined their inhibitory effect on the in-vitro enzymatic activity of 3CLpro of severe-acute-respiratory-syndrome-coronavirus. The IC50 values of the inhibitors were in the range of 4.6–49 μM, demonstrating that the nitrile warhead can effectively inactivate the 3CLpro autocleavage process. The best inhibitor, Cbz-AVLQ-CN with an N-terminal carbobenzyloxy group, was ∼10x more potent than the other inhibitors tested. Crystal structures of the enzyme–inhibitor complexes showed that the nitrile warhead inhibits 3CLpro by forming a covalent bond with the catalytic Cys145 residue, while the AVLQ peptide forms a number of favourable interactions with the S1–S4 substrate-binding pockets. We have further showed that the peptidomimetic inhibitor, Cbz-AVLQ-CN, has broad-spectrum inhibition against 3CLpro from human coronavirus strains 229E, NL63, OC43, HKU1, and infectious bronchitis virus, with IC50 values ranging from 1.3 to 3.7 μM, but no detectable inhibition against caspase-3. In summary, we have shown that the nitrile-based peptidomimetic inhibitors are effective against 3CLpro, and they inhibit 3CLpro from a broad range of coronaviruses. Our results provide further insights into the future design of drugs that could serve as a first line defence against coronaviral infection., Graphical abstract Highlights ► Four nitrile-based peptidomimetic inhibitors were synthesized and characterized. ► Crystal structures of 3C-like protease in complex with inhibitors were determined. ► The structures justified why the best inhibitor, Cbz-AVLQ-CN, was more potent. ► The peptidomimetic inhibited a broad-spectrum of coronaviral 3C-like proteases.

A highly facile and efficient electrophilic bromolactonization of cyclopropylcarboxylic acids could be effected by a Lewis basic sulfide catalyst. Mechanistic studies performed revealed that the cyclopropane substrates could undergo radical bromination upon exposure to light, yielding a mixture of regioisomers. In stark contrast, the Lewis basic sulfide catalyst could promote the electrophilic bromolactonization and yield the Markovnikov product exclusively.

Oxygen- and nitrogen-containing heterocyclic compounds are widely recognized as key components in many natural products and biologically relevant molecules, but often the problem comes down to methodologies in synthesizing them. Halocyclization of olefinic substrates is a promising strategy in the construction of O- and N-heterocyclic compounds, which further signifies the development of their asymmetric variants. Over the past years, our group has been devoted to this particular area of asymmetric electrophilic halocyclization with chalcogen-containing molecules as catalysts. In this account, the main focus is on the development of our novel chiral catalysts and applications derived from the reaction products.

A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.

The high density and orientation-ordered ZnO nanorod bundles with wurtzite structures were prepared on Cu substrates by electrochemical deposition in solution of ZnCl2 + tartaric acid at a temperature of 90 °C. This approach is a unique and size controlled synthetic method for the large-scale preparation of ZnO nanorod bundles. Cyclic voltammogram measured in solution of the mixture of ZnCl2 and tartaric acid shows a restraining role of tartaric acid for the electro-reduction of Zn(II). The formation mechanism of ZnO on the surface of the cathode can be explained that the high temperature (⩾90 °C) promotes the corrosion of electrodeposited Zn via reacting with H2O and O2 to form the stable passive phase of ZnO. The compositions of the nanorod bundles can be entirely ZnO or Zn and ZnO composites determined by the temperature and deposition rate. The photoluminescence (PL) properties indicate that these ZnO deposits are highly crystallized and of excellent optical quality. Keywords: Electrodeposition, ZnO, Tartaric acid, Nanorod bundles, Semiconductor

ZnO nanoporous structures were prepared on Cu substrates by electrochemical deposition in solutions of ZnCl2 + ethylenediaminetetraacetic acid (EDTA) at a temperature of 90 °C. Cyclic voltammetry was used to study the electrochemical reactions relevant to the film growth. The transfer coefficient and diffusion coefficient of Zn(II) in 0.05 mol L-1 ZnCl2 + 0.01 mol L-1 EDTA at 343 K were calculated as 0.276 and 5.12 × 10-10 m2 s-1, respectively. The synthetic parameters in this research allowed further structural manipulation for ZnO nanoporous films. The morphology evolvement from uniform planar foam structures to bricklike and spherelike foam structures could be realized by changing the current densities of electrodeposition. The PL spectra of the prepared ZnO samples show that few oxygen vacancies or interstitial Zn centers would be formed when the electrochemical deposition was carried out with a low current density (≤0.1 mA/cm2).

A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.

A dia- and enantioselective bromoetherification and desymmetrization of olefinic 1,3-diols is developed using a chiral tetrahydrothieno[3,4-d][1,3]dioxole as catalyst.

A one-pot electrophilic multicomponent phenoxyetherification using an olefin, a cyclic ether, a phenol, and NBS is developed.

A one-pot electrophilic phenoxyetherification using an olefin, a cyclic ether, a phenol, and N-bromosuccinimide has been developed. This type of multicomponent reaction (MCR) is useful in the synthesis of building blocks that are potentially applicable to self-assembly complex construction.

This Feature Article gives a summary on the conformational and supramolecular properties of a special type of click molecules, namely, main chain and cyclic oligo- and polytriazoles. The triazole ring is an interesting structural motif since it is a hydrogen bond donor and acceptor, a large molecular dipole and also a metal ligand. It can interact with a wide variety of functionalities, e.g. hydrogen bonding partners (e.g. amides or anions), molecular dipoles, and metal ions to generate many fascinating conformational features such as pseudo rod-like, U-turn, helical, double helical structures, β-strands and β-sheets. Oligo- and polytriazoles can also exhibit interesting supramolecular attributes such as host–guest complexation, self assembly, chemosensing and gelating properties. It is believed that many new and unique conformational and supramolecular properties can be created by incorporating the correct type of functional group partners into the oligo- and polytriazole backbone. This type of research can also advance our understanding on functional properties of such triazole-rich compounds.

This Feature Article gives a summary on the conformational and supramolecular properties of a special type of click molecules, namely, main chain and cyclic oligo- and polytriazoles. The triazole ring is an interesting structural motif since it is a hydrogen bond donor and acceptor, a large molecular dipole and also a metal ligand. It can interact with a wide variety of functionalities, e.g. hydrogen bonding partners (e.g. amides or anions), molecular dipoles, and metal ions to generate many fascinating conformational features such as pseudo rod-like, U-turn, helical, double helical structures, beta-strands and beta-sheets. Oligo- and polytriazoles can also exhibit interesting supramolecular attributes such as host-guest complexation, self assembly, chemosensing and gelating properties. It is believed that many new and unique conformational and supramolecular properties can be created by incorporating the correct type of functional group partners into the oligo- and polytriazole backbone. This type of research can also advance our understanding on functional properties of such triazole-rich compounds.