As intriguing as it may appear, natural products bearing an isocyanide function are well known in different kingdoms of living organisms. An important question in terms of biochemistry is, of course, the origin of such a functional group and the mechanisms that have evolved in biosynthetic pathways to afford the formation of isocyanides. The latest studies dedicated to such endeavours are analysed therein in view of the producing organism metabolisms ( e.g . micro‐organisms, marine invertebrates). The in‐situ reactivity of natural isocyanides is also discussed as well as their biological activities.

An efficient route to synthesize monosaccharide analogues in an enantio‐ and diastereoselective manner is described. Three contiguous stereocenters can be constructed via enantioselective benzoyloxylation of aldehydes using a chiral secondary amine catalyst and a subsequent aldol reaction of the resulting α‐benzoyloxyaldehydes with the protected dihydroxyacetones using chiral amino acid catalysts, and single diastereomers were obtained with excellent enantioselectivity.

Substrate‐directed reactions are well recognized as important reactions to distinguish sterically and electronically similar reactive sites based on polar functional groups to realize regioselective reactions. Sharpless asymmetric epoxidation is a representative substrate‐directed reaction and known as an exceptional reaction to provide useful chiral epoxides from allylic alcohols. Despite the considerable development of the Sharpless asymmetric epoxidation over the last four decades, some difficult and challenging problems still remain unsolved. This review describes three fascinating and attractive topics in enantioselective substrate‐directed epoxidation: (1) carboxylic acid‐ or amine derivative‐directed epoxidation, (2) regioselective epoxidation of non‐proximal alkenes, (3) enantioselective epoxidation of bishomoallylic alcohols.

The tetraene 7,7‐dimethoxy‐2,3,5,6‐tetramethylenebicyclo[2.2.1]heptane is a key compound for the preparation of a large variety of acenes protected by a carbonyl bridge. We report here a medium scale preparation in seven steps of this valuable starting material. Diels‐Alder addition between 6,6‐dimethtyl fulvene and maleic anhydride, followed by carboxylation, ozonolysis of the double bond, reduction of the four ester group, then chlorination of the alcohol groups and dehydrochlorination give the target compound in 17% overall yield.

Lipidation is a key modification affecting the physiochemical properties of peptides and widely used in the design of drug candidates. Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) enables rapid synthesis of a library of S‐lipidated peptides via a thiol‐ene reaction between a free sulfhydryl group on cysteine‐containing peptide and a vinyl ester bearing a lipid. Optimization of the CLipPA procedure was performed by replacing the malodorous tert‐butylthiol and modifying the work‐up procedure to facilitate the analysis and isolation of lipopeptides.

A metal‐free photo redox C‐H trifluorometlylation of imidazopyridines is described. The reaction is operationally simple and the easy‐handling CF 3 SO 2 Na serves as an effective fluoroalkyl radical precursor. Various functional groups were tolerated under blue LED light to access the desired products in satisfied yields at room temperature.

A strategy for the rapid synthesis of 3‐substituted N ‐sulfonyl pyrazoles via p ‐TSA‐promoted cyclization reactions of sulfonyl hydrazines with N , N ‐dimethyl enaminones has been developed. This method achieves both the formation of pyrazole ring and the continued retention of sulfonyl group, providing a series of 3‐substituted N ‐sulfonyl pyrazoles in moderate to good yields with good functional group tolerance, easily available starting materials, and can be scaled‐up.

Abstract: Imidazolin‐2‐iminato hafnium complexes of the type [(Im R N)Hf(CH 2 Ph) 3 ] were synthesized (Im t Bu N = 1,3‐di‐ tert ‐butylimidazolin‐2‐iminato); Im Dipp N = 1,3‐bis(2,6‐diisopropylphenyl)‐imidazolin‐2‐iminato. The complexes were crystallized and structurally characterized. Despite the oxophilicity of the hafnium center, both hafnium complexes were catalytically active in the hydroboration of aldehydes, ketones, and carbodiimides. Here we present the influence of different substrates bearing electron‐withdrawing or electron‐donating groups on the catalytic reactions. Based on stoichiometric reaction in each process, plausible mechanistic scenarios are presented.

An easy synthesis of photochromic naphthopyrans with a lactone ring linking the naphthalene core to the pyran double bond is described. UV irradiation (or exposure to sunlight) of these uncolored compounds provide a single photoisomer with an intense orange coloration that returns completely to the initial uncolored state much faster than common naphthopyrans used in commercial photochromic ophthalmic lenses. A polymeric uncolored material doped with one of these lactone‐fused naphthopyrans develops an intense orange coloration (ΔAbs= 0.73) when exposed to the UV light for 30 s, at room temperature, and returns to the uncolored state in just 1 min. The use of these photochromic compounds allows a faster adaptation of the material’s coloration to the surrounding UV‐light intensity, without compromising the color intensity, an important feature to create high performance photochromic ophthalmic lenses.

Herein we describe a simple general method for the synthesis of 4‐arylcoumarins using pentavalent organoantimony compounds. The reactions of 3‐(2‐hydroxyaryl)acrylates with triarylantimony difluorides in the presence of Pd(OAc) 2 (10 mol%) and 2,2'‐bipyridyl (10 mol%) at 80 ºC under aerobic conditions afforded 4‐arylcoumarins in good‐to‐excellent yields. This protocol involves a cascade oxidative Heck‐type arylation followed by cyclization, with all of the aryl groups in the triarylantimony difluoride transferred to the coupling products. Triarylantimony difluorides resulted in better outcomes than those obtained with other pentavalent organoantimony or bismuth compounds.

A diboron‐mediated rhodium‐catalysed transfer hydrogenation system using water as the hydrogen donor is developed. In addition to a series of alkenes with good functional group tolerance, this rhodium‐based catalytic system also effectively reduces aldehydes and ketones. A plausible mechanism involving the Rh(I)‐catalysed hydrogen generation and Rh(0)‐catalysed hydrogenation is proposed for the reaction.

A direct C‐H bond carbamoylation of quinoxalin‐2(1 H )‐ones with hydrazinecarboxamides has been developed. This reaction provides a series of 3‐carbamoylquinoxalin‐2(1 H )‐one derivatives in moderate to good yields under mild conditions with a broad range of substrates and functional group tolerance. The present methodology affords a convenient and practical access to pharmaceutically active 3‐carbamoylquinoxalin‐2(1 H )‐one derivatives.

An efficient and cost‐effective Vitamin‐B3‐catalyzed protocol towards the synthesis of diversely substituted quinazolines is illustrated using 2‐aminobenzylamines and nitriles as substrates. An organocatalytic transformation has been investigated where nitrile plays a role of C‐N bond donor. The developed approach is applicable on a wide range of 2‐aminobenzylamines and nitriles for the synthesis substituted quinazolines in high yields with a broad functional group tolerance.

A highly efficient electrochemically dehydrogenative C‐H/O‐H cross‐coupling between quinoxalin‐2(1 H )‐ones and alcohols was developed under mild conditions. Using different types of alcohols as solvent, various 3‐alkoxylated quinoxalin‐2(1 H )‐ones were synthesized in a simple undivided cell at room temperature. This novel electrochemical cross‐dehydrogenative coupling approach features broad functional group tolerance, metal‐ and oxidant‐free conditions, and moderate to good yields.

Peptoids ( N ‐substituted glycine oligomers) are an increasingly important class of peptidomimetic foldamers with conspicuous bioactivities, high degree of resistance to enzymatic degradation, and ability to form stable secondary structures. The intrinsic rigidity of their oligoamide framework (due to n →π*, side chains N C α –H … O=C n →σ*, and backbone C α –H … O=C interactions), can be magnified by cyclization to afford macrocyclic species with unexpected stereochemical, topological and biochemical attributes. In this minireview the implications of conformational chirality, a largely overlooked source of chirality in medium and large size cyclic peptoids, are addressed. The exploration of the unique structural and recognition properties of macrocyclic peptoid biomimetics unravels potential strategies for design and development of sequence‐defined (cyclo)oligomers where conformational isomerism is an issue.

Bisthiazolidines (BTZ) are bicyclic compounds considered penicillin analogs that inhibit the full range of Metallo‐b‐Lactamases (MBLs) and potentiate β‐lactam activity against resistant bacteria. Herein we present a new methodology to prepare 2‐substituted bisthiazolidines by aldehyde exchange. Thirteen new bisthiazolidines were prepared using this methodology, with yields ranging from 31 to 75%. The reaction is based on in situ imines formation which are able to exchange side chains. The reaction intermediates were studied based on NMR experiments and a key imine 1b‐II could be detected in the reaction mixture. Furthermore, a DFT computational analysis was performed to gain insights into the reaction mechanism, allowing us to unveil the different pathways and their activation barriers within the synthetic route. The results suggest that the most favorable route involve the formation of the thiazolidine 1b‐III by i) a N‐assisted N‐C bond cleavage, and ii) a thiol‐mediated 5 endo ‐trig cyclization followed by a C‐N bond cleavage. In contrast with previously reported evidence, the imine metathesis was discarded as a plausible pathway. Finally, the reaction of 1b‐III with aldehyde 2a leads to bicycle 4a via the iminium ion 1b‐V .

An efficient method has been devised for the synthesis of dihydroisobenzofuran derivatives through the reaction of in situ generated ynones with potentially C ‐nucleophilic malonate esters. All of the products are capable to be prepared by applying the tandem strategy at room temperature. The reaction was realized through a combination of the pivotal TBAF‐catalyzed conjugate addition and selective O ‐nucleophilic cyclization. As revealed by the control experiments, both the basicity of fluoride anion and ammonium cation‐π interaction with alkyne unit might play crucial roles in the cyclization reaction.

Herein, we report the palladium‐catalyzed synthesis of 3‐arylpropionate esters starting from secondary benzylic ethers. With this investigation it could be shown that ethers are suitable starting materials beside the established carbonylation reactions of olefines, alcohols or aryl Halides.

A novel method for the synthesis of 1,2,3‐triazolyl‐based ketoximes by direct using readily available calcium carbide as an acetylene source, ( Z )‐2‐azido‐1‐arylethan‐1‐one oximes as starting materials and copper(I) chloride as a catalyst is described. The method provides a simple route to ( Z )‐1‐aryl‐2‐(1 H ‐1,2,3‐triazol‐1‐yl)ethan‐1‐one oximes in good to excellent yields through [3+2] cyclization. The salient features of this protocol are the direct use of easy‐to‐handle acetylene source, inexpensive catalyst, high yield and simple work‐up procedures.

A series of linker‐free aza‐BODIPY‐glutamine conjugates were synthesized and investigated, both experimentally and computationally. The structures of the aza‐BODIPYs were confirmed spectroscopically, and in the case of 3a an X‐ray structure was obtained. All aza‐BODIPYs show intense absorption bands between 642‐667 nm and fluorescence emissions between 691‐703 nm. The fluorescence quantum yields of the 2,6‐unsubstituted compounds 1a‐4a were found to be Φf ~ 0.2 in chloroform, while those of the corresponding 2,6‐dibrominated derivatives 1b‐4b were less than 0.01. The cytotoxicity and cellular uptake of all aza‐BODIPYs were investigated in human carcinoma HEp2 cells. The most cytotoxic aza‐BODIPYs were found to be 3a and 3b, due to the presence of the cyclic N,O‐bidentate amino acid ring, rather than the presence of the 2,6‐bromine atoms. The results show that the mode of glutamine conjugation to the aza‐BODIPY determines the stability and cytotoxicity of the conjugates.

Enantiocomplementary hydroxylation of alkyl aromatics through a one‐pot photo‐biocatalytic cascade reaction is described. The photoredox process is implemented in aqueous phase with O 2 as oxidant and the subsequent ( R )‐ or ( S )‐selective bioreduction is performed by whole cell system without the addition of the expensive cofactor (NADPH). This mild, operationally simple protocol transforms a wide variety of readily available aromatic compounds into valuable chiral alcohols with high yield (up to 90%) and stereoselectivity (up to 99%), thereby displaying important potentials in organic synthesis.

Oligomers assembled from designed building blocks to fold in novel ways have emerged as tools and allow the creation of new structures and molecular properties. Here we describe the use of a highly constrained adamantane moiety with one amino group and three carboxylic acids as a monomer. It can be viewed as a constrained, α,α‐dialkylated γ‐amino tri‐acid with side‐chains that mimic glutamic acid. We alternated this amino acid with glycine to synthesize a heteropeptide adamantane‐based oligomer. We included an N‐terminal L‐ or D‐tyrosine to investigate possible chirality induction. The oligomer was assembled by solid‐phase peptide synthesis using Fmoc‐ and Boc‐protection strategies. This novel oligomer was characterized by circular dichroism spectroscopy, which revealed a clear effect from the chirality of the N‐terminal tyrosine. Molecular dynamics simulation indicated that the adamantane oligomers populated compact conformations, with a subset forming cyclic geometries by hydrogen bonding. Through these interactions the chirality of Tyr induced an overall chirality in the cyclic conformations. This is in agreement with the spectroscopic data. This points to the use of adamantane building blocks in novel chirality switches.

A simple, convenient and highly efficient I 2 ‐catalysed approach has been unfolded towards the synthesis of highly fluorescent β‐carboline C‐1(3)‐tethered thiazolo[4,5‐ c ]carbazoles, naphtho[2,1‐ d ]thiazoles and benzothiazole derivatives using Kumujian C as a template. This domino strategy proceeds through assembly of 1‐formyl‐9 H ‐β‐carbolines, aryl amines and elemental sulfur via formation of one C‐N and two C‐S bonds in a single operation. Importantly, the methodology was found applicable to β‐carboline acetals also. A diversely substituted library of 37 β‐carboline tethered arylthiazole hybrids was prepared in excellent yields. The strategy was found appropriate for gram scale synthesis also. The photophysical properties of these fluorophores were also estimated and showed excellent fluorescence properties with quantum yield ( Φ F ) up to 92%.

Organotellurium compounds exhibit a broad range of useful applications in organic synthesis, materials science and medicinal chemistry fields. Despite their increasing applicability, the synthesis of enantiomerically pure organotellurium compounds remains nowadays scarcely reported in the literature. Herein, the chemical synthesis and biocatalyzed reductions of a set of telluro‐acetophenones using both ( R ) and ( S )‐selective alcohol dehydrogenases (ADHs) is described for the first time, obtaining enantiomerically enriched hydroxy tellurides with excellent selectivities under very mild reaction conditions. On the one hand, enantiopure para ‐substiuted ( S )‐hydroxy tellurides were obtained using the Ras‐ADH (77‐95% conversion) and ADH‐A (52‐75%), the ADH‐A leading to the enantiopure ( S )‐hydroxy tellurides substituted at the meta ‐position (69‐75%). On the other hand, the evo‐1.1.200 displayed high selectivity towards the preparation of optically alcohols with substitutions at the para ‐position of the aromatic ring (60‐68% conversion and 92‐97% ee ), while the Lb‐ADH led to the best results when reducing bulky ketones at the meta ‐position (79‐82% conversion and 88‐99% ee ).

The synthesis of a G0 polyamidoamide (PAMAM) dendrimer end­capped with four β‐cyclodextrin (β­CD) units, named as Tetra‐CD was performed by using copper(I)­catalyzed alkyne‐azide cycloaddition (CuAAC). This new platform presents a considerable high water‐solubility in comparison to native β­CD. Tumbling process involving half of the CD cavities in D 2 O was evidenced by 1 H NMR spectroscopy. Interaction of adamantane with Tetra‐CD has been fully investigated by 1D/2D NMR techniques and mass spectrometry besides a joint study on new β­CD monomers (named as A and B ) and on a dimer ( Di‐CD ) and a trimer ( Tri­CD ). The obtained results demonstrate that the tumbling effect can be shifted in the presence of an appropriate hydrophobic guest resulting in the full host‐ability of the CD units in water for that guest.

Nucleus Independent Chemical Shift (NICS) was invented by the late Paul v.R. Schleyer as a computational tool for assessing aromaticity. It has considerably developed since its invention. This account describes the NICS‐based methods that are currently available and concludes with recommendations for appropriate NICS‐based methods to study given problems.

The catalytic [6π+2π]‐cycloaddition of terminal alkynes to N‐carbethoxyazepine and N‐carbophenoxyazepine catalyzed by the three‐component Co(acac)2(dppe)/Zn/ZnI2 system was accomplished for the first time to give a broad range of practically valuable substituted 9‐azabicyclo[4.2.1]nona‐2,4,7‐trienes in high yields (75‐96%). The structures of the azabicyclic products were proved using modern spectral methods and X‐ray crystallography. The synthesized 9‐azabicyclo[4.2.1]nona‐2,4,7‐trienes were found to exhibit high antitumor activity in vitro against the Jurkat, K562, U937, and HL60 tumor cell lines.

Herein, we have investigated the effect of an endocyclic group (forming the N–C–C–F fragment) on the conformational preferences of 2–fluorocyclohexanone analogs. A combined approach of nuclear magnetic resonance and density functional theory calculations was employed to assess the conformational equilibrium in several media. In turn, natural bond orbital analysis and the conformational behavior of other 2–halocyclohexanone analogs was used to get more insights about the intramolecular interactions governing the conformer stabilities. Our results reveal that any stabilization from interactions featured in the gauche effect are overcome by a short‐range interaction of the fluorine substituent with the carbonyl group. Consequently, the gauche effect in heterocyclic compounds is not as stabilizing as in their acyclic counterparts. Only the electrostatic gaucheeffect takes place even in polar solvents owing to an attraction between the axial fluorine and an endocyclic quaternary ammonium group.