In this work the patent landscape of catalytic hydrogenation reactions was evaluated with the aid of the online database Patbase®. The respective classifications were used to distinguish the development of trends among patents. The findings give a detailed picture of the patent activity on the field of hydrogenation catalysis and may give the user information on technological areas that occur more often in the patent literature than others.

Compared with biocatalysis in aqueous media, the use of enzymes in neat organic solvents enables increased solubility of hydrophobic substrates and can lead to more favorable thermodynamic equilibria, avoidance of possible hydrolytic side reactions and easier product recovery. ω‐Transaminases from Arthrobacter sp. (AsR‐ωTA) and Chromobacterium violaceum (Cv‐ωTA) were immobilized on controlled porosity glass metal‐ion affinity beads (EziG) and applied in neat organic solvents for the amination of 1‐phenoxypropan‐2‐one with 2‐propylamine. The reaction system was investigated in terms of type of carrier material, organic solvents and reaction temperature. Optimal conditions were found with more hydrophobic carrier materials and toluene as reaction solvent. The system’s water activity (αw) was controlled via salt hydrate pairs during both the biocatalyst immobilization step and the progress of the reaction in different non‐polar solvents. Notably, the two immobilized ωTAs displayed different optimal values of αw, namely 0.7 for EziG3‐AsR‐ωTA and 0.2 for EziG3‐Cv‐ωTA. In general, high catalytic activity was observed in various organic solvents even when a high substrate concentration (450‐550 mM) and only one equivalent of 2‐propylamine were applied. Under batch conditions, a chemical turnover (TTN) above 13000 was obtained over four subsequent reaction cycles with the same batch of EziG‐immobilized ωTA. Finally, the applicability of the immobilized biocatalyst in neat organic solvents was further demonstrated in a continuous flow packed‐bed reactor. The flow reactor showed excellent performance without observable loss of enzymatic catalytic activity over several days of operation. In general, ca. 70% conversion was obtained in 72 hours using a 1.82 mL flow reactor and toluene as flow solvent, thus affording a space‐time yield of 1.99 g L‐1 h‐1. Conversion reached above 90% when the reaction was run up to 120 hours.

Tandem catalysis, the use of a single catalyst to promote two or more mechanistically distinct cycles in one pot to assemble complex organic molecules, is an attractive target. In this paper, we report a reductant‐triggered tandem palladium catalysis process that rapidly assembles 3,4‐fused tricyclic indoles from three readily available starting materials. This tandem process involves a Pd0‐catalyzed in situ coupling/cyclization/Michael addition reaction to install simultaneously two functional groups at the C4 and the C3 positions of indoles. This is followed by a Pd0‐catalyzed intramolecular cyclization which builds a seven‐membered C4, C3‐bridge. Sodium formate is used to trigger the necessary switching between the palladium catalysed reactions.

A cascade procedure for the efficient and atom‐economical synthesis of spiro[5.n (n = 6‐8)]heterocycles has been developed. This process goes through the tandem reactions of base‐promoted ring‐expansion of cyclic ketones followed by Cu‐catalyzed intramolecular C‐2 spirocyclization of indoles. Easily accessible starting materials and broad substrate scope are the advantaged features of this protocol.

An organocatalyst‐controlled site‐selectivity switchable enantioselective Friedel‐Crafts reaction of unprotected 1‐naphthols has been established for the first time via the conjugate addition of 1‐azadienes. By two chiral complementary squaramide and phosphoric acid, both ortho‐ and para‐selective Friedel‐Crafts alkylations of 1‐naphthols were independently achieved with high efficiency and enantioselectivity. With this strategy, a wide range of optically active triarylmethanes have been achieved in high yields with good to excellent enantioselectivities.

The on water reaction of sodium telluride with electrophiles has been explored. Na₂Te, generated in situ through the rongalite (sodium hydroxymethanesulfinate)‐promoted reduction of elemental tellurium, reacts with a wide variety of electrophiles, including strained heterocycles, haloalkanes, Michael acceptors, and aryl diazonium salts, providing simple and rapid access to a broad range of novel functionalised symmetrical tellurides. The methodology well tolerated the presence of versatile functional groups such as alchohols, amines, esters, nitriles, and sulfones and allowed the incorporation of tellurium atoms into biologically relevant natural‐derived products. Furthermore, in the case of the nucleophilic ring opening of epoxides, a judicious tuning of the reaction conditions enabled the synthesis of unreported β‐hydroxy‐ and β‐amino‐ditellurides, which were further employed as precursors of new functionalised unsymmetrical dialkyl tellurides. The thiol‐peroxidase catalytic activity of hydroxy‐ditellurides has also been investigated in order to compare their antioxidant properties with those of homologous tellurides.

In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron‐withdrawing group for activation of double bonds in asymmetric copper‐catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing out the high activation of the alkene by using a boron dipyrromethene as electron‐withdrawing group. Experimental, theoretical studies and comparison with other common electron‐withdrawing groups in asymmetric copper‐catalyzed [3+2] cycloadditions show the reasons of the different reactivity of the boron dipyrromethene derivatives, which can be exploited as a useful activating group in asymmetric catalysis. Additional experiments show that the so obtained pyrrolidines can be employed as biocompatible biosensors, which can be located in the endosomal compartments and do not present toxicity in three cell lines.

Phosphorus‐substituted heterocycles represent an important class of organophosphorus compounds, which not only widely consist in biologically active pharmaceuticals, agrochemicals, but also have widespread applications in material science and organic synthesis as ligands for transition metal complexes. The synthesis of such compounds integrates developing new synthetic methods and exploring efficient catalytic systems, reflects the latest achievements in organic, transition metal‐, photo‐ and even electrochemical catalysis, and facilitates the synthesis of sufficient quantities of related compounds as potential medicinal agents and biological probes in this area. Over the past few decades, two major synthetic strategies have been established toward phosphorus‐substituted heterocycles. This review summarizes the recent progress in this field and talks about the reaction mechanisms in detail. The advantages and limitations of each subdivisional tactic are presented, and the synthetic opportunities still open are outlined.

The palladium‐catalyzed enantioselective C‐H alkenylation of ferrocenecarboxylic acid has been developed. A series of 2‐alkenyl ferrocenecarboxylic acids with planar chirality were obtained using molecular oxygen as an oxidant. This protocol starts from less expensive and readily available starting materials and provides the target products as a key intermediate in organic synthesis.

Access to unprotected 2‐cyano‐glycals via a mild palladium‐catalyzed cyanation of protecting groups‐free 2‐iodoglycals in aqueous media has been developed. Diverse glycal substrates including disaccharide‐type were successfully obtained in good to excellent yields. These unprotected 2‐cyano‐glycal scaffolds were successfully derivatized to different C2‐glycoanalogues.

A straightforward approach for the synthesis of 2‐(3‐arylallylidene)‐3‐oxindoles has been achieved by the dirhodium(II)‐catalyzed reaction of 3‐diazoindolin‐2‐imines with 1‐aryl‐substituted allylic alcohols. This protocol employs easily accessible feedstock to produce oxindole derivatives, which might be applicable in the dye industry. DFT calculations were carried out to gain a mechanistic insight into the reaction.

An efficient formation of synthetically and biologically relevant β‐ketosulfones via a photo‐mediated decarboxylative ketonization of atropic acids was disclosed. The approach features metal‐free conditions, good functional group compatibility, readily available starting materials and the use of ubiquitous dioxygen as both oxygen source and oxidant. Furthermore, mechanistic studies reveal that the decarboxylative ketonization reaction proceeds via a radical mechanism and may involve a radical chain reaction.

Synthesis of a wide variety of 3‐amnio‐1H‐inden‐1‐ones from N‐tert‐butyl‐2‐(1‐alkynyl)benzaldimines via intramolecular aminocarbonylation of alkynes using Cs2CO3 as catalyst and air as oxidant has been developed. This highly atom‐efficient, transition‐metal‐free reaction proceeds under thermal conditions. We propose that the reaction proceeds through an unprecedented 5‐exo‐dig cyclization of N‐tert‐butyl‐2‐(1‐alkynyl)benzaldimines and thermal rearrangement of 3‐methylene‐2λ2‐isoindolin‐1‐ols.

Direct electrochemical oxidative functionalization of caffeine under metal‐free and external‐oxidant‐free conditions have been achieved. Nucleophiles such as various substituted pyrazoles, alcohols and sodium trifluoromethanesulfonate can be utilized with high diastereoselectivity for the dearomatizative functionalization of caffeine. In addition, selective C2 functionalization of caffeine has also been realized with the modification of solvent and reaction time. Gram scale experiment demonstrate the potential application in the derivatization of caffeine.

We report herein a facile approach to tetrahydropyridazines, a scaffold found in many natural products and biologically active entities, via Pd‐catalyzed carboamination of readily available alkenyl hydrazones with aryl and alkenyl halides. Preliminary studies showed its promise for enantioselective synthesis. This work offers an expedient access to tetrahydropyridazine scaffold bearing a variety of substitution patterns, thus significantly increased the availability of these derivatives for downstream evaluation.

Abstract. A polystyrene‐immobilized isothiourea has been applied to the enantioselective acylative kinetic resolution (KR) of monoacylated BINOL(s) with inexpensive isobutyric anhydride in batch and flow. High selectivity values (s = 29 at 0 oC) and a remarkable stability of the catalytic system in the operation conditions have been recorded for unsubstituted BINOL. No significant loss of activity/selectivity is recorded after 10 consecutive KR cycles in batch. A continuous flow process has been implemented and operated with a 100 mmol (32.8 g) sample of racemic monoacetylated BINOL in dichloromethane solution in an 84 hours experiment with a packed bed reactor containing 1g (f = 0.37 mmol.g‐1) of the functional resin (s = 17‐21). Residence time can be decreased to 10 min with the same reactor to achieve a conversion of 58% with a selectivity factor s = 17 when a more highly functionalized catalyst (f = 0.88 mmol.g‐1) is used. This translates into a remarkable combined productivity of 5.5 mmolprod·mmolcat‐1·h‐1.

A novel Copper‐catalyzed cascade reaction between six‐membered cyclic diaryliodonium salts and nitriles is reported for the facile access to a variety of N‐carbonyl acridanes in good to excellent yields (up to 82%). The reaction is efficient and atom‐economical with a broad substrate scope (e.g. both aryl / alkyl nitriles and substituted / unsubstituted cyclic diaryliodonium salts compatible in the system). This method is particularly useful for the synthesis of substituted N‐carbonyl acridanes which are present in many pharmaceutically important compounds, but are not easy to obtain in conventional approaches. Furthermore, one of the newly synthesized acridanes displayed high antiproliferative activity against MB‐468 cancer cells (IC50 = 26 nM, comparable to paclitaxel and colchicine) by inhibiting tubulin polymerization. Together, these findings might grant a rapid access to a novel molecular scaffold with potential anticancer utilities.

We report a protocol for redox‐neutral Minisci C–H formylation of N‐heteroarenes using 1,3‐dioxoisoindolin‐2‐yl 2,2‐diethoxyacetate as a formyl equivalent at room temperature. This scalable benchtop protocol offers a distinct advantage over traditional reductive carbonylation and Minisci C–H formylation methods in not requiring the use of carbon monoxide, pressurized gas, a stoichiometric reductant, or a stoichiometric oxidant. The high efficiency, broad substrate scope, excellent functional group tolerance, and mildness of this protocol make it particularly suitable for installing an aldehyde on medicinally relevant heterocycles.

Two methods for the synthesis of norbornane‐fused indanes via palladium‐catalyzed three‐component reactions of iodoarenes, norbornenes, and CH2Br2 or α‐diazoesters have been developed. In the reactions, three C–C bonds were constructed and a wide range of norbornane‐fused indanes could be synthesized. The reactions with α‐diazoesters proceeded with a high degree of diastereoselectivity and indanes bearing an all‐carbon quaternary center were formed. The products obtained in the reactions of 1,4‐dihydro‐1,4‐epoxynaphthalene can be converted to fluorenes, providing an alternative way to access fluorene derivatives.

Abstract. The challenging bioamination of hydrophobic substrates has been attained through the employment of a disperse system consisting of a combination of a low polarity solvent (e.g. isooctane or methyl‐tert‐butylether), a non‐ionic surfactant and a minimal amount of water. In these conditions, amine transaminases (ATA) were shown to efficiently carry out the reductive amination of variously substituted cyclohexanones, providing good conversions often coupled with a superior stereoselectivity if compared with the corresponding chemical reductive amination. An array of synthetically useful 4‐substituted aminocyclohexanes was consequentially synthesized for the first time through biocatalysis, analyzed and stereochemically characterized.

An approach for iodofluoroalkylation of unactivated alkynes and alkenes facilitated by an earth‐abundant and inexpensive manganese catalyst, Mn2(CO)10, is reported. This protocol employs visible light as the energy input and shows a wide substrate scope and high functional‐group compatibility. A variety of synthetically useful fluoroalkylated alkyl and alkenyl iodides can be prepared in moderate to excellent yields. The reaction features high efficiency, operational simplicity, scalability, as well as excellent chemo‐, regio‐, and E/Z selectivities.

Abstract. The enantiopure Ni(II) helicates [Ni2L1RR.Cl2] (1), [Ni2L1SS.Cl2] (1’), [Ni2L2RR.Cl2] (2), [Ni2L2SS.Cl2] (2’) were synthesized by one‐pot self‐assembly technique from R‐(+)‐ or S‐(‐)‐1,1’‐binaphthyl‐2,2’‐diamine, with 4‐methyl‐2,6‐diformyl phenol or 4‐tert‐butyl‐2,6‐diformyl phenol and nickel salts. This binuclear double stranded Ni(II) helicates were characterized by ESI‐MS, IR and single crystal x‐ray structure wherever applicable. The extensive chiroptical studies suggest that the complexes are enantiopure in nature. The chirality transfer from ligand L1RR & L2RR to Ni(II) metal centre produced ΔΔ geometrical chirality, while their enantiomeric counterpart L1SS & L2SS produced ΛΛ chirality in their respective complexes.These enantiopure helicates were applied as catalysts in asymmetric Michael addition of 1,3‐dicorbonyl compounds with β‐nitrostyrene to produce nitroalkanes in good yield (96‐98%) and ee (78‐90%).

Abstract: A wide range of acridones and their cyclo[b]‐fused derivatives are efficiently constructed by a double annulation of o‐enoyl arylisocyanides with α, β‐unsaturated carbonyls under simple metal‐free condition. This protocol is general, efficient and practical, featuring the successive formation of two rings by a one‐pot domino transformation. A tandem process involing an isocyanide‐based [1 + 4] cycloaddition, an aminofuran‐based intramolecular [4 + 2] cycloaddition, ring opening and aromatization is proposed for the transformation.

An efficient biocatalytic approach for enantio‐ and regioselective ring‐opening of styrene oxides with cyanate was developed by using the halohydrin dehalogenase HheC from Agrobacterium radiobacter AD1, generating the corresponding chiral 5‐aryl‐2‐oxazolidinones in up to 47% yield and 90% ee. Additionally, the origin of enantioselectivity and regioselectivity of the HheC‐catalyzed cyanate‐mediated ring‐opening process was uncovered by single enantiomer bioconversions and molecular docking study.

Copper‐impregnated magnesium‐lanthanum mixed oxide [Cu(II)/Mg‐La] was used as catalyst in synthesis of homoallylic alcohols from aldehydes and ketones using allyltributylstannane as the allylating source. The present protocol provides a great application potential for the synthesis of corresponding allyl alcohols with excellent yields and selectivity. The catalyst exhibits broad functional group compatibility with a variety of substituted aldehydes and ketones to furnish the desired products in high yields under heterogeneous conditions. Importantly, the heterogeneous catalyst could be recovered from the reaction mixture by centrifugation and used up‐to three cycles.

In this work, a new chemodivergent domino approach for the preparation of multiple saturated heterocycles, based on phase‐transfer catalysis (PTC) is presented. The versatile nature of doubly electrophilic substrates, showing both a Michael acceptor and a ketone, tethered by a heteroatom, enables three different domino reaction pathways. The nucleophile dictates the chemoselectivity of the reaction. Sulfa‐Michael/aldol, cyanide addition/oxa‐Michael and a Michael/H‐shift/aldol processes, along with the variation of the tethering heteroatom, results in the formation of six different classes of saturated heterocycles. DFT calculations account for the observed chemo‐ and diastereoselectivity of the two most productive processes. Moreover, an extensive investigation on the sulfa‐Michael/aldol pathway was carried out, ultimately leading to the development of a new enantioselective domino approach to multi‐substituted piperidines based on PTC.

The current report represents a transition metal‐free synthesis of oxazoline and isoxazoline derivatives by a tandem electro‐oxidative chalcogenation‐cyclization process. Both C–Se and C–S bond‐forming protocols were developed without using any external oxidant and the reaction was performed at room temperature, open to the air. Using this methodology, twentynine substituted oxazoline and sixteen substituted isoxazoline derivatives were synthesized with up to 91% isolated yield.

The chemists’ pursuit of the ideal synthesis and functionalization of indole derivatives has lasted over 150 years as their scaffolds have been widely found in natural products, pharmaceuticals, agrochemicals and organic materials. In this regard, the recent resurgence of adopting green and sustainable electrochemistry in organic synthesis is a promising strategy. Indeed, many new intriguing applications of synthesis and functionalization of indole derivatives by direct and redox‐mediated electrochemical means have been disclosed. In this review, we highlight the fundamental aspects, reaction scopes, synthetic applications and reaction mechanisms of the electrochemical synthesis and functionalization of indole derivatives.