H-bonding, including H-bond donor (HBD) with electron-rich part of a substrate and H-bond acceptor (HBA) with electron-deficient part of a substrate, has achieved massive success. Faster transformation often correlates with more donicity of HBD. Besides the positive charge are employed to enhance the donicity of HBD, the electron withdrawing groups become a dissimilar approach for increasing the donicity of HBD. We describe newly designed H-bond donor catalysts, tris(monoalkylamino)cyclopropenium, implemented by vicinal positive charged on the cyclopropenium core. The counter anion became potential HBA to activate the electron-deficient part of a substrate. The tris(phenylamino)cyclopropenium chloride (TPAC·Cl) as a representative catalyst was applied in Friedel–Crafts alkylation of indoles with nitroalkenes. X-ray analyses of a single crystal of TPAC·Cl described the 3D architecture and the delocalized cationic charge in the solid state. Unit formal positive charge turned N–H moieties into H-bond donor (HBD) and the counter chloride anion exhibited potential H-bond acceptor (HBA). The HBD and HBA displayed cooperative organocatalysis in Friedel–Crafts alkylation of indoles with nitroalkenes. A new class of hydrogen bonding catalysis and working mechanism were proposed.

The exploitation of the metallacarboranes’ potential in various fields of research and practical ap-plications requires the availability of convenient and versatile methods for their functionalization with various functional moieties and/or linkers of different types and lengths. Herein we report a study on cobalt bis(1,2-dicarbollide) functionalization at 8,8’-boron atoms with different het-ero-bifunctional moieties containing protected hydroxyl function allowing further modification after deprotection. Moreover, an approach to the synthesis of three and four functionalized metallacarboranes, at boron and carbon atoms simultaneously, via additional functionalization at carbon to obtain derivatives carrying three or four rationally oriented and distinct reactive surfaces, is described

The synthesis 2-tert-butyl-4-methylphenol is of great significance because of its widely application in industry, and the development of highly efficient catalyst is necessary to the alkylation of p-cresol and tert-butyl alcohol. Here, an efficient and mild method was established, caprolactam was chosen as hydrogen-bonding acceptor, p-toluenesulfonic acid was employed as hydrogen-bonding donor, and deep eutectic solvent (DES) was prepared to catalyze the alkylation reaction. The structure of the DES catalyst was characterized by 1H NMR spectra, thermogravimetric analysis and fourier transform infrared spectra (FT-IR). In addition, response surface design based on Box-Behnken method was employed to optimize the alkylation reaction process parameters, the study of reaction kinetics was also carried out subsequently. The recycle performance of the catalyst was evaluated by recovery experiments, and a good result was obtained. Comparing with the literature reported, we here provide a mild method to the synthesis of 2-tert-butyl-4-methylphenol.

Using the colloidal method, Au NP’s were deposited onto 6 different supports (TiO2,  and -Al2O3, HFeO2, CeO2, and C), and their catalytic activity and selectivity were compared in the alkylation of aniline by benzyl alcohol. Correlations were made between the nature of the support, the Au NP size and H-binding energy.

The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated in the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.

The alkaloid tazopsine 1 was introduced in the late 2000's as a novel antiplasmodial hit compound active against Plasmodium falciparum hepatic stages, with potential to develop prophylactic drugs based on this novel chemical scaffold. However, the structural determinants of tazopsine 1 bioactivity, together with the exact definition of the pharmacophore, remained elusive, impeding further development. We found that the antitussive drug dextromethorphan (DXM) 3, although lacking the complex pattern of stereospecific functionalization of the natural hit, was harboring significant antiplasmodial activity in vitro despite suboptimal prophylactic activity in a murine model of malaria, which precluded its direct repurposing against malaria. The targeted N-alkylation of nor-DXM 15 delivered a small library of analogues with greatly improved activity over DXM 3 against P. falciparum asexual stages. Amongst these, N-2’-pyrrolylmethyl-nor-DXM 16i showed a 2- to 36-fold superior inhibitory potency compared to tazopsine 1 and DXM 3 against parasite liver and blood stages, with 760 ± 130 nM and 2.1 ± 0.4 µM IC50 values, respectively, as well as liver/blood phase selectivity of 2.8. Furthermore, cpd. 16i showed a 5 to 8-fold increase of activity relatively to DXM 3 against P. falciparum stages I-II and V gametocytes, with 18.5 µM and 13.2 µM IC50 values, respectively. Cpd. 16i can thus be considered a promising novel hit compound against malaria in the ent-morphinan series with putative pan-cycle activity, paving the way for further therapeutic development (e. g., investigation of its prophylactic activity in a mouse model of malaria).

A four-step synthesis of bifunctional, noncovalent organocatalysts based on the chiral (1R,2R)-cyclohexane-1,2-diamine scaffold containing a 1,2-benzenediamine H-bond donor was developed. Nucleophilic aromatic substitution of the 2-fluoronitrobenzene derivative with the commercial (1R,2R)-cyclohexane-1,2-diamine was followed by selective alkylation of the primary amino group, reduction of the aromatic nitro group and final derivatization of the primary aromatic amino group, i.e. acylation, sulfonation, reductive alkylation and arylation, leading to the four subtypes of organocatalysts. All new compounds were fully characterized. The prepared organocatalysts (32 examples) were tested in the Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the addition product with incomplete conversions (up to 93%) and enantioselectivities of up to 41% ee.