Abstract: Abstract Hydroxycinnamic acid amides are believed to have antioxidant, antidiabetic, cytotoxic, anticancer, neuroprotective, and antiinflammatory properties, making them interesting target molecules for potential applications in the food, cosmetics, and pharmaceutical industries. Here, we describe the synthesis of hydroxycinnamic acid amides starting from hydroxycinnamic acid esters and the corresponding amines by using variants of the promiscuous hydrolase/acyltransferase from Pyrobaculum calidifontis VA1 (PestE) in water as a solvent. Up to 97% conversion within two hours at 60 °C was achieved with methyl ferulate and tyramine as substrates. This is a promising, environmentally friendly alternative strategy to established chemical synthesis routes or enzymatic methods using lipases in nonaqueous organic solvents.

Abstract: Two novel copper-catalyzed cyclization reactions are disclosed via remote propargylic substitution/cyclization/isomerization cascade. Both seldomly studied heterocycles thieno[2,3-c]pyrrole and thieno[2,3-d]pyridazine derivatives are conveniently synthesized from primary amines and hydrazines through [4+1] and [4+2] reactions, respectively, and moderate to good yields are observed for two processes. Preliminary mechanistic experiments corroborate the designed cascade reactions.

Abstract: Abstract The field of C-H functionalization chemistry has experienced rapid growth in the past twenty years, with increasingly powerful applications in organic synthesis. Recognizing the potential of this emerging field to impact drug discovery, a dedicated effort was established in our laboratories more than ten years ago with a goal of facilitating the application of C-H functionalization chemistries to active medicinal chemistry programs. Our approach centered around the strategy of Late-Stage Functionalization (LSF) wherein C−H functionalization chemistry is employed in a systematic and targeted manner to generate high-value analogs from advanced drug leads. To successfully realize this approach, we developed broadly useful LSF chemistry platforms and workflows that increased the success rates of the C-H functionalization chemistries and accelerated access to new derivatives. The LSF strategy, when properly applied, enabled rapid synthesis of molecules designed to address specific medicinal chemistry issues. Several case studies are presented along with descriptions of the group’s platforms and workflows.

Abstract: In this account article, we give an overview of our contribution to the development of stable micellar carriers obtained by self-assembly and photo-polymerization of diacetylenic amphiphiles. The stabilized micelles can be loaded with active substances and used for diagnostic and therapeutic applications, or loaded with a metal catalyst to promote some synthetic transformations in fully aqueous medium.

Abstract: This paper summarizes the guidance provided by quantum chemical calculations to the biomimetic syntheses of polycyclic marine furanocembrane derivatives. Polycyclic furanocembrane derivatives are a group of structurally complex and biologically important marine natural products isolated from marine corals. Their syntheses are challenging due to their structural complexity. Biomimetic synthetic proposals have been made and some verified via chemical synthesis. Computational chemistry can support these biomimetic syntheses. Hence, here we describe the synthetic and computational attempts we have made in the biomimetic syntheses of polycyclic furanocembrane derivatives, including intricarene, bielschowskysin, providencin and plumarellide.

Abstract: Nucleophilic phosphine-catalyzed annulations are recognized as practical and powerful synthetic tools for various cyclic compounds. Phosphine acceptors play a key role in nucleophilic phosphine catalysis. Design and synthesis of new phosphine acceptors, which are able to introduce new zwitterionic intermediates with new reactivities into the phosphine-catalyzed annulations, are highly desirable. Recently, we applied the proton shift principles in the design of new phosphine acceptors and have developed several phosphine-catalyzed annulation reactions with the use of new phosphine acceptors. In this account, we present a brief introduction of design and application of a series of acidic hydrogen-tethered electron-deficient acceptors for phosphine-catalyzed annulation reactions, categorizing with the atom types (N-H, O-H, C-H) that acidic hydrogen is bounded to.

Abstract: We have been interested in the differences of properties between low-coordinated carbon compounds and their heavier homologues of group 14 based on e.g., Si and Ge. Fundamental research on the synthesis and characterization of divalent and multiple-bond compounds of heavier group-14 elements has led to a variety of isolated low-coordinated species of heavier group-14 elements that can serve in small-molecule transformations instead of transition metals. The author and his co-workers have focused especially on low-coordinated germanium compounds with double or triple bonds between germanium atoms, and germanium-containing aromatic compounds. Once isolated, the reactivity of these low-coordinated germanium compounds was examined with regard to small-molecule activation. In this account, the reactivity patterns of these compounds will be described.

Abstract: We report improved protocols for the synthesis of thiazolium precatalysts from primary amines, carbon disulfide and alpha-halogenoketones. For N-alkyl substituted derivatives, yields for the corresponding thiazolethiones can be dramatically improved when isolating the intermediate dithiocarbamates. In most cases, meta-chloroperbenzoic acid can replace advantageously H202 in acetic acid for the oxidation of thiazolethiones into thiazoliums. This approach was applied to the synthesis of a thiazolium featuring a 2-adamantyl N-substituent, the corresponding persistent carbene and its dimer.

Abstract: Diaryl diselenides and diaryl ditellurides are usually employed as the selenyl or telluryl source which show wide applications in organic synthesis. Herein, various diaryl diselenides/ditellurides are smoothly furnished in moderate to excellent yields under metal-free conditions are disclosed. This method feature high efficiency, good functional group tolerance, easy operation, and easy scale-up (running in 4 mmol-scale for most cases). The mechanistic experiments indicate that this reaction is possibly running via a radical pathway. Significantly, the correct matching of Br- and dimethyl sulfoxide under air atmosphere is critical to this transformation.

Abstract: We report the development of a straightforward, waste-reducing, environmentally friendly, FeIII-catalyzed domino aza-Michael/aldol/aromatization reaction in the presence of water to access high-value functionalized quinolines by using 2-aminobenzophenones and ethyl buta-2,3-dienoate as starting compounds. The tangible advantages, that is, the utilization of commercially available and/or easily accessible substrates, simplicity, mild reaction conditions, and application of water as a solvent, make this three-step domino process green and highly appealing for the direct construction of a wide variety of highly functionalized quinolines in up to 78% yield.

Abstract: Acinetobacter baumannii can cause many diseases including septiceamia, pneumonia, meningitis, soft tissue and urinary tract infections. Herein, we described the synthesis of one trisaccharide and two tetrasaccharide fragments derived from A. baumannii ATCC 17961 O-antigen, which can be used for screening novel glyco-epitope and developing synthetic carbohydrate-based vaccine against A. baumannii infection. The overall yields for the synthesis of trisaccharide 1, tetrasaccharide 2 and tetrasaccharide 3 are 26.8% (8 steps), 21.6% (9 steps) and 24.5% (6 steps), respectively.

Abstract: A general strategy was developed for synthesizing of 2-C-glycals through a nickel-catalyzed cross-electrophile coupling reaction of 2-iodoglycals with (hetero)aryl iodides. Key to the success of this methodology is the use of an electron-deficient bipyridyl ligand. This innovative approach facilitates the efficient construction of 2-C-glycals, thereby broadening the synthetic repertoire available for glycochemistry.

Abstract: The review summarizes various strategies that combine metathesis with different named and un-named reactions to create molecular diversity and produced carbocycles, macrocycles and heterocycles.

Abstract: In this study, the development of an improved process for the synthesis of a key cannabidiol intermediate, methyl olivetolate, is described. The process involves an improvement of the iodine-catalyzed aromatization of cyclohexanone using potassium persulfate as an oxidant. This approach enabled for the efficient synthesis of methyl olivetolate with a 90% yield and 99.84% HPLC purity on a 5 kg scale. Additionally, a total of 16 cyclohexanone substrates afforded higher yields (75-92%) of m-diphenol compounds compared to the established methods.

Abstract: A new nickel-catalyzed electrochemical, reductive cross-coupling for the trideuteromethylation of alkyl and aryl bromides is reported in which CD3 arenesulfonate derivatives were used as effective and readily available CD3 sources. The CD3-labeled products were obtained with good yields. It was demonstrated that this methodology is scalable and can be efficiently used for various methylations, including 13CH3 and 13CD3 labeling.

Abstract: A palladium-catalyzed cycloisomerization of carbamimidothioates with the formation of a quaternary carbon and a sulfide is described. The use of (IPr)Pd(allyl)Cl (CX21), K3PO4, and Me-C(OTBS)=NTBS in refluxing xylenes was optimal, and the methoxycarbonyl group was the most suitable substituent for the nitrogen atom of the carbamimidothioate. Phenyl and alkyl groups can be used as tethers for carbamimidothioates, and alkyl and aryl carbamimidothioates can undergo Pd-catalyzed cycloisomerization in high yields.

Abstract: Heteroatom-based olefinating reagents (e.g. organic phosphonates, sulfonates, etc.) are used to transform carbonyl compounds into alkenes, and their mechanism of action consists of aldol-type addition, cyclization, and fragmentation of four-membered ring intermediates. In our report, we demonstrate analogous process using ethyl hexafluoroisopropyl methylmalonate, which converts electrophilic arylaldehydes into α-methylcinnamates in up to 70% of yield. The reaction plausibly runs through formation of β-lactone, which spontaneously decarboxylates under the reaction conditions. The results shed light on the Knoevenagel-Doebner olefination, for which decarboxylative anti-fragmentation of aldol-type adducts is usually considered.

Abstract: This study explores the merged cycloaddition/cycloreversion of a 1,4-oxazinone substrate and conjugated bisalkyne precursors. Good regioselectivity in the Diels–Alder operation is observed and pyridines bearing 3-alkynyl functionality are afforded following cycloreversion and extrusion of CO2. Examples with both symmetric and nonsymmetric bisalkyne substrates are included.

Abstract: In this article, we have presented condensation of primary aryl and alkyl amines with S-methyl thiouronium salts to get N,N,N'-trisubstituted amidines. High yields, short reaction times and fair substrate scope are the noteworthy features of this protocol. Surprisingly, reaction of thiouronium salt with 4-aminopyridine yielded (4-methoxyphenyl)(piperidin-1-yl)methanone.

Abstract: A new type of functionalized BODIPY dyes is described. Utilizing an established procedure for Buchwald-Hartwig reactions, we have been able to convert -chloro BODIPYs to α-azo-BODIPYs using phenylhydrazines. Optimization of the reaction conditions and variation of the BODIPY core and the phenylhydrazine were conducted. Absorption and emission spectra were recorded.

Abstract: Abstract A practical method is introduced for the catalytic conversion of terminal alkynes into α-substituted vinyl boronic esters. The process employs catalytic amounts of nanoparticle-supported gold catalysts and catalytic amounts of copper to effect the overall transformation.

Abstract: Abstract An attempted aryl selenium-catalyzed formation of cis-chlorohydrins from alkenes was unsuccessful but led to an electrochemical investigation for the trans-selective chloroformyloxylation of cyclic and acyclic alkenes in moderate to good yields. Interestingly, when 1,1-disubstituted alkenes were used, the corresponding vinyl chloride derivatives were obtained, and the application of 1-phenylcyclohex-1-ene led to the formation of an allyl chloride derivative.

Abstract: The synthesis of multi-substituted 4-H Pyrans derivatives has drawn considerable attention due to its wide application in agrochemicals, pharmaceuticals, and other functional molecules. Herein, we report an N-heterocyclic carbene (NHC)-catalyzed [3+3] annulation reactions between -ketone esters and enynals for quick access to penta-substituted 4-H Pyran derivatives via a regioselective activation of ynals. A series of 4-H Pyrans derivatives bearing various substituents were obtained in moderate to excellent yields. This method may find further applications in the synthesis of structurally diverse 4-H Pyrans derived functional molecules from readily available starting materials.

Abstract: New α-Cyanophosphonates, which are useful reagents for Horner-Wittig reaction, were synthesized in a solvent-free condition, using choline chloride-zinc chloride deep eutectic solvent (DES) as a catalyst. This work is only the second report on the synthesis of these compounds. In the previous report, diethyltrimethylsilylphosphite was used as a reagent and TiCl4 as a catalyst while in this study, both employed reagent and catalyst (triphenyl phosphine and choline chloride-zinc chloride DES) are cheaper, more available and less harmful than the previous work. Moreover, the reaction involves an interesting cascade reaction between β-nitrostyrenes and two equivalents of triphenylphosphite led to the desired product as a new synthetic route. These compounds can be used in the pharmaceutical and agricultural industries, in addition to their synthetic applications in the preparation of α,β-unsaturated nitriles. The reactions were completed using 20 mol% of DES at 80 °C in 6 hours. 10 different β-nitrostyrenes were synthesized in 55-87% yield after purification. β-nitrostyrenes containing electron-donating groups showed higher yields. The reaction was failed when aliphatic and heteroaromatic nitroalkenes and β-nitrostyrenes with electron-withdrawing substituent were employed. Finally, three plausible mechanistic routes were proposed for the reaction, starting from the nucleophilic addition of triphenylphosphite to α-carbon, nitrogen and oxygen atoms.

Abstract: Transition-metal-catalyzed carbonylative transformations have been widely employed to convert CO gas into valuable carbonyl-containing molecules, which are mainly achieved by noble metals (Pd, Rh, Ir, Ru) and recently also been explored with nickel and other catalysts. Although noble metal catalysts have advantage in reaction efficiency, their high-cost lead scientist to explored alternative procedures. Also under these backgrounds, we carried out some studies on non-expensive metal-catalyzed carbonylative transformations. In this account, we summarize the carbonylation reactions developed in our research group by using manganese and iron catalysis. These carbonylation reactions proceeded either via SET (single electron transfer) or TET (two electron transfer) mechanism.

Abstract: Abstract Azo compounds with a high density, high enthalpy, and excellent detonation performance have received increasing research attention. The conventional method of chemical dehydrogenation that is used to form azo compounds involves the use of strong oxidants, resulting in environmental pollution. Electrochemical organic synthesis is considered an old method and a new technology. In this work, azofurazan tetrazole {H2AzFT; 5,5′-[diazene-1,2-diylbis(1,2,5-oxadiazole-4,3-diyl)]bis-1H-tetrazole} and azofurazan hydroxytetrazole (H2AzFTO) were synthesized by a green and efficient electrochemical dehydrogenation coupling of 5-(4-aminofurazan-3-yl)-1H-tetrazole and 5-(4-aminofurazan-3-yl)-1-hydroxytetrazole, respectively. The structures of H2AzFT and (NH4)2AzFTO were fully characterized by infrared spectroscopy, nuclear magnetic resonance, and elemental analysis, and their thermal stabilities were determined by differential thermal analysis.

Abstract: The dithioacetalization of lactaldehyde derivatives with ethane-1,2-, propane-1,3-; butane-1,4- and pentane-1,5-dithiols in the presence of 4 mol% of scandium triflate has been described. A series of cyclic dithioacetals were obtained with yields ranging from quantitative to 37%. The dithioacetalization of lactaldehyde derivatives with butane-1,4-dithiol and pentane-1,5-dithiol groups are accompanied by the formation of 14- and 16-membered macrocyclic sulfur structures with yields of 3% and 18%, respectively. In the case of a cyclic dithioacetal derivative with three methylene groups, a diastereoisomeric pair of enantiomers was obtained, the structure of which was confirmed by single-crystal X-ray diffraction analysis. Dithioacetals are useful building blocks in the synthesis of complex chemical structures, macrocyclic compounds can be used to complex metal ions.

Abstract: Brønsted acid-catalyzed intramolecular allylic substitution reaction of secondary and tertiary allylic alcohols has been developed. A variety of 2-vinylchromans were efficiently prepared in moderate to excellent yields. The given method features wide substrate scope, operational simplicity, metal-free, and mild reaction conditions. The practicability of the method was demonstrated by the gram-scale reaction and further derivations of the product. Catalytic asymmetric reaction was preliminarily studied.