Synlett

A mild and efficient one-pot, three-component ball-mill-assisted reaction of aldehydes, anilines, and dihydrofuran (or dihydropyran and cyclohexenone) has been described for the first time in the presence of the catalytic amount of aqueous perchloric acid (8 mol%) at room temperature under organic solvent- and metal-free conditions. The reactions are fast (1 h), providing the products with excellent yields and high diastereoselectivity. This procedure endows a simple, efficient, and cost-effective method for the diastereoselective synthesis of furano- and pyrano-tetrahydroquinolines and phenanthridinone derivatives, which are important biological compounds. The diastereomers with cis configuration were isolated as major products. The H–H COSY, NOESY experiments and X-ray crystallographic analysis of selected compounds were performed to confirm the cis isomer. The synthesized tetrahydroquinolines have been evaluated in vitro for their antibacterial and anticancer activities, and it was found that both the prepared compounds showed significant antibacterial and anticancer properties.

A simple, cost-effective, and modular strategy has been developed to synthesize synthetically and pharmaceutically active enaminones by oxidative amination of aryl alkenes with amines and CHCl3, using tert-butyl hydroperoxide as an oxidant. We describe the synthesis of enaminones from vinyl arenes and sterically hindered N,N-diisopropylethylamine (DIPEA) by employing an Earth-abundant cobalt salt as a catalyst within a very short reaction period for the first time. Furthermore, nitrogen- and oxygen-containing heterocyclic compounds have been synthesized from these highly functionalized enaminones. Moreover, various control experiments, such as radical trapping reaction, along with a Hammett analysis with various types of substituents on the styrene ring unraveled the detailed mechanism of this reaction pathway.

Aging alcohol is a timeless process that has seen little variation since the time of its invention. Molecules stored within the wood can be extracted by the alcohol to produce unique flavors. Among these molecules exist the whiskey and cognac lactones. Herein we report a short synthesis of the trans-whiskey and cognac lactones using a rearrangement of cyclopropane hemimalonates.

The enantioselective desymmetrization of 2,2-disubstituted cyclohexane-1,3-diones has been realized through an unprecedented chiral-bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction. The key to this work’s success lies in utilizing an electronically rich and sterically hindered chiral bisphosphine reagent, namely DuanPhos, as a catalyst. In addition, a unique reductive system was established to address the requisite PIII/PV = O redox cycle. The mechanism of the chiral-bisphosphine-catalyzed asymmetric Staudinger/aza-Wittig reaction has been elucidated through combined computational and experimental studies. Several crinine-type amaryllidaceae alkaloids have been synthesized concisely, hinging on the newly developed methodology.

We report a one-pot base-free protocol for the oxidative olefination of benzylic amines promoted by a hypervalent iodine reagent for the synthesis of α,β-unsaturated ketones. Mechanistically, (diacetoxyiodo)benzene oxidizes the benzylic amine to the corresponding imine, which, on reaction with a phenacyl(triphenyl)phosphonium bromide salt and an in situ generated acetoxy anion leads to an α,β-unsaturated ketone. A wide range of α,β-unsaturated ketones were easily accessed through direct oxidative olefination of substituted benzylic amines in good to excellent yields and with high E-selectivity.

A synthesis of the C19–C30 segment of the neuroprotective natural product colletotrichamide A has been achieved by performing a Sonogashira coupling of two advanced intermediate fragments: a vinyl iodide and an alkyne. A Maruoka–Keck allylation, an Evans syn-aldol reaction, and Takai olefinations served as the key steps in the synthesis of the vinyl iodide intermediate, whereas glycosidation and Ohira–Bestmann reactions were used as the pivotal steps for accessing the advanced alkyne intermediate.

N-Arylated piperidones are present as pharmacophores in many pharmaceuticals and serve as useful precursors for the construction of important new molecules. We have developed a transition-metal-free, cost-effective, and mild approach for the synthesis of N-(hetero)arylated piperidones and their ketals by using ketals of piperidones and 2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitriles as precursors. The desired products were obtained in two steps: amination of the 2-oxo-5,6-dihydro-2H-benzo[h]chromene-3-carbonitrile from piperidone, followed by ring transformation using a suitable nucleophile source. We have successfully tethered functionalized dihydrophenanthrenes, hydrobenzo[c]phenanthrenes, and benzoquinolines to piperidinone moieties under transition-metal-free conditions.

The bisoxindole motif is present in a variety of biologically active compounds. Here, we report an enantioselective oxidative homocoupling reaction of 2-oxindoles in the presence of a chiral bisguanidinium hypoiodite catalyst, providing access to the corresponding optically active bisoxindoles in excellent yields and with moderate to high diastereo- and enantioselectivities.

The C(sp3)–C(sp3) bond is one of the most prevalent motifs in organic compounds and holds significant importance in organic synthesis. The utilization of two alkyl electrophiles for cross-coupling stands as a vital strategy in building C(sp3)–C(sp3) bonds. Nowadays, synthetic electrochemistry is undergoing rapid development owing to its exceptional attributes not only in terms of green and economic properties by reducing the large amount of traditional chemical reductants, but also by its capacity to generate highly reactive radical intermediates under mild conditions, thereby opening up new reaction pathways and presenting novel opportunities to constructing C(sp3)–C(sp3) bonds. This article aims to comprehensively delineate the historical development of traditional electrophilic reagents in constructing C(sp3)–C(sp3) bonds, while also delving into the advantages of electrochemical electrophilic cross-coupling in this domain.1 Introduction2 Case Studies of Nickel-Catalyzed and Photochemical Alkyl Halide Cross-Coupling3 Case Studies of Electrocatalyzed Approaches for the Construction of C(sp3)–C(sp3) Bonds Using Electrophilic Reagents4 Nickel-Electrocatalyzed C(sp3)–C(sp3) Cross-Coupling of Unactivated Alkyl Halides5 Conclusion

Thiuram disulfides undergo a Cu(I)-catalyzed C–S cross-coupling with aryl iodides through Cu(OAc)2·H2O-assisted desulfurization to produce the S-thiocarbamate ester compounds efficiently. Various aryl iodides containing diverse substituents underwent a smooth reaction with a series of cyclic and acyclic secondary amine-based thiuram disulfides under an open-air atmosphere. A probable mechanistic pathway has been suggested based on control experiments and reports from the literature.