Abstract The present study describes the development of a sustainable and efficient methodology for the synthesis of 9,9-dimethyl-12-aryl-8,9,10,12-tetrahydro-benzo[a]xanthen-11-one derivatives employing Fe₃O₄@SiO₂@CeO₂ as a recyclable and environmentally benign nanocatalyst. The nanocatalyst was synthesized via a straightforward co-precipitation technique, and its successful formation and structural integrity were confirmed through powder X-ray diffraction (PXRD), high-resolution transmission electron microscopy (HRTEM), and vibrating sample magnetometry (VSM) analyses. The characterization techniques reveal that the catalyst is in its core–shell structure with a particle size of 20.98 nm, showing ferromagnetic behavior. The catalytic system exhibited excellent performance under solvent-free conditions, delivering the desired products in yields of up to 97%. The protocol demonstrated a broad substrate scope, effectively accommodating a variety of aromatic aldehydes with diverse substituents. The heterogeneous nature of the catalyst facilitated facile separation and reusability up to six consecutive cycles without any significant loss of activity thereby reducing waste generation and minimizing the environmental footprint. Furthermore, the proposed methodology addresses critical limitations associated with conventional synthetic routes, including the formation of undesired by-products, prolonged reaction times, and the use of toxic solvents. This work contributes significantly to the field of green chemistry by offering an environmentally responsible and operationally simple alternative for the synthesis of xanthenone derivatives.

Abstract The carbonyl group of two diastereomeric 1,2-oxazin-4-ones was employed to study routes to new enantiopure amino polyols. Addition of nucleophiles to the syn-configured diastereomer occurred with high stereoselectivity, whereas the reactions of the anti-configured 1,2-oxazine are less selective. Grignard reagents and an ester enolate were examined as nucleophiles. The carbonyl group of the 1,2-oxazin-4-ones could also be converted into an exo-methylene group by a Wittig reaction. The β-hydroxy esters derived from the ester enolate additions were treated with acid and provided bi- and tricyclic δ-lactones. Again, the configuration of the precursor compounds was crucial for the selectivity. Representative derivatives of the obtained products were either subjected to hydrogenolysis under palladium catalysis or treated with samarium diiodide as an N–O bond cleaving reagent. These reductions mostly provide the expected amino polyols. Two chain-elongated diastereomeric 1,2-oxazine derivatives bearing three contiguous stereogenic centers were also subjected to acidic conditions, which afford unique di- and tricyclic amino polyol derivatives.

We herein report newly developed C₂-symmetric 2,9-diarylphenanthroline ligands with easily modified chiral amide motifs, which enable Cu-catalyzed intramolecular C(sp³)-H amidation of mesylcarbamates to deliver 2-oxazolidone derivatives with up to 88:12 er.

Herein we report a new practical flow chemical synthesis of benzofurans starting from nitroalkanes and O-acetyl salicylaldehydes. The protocol involves two different sequential steps: (i) an initial base promoted nitroaldol condensation, and (ii) a Nef reaction promoted by tin (II) chloride dihydrate. The target benzofurans are obtained in satisfactory overall yields.

Enantiopure ferrocene-based phosphorus derivatives represent an important class of compounds with multiple applications in organic synthesis and coordination chemistry. Here, we report how the use of hexafluoroisopropanol can favour pseudo-benzylic substitutions towards both bulky diphosphine ligands and phosphonate derivatives. While the coordinating ability of the former was demonstrated through palladium and gold complexes formation, the latter were used to reach various phosphorus derivatives, including original ferrocenic primary mono- and diphosphines.

Abstract While medicinal chemistry campaigns are frequently carried out using non-stereoselective syntheses, the goal of most small molecule drug discovery programs involving chiral drug substances is to nominate and subsequently develop a single, unichiral entity. One of the consequences of this is that fit-for-purpose solutions like chiral SFC and HPLC, which are routinely employed during the discovery phase, must be replaced with more efficient approaches to obtaining the stereoisomer of interest as the program enters development. In this review, we examine twenty case studies from the last two decades of R&D in the pharmaceutical industry where non-stereoselective routes identified during medicinal chemistry campaigns were revised and new solutions for the stereoselective API candidate syntheses were identified during process development.1 Introduction2 Case Studies3 Conclusion and Outlook

Abstract An efficient and environmentally friendly protocol for the synthesis of 1-(α-hydroxyindole)-o-carboranes has been developed via Friedel–Crafts reaction of C3-H of indoles with 1-formyl-o-carborane in the absence of Lewis acid and solvent. The intermolecular σ-π interaction between indole and B–H bonds of o-carborane was proposed for promoting the Friedel–Crafts reaction of the C3-H of indole.

Abstract A novel [2+3] imine cage, derived from 1,3-diformylazulene and 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene, was synthesized and characterized. NMR spectroscopy and single crystal X-ray diffraction confirmed the formation of a symmetric hexaimine structure. The cage exhibits fluorescence, as well as characteristic azulene redox behavior. However, its stability in solution is sensitive to the acidity of the solvent. Reduction with NaBH4 led to the isolation of a more stable hexaamine cage, providing a means to further stabilize the structure.