Synlett

A simple and efficient method for the synthesis of symmetric 2,3,5,6-tetrasubstituted pyridines from enaminones and triethyl orthoformate, catalyzed by pyridinium p-toluenesulfonate, has been established in which triethyl orthoformate was applied as a carbon source. The procedure was smoothly executed, culminating in the synthesis of symmetrical 2,3,5,6-tetrasubstituted pyridines with moderate to exceptional yields across a diverse array of substrates.

Retrosynthesis refers to the process of deconstructing a target molecule step by step until simpler and commercially available synthetic precursors are identified to develop a valid synthetic pathway. As a powerful problem-solving tool, it has gradually been expanded to other fields of chemistry. The application of a ‘retrosynthesis mindset’ can be relevant beyond chemistry, such as in education, research management, and science advice. In this Letter, we discuss the concept of the retrosynthesis mindset and its implications within and beyond chemistry in the hope of highlighting a broader potential and encouraging the adoption of such a mindset to enhance problem solving and strategic planning across disciplines.1 Introduction2 Retrosynthesis Education3 Retrosynthesis Within and Beyond the Lab4 Conclusion

Retrosynthesis refers to the process of deconstructing a target molecule step by step until simpler and commercially available synthetic precursors are identified to develop a valid synthetic pathway. As a powerful problem-solving tool, it has gradually been expanded to other fields of chemistry. The application of a ‘retrosynthesis mindset’ can be relevant beyond chemistry, such as in education, research management, and science advice. In this Letter, we discuss the concept of the retrosynthesis mindset and its implications within and beyond chemistry in the hope of highlighting a broader potential and encouraging the adoption of such a mindset to enhance problem solving and strategic planning across disciplines.1 Introduction2 Retrosynthesis Education3 Retrosynthesis Within and Beyond the Lab4 Conclusion

A new synthetic approach has emerged for constructing 9H-pyrrolo[1,2-a]indole scaffolds by the reactions between indoles and chalcones under metal- and solvent-free conditions at 80 °C. The reaction occurs smoothly in the presence of a Brønsted acidic ionic liquid, 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium tosylate, as a catalyst, permitting the synthesis of the desired products with satisfactory yields. The developed protocol is applicable to the construction of biologically important pyrrolo[1,2-a]indole derivatives from easily accessible chalcones having various substituents. The process commences with Michael addition to chalcones, followed by annulations induced by the elimination of a water molecule, yielding the 9H-pyrrolo[1,2-a]indole scaffolds. Several control experiments were carried out to achieve a better understanding of the reaction pathway. The feasibility of recycling the catalyst was also demonstrated. This method produces water as the sole byproduct and represents a green synthetic protocol. The clean reaction, easily accessible reactants, and the metal- and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure.

A new synthetic approach has emerged for constructing 9H-pyrrolo[1,2-a]indole scaffolds by the reactions between indoles and chalcones under metal- and solvent-free conditions at 80 °C. The reaction occurs smoothly in the presence of a Brønsted acidic ionic liquid, 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium tosylate, as a catalyst, permitting the synthesis of the desired products with satisfactory yields. The developed protocol is applicable to the construction of biologically important pyrrolo[1,2-a]indole derivatives from easily accessible chalcones having various substituents. The process commences with Michael addition to chalcones, followed by annulations induced by the elimination of a water molecule, yielding the 9H-pyrrolo[1,2-a]indole scaffolds. Several control experiments were carried out to achieve a better understanding of the reaction pathway. The feasibility of recycling the catalyst was also demonstrated. This method produces water as the sole byproduct and represents a green synthetic protocol. The clean reaction, easily accessible reactants, and the metal- and solvent-free and environmentally friendly reaction conditions are the notable advantages of this procedure.

We present a novel and cost-effective method for synthesizing biologically important α-keto esters in a single-step reaction. This approach involves a sequential cascade process within a single reaction vessel facilitated by t-BuOK, which promoted the cleavage of the sp2 C(O)–N bond of an isatin and the formation of a new N–C(sp2)(O) bond with benzoyl chloride. To the best of our knowledge, this is the first instance of the construction of an α-keto ester scaffold adjacent to an amide group through a one-pot process. In comparison to existing methods, our protocol offers several advantages: readily available starting materials, mild reaction conditions, a concise synthetic pathway, high sustainability, and excellent tolerance towards various functional groups. Given these strengths, we anticipate widespread use of this method in the synthesis of related α-keto ester scaffolds.

In this contribution, a speedy and direct approach for the synthesis of benzo[1,2,4]triazine derivatives via a copper-catalyzed intermolecular N-arylation of 2-iodoaniline and hydrazonoyl chlorides is described. The reaction proceeds in THF at room temperature with no need for any ligand. The use of simple and readily available starting materials, mild copper-catalytic reaction conditions, and good yields (72–92%) are remarkable specifications of this protocol.

In this work, carbazoles, one of the most important types of nitrogenous compounds, were used as substrates to synthesize dicarbazolyl(aryl)methanols in moderate to excellent yields (up to 95%). This simple and efficient strategy can regioselectively form an sp3 quaternary carbon with two large sterically hindered carbazole rings, one benzene ring, and an active hydroxy group in a one-pot reaction. The resulting triarylmethanes are all new products, and have high potential as building blocks for medicinal chemistry or materials science.

The development of high-affinity ligands specifically targeting intrinsically disordered protein interactions has remained challenging due to the lack of well-defined binding pockets and shallow binding surfaces commonly found at their interfaces. Here, we employed our fluorine-thiol displacement reaction (FTDR) peptide-stapling platform to synthesize a library of peptide-based ligands derived from the αB-helix of the disordered pKID to target its binding partner KIX. Our library revealed that helical formation and affinity to KIX is highly favored when the αB peptide was stapled at sites corresponding to Arg135 and Ser142, further supporting the hypothesis that stabilization of αB significantly influences the overall binding affinity of pKID to KIX. We also found that the highest binding peptide, αB-RSpS, may form secondary contacts at the MLL site on KIX in addition to binding at the primary pKID site. Lastly, no binding to KIX was observed for any αB-stapled peptide that lacked the conserved helix-flanking prolines Pro132 and Pro146. Conserved helix-flanking prolines have previously been shown to modulate the binding affinities of other disordered domains in other proteins including MLL and p53. However, to our knowledge this is the first evidence within αB of pKID.

Herein, we report a straightforward approach for synthesizing C3-alkylated indoles selectively via an iron-catalyzed alkylation of indoles using alcohols as the alkylating agents. A well-defined, air-stable, and easy-to-prepare Fe(II) catalyst of a redox-active tridentate arylazo scaffold was used as a catalyst. Various C3-alkylated indoles were prepared selectively in moderate to good isolated yields by coupling indoles with different substituted alcohols. The methodology is compatible with the gram-scale synthesis. Control experiments were performed to unveil the mechanism, which revealed that the alkylation reaction proceeds via borrowing-hydrogen pathway where the coordinated azo-aromatic ligand actively participates during catalysis, acting as an electron and hydrogen reservoir.