Synlett

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.

An efficient N-heterocyclic carbene (NHC)-catalyzed asymmetric conjugate addition reaction to afford synthetically challenging benzofuranone derivatives having vicinal all-carbon quaternary and tertiary stereocenters is presented. The reaction operates solely through noncovalent interaction between a newly designed NHC and the substrates, providing access to a series of functionalized benzofuranones in good yields and with high ee values. The protocol applies to preparative-scale synthesis. A catalytic cycle involving a noncovalent substrate–NHC interaction is implicated in the process, based on a mechanistic control study.

Catalytic C(sp3)–H insertion reactions of arylalkanes generally proceed at the benzylic position as a consequence of the lower bond dissociation energy (BDE) of the corresponding C–H bond. This account gives a brief overview of recent studies aimed at designing catalyst-controlled amination reactions to go beyond this BDE-driven selectivity. They permit the selective conversion of neutral C–H bonds with a BDE greater than 95 kcal mol–1 for the formation of alkylamines.1 Introduction2 Catalyst-Controlled Site-Selective C–H Insertion Reactions3 Catalyst-Controlled Intermolecular Amination of Nonactivated C–H Bonds of Arylalkanes4 Conclusion

Saturated stereogenic centers containing C(sp3)–C(sp3) bonds comprise a major portion of organic molecules. Over the past decades, transition-metal-catalyzed asymmetric C(sp3)–C(sp3) cross-coupling has evolved into an efficient strategy for constructing such stereogenic centers. However, reaction modes to build asymmetric C(sp3)–C(sp3) bonds remain limited. Herein, a nickel-catalyzed enantioselective cross-hydrodimerization between distinct alkenes to enable the enantioselective construction of alkyl–alkyl bonds has been developed. In this reaction mode, N-acyl enamines (enamides) and unactivated alkenes undergo oxidative enantioselective cross-hydrodimerization with excellent levels of chemo- and head-to-tail regioselectivity to give enantioenriched N-acyl α-branched amines by forging the C(sp3)–C(sp3) bond with control of the enantioselectivity. The presence of both reducing and oxidizing reagents in the reaction allows the use of alkenes as sole precursors to forge enantioselective C(sp3)–C(sp3) bonds, representing a new reaction mode for asymmetric alkyl–alkyl cross-coupling. The asymmetric cross-hydrodimerization between distinct alkenes provides a new strategy for constructing saturated stereogenic centers containing C(sp3)–C(sp3) bonds.

A catalyst-controlled divergent alkylation of diarylamines with benzylic alcohols has been developed. A para C-alkylation of diarylamines could be achieved by using B(C6F5)3 as the catalyst, whereas ortho C-alkylation of diarylamines could be achieved by using HBF4·Et2O as the catalyst. The salient features of this transformation include readily available materials, a broad substrate scope, easily available catalysts, and simple and mild reaction conditions.

Recent developments in the isotopic labeling of heteroarenes may prove to be useful in the realms of biomedical science, materials chemistry, and fundamental organic chemistry. The use of the age-old Zincke reaction, or tactical variants thereof, has become particularly utilitarian in effecting single-atom nitrogen replacement in various azines to generate their desired isotopologues. This chemistry can be synthetically leveraged at an early stage for diversity-oriented heterocyclic labeling of pharmaceuticals and/or natural products. Additionally, given the prevalence of saturated azacycles in biologically relevant molecules, access to these isotopologues becomes relevant through dearomative retrosynthetic analysis from the corresponding 15N-labeled heteroarenes.1 Introduction2 Our Lab’s Development of the 15NRORC Reaction3 Other Recent Azine-Labeling Methods4 Expanded ANRORC Utilization5 Conclusion and Outlook

The metal hydride catalyzed alkene hydroalkylation enables efficient alkyl–alkyl coupling, yielding structurally diverse chiral organic compounds. However, the control of stereochemical selectivity in alkene hydroalkylation still heavily relies on the assistance of substrate Lewis basic functional groups or polar heteroatom functional groups. We have recently developed a cobalt hydride catalytic system and established a paradigm of enantioselective control assisted by C–H···π noncovalent interactions. This approach enables the asymmetric hydroalkylation of 1,1-disubstituted styrenes, thereby circumventing the limitations imposed by substrate heteroatom functional groups.1 Introduction2 Reaction Development3 Synthetic Applications4 Mechanistic Investigation5 Conclusion and Future Outlook

We report a visible-light-mediated, FeCl3-catalyzed, one-pot tandem strategy for the regioselective synthesis of unsymmetrically substituted tertiary and quaternary carbon-containing 3,3′-bis(indolyl)methanes under aerobic conditions. This strategy involves the coupling of 3-arylideneindolines with indoles through a photoinduced chlorine-radical-mediated hydrogen-atom-transfer reaction. The present strategy features mild and environmentally benign reaction conditions, low cost, high yields, and tolerance of a wide range of functional groups. Furthermore, to demonstrate the synthetic value of the reaction, a naturally occurring bioactive bisindolyl(phenyl)methane was synthesized.