Synlett

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.

This report outlines an intramolecular oxidative annulation process involving N-substituted o-amino phenylacetylene, performed under electrochemical conditions, which yields substituted quinoline in an undivided cell at room temperature. The reaction features mild conditions, requiring neither external oxidants nor metals, and achieves yields that range from good to excellent. Moreover, the synthetic potential of quinoline has been demonstrated resulting in the synthesis of substituted polycyclic isoindolinone and (aza-)isoindolinone compounds.

1,5-Diaza-3,7-diphosphacyclooctane (P2N2) scaffolds represent a readily accessible, tunable ligand class for transition metals. However, despite their prevalence in areas such as electrocatalysis and coordination chemistry, P2N2 ligands have been rarely used to make catalysts for organic synthesis. Research into Mizoroki–Heck-type aldehyde, alcohol, and alkene arylation reactions has revealed that the P2N2 family outperforms many commonly used phosphines. This Synpacts article summarizes our work and provides a broad overview on the preparation and application of P2N2 ligands in organic synthesis. It also serves to highlight how a simple, modular class of ligands can solve contemporary challenges with transition-metal catalysis, including novel reactivity and exceptional regioselectivity.

We have synthesized a series of tetramethylpiperidinyl triazolopyridazine derivatives and screened the molecules for their biological activity against a cancer (NCI-H460) cell line. Among the tested molecules, 2-[3-(2,2,6,6-tetramethylpiperidin-4-yl)-3H-[1,2,3]triazolo[4,5-c]pyridazin-6-yl]-5-(2H-1,2,3-triazol-2-yl)phenol significantly inhibited cell growth with an IC50 value of 5.2 μM. We hope that this study will help in the development of better candidates for the treatment of lung cancer.