Synlett

Pd-catalyzed cross-couplings of C–H bonds have been pursued by researchers to produce unsymmetrical C–C bonds directly for over 50 years. Such bonds are currently prepared by Suzuki, Kumada, Stille, Neigishi, Heck, or Sonogashira coupling of C–halogen with C–M or C–H bonds. A big challenge is to obtain high cross-selectivity of cross-coupling products, especially when the substrates have similar chemical C–H bonds, such as simple arenes. Lu and co-workers have studied Pd catalysis in the cross-couplings of aryl C–H bonds since 2003. This account introduces their strategy, understanding, and research in cross-selectivity control, C–H activation modes, and cross-coupling establishment, and discusses the applications of the approach in synthesis.1 Introduction2 Cross-Selectivity Control3 Conclusion

We describe the design, synthesis, and in vitro biological evaluation of contilistat, a novel polyfunctionalized indole derivative designed as a hybrid of contilisant and vorinostat containing key pharmacophoric groups of both parent ligands.

We describe the design, synthesis, and in vitro biological evaluation of contilistat, a novel polyfunctionalized indole derivative designed as a hybrid of contilisant and vorinostat containing key pharmacophoric groups of both parent ligands.

Synlett 2024; 35: VII-DOI: 10.1055/s-0043-1773503Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

Synlett 2024; 35: VII-DOI: 10.1055/s-0043-1773503Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents

Catalytic C(sp3)–H cross-coupling offers an attractive strategy for constructing C(sp3)-rich complex molecules from simple feedstock chemicals. However, simultaneously controlling chemo- and enantioselectivity in these transformations, particularly for C(sp3)–C(sp3) bond formation, remains a formidable challenge. To address this longstanding challenge, we have recently developed a general strategy leveraging nickel photoredox catalysis to achieve various enantioselective C(sp3)–H cross-coupling reactions, including acylation, alkenylation, arylation, (trideutero)methylation, and alkylation. Our approaches exploit photocatalytically generated bromine radicals for hydrogen atom transfer, converting common hydrocarbons into carbon-centered radicals. These radicals are then enantioselectively coupled with diverse electrophiles in the presence of a suitable chiral nickel catalyst. These methods open new avenues for enantioselective C(sp3)–H cross-coupling, offering broad substrate scope, high functional group tolerance, and potential for late-stage diversification of complex molecules. Our strategy holds great promise for unlocking previously elusive C(sp3)-rich chemical space, with significant implications for drug discovery and development.1 Introduction2 Enantioselective C(sp3)–C(sp2) Cross-Couplings3 Enantioselective C(sp3)–C(sp3) Cross-Couplings4 Conclusions and Outlook

In this letter, we present a synthesis of a-oxoamidines by the condensation of primary/secondary amines with N-aryl-α-oxothioamides catalyzed by benzoic acid in toluene at 80 °C. The required N-aryl-α-oxothioamide substrates were synthesized by the sodium hydride-induced condensation of aromatic amines with α-oxodithioesters. The amines reacted with high regioselectivity toward thiocarbonyl groups over carbonyl groups to afford α-oxoamidines. The present method overcomes the limitations of previously reported methods.

Herein, we report that orthoformate ester and N,N-dimethylformamide di-tert-butyl acetal can be a source of alkoxy radicals. We have developed a coupling reaction with aryl halides as a way of utilizing them. This has led to the synthesis of aromatic ethers with tertiary alkoxy groups, which are generally considered difficult to synthesize.

Selective oxidation of sulfides to sulfoxides using ‘air’ was achieved using a combination of 2,2′-azobis-(2,4-dimethyl-4-methoxyvaleronitrile) (a radical initiator) and isobutyraldehyde (a co-oxidant). Various sulfides were successfully converted into their corresponding sulfoxides using this method. This approach promotes a sustainable oxidation process by excluding harmful oxidants, such as peroxides and metal reagents.

Synlett 2024; 35: V-DOI: 10.1055/s-0043-1773501Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, GermanyArticle in Thieme eJournals:Table of contents