Copper(I)-Catalyzed Ketone, Amine, and Alkyne Coupling for the Synthesis of 2‑Alkynylpyrrolidines and -piperidines

A Cu­(I)-catalyzed coupling of a ω-chloro ketone, a primary amine, and an alkyne is described. This protocol allows for the synthesis of α-quaternary carbons in 2-alkynyl-substituted <i>N</i>-heterocycles. The key step is the in situ generation of a cyclic ketiminium species, which has enhanced reactivity for alkynylation compared to acyclic ketiminium species

“Base Effect” in the Auto-Tandem Palladium-Catalyzed Synthesis of Amino-Substituted 1‑Methyl‑1<i>H</i>‑α-carbolines

An auto-tandem Pd-catalyzed process consisting of an intramolecular direct arylation and an intermolecular Buchwald–Hartwig reaction for C-ring amino-substituted 1-methyl-1<i>H</i>-α-carboline synthesis has been developed. A mechanistic study of the direct arylation reaction revealed a rate effect of the inorganic base on the C–H activation step (“base effect”). The amines, reagents in the tandem protocol, appear to have a similar effect on the direct arylation

“Base Effect” in the Auto-Tandem Palladium-Catalyzed Synthesis of Amino-Substituted 1‑Methyl‑1<i>H</i>‑α-carbolines

An auto-tandem Pd-catalyzed process consisting of an intramolecular direct arylation and an intermolecular Buchwald–Hartwig reaction for C-ring amino-substituted 1-methyl-1<i>H</i>-α-carboline synthesis has been developed. A mechanistic study of the direct arylation reaction revealed a rate effect of the inorganic base on the C–H activation step (“base effect”). The amines, reagents in the tandem protocol, appear to have a similar effect on the direct arylation

2,6-Di(arylamino)-3-fluoropyridine Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors

New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di­(arylamino)­pyrimidines but featuring a 2,6-di­(arylamino)-3-fluoropyridine, 2,4-di­(arylamino)-5-fluoropyrimidine, or 1,3-di­(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains