Synthesis of aminopyridines via an unprecedented nucleophilic aromatic substitution of cyanopyridines

Cyanide Anion as a Leaving Group in Nucleophilic Aromatic Substitution: Synthesis of Quaternary Centers at Azine Heterocycles

“…In 2009, during a medicinal chemistry campaign that utilized the Klapars and Waldman α-nitrile arylation method, a third Merck group noted unintentional displacement of a nitrile functional group on the pyridine electrophile . Herein, we report further studies on the use of the cyanide leaving group in forming quaternary centers via S N Ar chemistry. − …”

Decyanative Cross‐Coupling of Cyanopyrimidines with O‐, S‐, and N‐Nucleophiles: A Route to Alkoxylpyrimidines, Aminopyrimidines and Alkylthiopyrimidines

“…Only one class of examples of the synthesis of aminopyridines by the direct nucleophilic aromatic substitution of cyanopyridines with lithium amides has been reported . To our delight, we found that the reactions of 1a with five‐ and six‐membered cyclic secondary amines gave the corresponding products 12a – 12e in 85–95 % yields.…”

Selective Phosphoranation of Unactivated Alkynes with Phosphonium Cation To Achieve Isoquinoline Synthesis

“…To shed light on the reaction mechanism, some 31 P NMR experiments were performed to elucidate the transformations between phosphorus-containing species (please refer to Section 15 in the Supporting Information). First, the 31 P NMR spectra indicate that mixing PPh 3 with Tf 2 O in DCE mainly produces (TfOPPh 3 ) + Tf − with a chemical shift of δ 54.3 ppm, 26 while PPh 3 with TfOH in DCE merely produces (HPPh 3 ) + (OTf) − with a chemical shift of δ 5.1 ppm.…”

“…In addition, the methyl group in compound 3aa can readily convert into aldehyde 7 by SeO 2 (90% yield) or phthalimidated compound 8 via a copper-catalyzed dehydrogenative C–H/N–H coupling (27% yield). Notably, exposure of compound 3aa to the Pd­(OAc) 2 /NHPI/ t BuONO system gave nitrile compound 9 (40% yield), which, after successive treatments with n -BuLi and N -methylpiperazine, was formally transformed into the antitumor agent CWJ-a-5 in 70% yield. Moreover, as pyrimidines are fundamental structural motifs in various function molecules, some elegant methods with nitriles and ketone or N -vinylacetamides as the regents and Lewis/Brønsted acids as the promoter have been developed .…”