Transition-Metal-Free Cross-Coupling of Aryl and N-Heteroaryl Cyanides with Benzylic Zinc Reagents
Functionalized 4-benzylated pyridines can be efficiently prepared by a transition-metal-free cross-coupling between various benzylic zinc chlorides and substituted 4-cyanopyridines in THF/DMPU under microwave irradiation (40 °C, 0.5-1.5 h). Selective benzylations on polycyano-aromatics have also been achieved under these mild conditions. We also report a novel oxidative nucleophilic substitution of a hydrogen on 1,3-dicyanobenzene using benzylic zinc reagents.
Quinio, Pauline,Roman, Daniela Sustac,León, Thierry,William, Sharankini,Karaghiosoff, Konstantin,Knochel, Paul
supporting information
p. 4396 - 4399
(2015/09/15)
Synthesis of ortho-substituted cyanopyridines through lithio intermediate trapping
Ortholithiation of 4-cyanopyridine using 2,2,6,6-tetramethylpiperidide (LiTMP) and trapping the lithio intermediate with electrophiles represents an efficient and straightforward access to ortho-substituted-4-cyanopyridines. The cyano group can be used as an ortho-directing group and allows the preparation of 3-halogeno-4-cyanopyridines. Reactivity of 2- and 3-cyanopyridines is also investigated and seems to give similar results.