Copper-Catalyzed, Ligand-Controlled N(sp³)- or N(sp)-Selective Arylation of Cyanamides

Abstract

Cyanamides possess both nucleophilic and electrophilic centers, and their arylation reactions are known to proceed at N(sp 3 ) and C(sp) sites, leading to N-aryl cyanamides or amidines. N(sp) selectivity has also been reported only in the presence of amines, thus leading to guanidines. Herein, we report a general copper-catalyzed ligand-controlled Chan-Lam-Evans arylation of cyanamides proceeding regioselectively at the N(sp 3 ) or N(sp) atoms and leading to either N-aryl cyanamides or dissymmetric carbodiimides. The nature of the ligand, either a bipyridine or a diamine, controls the product distribution and thus offers a divergent entry to useful building blocks from readily available cyanamides.

Ring-closing enyne metathesis of allylic and propargylic cyanamides

“…Cyanamides are also commonly utilized in agrochemicals and a variety of insecticides contain a cyanamide moiety, sulfoxalor 6, 9 thiacloprid 7, 10 and acetamiprid 8 11 being representative examples. Due to the importance of cyanamides, notably in medicinal chemistry where nitrogen-containing heterocycles are among the most significant structural components of pharmaceuticals, 12 and based on our recent interest in the chemistry of cyanamides, 13,14,15,16 we report in this manuscript an efficient and rapid entry to 5-membered cyclic cyanamides from readily available allylic and propargylic cyanamides. The ring-closing metathesis reaction of N-alkenyl-cyanamides 9 to cyclic unsaturated cyanamides 10 we reported in 2021 15 (Scheme 1, top) indeed prompted us to investigate the related cyclization of N-allyl,N-propargyl-cyanamides 11, compounds that are readily available through a A 3 coupling 17 followed by a von Braun reaction, to the corresponding highly functionalized cyclic cyanamides 12 that would result from a ring-closing enyne metathesis 18 (Scheme 1, bottom).…”