A “Thiocarbonyl‐Directed” Regiospecific C−H/S−H Annulation of Quinoline‐4(1 H )‐thiones with Alkynes

Abstract

A regiospecific C−H/S−H annulation of quinoline-4(1H)-thiones with alkynes have been demonstrated using a ruthenium(II) catalyst. This C−H/S−H annulation is directed via the C=S group, where preferential annulation takes place at the sterically hindered position even in the presence of three other competing sites viz. two C−H/N−H and one C−H/O−H. This type of annulation is unsuccessful for simple aryl thiol such as 1-naphthylthiol, giving only an oxidative dimerized product. The reaction proceeds via ruthenium-catalyzed oxidative annulation followed by a hydrolytic cleavage of an amidic bond (loss of −COPh group), leading to the synthesis of thiopyrano[2,3,4-de]quinolines. Isotopic labelling experiments suggest an irreversible initial C−Ru bond formation and the cleavage of C−H bond to be the rate-limiting step. The reaction with unsymmetrical and terminal alkynes gave single regioisomeric product, where the new C−S bond formation takes place at the sp-carbon of alkyne having more electron density. The reaction shows wide substrate scope both for quinoline-4(1H)-thiones as well as alkynes giving up to 91% product yields.