Concise Synthesis of Vesnarinone and Its Analogues by Using Pd‐Catalyzed C–N Bond‐Forming Reactions

Abstract

An efficient and concise synthesis of vesnarinone and its analogues from readily available starting materials and by using catalytic C–N bond‐forming reactions is reported. In this protocol, a homogeneous Pd‐catalyzed Buchwald–Hartwig amination and a supported Pd nanoparticles catalyzed aminocarbonylation were utilized as the two key reactions to prepare vesnarinone in an overall yield of 73 %. Sixteen analogues were also synthesized in up to 89 % overall yield.

Enantiodivergent dearomative skeletal ring expansion of indoles through carbon atom insertion

“…Vesnarinone is a class of quinolinone-based inotropic drugs clinically used to treat heart failure. 53 Using our (R)-selective reaction conditions, it is possible to access the vesnarinone analogue containing a tri uoromethyl quaternary center with high enantioselectivity in four steps directly from (R)-19 (Fig. 4D and Supplementary Fig.…”