Metal‐Free Decarboxylative A<sup>3</sup>‐Coupling/Pictet–Spengler Cascade Accessing Polycyclic Scaffolds: Propiolic Acids Exceed Alkynes
Yingxin Hu, Yangpeng Shen, Liliang Huang, Erik V. Van der Eycken, Huangdi Feng
Abstract
Herein, we describe the development of a metal‐free decarboxylative A 3 ‐coupling and Pictet–Spengler cascade process to directly generate functionalized tetrahydroisoquinolines from a 2‐phenylethanamine, formaldehyde, and a propiolic acid. The key feature of this efficient reactivity is the utilization of a propiolic acid as the alkyne source, with TFA as promoter. This transformation was also demonstrated to be amenable to the construction of N ‐propargyl thienotetrahydropyridine and benzodiazepine skeletons under mild conditions.
Topics & Concepts
ChemistryCascadePictet–Spengler reactionAlkynePropargylFormaldehydeDecarboxylationElectrocyclic reactionOrganic chemistryMetalCombinatorial chemistryCatalysisBicyclic moleculeChromatographySynthesis and Biological ActivityChemical synthesis and alkaloidsCatalytic C–H Functionalization Methods