Metal-Free Decarboxylative A3-Coupling/Pictet–Spengler Cascade Accessing Polycyclic Scaffolds: Propiolic Acids Exceed Alkynes

Herein, we describe the development of a metal-free decarboxylative A3-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. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim