Tandem Approach to Benzothieno- and Benzofuropyridines from o-Alkynyl Aldehydes via Silver-Catalyzed 6-endo-dig Ring Closure

Abstract

An operationally simple silver-catalyzed tandem strategy for the synthesis of benzothienopyridines 7a-t and benzofuropyridines 8a-p by the reaction of o-alkynyl aldehyde 4a-t and 5a-p with tert-butylamine 6 under mild reaction conditions is described. The present methodology provides a facile conversion of easily accessible o-alkynyl aldehydes into medicinally useful heterocycles in good to excellent yields under mild and environmentally friendly reaction conditions with excellent regioselectivity. The developed chemistry has been successfully extended for the selective synthesis of C-4 deuterated benzothienopyridines 7u-v and benzofuropyridines 8q-r. The role of the ethanolic proton in the reaction was validated by deuterium-labeling experiments.

Copper-Catalyzed Tandem Imine Formation, Sonogashira Coupling and Intramolecular Hydroamination: A Facile Synthesis of 3-Aryl-γ−carbolines

“…Similar strategy has also been adopted for the synthesis of several other heterocycles in recent times. For example, Ag‐catalyzed tandem approach led to the synthesis of benzothienopyridines and benzofuropyridines by the reaction of o ‐alkynyl aldehydes with tert ‐butylamine . 3‐substituted isoquinolines, steroidal pyridines, 5,6‐dihydrobenzo[f]isoquinolines and 1,6‐naphthyridine were synthesized via a ligand‐free Cu‐catalyzed three component reaction of β‐halovinyl/aryl aldehyde, aromatic/aliphatic terminal alkyne and tert ‐butylamine/benzamidine in DMF under microwave irradiation .…”

Modular Tandem Mizoroki‐Heck/Reductive Heck Reactions to Construct Fluorenes from Cyclic Diaryliodoniums

“…[6] Recently, Chen and co-workers reported that 9Hfluorene-based compound 1 d acted as a photoredox catalyst for decarboxylative arylation. [7] A variety of synthetic methods have been reported to construct the fluorene scaffolding over the past a few years, [8] including Freidel-Crafts reaction, [9] the late-stage derivatization of existing fluorene cores, [10] and miscellaneous methods. [11] However, the present methods still suffer from limited substrate scopes, poor accessibility of starting materials, or harsh reaction conditions.…”