Dual Heterogeneous Catalysis for a Regioselective Three‐ Component Synthesis of Bi‐ and Tri(hetero)arylpyridines

Abstract

International audienceWe designed a new, user-friendly oxidative dual heterogeneous catalytic system capable of promoting polysubstituted pyridines as unique products from simple activated Michael acceptors, 1,3-dicarbonyls and ammonium acetate. This metal-free environmentally-respectful and totally regioselective domino reaction proved to be a great strategy to access bi- and tri-aryl type pyridines as well as challenging bi- and tri-heteroaryl type pyridines in a single operation

Bio-Catalysis in Multicomponent Reactions

“…It has undergone many modifications and improvements and is now the method of choice for fast access to DHP derivatives, which are useful for various bioactivities such as calcium channel blockers and antihypertensive agents [ 10 , 46 ] but, also, as scaffolds in medicinal chemistry [ 14 ]. Under oxidative conditions, these so-called Hantzsch esters can be transformed into the corresponding pyridines, a strategy used to prepare single regio-isomers of poly-substituted pyridines [ 47 , 48 , 49 ] ( Scheme 9 ).…”

External-Oxidant-Based Multicomponent Reactions

“…In some instances, the use of stoichiometric amounts of MnO 2 replacing acetic acid and activated carbon was found to be essential. 42 The use of 1,3-dicarbonyl derivatives such as 51 limited the synthesis to pyridines with a 3-carbonyl substituent. However, in 2015, Chunyin Zhu reported that aldehydes and ketones 59 could also take part in this multicomponent reaction in the presence of an amine 60 and a catalytic amount of CAN.…”

Metal‐Free Michael‐Addition‐Initiated Three‐Component Reaction for the Regioselective Synthesis of Highly Functionalized Pyridines: Scope, Mechanistic Investigations and Applications

“…As an improvement of this methodology, the use of activated Michael acceptors 2 (R 5 = EWG) under appropriate heterogeneous oxidative conditions combining molecular sieves with activated carbon allowed the introduction of various functionalities at the strategic C‐212 and C‐413 positions of the heteroaryl ring (Scheme , method B denoted “dual heterogeneous catalysis”) 14. This environmentally friendly methodology has proved to be a valuable strategy for the challenging metal‐free access to di‐ and tri(hetero)arylpyridines 15…”