Zn(II)-Catalyzed Multicomponent Sustainable Synthesis of Pyridines in Air

Abstract

Herein, we report a Zn­(II)-catalyzed solvent-free sustainable synthesis of tri- and tetra-substituted pyridines using alcohols as the primary feedstock and NH4OAc as the nitrogen source. Using a well-defined air-stable Zn­(II)-catalyst, 1a, featuring a redox-active tridentate azo-aromatic pincer, 2-((4-chlorophenyl)­diazenyl)-1,10-phenanthroline (La ), a wide variety of unsymmetrical 2,4,6-substituted pyridines were prepared by three-component coupling of primary and secondary alcohols with NH4OAc. Catalyst 1a is equally compatible with the four-component coupling. Unsymmetrical 2,4,6-substituted pyridines were also prepared via a four-component coupling of a primary alcohol with two different secondary alcohols and NH4OAc. A series of tetra-substituted pyridines were prepared up to 67% yield by coupling primary and secondary alcohols with 1-phenylpropan-1-one or 1,2-diphenylethan-1-one and NH4OAc. The 1a-catalyzed reactions also proceeded efficiently upon replacing the secondary alcohols with the corresponding ketones, producing the desired tri- and tetra-substituted pyridines in higher yields in a shorter reaction time. A few control experiments were performed to unveil the mechanistic aspects, which indicates that the active participation of the aryl-azo ligand during catalysis enables the Zn­(II)-complex to act as an efficient catalyst for the present multicomponent reactions. Aerial oxygen acts as an oxidant during the Zn­(II)-catalyzed dehydrogenation of alcohols, producing H2O and H2O2 as byproducts.

Zn(II)‐Stabilized Azo‐Anion Radical Catalyzed Sustainable C−C Bond Formation: Regioselective Alkylation of Fluorene, Oxindole, and Indoles

“…The sharp decrease in the products yield in presence of TEMPO was noticed in each case (see SI, Scheme S1, entries d–h), that strongly supports the involvement of the radical pathway, as observed before [9b,11a,25] . Formation of ring cleavage products when the radical‐clock substrate cycobutanol was subjected to dehydrogenation or as coupling partner with 9 H ‐fluorene confirms the formation of ketyl‐type radical intermediate during 1 a ‐catalyzed alcohol dehydrogenation (see SI, Fig.…”

“…Based on the above experimental evidence and available literature, a plausible mechanism is depicted in Scheme 8 [9b,11a,25a,b] . The catalyst 1 a undergoes a single‐electron reduction in the presence of a reducing agent i. e., KO t Bu or Zn dust, to generate the one‐electron‐reduced active species [ 1 a ] − ( A ).…”

Electron transfer catalysis mediated by 3d complexes of redox non-innocent ligands possessing an azo function: a perspective

“…The above-mentioned complexes 27 and 28 have also been used as a catalyst in the solvent-free, multi-component synthesis of tri- and tetra-substituted pyridines 136 starting from 1° and 2° aromatic alcohols and ketones (Scheme 43). The scope of catalysis is given in Schemes S41–S44 (ESI†) and the reaction is anticipated to follow a similar pathway.…”

Ruthenium complexes of redox non-innocent aryl-azo-oximes for catalytic α-alkylation of ketones and synthesis of 2-substituted quinolines

“…We have been striving to explore and figure out the electron extracting ability of coordinated diaryl-azo-oximes in order to effectuate certain unusual redox transformations. [63][64][65][66][67] We are further motivated to synthesize suitable complexes of azooximes where the ligand skeleton may become redox active in the presence of ruthenium(II) and they may be skillfully employed to bring about electron-transfer catalysis for synthesis of useful organic compounds in an atom efficient manner. It is worth mentioning that there has been no report on electron-transfer catalysis mediated by azo-oximates.…”