Dehydrogenative Synthesis of Quinolines, 2-Aminoquinolines, and Quinazolines Using Singlet Diradical Ni(II)-Catalysts

Abstract

Simple, straightforward, and atom economic methods for the synthesis of quinolines, 2-aminoquinolines, and quinazolines via biomimetic dehydrogenative condensation/coupling reactions, catalyzed by well-defined inexpensive and easy to prepare singlet diradical Ni(II)-catalysts featuring two antiferromagnetically coupled singlet diradical diamine type ligands are described. Various polysubstituted quinolines, 2-aminoquinolines, and quinazolines were synthesized in moderate to good yields from different low-cost and readily accessible starting materials. Several control experiments were carried out to get insight into the reaction mechanism which shows that the nickel and the coordinated diamine ligands participate in a synergistic way during the dehydrogenation of alcohols.

Nickel‐Catalyzed Synthesis of Pyrimidines via Dehydrogenative Functionalization of Alcohols

“…For catalyst 1 a inert condition and slightly higher temperature is required to get the products in satisfactory yields while the catalyst 2 a affords the respective pyrimidines in even higher yields under comparatively mild aerobic conditions. Moreover, the metal‐ligand cooperativity and active involvement of ligand centered radical in 2 a allow to achieve pyrimidines in good yields even starting from unactivated alcohols bearing strongly electron‐withdrawing substituents. Overall, the metal‐ligand cooperative approach via active involvement of the ligand centered redox process during catalysis allow to avoid the energetically demanding high energy nickel centered redox processes and allow to achieve the reactions under mild and aerobic conditions.…”

“…In this regard, the metal‐ligand cooperative catalysis involving synergistic participation of both metal and ligand centered redox events would be useful. Synergistic participation of both metal and ligand centered redox processes during catalysis may indeed allow us to avoid energetically uphill metal‐centered two‐electron processes and can allow us to achieve these reactions at comparatively low temperature …”

“…Herein we report a comparative study of nickel catalyzed synthesis of pyrimidines via dehydrogenative multi‐component coupling of alcohols and amidines using two different classes of nickel catalysts 1 a/1 b and 2 a/2 b (Figure ), differing with respect to their mode of action during catalysis . The catalysts 1 a and 1 b represent two tetraaza macrocyclic nickel(II)‐complexes, whereas catalysts 2 a and 2 b are two diamine‐based nickel(II)‐complexes.…”

“…During our recent works, we observed that the nickel catalysts 1 a and 1 b involve exclusively nickel‐centered redox events during catalysis and the dehydrogenation of alcohols proceeds via two‐electron hydride transfer process involving energetically demanding nickel centered redox states at high temperature . On the other hand, in presence of 2 a and 2 b dehydrogenation of alcohols proceed via one‐electron hydrogen atom transfer (HAT) process (avoiding the unfavourable nickel centered two‐electron process) where the coordinated redox‐active ligand abstract a α‐hydrogen atom of the alcohol to form an O‐coordinated ketyl radical intermediate which undergo rapid one‐electron oxidation to yield the respective carbonyls . In the subsequent steps, the in‐situ formed carbonyls upon further inter/intramolecular cyclization afforded the desired N‐heterocycles …”

“…Synergistic participation of both metal and ligand centered redox processes during catalysis may indeed allow us to avoid energetically uphill metal-centered two-electron processes and can allow us to achieve these reactions at comparatively low temperature. [18][19][20] Herein we report a comparative study of nickel catalyzed synthesis of pyrimidines via dehydrogenative multi-component coupling of alcohols and amidines using two different classes of nickel catalysts 1 a/1 b and 2 a/2 b (Figure 1), differing with respect to their mode of action during catalysis. [16,19] The catalysts 1 a and 1 b represent two tetraaza macrocyclic nickel (II)-complexes, whereas catalysts 2 a and 2 b are two diaminebased nickel(II)-complexes.…”