Metal–Ligand Cooperative Approach To Achieve Dehydrogenative Functionalization of Alcohols to Quinolines and Quinazolin-4(3H)-ones under Mild Aerobic Conditions

Abstract

A simple metal–ligand cooperative approach for the dehydrogenative functionalization of alcohols to various substituted quinolines and quinazolin-4­(3H)-ones under relatively mild reaction conditions (≤90 °C) is reported. Simple and easy-to-prepare air-stable Cu­(II) complexes featuring redox-active azo-aromatic scaffolds, 2-arylazo-(1,10-phenanthroline) (L 1,2 ), are used as catalyst. A wide variety of substituted quinolines and quinazolin-4­(3H)-ones were synthesized in moderate to good isolated yields via dehydrogenative coupling reactions of various inexpensive and easily available starting materials under aerobic conditions. A few control experiments and deuterium labeling studies were carried out to understand the mechanism of the dehydrogenative coupling reactions, which indicate that both copper and the coordinated azo-aromatic ligand participate in a cooperative manner during the catalytic cycle.

Nickel‐Catalyzed Synthesis of Pyrimidines via Dehydrogenative Functionalization of Alcohols

“…Therefore, to make these alcohol functionalization reactions more sustainable and economically affordable, the heavier metal catalysts need to be substituted by low‐cost and abundantly available first‐row base metal catalysts. In the last few years, several new first‐row base metal catalysts were developed, and functionalization of alcohols to different complex organic compounds was achieved . However, the primary drawback of most of these base metal catalyzed protocols is the requirement of high temperature (>100 °C).…”

“…It is worth mentioning here that transition metal catalyzed functionalization of alcohols usually proceeds via initial dehydrogenation of alcohols to the corresponding carbonyl compounds followed by subsequent condensation, inter‐, or intramolecular cyclization steps . The first dehydrogenation step mostly goes via two‐electron hydride transfer pathway involving the formation of metal‐hydride intermediates .…”

“…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 …”

“…In the last few years, several new first-row base metal catalysts were developed, and functionalization of alcohols to different complex organic compounds was achieved. [13][14][15][16][17][18] However, the primary drawback of most of these base metal catalyzed protocols is the requirement of high temperature (> 100°C). Therefore, the main challenge at present is to achieve these first row base metal catalyzed alcohol functionalization reactions under relatively mild conditions so that these become more economically viable for large scale industrial utilization.…”

“…It is worth mentioning here that transition metal catalyzed functionalization of alcohols usually proceeds via initial dehydrogenation of alcohols to the corresponding carbonyl compounds followed by subsequent condensation, inter-, or intramolecular cyclization steps. [7][8][9][10][11][12][13][14][15][16][17][18] The first dehydrogenation step mostly goes via two-electron hydride transfer pathway involving the formation of metal-hydride intermediates. [7][8][9][10][11][12][13][14][15][16][17] However, the first-row base metals mostly prefer to react via one-electron pathway, and the corresponding two-electron transfer pathways are thermodynamically unfavorable and are associated with high energy barrier requiring elevated temperature.…”