Nickel‐Catalyzed Sequential Dehydrogenation and Cyclization of 2‐Amino(Nitro)‐benzyl Alcohols with Alkyl Alcohols: Synthesis of C‐3‐Substituted Quinolines

Abstract

We herein reported a general and efficient Ni‐catalyzed protocol for sequential double de‐hydrogenative cyclization of 2‐amino(nitro)‐benzyl alcohols with primary alcohols to C‐3‐substituted quinolines releasing water and dihydrogen as by products. As a special highlight, late stage functionalization of cholesterol derivative including chemo‐selective transformations of citronellol, fatty acid derived oleyl alcohol and long chain C4−C14 alkyl alcohols were reported. Initial mechanistic studies including deuterium‐labelling experiments were perform to establish the de‐hydrogenative cyclization.

Challenges and opportunities on sustainable electrochemical transformations: application towards the synthesis of pharmaceuticals and precursors of drug-like molecules

“…However, it is necessary to pay attention towards more sustainable approaches, where potential emphasis on electrochemical transformations for such applications is in demand. It is noteworthy to mention that since the past couple of years, we are actively involved in base-metal catalysed sustainable strategies for organic transformations 14,15 and have focused our attention towards emerging electrocatalysis approaches for organic transformations.…”

Designing Cobalt(II) Complexes for Tandem Dehydrogenative Synthesis of Quinoline and Quinazoline Derivatives

“…In 2022, Balaraman and his group utilized Mn(I)-MACHO to effectively circumvent this problem and produce C-3-substituted quinolines in good yield . Later, a nickel system was used for this purpose with relatively high catalyst loading using an excess of primary alcohols . Thus, there is a demand to devise a sustainable catalytic route to synthesize functionally diverse C-3-substituted (Scheme a) quinolines using earth-abundant nontoxic metals like cobalt.…”

“…15 Later, a nickel system was used for this purpose with relatively high catalyst loading using an excess of primary alcohols. 16 Thus, there is a demand to devise a sustainable catalytic route to synthesize functionally diverse C-3-substituted (Scheme 1a) quinolines using earth-abundant nontoxic metals like cobalt. In this work, we developed new well-defined Co(II) complexes to synthesize a wide range of functionalized C-3-substituted quinolines.…”

“…In addition, the deuterium labeling experiment confirms the dehydrogenative pathway and underpins the idea that the dehydrogenation of alcohols might be the rate-determining step (Scheme e). Accounting for all controlled experiments and preceding literature reports, , we propose a plausible mechanistic cycle (Scheme ). Initially, the active Co catalyst ( Co-2-A ) was generated from precatalyst Co-2 in the presence of KOH, which dehydrogenates both alcohols ( 1a and 2a ) to their corresponding aldehydes ( 8 and 9 , respectively) via metal–ligand cooperation (MLC) at the alkoxy site to form Co–H species ( Co-2-D ).…”