Phosphine‐Free NNN Pincer Supported Cu(II) Catalysts for Sustainable Multi‐Component Synthesis of Pyrazolines and Pyrimidines via Dehydrogenation of Renewable Primary Alcohols

Herein, we present the first NNN pincer bis-imino pyridine-supported copper(II) catalysts for sustainable, eco-friendly, and practical multicomponent synthesis (MCS) of 1,3,5-trisubstituted pyrazolines (TriPyz) and 2,4,6-trisubstituted pyrimidines (TriPym) from alcohols.

Abstract

In this study, we report NNN pincer bis-imino pyridine-supported copper(II) catalysts for the sustainable, eco-friendly, and practical multi-component synthesis (MCS) of pyrazolines and pyrimidines driven by the acceptorless dehydrogenation of benzyl alcohols. Herein, we synthesize and characterize two well-defined phosphine-free NNN pincer-supported copper(II) complexes, C1 and C2, using IR, UV–vis, HRMS, and single-crystal XRD. Utilizing these complexes, we develop the first multi-component synthetic route for 1,3,5-trisubstituted pyrazolines (TriPyz) from the dehydrogenative coupling of renewable benzyl alcohols and aromatic ketones with phenyl hydrazine, generating ecologically benign H₂O and H₂ as side products. The catalytic potential of C1 and C2 is further extended for the MCS of 2,4,6-trisubstituted pyrimidines (TriPym) using primary alcohols, aromatic ketones, and amidine hydrochloride. Following the current methodology, we explore a broad range of TriPyz (30 examples) and TriPym (37 examples) with isolated yields of up to 94%. A series of control experiments and HRMS analysis of the catalytic cycle are carried out to reveal the possible reaction mechanism involving Cu(II)-hydride as a key intermediate.

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