Ruthenium-Catalyzed Dehydrogenative Functionalization of Alcohols to Pyrroles: A Comparison between Metal–Ligand Cooperative and Non-cooperative Approaches

Abstract

Herein, we report the synthesis and characterization of two ruthenium-based pincer-type catalysts, [1]X (X = Cl, PF 6 ) and 2, containing two different tridentate pincer ligands, 2-pyrazolyl-(1,10phenanthroline) (L 1 ) and 2-arylazo-(1,10-phenanthroline) (L 2a/2b , L 2a = 2-(phenyldiazenyl)-1,10-phenanthroline; L 2b = 2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline), and their application in the synthesis of substituted pyrroles via dehydrogenative alcohol functionalization reactions. In catalyst [1]X (X = Cl, PF 6 ), the tridentate scaffold 2pyrazolyl-(1,10-phenanthroline) (L 1 ) is apparently redox innocent, and all the redox events occur at the metal center, and the coordinated ligands remain as spectators. In contrast, in catalysts 2a and 2b, the coordinated azo-aromatic scaffolds are highly redox-active and known to participate actively during the dehydrogenation of alcohols. A comparison between the catalytic activities of these two catalysts was made, starting from the simple dehydrogenation of alcohols to further dehydrogenative functionalization of alcohols to various substituted pyrroles to understand the advantages/disadvantages of the metal−ligand cooperative approach. Various substituted pyrroles were prepared via dehydrogenative coupling of secondary alcohols and amino alcohols, and the N-substituted pyrroles were synthesized via dehydrogenative coupling of aromatic amines with cis-2butene-1,4-diol and 2-butyne-1,4-diol, respectively. Several control reactions and spectroscopic experiments were performed to characterize the catalysts and establish the reaction mechanism.

Co‐Catalyzed Metal‐Ligand Cooperative Approach for N‐alkylation of Amines and Synthesis of Quinolines via Dehydrogenative Alcohol Functionalization

“…To investigate the source of hydrogen in the final N ‐alkylated product 5 j , aniline ( 3 a ) was reacted with deuterated diphenylcarbinol ( 2 z ‐ D ). Deuterium incorporation of 29 % in 5 j ‐ D validates the transfer of the benzylic hydrogen to imine intermediate affording the N ‐alkylated amines, which indeed also confirms the borrowing hydrogen transfer pathway (Scheme 6, entry 4) [9a,13a] …”

“…However, after repeated trials, we could isolate the desired N ‐benzylpyridin‐2‐amine ( 6 a ) in <10 % yield under aerobic conditions. On securitizing the reaction mixture, H 2 O 2 was identified as one of the byproducts [9a,22,23] . Interestingly, under an inert atmosphere, the yield of 6 a increased drastically.…”

“…Several reports of such N ‐alkylation of primary amines by alcohols and preparation of N ‐heterocycles have come up over the years (Scheme 1). However, most of these reports are confined to noble metal‐based catalysts, which are scarce and expensive [8–9,16,17,22a] . Very recently a number of reports have been documented with 3d‐metal based catalyst including cobalt which counts air‐sensitive phosphine‐based [11,12,18] as well as some phosphine free ligands [13–15,19,20]…”

Metal–Ligand Cooperativity Promotes Reversible Capture of Dilute CO2 as a Zn(II)-Methylcarbonate

“…Metal–ligand cooperativity has been used in various catalysis applications such as C–C bond activation, − C–N bond activation, − cycloaddition/cyclization, − and hydrogenation. − There are four known classes of MLC: (1) the use of the metal or ligand as a Lewis base or (2) Lewis acid to cleave the substrate bond; (3) aromatic chelating ligands where dearomatization of the ligand allows for cooperation between the metal and ligand; and (4) use of redox non-innocent ligands that act as an electron reservoir during catalysis . Many studies have focused on the use of MLC to capture and activate CO 2 during its electrocatalytic reduction. − However, few studies have systematically evaluated modification of ligand structure to tune MLC in order to control CO 2 capture and release …”

Sustainable synthesis of pyrazoles using alcohols as the primary feedstock by an iron catalyzed tandem C–C and C–N coupling approach

“…Noteworthy progress has been made over the last decade in synthesizing various N-heterocycles such as pyrrole, benzazoles, quinoline, quinazoline, quinazolinone, purine, pyrimidine, pyridine, etc ., using alcohol as the primary feedstock. 13–28 In 2012, Panda and co-workers reported an iron-catalyzed oxidative cyclization of 1,2-ethanediol and ( E )-1-arylidene-2-arylhydrazine using TBHP as the oxidant. 29 a In 2018, the same group improvised the strategy using Fe(NO 3 ) 2 as the catalyst and K 2 S 2 O 8 as the oxidant.…”