A Cp*Ir(III) complex (1) of a newly designed ligand L 1 featuring a proton-responsive pyridyl(benzamide) appended on N-heterocyclic carbene (NHC) has been synthesized. The molecular structure of 1 reveals a dearomatized form of the ligand. The protonation of 1 with HBF 4 in tetrahydrofuran gives the corresponding aromatized complex [Cp*Ir(L 1 H)Cl]BF 4 (2). Both compounds are characterized spectroscopically and by X-ray crystallography. The protonation of 1 with acid is examined by 1 H NMR and UV-vis spectra. The proton-responsive character of 1 is exploited for catalyzing α-alkylation of ketones and β-alkylation of secondary alcohols using primary alcohols as alkylating agents through hydrogen-borrowing methodology. Compound 1 is an effec-tive catalyst for these reactions and exhibits a superior activity in comparison to a structurally similar iridium complex [Cp*Ir(L 2 )Cl]PF 6 (3) lacking a proton-responsive pendant amide moiety. The catalytic alkylation is characterized by a wide substrate scope, low catalyst and base loadings, and a short reaction time. The catalytic efficacy of 1 is also demonstrated for the syntheses of quinoline and lactone derivatives via acceptorless dehydrogenation, and selective alkylation of two steroids, pregnenolone and testosterone. Detailed mechanistic investigations and DFT calculations substantiate the role of the proton-responsive ligand in the hydrogen-borrowing process.À OH/=O, À CH 2 /=CH and À NH/ = N motifs on pyridine, [25][26][27] bipyridine, [28][29][30][31][32] bipyrimidine [33] and azole-pyridine/ pyrimidine [34][35][36][37] are particularly effective. Some of the representative examples that have been employed for catalyzing (de) hydrogenation and alkylation reactions are given in Scheme 1. Yamaguchi and co-workers reported a Cp*Ir(III) compound with
A Mn(I) complex (1) bearing a proton responsive hydroxy unit on 1,8-naphthyridine-N-oxide scaffold (L 1 H) was synthesized. The molecular structure of 1 revealed the lactim form of the ligand. The corresponding deprotonated lactam complexes [18-C-6-K·2] and 3 were prepared and structurally characterized. The acid–base equilibrium between the lactim and lactam forms was studied by 1H NMR and UV–vis spectra. The catalytic efficiency of 1 was evaluated by performing α-alkylation reaction of ketones with primary alcohols. The scope of the α-alkylation reaction is broad in terms of both ketones and alcohols. The efficacy of the protic catalyst is demonstrated in the alkylation of the bioactive steroids progesterone and pregnenolone. A controlled catalyst [Mn(L2)(CO)3Br] (4), which is structurally similar to 1 but devoid of the proton responsive hydroxy unit, shows significantly reduced catalytic efficiency validating the crucial role of the hydroxy functionality in 1. Kinetic study, control reactions, and deuterium labeling experiments were conducted to gain mechanistic insights.
Polyaromatic N-heterocycles are some of the most common building blocks in natural products and active pharmaceutical ingredients. Significant efforts have been devoted to developing catalytic protocols, including those which use an acceptorless dehydrogenation strategy at elevated temperatures, to produce polyaromatic N-heterocycles like quinolines and naphthyridines. However, photoinitiated catalysis driven by visible light offers a milder and often more selective protocol as an alternative to thermal reactions. Here, we present the catalytic syntheses of quinolines and naphthyridines from ortho-aminobenzyl alcohols and ketones using the photocatalyst [Mn(L 1 H)(CO) 3 Br] (L 1 H = 7-hydroxy-2-methyl-1,8-naphthyridine-N-oxide), bearing a phenolic unit on a 1,8-naphthyridine-N-oxide scaffold, under ambient and aerobic conditions with visible light illumination. We describe a broad, functional group-tolerant substrate scope of >30 examples under modest reaction conditions. A variety of 2-aminobenzyl alcohols containing electron-donating and electron-deficient groups and (2-aminopyridin-3-yl)methanol are converted to the corresponding quinolines and naphthyridines using ambient air as an oxidant in the presence of KOH. We synthesized a wide range of derivatives, including some of the bioactive antimalarial drug chloroquine and the steroids progesterone and pregnenolone to highlight the value-added applications of this catalytic protocol for pharmaceutical ingredient and natural product syntheses. We performed substrate viability, ultraviolet−visible, electron paramagnetic resonance, and X-ray photoelectron spectroscopy studies, as well as density functional theory calculations to gain mechanistic insights to the reaction pathway. The catalytic cycle involves condensation of the amino group in the ortho-aminobenzyl alcohol with the ketone initially, which is followed by aerobic oxidation of the benzyl alcohol to the corresponding benzaldehyde catalyzed by the photoinitiator [Mn(L 1 H)(CO) 3 Br] in the presence of visible light, and finally, a KOH-promoted condensation and cyclization to afford quinolines as the final products.
Reactions of a host of metal precursors with pyridyl-(benzamide)-functionalized C 2 -methyl-protected imidazolium salts [L 1 H 2 ]I and [L 2 H]I afforded the metal−methyleneimidazoline (MIz) compounds [Ru(L 1 -κC 1 )(p-cymene)]I (1), [Mn(L 1 -κC 1 )(CO) 3 ] (2), [Ru(L 2 -κC 1 )(pcymene)Cl]PF 6 (3), and [Ir(L 2 -κC 1 )(Cp*)Cl]PF 6 (4) in the presence of different external bases, such as LiHMDS, Na 2 CO 3 , t BuOK, and NaH. However, the use of NaOAc led to the selective formation of the metal− mesoionic carbene (MIC) compounds [Ru(L 2 -κC 5 )(p-cymene)Cl]PF 6 (5), [Ir(L 2 -κC 5 )(Cp*)Cl]PF 6 (6), [Ir 2 (L 1 -κC 5 )(Cp*) 2 I]PF 6 (8), and the orthometalated compound [Ir(L 1 )(Cp*)I] (7). All compounds have been characterized by spectroscopic techniques and X-ray crystallography. Being more acidic, the C 2 -methyl is readily deprotonated by the external base to give the metal−MIz products. A metal-bound acetate, in contrast, interacts selectively with the imidazolium C 5 −H and drives the reaction toward the metal−MIC formation. DFT calculations support a concerted metalation−deprotonation pathway for selective C−H activation and metalation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.