Cover Feature: Copper and Nickel Complexes of Oxamate−Phenol Containing Ligands: A Structural Dichotomy in Oxidized Species (Eur. J. Inorg. Chem. 15/2023)

The copper and nickel complexes of two tetradentate ligands derived from bis(aminophenol) and bis(phenol) architectures connected by an oxamate linker were isolated. Depending on the metal and ligand, the complex is isolated with either an intact (deprotonated) ligand ( 1²⁻ ), one-electron oxidized ligand ( 2⁻ ) or quinone form ( 3 ). Surprisingly, the Mannich base is easier to oxidize than the amidophenol derivatives. The complexes were characterized by X-ray diffraction, cyclic voltammetry, UV-Vis-NIR and EPR spectroscopies. Complex 1 shows two reversible oxidation waves assigned to the successive iminosemiquinone/aminophenolate redox systems. Complex 2⁻ shows an intense NIR feature, as well as an EPR signal at g_iso=2.043, consistent with a metallic contribution to the main ligand radical SOMO. Complex 3 shows the typical feature of an isolated Cu(II) complex. Spectro-electrochemistry coupled to DFT calculations demonstrate a ligand-centered oxidative redox chemistry for all the complexes.     

Enantioselective Synthesis of [b]-Annulated Azepane Scaffolds

Cyclopenta-, benzo-, and cyclohepta[b]-annulated azepane scaffolds were prepared in two steps from optically active cyclic α-allyl-β-oxoesters. The first step was ruthenium-catalyzed olefin cross metathesis with acrylonitrile. The second step was palladium-catalyzed dihydrogenation which consists of three consecutive processes: The hydrogenation of the C−C double and C−N triple bonds was followed by the reductive amination via the iminium ion formed in situ from the primary amino function and the endocyclic carbonyl group. This last step gave, stereoselectively, the annulated azepanes with relative trans-configuration. The amino function and the ester group define two points for further diversification of the scaffolds. The trifluoroacetyl derivatives allowed to establish the enantiopurity of the products to be 97–98 % ee by GLC on a chiral phase. The relative trans-configurations and in one case also the absolute (R,R)-configuration was established by X-ray crystallography.     

A Golgi Apparatus-Targetable Probe Based on Lanthanide Complexes for Ratiometric Time-Gated Luminescence Detection of Hydrogen Sulfide

Development of bioanalytical methods for selective and accurate detection of H₂S in living samples is essential for understanding the pathological and physiological functions of this gasotransmitter in biological systems. Here we report a Golgi apparatus-targetable lanthanide complex-based luminescent probe, Golgi-ABTTA-Eu³⁺/Tb³⁺, that can be used for accurately determining H₂S in aqueous solution and living cells via the ratiometric time-gated luminescence (RM-TGL) technique. This probe is composed of 2,2′:6′,2′′-terpyridine-Eu³⁺/Tb³⁺ mixed complexes as the luminophore, 4-azidobenzyl-ether as the responsive moiety, and sulfanilamide as the Golgi apparatus-targeting moiety. Upon reaction with H₂S, accompanied by the cleavage of 4-azidobenzyl group from the probe molecule, the long-lived emission of Tb³⁺ complex at 540 nm is significantly enhanced, while that of Eu³⁺ complex at 610 nm is obviously reduced. It was noted that the I₅₄₀/I₆₁₀ ratio increased by 8.8 times after the probe was exposed to H₂S, which enabled H₂S to be detected with RM-TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in the Golgi apparatus, which allowed H₂S in the Golgi apparatus to be successfully imaged in RM-TGL mode.     

Conformational Effects of Regioisomeric Substitution on the Catalytic Activity of Copper/Calix[8]arene C−S Coupling

Functionalization of the phenolic rim of p-tert-butylcalix[8]arene with phenanthroline to create a cavity leads to formation of two regioisomers. Substitution of positions 1 and 5 produces the known C_2v-symmetric regioisomer 1,5-(2,9-dimethyl-1,10-phenanthroyl)-p-tert-butylcalix[8]arene ( L^1,5 ), while substitution of positions 1 and 4 produces the C_s-symmetric regioisomer 1,4-(2,9-dimethyl-1,10-phenanthroyl)-p-tert-butylcalix[8]arene ( L^1,4 ) described herein. [ Cu(L^1,4)I ] was synthesized from L^1,4 and CuI in good yield and characterized spectroscopically. To evaluate the effect of its cavity on catalysis, Ullmann-type C−S coupling was chosen as proof-of-concept. Selected aryl halides were used, and the results compared with the previously reported Cu(I)/ L^1,5 system. Only highly activated aryl halides generate the C−S coupling product in moderate yields with the Cu(I)/ L^1,4 system. To shed light on these observations, detailed computational investigations were carried out, revealing the influence of the calix[8]arene macrocyclic morphology on the accessible conformations. The L^1,4 regioisomer undergoes a deformation that does not occur with L^1,5 , resulting in an exposed catalytic center, presumably the cause of the low activity of the former system. The 1,4-connectivity was confirmed in the solid-state structure of the byproduct [ Cu(L^1,4 − H) (CH₃CN)₂] that features Cu(I) coordinated inside a cleft defined by the macrocyclic framework.     

Transition-Metal-Free One-Pot [3+3] Heteroannulative Coupling of Thioamides with Epichlorohydrin: Access to Diverse 1,3-Thiazinanes

An operationally simple and efficient cascade approach to access a series of 1,3-thiazinanes has been developed through intermolecular [3+3] heteroannulative coupling employing β-ketothioamide as a C1 N1S1 unit and epichlorohydrin as a C3 unit at room temperature for the first time. The reaction proceeds by nucleophilic attack of thiocarbonyl sulfur to less hindered primary carbon of oxirane followed by sequential intramolecular N-cyclization and dehydrochlorination enabling the coupling by cleavage of C−O bond and formation of two new C−S and C−N bonds in one stretch. This protocol not only avoids potential toxicity and tedious work up procedures, but also features open atmosphere, good to high yields, gram-scalability, and easy performance from inexpensive, readily available starting materials under transition-metal-free conditions. A probable mechanism for the formation of 1,3-thiazinanes has been suggested.     

Design,Synthesis, and Biomedical Applications of Glycotripods for Targeting Trimeric Lectins

In the last decades, various efforts have been made to synthesize optimal glycotripods for targeting trimeric glycoproteins like asialoglycoprotein receptor, hemagglutinin, and langerin. All these trimeric glycoproteins have sugar binding pockets which are highly selective for a particular carbohydrate ligand. Optimized glycotripods are high affinity binders and have been used for delivering drugs or even applied as drug candidates. The selection of the tripodal base scaffold together with the length and flexibility of the linker between the scaffold and sugar residue, as important design parameters are discussed in this review.     

NHC-Adducts of Cyclopentadienyl-Substituted Alanes

The mono- and bis-iodo-substituted NHC-stabilized alanes (NHC) ⋅ AlH₂I and (NHC) ⋅ AlHI₂ offer a convenient entry for further substitution reactions at aluminum. Reactions of (NHC) ⋅ AlH₂I 1 – 4 with one equivalent of NaCp afforded the adducts (NHC) ⋅ AlH₂Cp 9 – 12 (NHC=Me₂Im^Me ( 9 ), iPr₂Im^Me ( 10 ), iPr₂Im ( 11 ), Dipp₂Im ( 12 )). Alane adducts with two Cp substituents (NHC) ⋅ AlHCp₂ 13 – 16 (NHC=Me₂Im^Me ( 13 ), iPr₂Im^Me ( 14 ), iPr₂Im ( 15 ), Dipp₂Im ( 16 )) were prepared by the analogous reaction of (NHC) ⋅ AlHI₂ 5 – 8 using two equivalents of NaCp. The unusual dimeric adducts ((NHC) ⋅ AlH₂Cp ⋅ CpMgI)₂ 17 – 19 (NHC=Me₂Im^Me ( 17 ), iPr₂Im^Me ( 18 ), iPr₂Im ( 19 )) were obtained from the reaction of 1 – 3 with MgCp₂.     

Chiral-at-Molybdenum – A Computational Study on N-Substituted cis-MoO2(nacnac)2

Cis-MoO₂(nacnac)₂ (nacnac=β-diketiminate) can be a viable chiral-at-metal catalyst when its two β-diketiminate (nacnac) ligands are N-substituted to prevent Λ⇌Δ racemization. Even simple methyl groups raise the barriers for racemization significantly for the Bailar, Rây-Dutt, Conte-Hippler, and Dhimba-Muller-Lammertsma (DML) twists to a respectable 28.5, 37.8, 30.5, and 25.1 kcal/mol, respectively, at ωB97X-D/6-311+G(2d,p) (LANL2DZ for Mo) including acetonitrile solvation. The lowest energy DML barrier increases to ΔG^o=27.4 kcal/mol with N-substituted t-butyl groups. The nacnac ligands’ electronic and steric components to the racemization barriers are discussed.     

Ruthenium-Catalyzed Direct Reductive Amination of Carbonyl Compounds for the Synthesis of Amines: An Overview

Reductive amination is a valuable method for amine synthesis that has been the topic of a century‘s worth of in-depth study in both academia and industry. Amines and their derivatives serve as incredibly adaptable building blocks for a broad array of organic substrates and are significant precursors for a myriad of advanced chemicals, physiologically active compounds, agrochemicals, biomolecules, pharmaceuticals, and polymers. The creation of innovative catalytic processes for the long-term and selective synthesis of amines from readily accessible and environmentally benign reagents remains a top priority in chemical research. Both heterogeneous and homogeneous catalysts have been designed with success to enable these reactions to explore new amines. Ruthenium catalysts are employed in reductive amination owing to their stability, selectivity, versatility, low toxicity, and high efficiency. This review comprehensively overviews the Ru-catalyzed reductive amination processes and includes the literature from 2009 to 2022.     

Palladium-Catalyzed Ring-Opening Addition of Activated Vinyl Cyclopropanes with N-Tosylhydrazones

Ring-opening addition reaction of activated vinyl cyclopropanes with N-tosylhydrazones in the presence of palladium(0) and triphenylphosphine affords N-tosylhydrazone butenylmalonate compounds. Aromatic aldehyde-derived N-tosylhydrazones produced terminal and internal N-allylated products, in which the terminal products are the main. While ketone-derived tosylhydrazones produced only terminal addition products. The transformation relationship of the terminal and internal N-allylated products in the reaction was also observed. A reasonable mechanism is proposed based on preliminary experimental results.