Cyclic Deracemization of rac‐Sulfoxides via Alternating Biocatalytic Reduction and Light‐Dependent Oxidation Employing Eosin Y as Photocatalyst

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Cyclic Deracemization of rac-Sulfoxides via Alternating Biocatalytic Reduction and Light-Dependent Oxidation Employing Eosin Y as Photocatalyst

A cyclic deracemization process that utilizes alternately a biocatalytic enantioselective reduction employing (S)-selective methionine sulfoxide reductase from Pseudomonas alcaliphila (paMsr) supplemented with DTT as external reducing equivalent, and a stereo-unselective photocatalytic oxidation reaction using the readily accessible Eosin Y as photocatalyst to achieve chiral sulfoxides is presented. Evaluation of the substrate scope demonstrates a general applicability of this modular system.


Abstract

The synergistic combination of biocatalysis and photocatalysis is emerging as powerful tool for the development of sustainable and atom-efficient synthetic concepts facilitating an enormous portfolio of possible reactions which even goes beyond the capabilities found in nature. Here, a cyclic deracemization process is presented tailored for the synthesis of optically pure sulfoxides which are versatile structural motifs in asymmetric synthesis as well as in bioactive compounds. Enantioselective enzyme-catalyzed reduction of rac-sulfoxides was combined with a stereo-unselective photocatalytic oxidation of the corresponding sulfide intermediate. The utilization of the readily accessible and rather inexpensive photocatalyst Eosin Y increases the usability of this synthetic method. To overcome the incompatibility between the photocatalyst Eosin Y and the biocatalytic step, the cyclic deracemization process was performed in a step-wise fashion via alternated reduction in the darkness and oxidation under illumination. This modular system allowed precise adjustments of reaction parameters yielding the desired sulfoxide targets with up to >99 % ee. Evaluation of the substrate scope including a range of structurally diverse molecules demonstrated its broad applicability.

Nucleophilic Selenocyclization Reaction of Benzodiynes Promoted by Sodium Selenide: Synthesis of Isoselenochromenes

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We describe here the synthesis of isoselenochromenes via a nucleophilic selenocyclization reaction of benzodiynes with sodium selenide.  The central parameters that affect this cyclization reaction were studied, and the best reaction conditions were applied to different substrates to determine the scope of the method. The results indicated that isoselenochromenes were obtained in higher yields when the reactions were performed by the addition of NaBH4 (3 equiv), at room temperature, under nitrogen atmosphere, to a solution of elemental selenium (2 equiv) in dimethylformamide (2 mL). After 1 h, a benzodiynes (0.25 mmol) solution in EtOH (2 mL) was added at room temperature. The reaction was stirred at 75 oC until the starting material was consumed.  The best conditions were applied to benzodiynes having electron-rich, electron poor aromatic rings, and alkyl groups directly bonded to the alkynes. The same reaction condition was extended to isothiochromene derivatives but failed to prepare isotelurochromenes.  The isoselenochromenes were easily transformed into three new classes of organoselenium compounds using classical methods available in the literature.  We also conducted several control experiments to propose a reaction mechanism.

Synthesis of R‐GABA Derivatives via Pd(II) Catalyzed Enantioselective C(sp3)‐H Arylation and Virtual Validation with GABAB1 Receptor for Potential leads

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GABA (γ-amino butyric acid) analogues like baclofen, tolibut, phenibut, etc., are well-known GABAB1 inhibitors and pharmaceutically important drugs. However, there is a huge demand for more chiral GABA aryl analogues with promising pharmacological actions. Here, we demonstrate the chiral ligand acetyl-protected amino quinoline (APAQ) mediated enantioselective synthesis of GABAB1 inhibitor drug scaffolds from easily accessible GABA via Pd-catalyzed C(sp3)-H activation. The synthetic methodology shows moderate to good yields, up to 74% of ee. We have successfully demonstrated the deprotection and removal of the directing group to synthesize R-tolibut in  86% yield. Further, we employed computation to probe the binding of R-GABA analogues to the extracellular domain of the human GABAB1 receptor. Our Rosetta-based molecular docking calculations show better binding for four R-enantiomers of GABA analogues than R-baclofen and R-phenibut. In addition, we employed GROMACS MD simulations and MMPB(GB)SA calculations to identify per-residue contribution to binding free energy. Our computational results suggest analogues (3R)-4-amino-3-(3,4-dimethylphenyl)butanoic acid, (3R)-4-amino-3-(3-fluorophenyl)butanoic acid, (3R)-3-(4-acetylphenyl)-4-aminobutanoic acid, (3R)-4-amino-3-(4-methoxyphenyl)butanoic acid, and (3R)-4-amino-3-phenylbutanoic acid are potential leads which could be synthesized from our methodology reported here.

Influence of Acid‐Base Characteristics of Different Structural‐Type Zeolites (FER, MFI, FAU, BEA) on Their Activity and Selectivity in Isobutanol Dehydration

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The different structural-type zeolites (FER, MFI, FAU, BEA) are investigated as catalysts in (bio)isobutanol conversion into linear butenes. The zeolites’ structure and morphology are confirmed by XRD, N2 (77 K) ad(de)sorption, SEM, EDX, XPS, and 27Al, 29Si, 1H MAS NMR, 1H-29Si CP MAS NMR. The nature and strength of acid-base sites are determined by FTIR spectroscopy of adsorbed pyridine, potentiometric titration, and TPD of NH3/CO2/H2O with MS control. The acid-base properties of the zeolites' surfaces influence their catalytic properties in the target process. The higher selectivity towards linear butene isomers achieved over FER and MFI can be explained by the high strength and density of Brønsted acid sites (over 90% of the total surface acidity). MFI might be regarded as a potential material for the creation of novel catalysts for isobutanol conversion into linear butenes at moderate temperatures (448-473 K) since it offers greater operating stability throughout the process.

Palladium(II) NCS‐Pincer Complexes Mediated Regioselective Cross Dehydrogenative Alkenation of 2‐Arylthiophenes

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In this report, we have synthesized two NCS pincer ligands by the Schiff base reaction of 3-((phenylthio)methoxy)benzaldehyde (P) with alkyl amines (tbutylamine (L1) and 1-adamantylamine (L2)). The palladium pincer complexes (tbutylamine = C1 and 1-adamantylamine = C2) of these ligands were synthesized by their reaction with PdCl2(CH3CN)2. The newly synthesized ligands and complexes were characterized using various techniques such as 1H, 13C{1H} Nuclear Magnetic Resonance (NMR), Ultraviolet–visible (UV-Visible), Fourier Transform Infrared (FTIR) Spectroscopy, and High-Resolution Mass Spectrometry (HRMS). The structure of ligand and its coordination mode with palladium precursor were studied with the help of single-crystal X-ray diffraction. The complexes showed distorted square planar geometry around the palladium center. The palladium pincer complexes were used as catalysts for the regioselective cross-dehydrogenative alkenation of 2-arylthiophene derivatives. The complex C2, where sterically bulky adamantyl ligand is part of the side arm showed a higher yield of alkenation reaction. Only 2.5 mol% catalyst loading was sufficient to achieve 74-95% yields of desired products with excellent functional group tolerance under mild reaction conditions. The poisoning experiments (PPh3 and Hg) showed the homogeneous nature of the catalytic process. The plausible mechanism of the reaction was proposed based on the control experiments and time-dependent HRMS studies.

Synthesis, Characterization, and Polymorphism of [H3O][NbF6]: A Polar and Possibly Ferroelectric Oxonium Salt

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Synthesis, Characterization, and Polymorphism of [H3O][NbF6]: A Polar and Possibly Ferroelectric Oxonium Salt

[H3O][NbF6] was synthesized and characterized. At room temperature, it adopts a polar structure with the dipole momentum of the [H3O]+ ions directed along the polar axis. A phase transition at 363 K leads to a plastic high-temperature polymorph hinting towards potential ferroelectric properties of the compound as the [H3O]+ and [NbF6]− ions are able to rotate freely. A second phase transition at 137 K leads to a cubic non-centrosymmetric low-temperature polymorph.


Abstract

[H3O][NbF6] was obtained from the controlled hydrolysis of NbF5 in anhydrous liquid HF. It adopts a polar, orthorhombic crystal structure with space group Iba2 (no. 45, oI88) at room temperature. A first-order phase transition at 137 K leads to a cubic non-centrosymmetric polymorph in space group I213 (no. 199, cI88). This low-temperature modification results from a distinct rotation of the [H3O]+ cations canceling their polar orientation in the room temperature phase. Quantum-chemical calculations estimate a rotational barrier between 5.8 to 6.4 kJ/mol. At a temperature of 363 K, the compound adopts a centrosymmetric, cubic crystal structure in space group Pm m (no. 221, cP11) that shows rotational disorder of cations and anions. The transition from the polar phase at room temperature to the centrosymmetric phase at high temperature not only reveals the plastic nature of the high-temperature structure but also hints at potential ferroelectric properties, underscoring the multifaceted behavior of [H3O][NbF6] across different temperature regimes.