Featured Reviews in Organic Chemistry

The field of Organic Chemistry represents one of the most traditional areas of chemistry that has delivered many benefits to the community of chemists. This Special Issue of Molecules is a compilation of the most recent innovative developments in organic chemistry, synthesis, etc. The collected articles provide summaries and assessments of a range of pharmaceutical expansions, organic and bioorganic studies, methodologies, and reactions, as well as critical views and perspectives with regard to future developments. The Editors were fortunate to assemble a compendium of articles, written by prominent authors, which represent the broad field of organic and related chemistry

(SP-4-4)-[Hydrogen N-({2-[(2S)-1-benzyl­pyrrolidine-2-carboxamido]phen­yl}(phen­yl)methyl­ene)-l-glutamato(2−)]nickel(II)

In the mol­ecule of the title complex, [Ni(C30H29N3O5)], the Ni atom is coordinated in a distorted square-planar geometry by three N and one O atoms. The aromatic rings are oriented at dihedral angles of 29.01 (3), 79.73 (3) and 83.37 (3)°. The remaining rings adopt envelope conformations with the C and N atoms at the flap positions. In the crystal structure, inter­molecular O—H⋯O hydrogen bonds link the mol­ecules into chains along the b axis. There is also a weak C—H⋯π inter­action

Recommended Tests for the Self-Disproportionation of Enantiomers (SDE) to Ensure Accurate Reporting of the Stereochemical Outcome of Enantioselective Reactions

The purpose of this review is to highlight the necessity of conducting tests to gauge the magnitude of the self-disproportionation of enantiomers (SDE) phenomenon to ensure the veracity of reported enantiomeric excess (ee) values for scalemic samples obtained from enantioselective reactions, natural products isolation, etc. The SDE always occurs to some degree whenever any scalemic sample is subjected to physicochemical processes concomitant with the fractionation of the sample, thus leading to erroneous reporting of the true ee of the sample if due care is not taken to either preclude the effects of the SDE by measurement of the ee prior to the application of physicochemical processes, suppressing the SDE, or evaluating all obtained fractions of the sample. Or even avoiding fractionation altogether if possible. There is a clear necessity to conduct tests to assess the magnitude of the SDE for the processes applied to samples and the updated and improved recommendations described herein cover chromatography and processes involving gas-phase transformations such as evaporation or sublimation

A Call for a Change in Policy Regarding the Necessity for SDE Tests to Validate the Veracity of the Outcome of Enantioselective Syntheses, the Inherent Chiral State of Natural Products, and Other Cases Involving Enantioenriched Samples

We wish to draw attention to an important issue concerning scientific practice with regard to enhancing the quality of publications in Molecules (as well as for other journals) [...

Synthesis of Aminoalkyl Sclareolide Derivatives and Antifungal Activity Studies

Sclareolide was developed as an efficient C-nucleophilic reagent for an asymmetric Mannich addition reaction with a series of N-tert-butylsulfinyl aldimines. The Mannich reaction was carried out under mild conditions, affording the corresponding aminoalkyl sclareolide derivatives with up to 98% yield and 98:2:0:0 diastereoselectivity. Furthermore, the reaction could be performed on a gram scale without any reduction in yield and diastereoselectivity. Additionally, deprotection of the obtained Mannich addition products to give the target sclareolide derivatives bearing a free N-H group was demonstrated. In addition, target compounds 4–6 were subjected to an antifungal assay in vitro, which showed considerable antifungal activity against forest pathogenic fungi.Financial support from the National Natural Science Foundation of China (Nos. 21761132021 and 21606133) and IKERBASQUE, Basque Foundation for Science

New Approved Drugs Appearing in the Pharmaceutical Market in 2022 Featuring Fragments of Tailor-Made Amino Acids and Fluorine

The strategic fluorination of oxidatively vulnerable sites in bioactive compounds is a relatively recent, widely used approach allowing us to modulate the stability, bio-absorption, and overall efficiency of pharmaceutical drugs. On the other hand, natural and tailor-made amino acids are traditionally used as basic scaffolds for the development of bioactive molecules. The main goal of this review article is to emphasize these general trends featured in recently approved pharmaceutical drugs.This research was funded by the National Natural Science Foundation of China (No. 21761132021) and IKERBASQUE, Basque Foundation for Science

Kitamura Electrophilic Fluorination Using HF as a Source of Fluorine

This review article focused on the innovative procedure for electrophilic fluorination using HF and in situ generation of the required electrophilic species derived from hypervalent iodine compounds. The areas of synthetic application of this approach include fluorination of 1,3-dicarbonyl compounds, aryl-alkyl ketones, styrene derivatives, α,β-unsaturated ketones and alcohols, homoallyl amine and homoallyl alcohol derivatives, 3-butenoic acids and alkynes.This research was funded by the National Natural Science Foundation of China (No. 21761132021), and IKERBASQUE, Basque Foundation for Science

Asymmetric Michael Addition in Synthesis of β-Substituted GABA Derivatives

γ-Aminobutyric acid (GABA) represents one of the most prolific structural units widely used in the design of modern pharmaceuticals. For example, β-substituted GABA derivatives are found in numerous neurological drugs, such as baclofen, phenibut, tolibut, pregabalin, phenylpiracetam, brivaracetam, and rolipram, to mention just a few. In this review, we critically discuss the literature data reported on the preparation of substituted GABA derivatives using the Michael addition reaction as a key synthetic transformation. Special attention is paid to asymmetric methods featuring synthetically useful stereochemical outcomes and operational simplicity.This research was funded by the National Natural Science Foundation of China (No. 21761132021), and IKERBASQUE, Basque Foundation for Science. The financial support from the University of the Basque Country UPV/EHU (UFIQOSYC11/22), Basque Government (GVgrant IT1236-19), and Ministerio de Ciencia e Innovación (grant PID2019-109633GBC21) for. A.L. are also acknowledged

Potentially Mistaking Enantiomers for Different Compounds Due to the Self-Induced Diastereomeric Anisochronism (SIDA) Phenomenon

The NMR phenomenon of self-induced diastereomeric anisochronism (SIDA) was observed with an alcohol and an ester. The alcohol exhibited large concentration-dependent chemical shifts (δ’s), which initially led us to erroneously consider whether two enantiomers were in fact atropisomers. This highlights a potential complication for the analysis of chiral compounds due to SIDA, namely the misidentification of enantiomers. A heterochiral association preference for the alcohol in CDCl3 was determined by the intermolecular nuclear Overhauser effect (NOE) and diffusion measurements, the same preference as found in the solid state. The ester revealed more subtle effects, but concentration-dependent δ’s, observation of intermolecular NOE’s, as well as distinct signals for the two enantiomers in a scalemic sample all indicated the formation of associates. Intermolecular NOE and diffusion measurements indicated that homochiral association is slightly preferred over heterochiral association in CDCl3, thus masking association for enantiopure and racemic samples of equal concentration. As observed with the alcohol, heterochiral association was preferred for the ester in the solid state. The potential problems that SIDA can cause are highlighted and constitute a warning: Due care should be taken with respect to conditions, particularly the concentration, when measuring NMR spectra of chiral compounds. Scalemic samples of both the alcohol and the ester were found to exhibit the self-disproportionation of enantiomers (SDE) phenomenon by preparative TLC, the first report of SDE by preparative TLC

Advances in the Development of Trifluoromethoxylation Reagents

This review provides a short summary of the traditional methods for synthesis of CF3-O-containing compounds, followed by a critical overview of known trifluoromethoxylating reagents, focusing on their preparation, synthetic generality and limitations