Divergent Electrolysis for the Controllable Coupling of Thiols with 1,2-Dichloroethane: a Mild Approach to Sulfide and Sulfoxide

Organosulfurs are important commodity chemicals and indispensable synthetic intermediates in modern chemistry that traditionally synthesized using metal catalysts, oxidants or strong bases, which caused numerous issues of environment pollutions. The...

1-(4-Nitrophenyl)-1H-1,2,3-Triazole-4-carbaldehyde: Scalable Synthesis and Its Use in the Preparation of 1-Alkyl-4-Formyl-1,2,3-triazoles

1,2,3-Triazole-4-carbaldehydes are useful synthetic intermediates which may play an important role in the discovery of novel applications of the 1,2,3-triazole moiety. In this work, a one-step multigram scale synthesis of 4-formyl-1-(4-nitrophenyl)-1H-1,2,3-triazole (FNPT) as a preferred reagent for the synthesis of 1-alkyl-4-formyltriazoles is described, making use of the commercially available 3-dimethylaminoacrolein and 4-nitrophenyl azide. Next, the earlier reported reaction of FNPT with alkylamines is further explored, and for hexylamine, the one-pot sequential cycloaddition and Cornforth rearrangement is demonstrated. In addition, a useful protocol for the in situ diazotization of 4-nitroaniline is provided. This facilitated the complete hydrolysis of rearranged 4-iminomethyl-1,2,3-triazoles and allowed for the recycling of 4-nitrophenyl azide.

Recent Trends in Group 9–Catalyzed C−H Borylation Reactions: Different Strategies to Control Site-, Regio-, and Stereoselectivity

Organoboron compounds continue contributing substantially to advances in organic chemistry with their increasing role as both synthetic intermediates and target compounds for medicinal chemistry. Particularly attractive methods of their synthesis are based on the direct borylation of C−H bonds of available starting materials since no additional pre-functionalization steps are required. However, due to the high abundance of C−H bonds with similar reactivity in organic molecules, synthetically useful C−H borylation protocols demand sophisticated strategies to achieve high regio- and stereoselectivity. For this purpose, selective transition-metal-based catalysts have been developed, with group 9-centered catalysts being among the most commonly utilized. Recently, a multitude of diverse strategies has been developed to push the boundaries of C−H borylation reactions with respect to their regio- and enantioselectivity. Herein, we provide an overview of approaches for the C−H borylation of arenes, alkenes, and alkanes based on group 9-centered catalysts with a focus on the recent literature. Lastly, an outlook is given to assess the future potential of the field.

Recognition of Symmetry as a Powerful Tool in Natural Product Synthesis

The design of concise and efficient synthetic strategies to access naturally occurring, pharmaceutically active complex molecules is of utmost importance in current chemistry. It not only enables rapid access to these molecules and their analogues but also provides sufficient quantities for their biological evaluation. Identification of any symmetric or pseudosymmetric synthetic intermediates upon retrosynthetic bond disconnection of the target molecule holds the promise to significantly streamline the route towards the compound of interest. This review will highlight recent examples of successful natural product syntheses reported within the past five years that benefited from the recognition of symmetry elements during the retrosynthetic design.

Recent Advance in Organocatalyzed Asymmetric Reduction of Prochiral Ketones: An Update

Chiral alcohols are important synthetic intermediates or building blocks for the diverse synthesis of drugs, agrochemicals, and natural products. Asymmetric reduction of prochiral ketones has been the most popularly investigated method for accessing chiral alcohols. In this regard, the organocatalyzed asymmetric reduction as a complementary of transition-metal- and enzyme-catalyzed reactions have attracted tremendous interest in the past decades due to the nature of metal-free and easy operation, as well as, principly, the ease of recovery and reuse of catalysts. Following up a comprehensive overview on organocatalyzed asymmetric reduction of prochiral ketones in early 2018, this short review is intended to summarize the recent progress in this area from the beginning of the year 2018 to the end of Aug. 2021.

Stereoselective Synthesis of 24-Fluoro-25-Hydroxyvitamin D3 Analogues and Their Stability to hCYP24A1-Dependent Catabolism

Two 24-fluoro-25-hydroxyvitamin D3 analogues (3,4) were synthesized in a convergent manner. The introduction of a stereocenter to the vitamin D3 side-chain C24 position was achieved via Sharpless dihydroxylation, and a deoxyfluorination reaction was utilized for the fluorination step. Comparison between (24R)- and (24S)-24-fluoro-25-hydroxyvitamin D3 revealed that the C24-R-configuration isomer 4 was more resistant to CYP24A1-dependent metabolism than its 24S-isomer 3. The new synthetic route of the CYP24A1 main metabolite (24R)-24,25-dihydroxyvitamin D3 (6) and its 24S-isomer (5) was also studied using synthetic intermediates (30,31) in parallel.

Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates

Aryl sulfonate esters are versatile synthetic intermediates in organic chemistry as well as attractive architectures due to their bioactive properties. Herein, we report the synthesis of alkyl-substituted benzenesulfonate esters by iron-catalyzed C(sp2)–C(sp3) cross-coupling of Grignard reagents with aryl chlorides. The method operates using an environmentally benign and sustainable iron catalytic system, employing benign urea ligands. A broad range of chlorobenzenesulfonates as well as challenging alkyl organometallics containing β-hydrogens are compatible with these conditions, affording alkylated products in high to excellent yields. The study reveals that aryl sulfonate esters are the most reactive activating groups for iron-catalyzed alkylative C(sp2)–C(sp3) cross-coupling of aryl chlorides with Grignard reagents.

The 1,3-Dipolar Cycloaddition Reactions of Nitrile Oxides in Water Media

: The 1,3-dipolar cycloadditions (DCs) of nitrile oxides (NOs) have been used as a powerful tool in synthetic organic chemistry. The cycloadducts arising from cycloadditions (CAs) of NOs to alkenes and alkynes (2-isoxazolines and isoxazoles respectively) are valuable synthetic intermediates because, among others, their capacity to mask other functionalities including α, β-unsaturated ketones, β-hydroxy carbonyl compounds and 1,3-aminoalcohols. In particular, the β-hydroxy ketone functionality is an illustrative example, making the NOs alkenes CAs reactions a synthetically equivalent methodology of aldol reactions. The vast majority of these reactions are carried out in organic solvents. Nevertheless, the use of water as an alternative solvent has evident advantages on the “Green Chemistry” concept. The critical discussion on the use of water instead of “conventional” solvents in the 1,3-DCs reactions of NOs is the objective of the present review.

Preferential Solvation of 4-Carboxyl-2, 6-Dinitrophenylazohydroxynaphthalenes in Mixed Hydroxylic Solvents

Background: The applications of a group of 4-carboxyl-2,6-dintrophenylazohydroxynaphathalenes, AZ-01 to 04, as colourants, chemosensors or synthetic intermediates have been limited by their solubility.Aim: To investigate the effect of solvent mixture composition on the solubility, solution thermodynamics and position of equilibrium processes of the dyes.Method: The UV-visible spectral patterns of the dyes in binary mixtures including Methanol:Water, Ethanol:Water, Methanol:Ethanol, Methanol:Propan-1-ol, Methanol:Propan-2-ol, Propan-1-ol:Water and Propan-2-ol:Water were acquired. The type and quantitative estimation of solute-solvent interactions at play were determined by fitting spectral patterns to solvent parameters using multilinear regression.Results: Preferential solvation was detected by the non-ideality of the plots of E12 as against the mole fractions of co-solvent in all binary mixtures. In pure solvents, the spectral shifts of AZ-01, 03 and 04, which exist predominantly in the hydrazone form, were affected by polarity of solvent milieu while solvent basicity and acidity, in that order, were the significant parameters for AZ-02. In aqueous alcoholic mixtures, solvent polarity was contributory, although to different degrees, to the observed spectral data of the four dyes. However, solvent acidity and basicity were the primary determinants of spectral shifts observed with AZ-04 and AZ-03 respectively. Spectra-structure relationships identified the formation of the charged hydrazone tautomer which requires stabilisation by polar solvent milieu as responsible for the observed trend. In addition, interactions between new aggregated solvent-solvent species and the propionic acid substituent present in AZ-03 contributed to its spectral shifts.Conclusion: The solvatochromic properties of the phenylazonaphthalene series in binary mixtures have been successfully studied.

A Review on Recent Advances in the Synthesis of Aziridines and their Applications in Organic Synthesis

: Aziridines are the saturated three-membered cyclic amines that constitute an important group of synthetic intermediates. These could act as a precursor for diverse organic compounds owing to the reactivity due to the ring strain associated with them. The outstanding property of aziridines is their high reactivity towards various nucleophilic and electrophilic reagents to acquire more stable ring-opened or ring-expanded amines that could be obtained from the release of strain energy intrinsic in a small ring. As such, aziridines could be used in the synthesis of 4-7 membered heterocycles of biological and industrial significance, such as azetidines, imidazoles, thiazoles, pyrazines, pyrimidines, benzothiazines, benzodiazepines, etc. Earlier synthesis of aziridines was considered a laborious task due to their instability. However, various synthetic approaches leading to the formation of aziridines are now available in the literature. Recently, green, cost-effective and approaches based on simpler work-up for these reactions have attracted researcher's attention. This review article deals with synthetic routes of aziridines and aziridine applications in organic synthesis.