The diverse applicability of diazo compounds as versatile reagents has enlarged the chemical toolbox in organic synthesis. Over the past few decades, transition-metal-catalyzed diazo compound activation has ignited the classical synthetic methodology via utilizing highly reactive metal carbenoid species. Many reviews have also appeared in the literature that show the advantages and disadvantages of metal-catalyzed activation of diazo compounds. Recently, tris(pentafluorophenyl)borane-mediated diazo activation reactions has remodeled this research area due to the potential for mild, environmentally friendly, metal-free, nontoxic reaction conditions, and the diverse reactivity patterns of boranes towards diazo compounds. In this review, we discuss the reactivity of the boron–diazo precursor adducts with compounds using catalytic and stoichiometric halogenated triarylboranes and, the mechanism of N2 release from the diazo reagent. This generates the reactive carbene species as a key intermediate which can further be exploited for O–H, N–H, S–H, and C–H insertions, azide insertion, carbonate transfer, C–C and C=C bond forming reactions, [2+2] or [2+4] cascade cyclization reactions, annulation reactions, etc. 1 Introduction 2 Diazo Activation Using Stoichiometric Boranes 3 Diazo Activation Using Catalytic B(C6F5)3 4 B(C6F5)3-Catalyzed Diazo Activation Reactions 5 Conclusions

The syntheses of bidentate and tripodal phosphine ligands containing aryl chlorides were achieved in 4 and 7 steps respectively, starting from diethyl malonate.

Reported herein is an efficient α-arylation of α-fluoro-α-nitro­sulfonylmethanes using diaryliodonium salts. A wide range of α-fluoronitrosulfonylmethane substrates underwent α-arylation smoothly to produce the corresponding adducts bearing a fully substituted fluorocarbon center in good to excellent yields. The protocol was subsequently shown viable for the α-arylation of α-cyano-α-fluorosulfonylmethane derivatives yielding highly valuable cyano building blocks.

We herein report a transition-metal-free cross-coupling reaction of acetals and Grignard reagents. The method provides a modular preparation of diarylmethyl alkyl ethers, triarylmethanes, and 1,1-diarylalkanes that constitute the core structures of many bioactive molecules and synthetic motifs. A series of readily accessible acetals bearing aryl, alkenyl, and alkyl substituents efficiently coupled with commercially available aryl, alkyl, and allylic magnesium bromides to give the products in high yields. In addition to acyclic and cyclic acetals, ketal and orthoester also serve as viable substrates to afford sterically hindered tertiary ether and ketal respectively. A sequential difunctionalization of acetals led to the rapid synthesis of triarylmethanes and diarylalkanes.

Protein PEGylation is a traditional bioconjugation technology that enhances the therapeutic efficacy and in vivo half-life of proteins by the formation of covalent bonds with highly activated ester group linked polyethylene glycol (PEG). However, the high reactivity of these reagents induces a random reaction with lysine residues on the protein surface, resulting in a heterogeneous mixture of PEGylated proteins. Moreover, the traditional batch-mode reaction has risks relating to scalability and aggregation. To overcome these risks of traditional batch-mode PEGylation, a manufacturing strategy utilizing structural analysis and a continuous-flow-mode reaction was examined. A solvent exposure analysis revealed the most reactive lysine of a protein, and the continuous-flow mode modified this lysine to achieve the mono-PEGylation of two different proteins within 2 seconds. This ultrarapid modification reaction can be applied to the gram-scale manufacturing of PEGylated bioconjugates without generating aggregates. A similar trend of the exposure level of protein lysine and mono-selectivity performed by continuous-flow PEGylation was observed, which indicated that this manufacturing strategy has the potential to be applied to the production of a wide variety of bioconjugates.

The addition of organometallic reagents to the carbonyl group represents a key transformation, both in academia and industry. Most of these transformations rely on a mechanism in which accessible and reactive halides are transformed into the corresponding nucleophilic organometallic reactive compounds through a redox mechanism, using a metal (Cr, Mg, In, etc.) in low oxidation state, by electron transfer. With the advent of photoredox catalysis, the formation of radicals, through oxidation or reduction of suitable and tailored organic precursors, was merged with transition metal catalysis. By radical-to-polar crossover (RPCO­), a radical metal is combined with an organic radical to produce, via radical-radical trapping, a polar nucleophilic organometallic reagent. Using dual photoredox catalysis (metallaphotoredox catalysis), a reactive organometallic reagent can be prepared, avoiding the use of metals in low oxidation state. Herein, in addition to the description of the results obtained by our group and the contributions of others on the connection between carbonyl addition and radical-based photochemistry, we provide core guidance for further synthetic developments. We anticipate that extending the photoredox dual strategy beyond the Barbier reactions described here, taming less-activated carbonyls, studying other important electrophiles, will soon realize important breakthroughs. 1 Introduction 2 Photoredox Catalysis: A Survival Guide for the ‘Photo-Curious’ 3 Chromium Nucleophilic Organometallic Reagents 3.1 Allylation of Aldehydes 3.2 Allylation of Aldehydes via Dienes 3.3 Propargylation of Aldehydes via 1,3-Enynes 3.4 Alkenylation of Aldehydes 3.5 Alkylation of Aldehydes 3.6 Enantioselective Chromium-Mediated Photoredox Reactions 4 Titanium Nucleophilic Organometallic Reagents 4.1 Allylation Reactions 4.2 Propargylation Reactions 4.3 Allylation Reactions via Dienes 4.4 Benzylation Reactions 4.5 Alkylation Reactions 5. Cobalt Nucleophilic Organometallic Reagents 5.1 Allylation Reactions 6 Conclusion

Dibenzophospholes, phosphorus-containing π-conjugated cyclic compounds, have attracted considerable attention because of their potential applications in various functional materials such as those required for organic electroluminescent devices. Moreover, their synthetic methods have been widely developed. This review summarizes the construction strategies of dibenzophosphole scaffolds, including those developed recently. 1 Introduction 2 Construction of a Phosphole Skeleton Using Aryl Compounds 2.1 [4+1] Cyclization between Biaryl Derivatives and P1 Units 2.2 Intramolecular P–C Bond Formation of Biarylphosphines 2.3 Intramolecular C–C Bond Formation of Diarylphosphines 2.4 [3+2] Cyclization between Arylphosphines and Arenes 3 Fused-Benzene Ring Formation 4 Successive Phosphole Skeleton and Fused-Benzene Ring Formation 5 Conclusions

Present study involves the synthesis of bis-coumarins and novel polycyclic pyranodichromenones using a catalyst-free approach under ultrasonic irradiation in an aqueous medium. The chemical structures of the synthesized compounds were characterized using FTIR, 1H NMR, and 13C NMR spectroscopy. The antibacterial and antifungal activities of the compounds were evaluated against Gram-positive (S. aureus, B. cereus) and Gram-negative bacteria (P. aeruginosa, E. coli), as well as the fungus C. albicans, using the disc diffusion method. Several compounds exhibited excellent activity against the tested microorganisms. Moreover, the antioxidant potential of the synthesized products was assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethyl­benzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging, and total antioxidant capacity (TAC) assays. Promising antioxidant activity was observed for certain compounds. Computational studies using density functional theory (DFT) were conducted to investigate the molecular reactivity and electronic properties of the synthesized compounds. Quantum mechanical parameters such as Ionization Potential (IP), Electron Affinity (EA), Mulliken Electronegativity (χ), Chemical Potential (μ), and Electrophilicity Index (ω) were calculated. The study highlights the efficiency and eco-friendliness of ultrasonic-assisted processes, contributing to the advancement of sustainable chemistry.

Forced intercalation probes (FIT probes) are nucleic acid probes in which an intercalator dye of the thiazole orange (TO) family serves as a surrogate nucleobase. Hybridization of FIT probes is accompanied by enhancements of fluorescence. Looking for ways to increase turn-on and brightness of fluorescence, we herein report the synthesis of new fluorogenic base surrogates. In total, nine different TO derivatives were introduced into FIT probes. Fluorescence measurements in six different sequences revealed that substitution at both the quinoline and the benzothiazole part affects fluorescence turn-on upon hybridization and brightness of probe–target duplexes. A TO derivative containing a tricyclic benzothiazole provided FIT probes signaling hybridization by up to 18.6-fold enhancement of fluorescence. Improved fluorescence quantum yields (Φds up to 0.53) and high extinction coefficients (ε518 up to 91000 M–1·cm–1) make this dye an interesting, and in some sequences superior, alternative to the canonical thiazole orange used previously in FIT probes.

An ongoing challenge in the pharmaceutical sector is the need to find and implement novel synthetic approaches because traditional methods sometimes violate the principles of green chemistry. While benzimidazoles are of great importance as building blocks for the creation of molecules having pharmacological activity, the development of methods for their sustainable synthesis has been a challenge for organic synthesis. Herein, we have carried out a one-pot telescopic approach to the synthesis of disubstituted benzimidazole derivatives in a deep eutectic solvent (DES) medium to investigate an alternate synthetic technique. Starting with methyl 4-fluoro-3-nitrobenzoate, SNAr reaction, reduction, and cyclization were performed with choline chloride/glycerol/H2O as DES medium, which gave the best performance out of the five DESs examined. We report the synthesis of disubstituted benzimidazoles via one-pot telescopic approach.

Synthesis of the octasaccharide repeating unit of the K55 capsular polysaccharide of Acinetobacter baumannii BAL_204 strain has been achieved in very good yield using a convergent [5+3] block glycosylation strategy. The pentasaccharide and trisaccharide components were synthesized using sequential stereoselective glycosylations. The p-methoxybenzyl (PMB) group was used as temporary alkyl protecting group, which was removed under the thiophilic glycosylation condition by raising the temperature. A late-stage TEMPO-mediated selective oxidation of primary hydroxyl group into carboxylic acid allowed getting the d-glucuronic acid moiety in the octasaccharide. A combination of N-iodosuccinimide (NIS) and perchloric acid supported over silica (HClO4­-SiO2) was used as a thiophilic promoter for the activation of thioglycosides. HClO4-SiO2 was also used as a solid acid activator for glycosyl trichloroacetimidate derivative.

The Myrioneuron alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids. 1 Introduction 1.1 Biological Activity 1.2 Proposed Biosynthesis 2 Synthetic Studies toward the Myrioneuron Alkaloids 2.1 Total Synthesis of Myrioxazines A and B 2.2 Total Synthesis of Myrionine, Myrionidine, and Schoberine 2.3 Total Synthesis of Myrifabrals A and B 2.4 Total Synthesis of Myrioneurinol 3 Conclusions and Outlook

Over the past 30 years, the synthesis of α-chiral allylsilanes have attracted much interest. These compounds are indeed versatile building blocks and linchpins ranking among the most useful organic scaffolds due to the large number of transformations that both their C–Si bond and C–C double bond can undergo. They therefore occupy a unique place in the arsenal of the organic chemist, particularly for the synthesis of complex molecules. In this review, an overview of transition-metal-catalyzed syntheses of α-chiral allylsilanes is presented. 1 Introduction 2 Addition of Silylmetals 2.1 Silylation of Allylic Electrophiles 2.2 Conjugate Addition 2.3 1,2-Addition to N-tert-Butylsulfonyl Imines 2.4 Silaboration 3 Addition of Nucleophiles 3.1 Substitution of γ-Silylated Allylic Electrophiles 3.2 1,4-Conjugate Addition to β-Silyl Enones and Enoates 3.3 Reduction of γ-Silylated Allylic Carbonates 4 Hydrosilylation 4.1 1,4-Hydrosilylation of 1,3-Dienes 4.2 1,2-Hydrosilylation of 1,3-Dienes 4.3 1,2-Hydrosilylation of Allenes 5 Cross-Coupling Reactions 5.1 Cross-Coupling of Vinyl Halides 5.2 Retroallylation of δ-Silylated Homoallylic Alcohols 5.3 Multicomponent Cross-Coupling of 1,3-Dienes 6 Insertion Reactions 6.1 Vinylcarbenoid Insertion into Si–H Bonds 6.2 Silylene Insertion into Allylic C–O Bonds 7 Rearrangements 7.1 Intramolecular γ-Silylation of Allylic Disilanyl Ethers 7.2 Domino Isomerization–Claisen Rearrangement of γ-Silylated Bis(allylic) Ethers 8 Miscellaneous 9 Conclusion

Atropisomeric molecules are a privileged class of stereogenic material that have important applications in catalysis, materials science and medicines. To date, the majority of work has been focused upon biaryl and heterobiaryl scaffolds involving restricted rotation between a pair of cyclic fragments, but C–N atropisomeric molecules based upon amines and amides, where the nitrogen atom is not part of a ring system, are rapidly emerging as an important class of stereogenic molecules. This is the focus of this Short Review, which begins by discussing the factors which influence the configurational stability of such molecules and provides a historical background to their synthesis. This is followed by a detailed discussion of state-of-the-art catalytic asymmetric strategies that are now available to access C–Nacyclic atropisomers including carboxamides, sulfonamides, sulfinamides, phosphamides and diarylamines. A variety of different synthetic approaches are discussed, including kinetic resolution/desymmetrization, amination, C–H functionalization, N-functionalization, and annulation. 1 Introduction 2 Atropisomerism in Acyclic Amines and Amides 3 Synthesis Directed by a Chiral Auxiliary 4 Atropselective Synthesis 4.1 Kinetic Resolution and Desymmetrization 4.2 Electrophilic Amination 4.3 C–H Functionalization 4.4 N-Functionalization 4.5 Annulation 5 Conclusions and Outlook

An atom-economic reaction sequence on a multigram scale for synthesizing 2-pyrone was developed starting from furfuryl alcohol, a renewable resource made from bran or bagasse, utilizing a large-scale thermal rearrangement of cyclopentadienone epoxide as the key step. Additionally, 6-substituted 2-pyrone natural product derivatives are readily accessible by this approach.

Pent-4-yn-1-ol was prepared in a high yield by the reaction of tetrahydrofurfuryl chloride with n-BuLi in t-BuOMe at 0 °C. Pent-4-en-1-ol was prepared in a high yield by either the reaction of tetrahydrofurfuryl chloride or tetrahydrofurfuryl bromide with lithium in tetrahydrofuran at temperatures from 0 °C to ambient temperature.

The synthesis of trifunctional isomeric benzothiazoles derived from nitroanthranilic acids and their corresponding anthranilonitrile analogues is studied. Compared to previous work, the reaction sequence affords convenient access to hitherto undescribed 2-cyanobenzothiazoles. For further synthetic applications of these polyfunctional compounds, a hydrolysis–decarboxylation sequence is performed in an acidic medium (HCl or HBr), leading to an enlarged array of relevant building blocks.

Deoxygenative alkylation of benzyl alcohols was realized by using acetate as the alcohol activation group. The C–O bond homolysis is achieved by a boryl radical-promoted β-scission process. The strategy is amenable to a variety of benzyl alcohols, including primary, secondary, and more challenging tertiary alcohols. The synthetic practicability was demonstrated by a gram-scale one-pot reaction.

The synthesis of two diastereomeric steroid spiroketals bearing a 2,3-dihydrobenzofuran moiety is described. The structure of the obtained compounds was elucidated by combined 1D and 2D NMR techniques and corroborated by X-ray crystallography studies.

Although known for millennia, it is only recently that mechanochemistry has received serious attention by chemists. Indeed, during the past 15 years an extraordinary number of reports concerning solid-state chemical transformations through grinding and milling techniques have been recorded. This short review discusses the circumstances that led this renaissance, highlighting the present intense interest in so-called green chemistry, the enabling capacity of mechanochemistry to handle insoluble substrates, and the identification of the profound influence that additives can have on mechanochemically activated reactions. The core of this account focuses on salient developments in synthetic organic chemistry, especially in amino acid and peptide­ mechanosynthesis, the successful employment of mechanochemical activation in combination with asymmetric organocatalysis, the promising combination of mechanochemical activation with enzymatic and whole cell biocatalysis, the remarkable achievement of multicomponent selective reactions via complex, multistep reaction pathways, and the mechanosynthesis of representative heterocycles. The final section comments on some pending tasks in the area, such as scaling-up of milling processes to be of practical use in the chemical industry, the requirement of easier and more efficient control of reaction parameters and monitoring devices, and consequently the careful analysis of additional procedures for a proper understanding of mechanochemical phenomena. 1 Introduction 2 Brief History of Mechanochemistry 3 Milling Equipment and Reaction Parameters 4 Attributes of Mechanochemistry That Propelled Its Present Renaissance 4.1 Enormous Attention Being Presently Paid to Sustainable Chemistry 4.2 Reduced Energy Consumption 4.3 Additive-Based Mechanochemistry 4.4 Handling of Insoluble Reactants 4.5 ‘Impossible’ Reactions That Are Successful by Milling 4.6 Successful Handling of Air- and Water-Sensitive Reagents by Ball Milling 5 Salient Developments in the Mechanochemical Activation of Synthetic Organic Chemistry 5.1 Amino Acid and Peptide Mechanosynthesis 5.2 Asymmetric Organic Synthesis and Asymmetric Organocatalysis under Ball-Milling Conditions 5.3 Mechanoenzymology 5.4 Multicomponent Reactions Activated by Mechanochemistry 5.5 Mechanosynthesis of Heterocycles and Modification of Heterocycles 6 Future Directions 6.1 Scaling-Up Mechanochemical Protocols 6.2 Temperature-Controlled Mechanochemistry 6.3 Understanding Mechanochemical Transformations 6.4 Emerging Mechanochemical Techniques 7 Conclusions