Spontaneous Alternating Copolymerization via Zwitterion Intermediates

This article describes a new concept of copolymerization which occurs spontaneously without any added catalyst. A nucleophilic monomer (M_N) combines with an electrophilic one (M_E) to generate a zwitterion ^[+]M_N—M, which is responsible for the initiation and propagation of copolymerization. Twenty-three novel copolymerizations have been explored on the basis of the new concept. M_N monomers which have been investigated are five- and six-membered cyclic imino ethers, dihydro-2(3H)-furanimine, an azetidine, a cyclic phosphinic acid ester and a Schiff base; the M_E monomers include β-propiolactone, a cyclic dicarboxylic acid anhydride, a sultone, acrylic acid, acrylamide, a β-hydroxyalkyl acrylate and ethylenesulfonamide. In most combinations, alternating 1 : 1 copolymers were produced. In addition to the above-mentioned combinations, the alternating 1 : 1 copolymerization of cyclic phosphite with α-keto acid was discovered.     

Catalytic Photochemical Deracemization via Short-Lived Intermediates

Upon irradiation in the presence of a suitable chiral catalyst, racemic compound mixtures can be converted into enantiomerically pure compounds with the same constitution. The process is called photochemical deracemization and involves the formation of short-lived intermediates. By opening different reaction channels for the forward reaction to the intermediate and for the re-constitution of the chiral molecule, the entropically disfavored process becomes feasible. Since the discovery of the first photochemical deracemization in 2018, the field has been growing rapidly. This review comprehensively covers the research performed in the area and discusses current developments. It is subdivided according to the mode of action and the respective substrate classes. The focus of this review is on the scope of the individual reactions and on a discussion of the mechanistic details underlying the presented reaction.     

Synthesis of 3-Aminopyrocatechol via Lithiated Intermediates

We report the synthesis of 3-aminopyrocatechol (7) through electrophilic amination of lithiated pyrocatechol, protected in the form of a ketal. For this purpose the lithiation reaction of protected pyrocatechol (1) was studied. The synthesis of compounds (3) was achieved by the reaction of organolithium derivative (2) and a series of electrophilic reagents. Lithium-t-butyl-N-tosyloxycarbamate (5) was used as the electrophilic aminating reagent. With the cupro derivative (4) the protecting groups in compound (6) are removed in an acid medium by heating in ethanol-HCl solution (4:1).     

Acid-Catalyzed Cyclodimerizations via Vinyl Cations as Intermediates

The electrophilic addition of hydrogen chloride and bromide to allene and of hydrogen bromide to methylacetylene at ?70 °C leads not only to the simple Markownikoff adducts but also to cis- and trans-1,3-dihalo-1,3-dimethylcyclobutanes. These cyclodimerizations, which evidently proceed via vinyl cations, have opened up new short routes for the synthesis of cyclobutane-, cyclobutene-, and bicyclobutane derivatives starting from substrates that are industrially readily accessible.     

Synthesis of 1,3,6,8-Tetrabromophenanthrene via a Stoichiometric Ullmann Reaction

1,3,6,8-Tetrabromophenantherene (1) is prepared in four steps from 2,4,6-tribromobenzoic acid (4) in an overall yield of 12%. The key transformation used in the synthesis is a stoichiomteric Ullmann reaction.     

Nucleophilic Substitution of Aliphatic Fluorides via Pseudohalide Intermediates

A method for aliphatic fluoride functionalization with a variety of nucleophiles has been reported. Carbon–fluoride bond cleavage is thermodynamically driven by the use of silylated pseudohalides TMS-OMs or TMS-NTf₂, resulting in the formation of TMS-F and a trapped aliphatic pseudohalide intermediate. The rate of fluoride/pseudohalide exchange and the stability of this intermediate are such that little rearrangement is observed for terminal fluoride positions in linear aliphatic fluorides. The ability to convert organofluoride positions into pseudohalide groups allows facile nucleophilic attack by a wide range of nucleophiles. The late introduction of the nucleophiles also allows for a wide range of functional-group tolerance in the coupling partners. Selective alkyl fluoride mesylation is observed in the presence of other alkyl halides, allowing for orthogonal synthetic strategies.     

Monobenzylation Of 1,n-Diols via Dibutylstannylene Intermediates

Symmetrical primary l,n-diols, HO(CH_2)nOH, of any chain length from n = 2-10, can be selectively monobenzylated via sequential treatment with dibutyltin oxide and benzyl bromide.     

Azirine/Oxindole Ring Enlargement via Amidinium Intermediates

A novel general method for the synthesis of oxindoles, namely the ‘azirine/oxindole ring enlargement via amidinium‐intermediates’ has been established: the reaction of 2H‐azirin‐3‐amines 1 with BF₃?OEt₂ in THF solution at ?78° leads to 1,3,3‐trialkyl‐2‐amino‐3H‐indolium tetrafluoroborates 14 in good yields (Scheme 5). Treatment of aqueous solutions of 14 at 0° with aqueous NaOH (30%) and extraction with CH₂Cl₂ gives oily substances that are either hydrates of 1,3,3‐trialkyl‐2‐dihydroindol‐2‐imines 15 or the corresponding indolium hydroxides. These products are transformed to the corresponding 1,3,3‐trialkyl‐2,3‐dihydroindol‐2‐ones 17 in modest yields upon refluxing in H₂O/THF. Reaction of 14 with Ac₂O in pyridine at ca. 23° for 16 h followed by aqueous workup and chromatographic separation leads to mixtures of N‐(1,3,3‐trialkyl‐2,3‐dihydro‐indol‐2‐yliden)acetamides 16 and oxindoles 17 (Scheme 6). Hydrolysis of 16 with aqueous HCl under reflux for 1–2 h gives oxindoles 17 in a good yield. Several oxindoles, spiro‐oxindoles, and 5‐substituted oxindoles were synthesized by means of the reactions mentioned above.     

Substitution Reactions Which Proceed via Radical Anion Intermediates

A new type of substition process at a saturated carbon atom is described. These reactions, which proceed via a chain sequence in which radical anions and free radicals are intermediates, are noteworthy for providing novel and powerful means of synthesis: they occur readily under mild conditions, they give excellent yields of pure products, and, in contrast to S_N2 displacements, they are rather insensitive to steric hindrance. As a consequence, radical anion processes are especially valuable for the preparation of highly branched structures. Many inorganic and organic anions readily enter into these displacements and, indeed, amines are also effective. Systems which undergo substitutions via this electron transfer mechanism include benzylic, cumylic, strictly aliphatic, and heterocyclic molecules. It is of interest that a number of groups which do not behave as leaving groups in S_N2 displacements are readily displaced at room temperature from a satureted carbon atom via the radical anion-free radical pathway, e.g., nitro, azide, sulfone, and ether groups.     

Stoichiometric and Catalytic C−C and C−H Bond Formation with B(C6F5)3 via Cationic Intermediates

This work showcases a new catalytic cyclization reaction using a highly Lewis acidic borane with concomitant C−H or C−C bond formation. The activation of alkyne‐containing substrates with B(C₆F₅)₃ enabled the first catalytic intramolecular cyclizations of carboxylic acid substrates using this Lewis acid. In addition, intramolecular cyclizations of esters enable C−C bond formation as catalytic B(C₆F₅)₃ can be used to effect formal 1,5‐alkyl migrations from the ester functional groups to unsaturated carbon–carbon frameworks. This metal‐free method was used for the catalytic formation of complex dihydropyrones and isocoumarins in very good yields under relatively mild conditions with excellent atom efficiency.     

1,3‐Difunctionalization of Aminocyclopropanes via Dielectrophilic Intermediates

We report an oxidative ring‐opening strategy to transform acyl, sulfonyl or carbamate protected aminocyclopropanes into 1,3‐dielectrophilic carbon intermediates bearing a halide atom (Br, I) and a N,O‐acetal. Replacing the alkoxy group of the N,O‐acetal can be achieved under acidic conditions through an elimination–addition pathway, while substitution of the halides by nucleophiles can be done under basic conditions through a S_N2 pathway, generating a wide range of 1,3‐difunctionalized propylamines. A proof of concept for asymmetric induction was realized using a chiral phosphoric acid (CPA) as catalyst, highlighting the potential of the method in enantioselective synthesis of important building blocks.     

Synthesis of Benzazepinones via Intramolecular Cyclization Involving Ketene Iminium Intermediates

Herein, we describe a very straightforward and metal free method for the synthesis of benzazepinones through an intramolecular cyclization. This involves an ortho‐vinyl‐anilino‐amide as starting material which is converted to a keteniminium intermediate that spontaneously cyclize to form a 7‐membered ring iminium. Under slightly basic hydrolysis conditions, this latter is ultimately converted to the desired benzazepinone. Control experiments on the electron density of the nitrogen constituting the aniline were performed to support our proposed mechanism and rationalize the selectivity of the reaction.     

Recent Advances in Catalytic Alkyne Transformation via Copper Carbene Intermediates

As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed advances, copper carbenes are versatile and reactive intermediates that can mediate a variety of transformations, which have attracted much attention in the past decades. The present review summarizes two different reaction models that take place between a copper carbene intermediate and alkyne species, including the cross-coupling reaction of copper carbene intermediate with terminal alkyne, and the addition of copper carbene intermediate onto the C–C triple bond. This article will cover the profile from 2010 to 2021 by placing emphasis on the detailed catalytic models and highlighting the synthetic applications offered by these practical and mild methods.     

Elucidating Electrocatalytic Oxygen Reduction Kinetics via Intermediates by Time-Dependent Electrochemiluminescence

Facile evaluation of oxygen reduction reaction (ORR) kinetics for electrocatalysts is critical for sustainable fuel-cell development and industrial H₂O₂ production. Despite great success in ORR studies using mainstream strategies, such as the membrane electrode assembly, rotation electrodes, and advanced surface-sensitive spectroscopy, the time and spatial distribution of reactive oxygen species (ROS) intermediates in the diffusion layer remain unknown. Using time-dependent electrochemiluminescence (Td-ECL), we report an intermediate-oriented method for ORR kinetics analysis. Owing to multiple ultrasensitive stoichiometric reactions between ROS and the ECL emitter, except for electron transfer numbers and rate constants, the potential-dependent time and spatial distribution of ROS were successfully obtained for the first time. Such exclusively uncovered information would guide the development of electrocatalysts for fuel cells and H₂O₂ production with maximized activity and durability.     

De Novo Synthesis of Mono‐ and Oligosaccharides via Dihydropyran Intermediates

The importance of carbohydrates is evident by their essential role in all living systems. Their syntheses have attracted attention from chemists for over a century. Most chemical syntheses in this area focus on the preparation of carbohydrates from naturally occurring monosaccharides. De novo chemical synthesis of carbohydrates from feedstock starting materials has emerged as a complementary method for the preparation of diverse mono‐ and oligosaccharides. In this review, the history of de novo carbohydrate synthesis is briefly discussed and particular attention is given to methods that address the formation of glycosidic bonds for potential de novo synthesis of oligosaccharides. Almost all methods of this kind involve the formation of dihydropyran intermediates. Recent progress in forming dihydropyrans by Achmatowicz rearrangement, hetero‐Diels–Alder cycloaddition, ring‐closing metathesis, and other methods is also elaborated.