Covalent Photosensitizer–Polyoxometalate‐Catalyst Dyads for Visible‐Light‐Driven Hydrogen Evolution

A general concept for the covalent linkage of coordination compounds to bipyridine‐functionalized polyoxometalates is presented. The new route is used to link an iridium photosensitizer to an Anderson‐type hydrogen‐evolution catalyst. This covalent dyad catalyzes the visible‐light‐driven hydrogen evolution reaction (HER) and shows superior HER activity compared with the non‐covalent reference. Hydrogen evolution is observed over periods >1 week. Spectroscopic, photophysical, and electrochemical analyses give initial insight into the stability, electronic structure, and reactivity of the dyad. The results demonstrate that the proposed linkage concept allows synergistic covalent interactions between functional coordination compounds and reactive molecular metal oxides.     

Versatile In Situ Generated N‐Boc‐Imines: Application to Phase‐Transfer‐Catalyzed Asymmetric Mannich‐Type Reactions

The efficient construction of nitrogen‐containing organic compounds is a major challenge in chemical synthesis. Imines are one of the most important classes of electrophiles for this transformation. However, both the available imines and applicable nucleophiles for them are quite limited given the existing preparative methods. Described herein are imine precursors which generate reactive imines with a wide variety of substituents under mild basic conditions. This approach enables the construction of various nitrogen‐containing molecules which cannot be accessed by the traditional approach. The utility of the novel imine precursor was demonstrated in the asymmetric Mannich‐type reaction under phase‐transfer conditions.     

Columnar Liquid‐Crystalline Dinaphthoperylenetetracarboxdiimides

Although the double Friedel–Crafts acylation of arenes with ethyl chloroglyoxylate is hindered by the strongly deactivating effect of the first‐entering glyoxylic substituent, the double reaction is successful with the reactive arene perylene under long reaction times and with concomitant ester hydrolysis. The reaction is regiospecific, giving the 3,9‐regioisomer exclusively. This perylenylenediglyoxylic acid is condensed first with o‐bromophenylacetic acid and then with α‐branched alkylamines to yield the title compounds. Whilst the corresponding tetraalkyl esters only show monotropic mesophases, these diimides show enantiotropic columnar mesophases that can be maintained at room temperature if racemically branched alkyl chains of moderate size are used. A palladium‐induced C?C bond migration during the build‐up of the arene system leads to an isomeric side product of reduced symmetry that can be isolated by aggregation‐controlled chromatographic separation. The HOMO and LUMO energies of the title compounds are considerably higher than those of established perylenetetracarboxdiimides.     

Maleimide‐Modified Phosphonium Ionic Liquids: A Template Towards (Multi)Task‐Specific Ionic Liquids

The synthesis and characterization of several compounds representing a new class of multitask‐specific phosphonium ionic liquids that contain a maleimide functionality is reported. The maleimide moiety of the ionic liquid (IL) is shown to undergo Michael‐type additions with substrates containing either a thiol or amine moiety, thus, serving as a template to introduce wide structural diversity into the IL. Multitask‐specific ILs are accessible by reaction of the maleimide with Michael donors that are capable of serving some function. As a model example to illustrate this concept, a redox active ferrocenyl thiol was incorporated and examined by cyclic voltammetry. Because the maleimide moiety is highly reactive to additions, the task‐specific ionic liquids (TSILs) are prepared as the furan‐protected Diels–Alder maleimide. The maleimide moiety can then be liberated when required by simple heating.     

Visible‐Light‐Induced Passerini Multicomponent Polymerization

Herein, we introduce an additive‐free visible‐light‐induced Passerini multicomponent polymerization (MCP) for the generation of high molar mass chains. In place of classical aldehydes (or ketones), highly reactive, in situ photogenerated thioaldehydes are exploited along with isocyanides and carboxylic acids. Prone to side reactions, the thioaldehyde moieties create a complex reaction environment which can be tamed by optimizing the synthetic conditions utilizing stochastic reaction path analysis, highlighting the potential of semi‐batch procedures. Once the complex MCP environment is understood, step‐growth polymers can be synthesized under mild reaction conditions which—after a Mumm rearrangement—result in the incorporation of thioester moieties directly into the polymer backbone, leading to soft matter materials that can be degraded by straightforward aminolysis or chain expanded by thiirane insertion.     

New conditions for synthesis of (±)‐2‐monosubstituted and (±)‐2,2‐disubstituted 2,3‐dihydro‐4(1H)‐quinazolinones from 2‐nitro‐ and 2‐aminobenzamide

An efficient synthesis of (±)‐2‐monosubstituted and (±)‐2,2‐disubstituted 2,3‐dihydro‐4(1H)‐quinazolinones has been developed using a dissolving metal reduction‐condensative cyclization strategy. Treatment of 2‐nitrobenzamide and an aldehyde or ketone with iron powder in refluxing acetic acid affords high yields of the title compounds. More complex ring systems are available by incorporating additional reactive functionality γ to the carbonyl of the aldehyde or ketone substrate. The scope and limitations of the process along with optimized procedural details are presented. The same target molecules are also accessible by reaction of 2‐aminobenzamide with aldehydes and ketones in refluxing acetic acid. J. Heterocyclic Chem., (2011).     

A Cascade Synthesis of Aminohydantoins Using In Situ‐Generated N‐Substituted Isocyanates

Nitrogen‐substituted isocyanates are rarely utilized but powerful building blocks for the development of cascade reactions in heterocyclic synthesis. These reactive amphoteric intermediates can be accessed in situ via an equilibrium that allows controlled reactivity in the presence of bifunctional partners such as α‐amino esters. A cascade reaction has been carried out that forms 3‐aminohydantoin derivatives using simple phenoxycarbonyl derivatives of hydrazides and hydrazones as precursors of N‐substituted‐isocyanates. This method allows rapid assembly of complex aminohydantoin derivatives, including analogues of medicinally‐relevant compounds, using simple reactants.     

Direct N‐Alkylation and Kemp Elimination Reactions of 1‐Sulfonyl‐1H‐Indazoles

The reactions of 1‐sulfonyl‐1H‐indazoles under basic conditions are discussed, and the direct N‐alkylation and Kemp elimination reactions of these compounds are reported. A series of 2‐(p‐tosylamino)benzonitriles and N‐alkyl indazoles were prepared in good yields. Moreover, the 2‐(p‐tosylamino)benzonitriles could be transformed into a diverse range of important derivatives in a one‐pot reaction. This method was successfully applied to the total syntheses of quindolinone and cryptolepinone; quindolinone was prepared in a one‐pot reaction from 1‐sulfonyl‐1H‐indazole.     

Transition‐Metal‐Free Decarboxylative Propargylic Substitution/Cyclization with either Azolium Enolates or Acyl Anions

Presented herein is an unprecedented transition‐metal‐free propargylic substitution reaction with either azolium enolates or acyl anions, which are generated from aldehydes under N‐heterocyclic carbene catalysis. This new catalytic activation operates on readily available cyclic propargylic carbamates through decarboxylation, and generates reactive allene intermediates that can undergo divergent cyclization pathways to deliver skeletally diverse polycyclic compounds with high levels of efficiency and excellent enantioselectivities.     

Access to 1‐Phospha‐2‐azanorbornenes by Phospha‐aza‐Diels–Alder Reactions

The unprecedented phospha‐aza‐Diels–Alder reaction between an activated electron‐poor imine and 2H‐phospholes yields 1‐phospha‐2‐azanorbornenes in a highly chemoselective and moderately diastereoselective reaction. The intermediate 2H‐phospholes, which act as dienes, are formed in situ from the corresponding 1H‐phospholes. Theoretical calculations confirm that the phospha‐aza‐Diels–Alder reaction is of normal electron demand. The reactive P?N bond in 1‐phospha‐2‐azanorbornenes can be cleaved by nucleophiles leading to the formation of 2,3‐dihydrophospholes.     

Synthesis of 1‐methyl‐, 4‐nitro‐, 4‐amino‐and 4‐iodo‐1,2‐dihydro‐3H‐pyrazol‐3‐ones

4‐Aminopyrazole‐3‐ones 4b, e, f were prepared from pyrazole‐3‐ones 1b‐d in a four‐step reaction sequence. Reaction of the latter with methyl p‐toluenesulfonate gave 1‐methylpyrazol‐3‐ones 2b‐d . Compounds 2b‐d were treated with aqueous nitric acid to give 4‐nitropyrazol‐3‐ones 3b‐d. Reduction of compounds 3b‐d by catalytic hydrogenation with Pd‐C afforded the 4‐amino compounds 4b, e, f. Using similar reaction conditions, nitropyrazole‐3‐ones derivatives 2c, d were reduced into aminopyrazole‐3‐ones 5e, f. 4‐Iodopyrazole‐3‐ones 7a, 7c and 8 were prepared from the corresponding pyrazol‐3‐ones 2a, 2c and 6 and iodine monochloride or sodium azide and iodine monochloride.     

Diethylphosphonate‐containing benzoxazine compound as a thermally latent catalyst and a reactive property modifier for polybenzoxazine‐based resins

A diethylphosphonate‐containing benzoxazine compound (DEP‐Bz) to be used as a multi‐functional reaction agent for preparation of high performance polybenzoxazine thermosetting resins has been reported. The chemical structure of DEP‐Bz has been characterized with FTIR, ¹H NMR, and elemental analysis. The phosphonate groups of DEP‐Bz could convert into phosphonic acid groups which could catalyze the ring‐opening addition reaction of benzoxazines, to demonstrate the thermally latent catalytic effect of DEP‐Bz on the polymerization of benzoxazine compounds. Moreover, DEP‐Bz could also serve as a reactive‐type modifier for polybenzoxazines and other thermosets. DEP‐Bz modified polybenzoxazine resins have shown relatively low reaction temperature (about 190 °C), high mechanical strength with a storage modulus of about 3.0 GPa, and high flame retardancy with a limit oxygen index of about 32. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 3523–3530     

Synthesis of homoallylic amines and acylhydrazides by tin powder‐promoted multicomponent one‐pot allylation reactions

An efficient process for the synthesis of homoallylic amines and N′‐homoallylic hydrazides is developed from the one‐pot reaction of carbonyl compounds, amines or N‐acylhydrazines, allyllic bromide and tin powder using water as solvent. N‐Acylhydrazines are found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give the corresponding N′‐homoallylic hydrazides. Copyright © 2016 John Wiley & Sons, Ltd.     

High‐Throughput Kinetic Analysis for Target‐Directed Covalent Ligand Discovery

Cysteine‐reactive small molecules are used as chemical probes of biological systems and as medicines. Identifying high‐quality covalent ligands requires comprehensive kinetic analysis to distinguish selective binders from pan‐reactive compounds. Quantitative irreversible tethering (qIT), a general method for screening cysteine‐reactive small molecules based upon the maximization of kinetic selectivity, is described. This method was applied prospectively to discover covalent fragments that target the clinically important cell cycle regulator Cdk2. Crystal structures of the inhibitor complexes validate the approach and guide further optimization. The power of this technique is highlighted by the identification of a Cdk2‐selective allosteric (type IV) kinase inhibitor whose novel mode‐of‐action could be exploited therapeutically.     

Clarification of Decomposition Pathways in a State‐of‐the‐Art Lithium Ion Battery Electrolyte through 13C‐Labeling of Electrolyte Components

The decomposition of state‐of‐the‐art lithium ion battery (LIB) electrolytes leads to a highly complex mixture during battery cell operation. Furthermore, thermal strain by e.g., fast charging can initiate the degradation and generate various compounds. The correlation of electrolyte decomposition products and LIB performance fading over life‐time is mainly unknown. The thermal and electrochemical degradation in electrolytes comprising 1 m LiPF₆ dissolved in ¹³C₃‐labeled ethylene carbonate (EC) and unlabeled diethyl carbonate is investigated and the corresponding reaction pathways are postulated. Furthermore, a fragmentation mechanism assumption for oligomeric compounds is depicted. Soluble decomposition products classes are examined and evaluated with liquid chromatography‐high resolution mass spectrometry. This study proposes a formation scheme for oligo phosphates as well as contradictory findings regarding phosphate‐carbonates, disproving monoglycolate methyl/ethyl carbonate as the central reactive species.     

Unique Structural Properties of 2,4,6‐Tri‐tert‐butylanilide: Isomerization and Switching between Separable Amide Rotamers through the Reaction of Anilide Enolates

Herein, we report a unique structural property of 2,4,6‐tri‐tert‐butylanilide, which can be separated into its amide rotamers at room temperature. Interconversion between the rotamers of anilide enolates occurs readily at room temperature and their reaction with electrophiles gives mixtures of the rotamers in a ratio that depends on the reactivity of the corresponding electrophile. That is, the reaction of the 2,4,6‐tri‐tert‐butylacetanilide enolate with reactive electrophiles, such as allyl bromide or protic acids, gives mixtures of the anilide rotamers in which the E rotamer is the major component, whereas less‐reactive electrophiles, such as 1‐bromopropane and 2‐iodopropane, yield mixtures of the rotamers in which the Z rotamer is the major component. The rotameric ratio of the product is also strongly dependent on the reactivity of the anilide enolate. Switching between the anilide rotamers can be achieved through protonation of a less‐reactive enolate by a less‐reactive protic acid and thermal isomerization of the anilide.     

Affinity‐Labeling‐Based Introduction of a Reactive Handle for Natural Protein Modification

A new chemical method to site‐specifically modify natural proteins without the need for genetic manipulation is described. Our strategy involves the affinity‐labeling‐based attachment of a unique reactive handle at the surface of the target protein, and the subsequent selective transformation of the reactive handle by a bioorthogonal reaction to introduce a variety of functional probes into the protein. To demonstrate this approach, we synthesized labeling reagents that contain: 1) a benzenesulfonamide ligand that directs specifically to bovine carbonic anhydrase II (bCA), 2) an electrophilic epoxide group for protein labeling, 3) an exchangeable hydrazone bond linking the ligand and the epoxide group, and 4) an iodophenyl or acetylene handle. By incubating the labeling reagent with bCA, the reactive handle was covalently attached at the surface of bCA through epoxide ring opening. Either after or before removing the ligand by a hydrazone/oxime‐exhange reaction, which restores the enzymatic activity, the reactive handle incorporated could be derivatized by Suzuki coupling or Huisgen cycloaddition reactions. This method is also applicable to the target‐specific multiple modification in a protein mixture. The availability of various (photo)affinity‐labeling reagents and bioorthogonal reactions should extend the flexibility of this strategy for the site‐selective incorporation of many functional molecules into proteins.     

Insertion of Isolated Alkynes into Carbon–Carbon σ‐Bonds of Unstrained Cyclic β‐Ketoesters via Transition‐Metal‐Free Tandem Reactions: Synthesis of Medium‐Sized Ring Compounds

The transition‐metal‐free insertion of isolated alkynes into carbon–carbon σ‐bonds of unstrained cyclic β‐dicarbonyl compounds has been reported. These tandem reactions offer an efficient synthesis of medium‐sized ring or fused‐ring compounds through ring expansion. The methodology has the potential to be widely used throughout organic synthesis due to the easily accessible starting materials and mild reaction conditions.     

Synthesis of 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives through cyclic transformations of 3‐(2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives

Four 3‐(3‐benzylidene‐2‐phenylcarbazoyl)‐2(3H)‐benzoxazolone derivatives 3 have been synthesized from benzoxazolone derivatives 1 and benzaldehyde N‐chloroformylphenylhydrazone 2. By acid hydrolysis, these compounds yielded 3‐(2‐phenylcarbazoyl)‐2(3H)benzoxazolone derivatives 4 which were not isolated and were transformed via an intramolecular reaction into 4‐(2‐hydroxyphenyl)‐1‐phenyl‐1,2,4‐triazolidine‐3,5‐dione derivatives 5 in a good yield. Attempts to cyclize these compounds by intramolecular elimination of water into tricyclic compounds 6 with various dehydrating agents were unsuccessful.     

Gold‐Catalyzed Formal C−C Bond Insertion Reaction of 2‐Aryl‐2‐diazoesters with 1,3‐Diketones

The transition‐metal‐catalyzed formal C−C bond insertion reaction of diazo compounds with monocarbonyl compounds is well established, but the related reaction of 1,3‐diketones instead gives C−H bond insertion products. Herein, we report a protocol for a gold‐catalyzed formal C−C bond insertion reaction of 2‐aryl‐2‐diazoesters with 1,3‐diketones, which provides efficient access to polycarbonyl compounds with an all‐carbon quaternary center. The aryl ester moiety plays a crucial role in the unusual chemoselectivity, and the addition of a Brønsted acid to the reaction mixture improves the yield of the C−C bond insertion product. A reaction mechanism involving cyclopropanation of a gold carbenoid with an enolate and ring‐opening of the resulting donor–acceptor‐type cyclopropane intermediate is proposed. This mechanism differs from that of the traditional Lewis‐acid‐catalyzed C−C bond insertion reaction of diazo compounds with monocarbonyl compounds, which involves a rearrangement of a zwitterion intermediate as a key step.