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In diesem Beitrag wird ein Schülerlaborkonzept zum Graduiertenkolleg 1,2,3H vorgestellt. Aus diesem Forschungsprojekt wurde beispielhaft ein Teilprojekt zur photokatalytischen Deuterierung ausgewählt, um Schüler:innen einen Einblick in chemische Forschung und die Arbeit von in der Chemie Forschenden zu ermöglichen. Die Schüler:innen erarbeiten im Schülerlabor durch modellhafte Experimente Wissen zu Wasserstoff (1H) und Deuterium (2H), der Photokatalyse sowie der Deuterierung mittels Photokatalyse. Sie lernen zudem einzelne Forscher:innen aus diesem Projekt durch videobasierte Interviews kennen. [ABSTRACT FROM AUTHOR]

The multicatalytic generation of 3,5,6-trisubstituted 3,4-dihydropyranones with high enantioselectivity using a highly convergent strategy starting from commercially available precursors is reported. The operationally simple three-step, one-pot protocol merges H-bond and NHC catalysis to provide crucial, reactive β-unsubstituted enones from nitroalkenes as latent 1,2-biselectrophiles. These intermediates are directly funneled into a further NHC-catalyzed formal hetero-Diels-Alder reaction to deliver manifold chiral C(4)-unsubstituted dihydropyranones (typical ee >98%), allowing aliphatic and heteroaromatic substituents and hence expanding the scope of this Michael addition/lactonization. [ABSTRACT FROM AUTHOR]

An NHC-catalyzed nitro-Stetter/elimination/Stetter reaction sequence employs nitroalkenes as latent 1,2-dication synthons providing a novel access to highly useful symmetrical and unsymmetrical 2-aryl substituted 1,4-diketone building blocks from commercially available aldehyde precursors. For less activated (aliphatic) aldehydes, a cooperative catalytic strategy has been developed via the merger of NHC and H-bonding catalysis. To further showcase the versatility of our approach, a great variety of these unprecedented 1,4-diketones are used to efficiently synthesize polysubstituted pyrroles--including those with hetaryl substituents--in good to excellent yields in a multicatalytic metal-free, four-step one-pot cascade reaction under mild, yet robust, conditions. [ABSTRACT FROM AUTHOR]

Metal‐free cooperation: The cooperative combination of Eosin Y as a photoredox catalyst with organocatalytic thiourea allows for the highly diastereoselective construction of trans‐1,2‐cycloalkanes and heterocycles. This new efficient, cooperative organophotoredox/organocatalysis protocol presents a valuable alternative to metal‐based photoredox approaches and is the first example of combining photoredox with hydrogen‐bond catalysis (see scheme). [ABSTRACT FROM AUTHOR]

Enamine key intermediates in organocatalysis, derived from aldehydes and prolinol or J&3x00F8;rgensen-Hayashi- type prolinol ether catalysts, were generated in different sol- vents and investigated by NMR spectroscopy. Depending on the catalyst structure, trends for their formation and amounts are elucidated. For prolinol catalysts, the first enamine detection in situ is presented and the rapid cydization of the enamine to the oxazolidine ("parasitic equilibrium") is monitored. In the case of diphenyiprolinol, this equilibrium is fully shifted to the endo-oxazolidine ("dead end") by the two geminal phenyl rings, most probably because of the Thorpe-Ingold effect. With bulkier and electron-withdrawing aryl rings, however, the enamine is stabilized relative to the oxazolidine, allowing for the parallel detection of the enamine and the oxazolidine. In the case of prolinol ethers, the enamine amounts decrease with increasing sizes of the aryl meta-substituents and the 0-protecting group. In addition, for small aldehyde alkyl chains, Z-configured enamines are observed for the first time in solution. Prolinöl silyl ether enamines are evidenced to undergo slow desilylation and subsequent rapid oxazolidine formation in DMSO. For unfortunate combinations of aldehydes, catalysts, solvents, and additives, the enamine formation is drastically decelerated but can be screened for by a rapid and facile NMR approach. Altogether, especially by clarifying the delicate balances of catalyst selectivity and reactivity, our NMR spectroscopic findings can be expected to substantially aid synthetically working organic chemists in the optimization of organocatalytic reaction conditions and of prolinol (ether) substitution patterns for enamine catalysis. [ABSTRACT FROM AUTHOR]

The proline-catalyzed self-condensation of aliphatic aldehydes in DMSO with varying amounts of catalyst was studied by in situ NMR spectroscopy. The reaction profiles and intermediates observed as well as deuteration studies reveal that the proline-catalyzed aldol addition and condensation are competing, but not consecutive, reaction pathways. In addition, the rate-determining step of the condensation is suggested to be the C-C bond formation. Our findings indicate the involvement of two catalyst molecules in the C-C bond formation of the aldol condensation, presumably by the activation of both the aldol acceptor and donor in a Mannich-type pathway. This mechanism is shown to be operative also in the oligomerization of acetaldehyde with high proline amounts, for which the first in situ detection of a proline-derived dienamine was accomplished. In addition, the diastereoselectivity of the aldol addition is evidenced to be time-dependent since it is undermined by the retro-aldolization and the competing irreversible aldol condensation; here NMR reaction profiles can be used as a tool for reaction optimization. [ABSTRACT FROM AUTHOR]

A reactivity based fluoride sensing method exploiting both its nucleophilic and basic character has been developed. This novel dual mode strategy offers both a visible “naked-eye” and a “fluorescence-on” detection. Upon nucleophilic addition of F−to fluorochromic maleimides this approach allows for selective detection of fluoride from other (critical) basic anions, such as acetate, hydroxide or cyanide. [ABSTRACT FROM AUTHOR]

Dihydrocoumarins play an important role as flavor and fragrance compounds and can be prepared efficiently from o-hydroxycinnamaldehydes in a mild, atom-economic N-heterocyclic carbene-catalyzed redox lactonization. Corresponding coumarins are accessible via a one-pot domino oxidation lactonization procedure in the presence of oxidants. [ABSTRACT FROM AUTHOR]

Homogeneous, Rh-catalyzed hydrogenation of heteromeric olefinic glycine dimers presents an efficient route to diastereomerically pure, orthogonally protected diaminosuccinic acid derivatives depending on the double bond geometry of the starting material. The products were obtained as racemates. [ABSTRACT FROM AUTHOR]

Mechanistic details of transformations catalyzed by N‐heterocyclic carbenes (NHC) are currently of great interest, targeting questions on the active catalyst in operation and the structure and reactivity of key intermediates. These mechanistic studies are driven by the need to understand the big impact of subtle changes on the catalyst system on its reactivity, as well as to clarify the situation around the elusive intermediates in the classical catalytic cycle. In the activation process of aldehydes the formation of an enaminol structure, coined the Breslow intermediate, is widely accepted. Previously, however, we could prove that this enaminol has, besides its ionic reaction pathway, also the option to follow a radical pathway, by undergoing redox processes with the starting material. In the present study we aim to elucidate if these radical pathways are a more general phenomenon, specifically in the formal hydroacylation reaction of alkynes. The observation of radical species and computational analysis of key elemental steps in the radical and ionic pathways may lead to an onward development of chemistry based on NHC‐stabilized carbon radicals. The NHC‐catalysed transformations continue to surprise with their mechanistic details. In the formal hydroacylation reaction of alkynes, radical intermediates were discovered, and their origin and reactivity analysed by EPR spectroscopy and computational chemistry and compared to the radicals observed in the benzoin reaction. [ABSTRACT FROM AUTHOR]

Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy)3](PF6)2-catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples. [ABSTRACT FROM AUTHOR]

This new method gives trans-1,2-cycloalkanes and heterocycles providing the first example of combining photoredox approach with hydrogen-bond catalysis. [ABSTRACT FROM AUTHOR]

A visible light mediated, but photocatalyst-free method for the oxidative α-CH functionalization of tertiary amines with a broad scope of carbon- and heteroatom nucleophiles using polyhalomethanes has been developed. In addition, the pivotal visible light triggered activation of polyhalomethanes offers mild conditions for efficient Kharasch-type additions onto non-activated olefins. Preliminary mechanistic studies are reported. [ABSTRACT FROM AUTHOR]

Detailed 31P{1H} NMR spectroscopic investigations provide deeper insight into the complex, multi‐step mechanisms involved in the recently reported photocatalytic arylation of white phosphorus (P4). Specifically, these studies have identified a number of previously unrecognized side products, which arise from an unexpected non‐innocent behavior of the commonly employed terminal reductant Et3N. The different rate of formation of these products explains discrepancies in the performance of the two most effective catalysts, [Ir(dtbbpy)(ppy)2][PF6] (dtbbpy=4,4′‐di‐tert‐butyl‐2,2′‐bipyridine) and 3DPAFIPN. Inspired by the observation of PH3 as a minor intermediate, we have developed the first catalytic procedure for the arylation of this key industrial compound. Similar to P4 arylation, this method affords valuable triarylphosphines or tetraarylphosphonium salts depending on the steric profile of the aryl substituents. [ABSTRACT FROM AUTHOR]

Detailed 31P{1H} NMR spectroscopic investigations provide deeper insight into the complex, multi‐step mechanisms involved in the recently reported photocatalytic arylation of white phosphorus (P4). Specifically, these studies have identified a number of previously unrecognized side products, which arise from an unexpected non‐innocent behavior of the commonly employed terminal reductant Et3N. The different rate of formation of these products explains discrepancies in the performance of the two most effective catalysts, [Ir(dtbbpy)(ppy)2][PF6] (dtbbpy=4,4′‐di‐tert‐butyl‐2,2′‐bipyridine) and 3DPAFIPN. Inspired by the observation of PH3 as a minor intermediate, we have developed the first catalytic procedure for the arylation of this key industrial compound. Similar to P4 arylation, this method affords valuable triarylphosphines or tetraarylphosphonium salts depending on the steric profile of the aryl substituents. [ABSTRACT FROM AUTHOR]

Abstract: Functionalized 2,2-disubstituted benzofuran-3-(2H)-ones have been synthesized from simple aldehyde building blocks in a combined NHC- and base-catalyzed one-pot cascade reaction in moderate to excellent yields. This modular approach comprises a NHC-catalyzed hydroacylation/Stetter reaction sequence followed by a retro-Michael, 1,3-H shift and oxa-Michael cascade rearrangement promoted by strong bases. [Copyright &y& Elsevier]

Improved catalyst design by incorporating a hydrogen bond donating substituent to improve enantiocontrol together with an acidifying pentafluorophenyl substituent to enhance catalyst efficiency results in a triazolium ion precatalyst that promotes the asymmetric archetypal benzoin condensation with excellent efficiency and unprecedented enantioselectivity. [ABSTRACT FROM AUTHOR]

By the on-chip integration of a droplet generator in front of an emitter tip, droplets of non-polar solvents are generated in a free jet of an aqueous matrix. When an IR laser irradiates this free liquid jet consisting of water as the continuous phase and the non-polar solvent as the dispersed droplet phase, the solutes in the droplets are ionized. This ionization at atmospheric pressure enables the mass spectrometric analysis of non-polar compounds with the aid of a surrounding aqueous matrix that absorbs IR light. This works both for non-polar solvents such as n-heptane and for water non-miscible solvents like chloroform. In a proof of concept study, this approach is applied to monitor a photooxidation of N-phenyl-1,2,3,4-tetrahydroisoquinoline. [ABSTRACT FROM AUTHOR]

Asymmetrically substituted tertiary phosphines and quaternary phosphonium salts are used extensively in applications throughout industry and academia. Despite their significance, classical methods to synthesize such compounds often demand either harsh reaction conditions, prefunctionalization of starting materials, highly sensitive organometallic reagents, or expensive transition‐metal catalysts. Mild, practical methods thus remain elusive, despite being of great current interest. Herein, we describe a visible‐light‐driven method to form these products from secondary and primary phosphines. Using an inexpensive organic photocatalyst and blue‐light irradiation, arylphosphines can be both alkylated and arylated using commercially available organohalides. In addition, the same organocatalyst can be used to transform white phosphorus (P4) directly into symmetrical aryl phosphines and phosphonium salts in a single reaction step, which has previously only been possible using precious metal catalysis. [ABSTRACT FROM AUTHOR]

The visible-light photocatalytic E/Z isomerization of olefins can be mediated by a wide spectrum of triplet sensitizers (photocatalysts). However, the search for the most efficient photocatalysts through screenings in photo batch reactors is material and time consuming. Capillary and microchip flow reactors can accelerate this screening process. Combined with a fast analytical technique for isomer differentiation, these reactors can enable high-throughput analyses. Ion mobility (IM) spectrometry is a cost-effective technique that allows simple isomer separation and detection on the millisecond timescale. This work introduces a hyphenation method consisting of a microchip reactor and an infrared matrix-assisted laser desorption ionization (IR-MALDI) ion mobility spectrometer that has the potential for high-throughput analysis. The photocatalyzed E/Z isomerization of ethyl-3-(pyridine-3-yl)but-2-enoate (E-1) as a model substrate was chosen to demonstrate the capability of this device. Classic organic triplet sensitizers as well as Ru-, Ir-, and Cu-based complexes were tested as catalysts. The ionization efficiency of the Z-isomer is much higher at atmospheric pressure which is due to a higher proton affinity. In order to suppress proton transfer reactions by limiting the number of collisions, an IM spectrometer working at reduced pressure (max. 100 mbar) was employed. This design reduced charge transfer reactions and allowed the quantitative determination of the reaction yield in real time. Among 14 catalysts tested, four catalysts could be determined as efficient sensitizers for the E/Z isomerization of ethyl cinnamate derivative E-1. Conversion rates of up to 80% were achieved in irradiation time sequences of 10 up to 180 s. With respect to current studies found in the literature, this reduces the acquisition times from several hours to only a few minutes per scan. [ABSTRACT FROM AUTHOR]

Herein we report an unprecedented, convenient NHC‐catalyzed one‐pot cascade reaction to afford α,ω‐difunctionalized hydroxytrifluoromethyl alkynones and allenones in a single step. The critical fragile aliphatic aldehydes are introduced by a base‐mediated in situ Grob‐type fragmentation of their corresponding latent cyclic vinylogous hemiacetal triflate (VHAT) and γ‐hydroxy vinyl triflate (GHVT) precursors, avoiding typical problems and losses upon isolation. The ′demasked′ aldehydes are subsequently trapped by NHC‐catalyzed umpolung and further metal‐free C−C‐cross‐coupling to access a broad scope of terminally modified alkynyl or allenyl aliphatic, aromatic and heteroaromatic trifluoromethyl ketones as multifunctionalized, high‐value building blocks for advanced synthetic applications. Additional synthetic utility of this approach is demonstrated with the possibility for asymmetric variants using chiral NHC‐catalysts. [ABSTRACT FROM AUTHOR]

Conjugated enynes as well as cyclic nitronates are crucial building blocks for numerous natural products and pharmaceuticals. However, so far, no common and metal‐free synthetic route to both conjugated enynes and cyclic nitronates has been reported. Herein, in situ NMR, labelling studies and theoretical calculations were combined to investigate the mechanism of the unusual triple bond formation towards conjugated enynes. Starting from nitroalkene dimers, first an isoxazolidine‐2,5‐diol derivative is formed as central intermediate. From this, enynes were generated by a combination of oxidation, dehydration, and retro 1,3‐dipolar cycloaddition, whereas for nitronates a base induced intramolecular reorganization is proposed. While the product distribution could be controlled and high yields of nitronate were achieved, only medium to good yields for enynes were obtained due to polymerization losses. Nevertheless, we hope that these mechanistic investigations may provide a basis for further developments of organocatalytic or metal‐free preparations of conjugated enynes and nitronates. In situ NMR, isotope labelling, and theoretical calculations revealed an organocatalytic mechanism to conjugated enynes. This mild route to enynes proceeds through an unusual build‐up of the triple bond out of a single bond and provides a mechanistic junction to cyclic nitronates, which can be selectively switched by certain basic and acidic additives. [ABSTRACT FROM AUTHOR]

The article focuses on the importance of domino catalysis to improve the efficiency of organic synthesis. Topics discussed include the improvement in organocatalysis, the synthesis of bioactive substances and natural products, and the use of N-heterocyclic carbenes (NHCs) as catalysts. Also mentioned are the visible-light photocatalysis, the hydrogen-bonding catalysts, and the organocatalytic activation

Modern catalysis takes advantage of aryl-based interactions to tune and control reactions. In the design of N-heterocyclic-carbene catalysts, both the electronic and steric nature of the nitrogen substituents play a crucial role. Although hydrocarbon-based systems and especially aryl residues have contributed considerably to overcome multifaceted catalytic challenges, the unique properties of carborane moieties, including delocalized charge, potential planar chirality, and well-known thermodynamic stability, offer unprecedented opportunities to develop new catalysts while being employed as aryl mimetics. We report a straightforward synthetic route to a novel zwitterionic triazolium-based N-heterocyclic carbene (NHC) precatalyst bearing a 7,8-dicarba- nido-undecaboranyl substituent. The catalyst's excellent activity and its broad applicability are demonstrated in a wide range of organocatalytic transformations. Comparison of the performance with known N-aryl NHC catalysts offers preliminary insights into the stereoelectronic nature of this nido-carboranyl substituent. [ABSTRACT FROM AUTHOR]

We present a microfluidic system, seamlessly integrating microflow and microbatch synthesis with a HPLC/nano-ESI-MS functionality on a single glass chip. The microfluidic approach allows to efficiently steer and dispense sample streams down to the nanoliter-range for studying reactions in quasi real-time. In a proof-of-concept study, the system was applied to explore amino-catalyzed reactions, including asymmetric iminium-catalyzed Friedel–Crafts alkylations in microflow and micro confined reaction vessels. [ABSTRACT FROM AUTHOR]

A mild and effective method for the photocatalytic deoxygenation of simple O-acrylbenzoin and -acyloin derivatives is developed. [ABSTRACT FROM AUTHOR]

Tetrahydroisoquinolines (I) are oxidized in the presence of CBrCl3 under blue LED irradiation to the corresponding 3,4-dihydroisoquinolinium bromides (II). [ABSTRACT FROM AUTHOR]

It has been shown for the first time that triazolium precatalysts promote (in the presence of base) highly chemoselective crossed acyloin condensation reactions between aliphatic and ortho-substituted aromatic aldehydes. An o-bromine atom can serve as a temporary directing group to ensure high chemoselectivity (regardless of the nature of the other substituents on the aromatic ring) which then can be conveniently removed. The process is of broad scope and is operationally simple as it does not require the preactivation of any of the coupling partners to ensure selectivtiy. Preliminary data indicate that highly enantioselective variants of the reaction are feasible using chiral precatalysts. [ABSTRACT FROM AUTHOR]

The synthesis of the slime mold pigments arcyroxocin A and B is described. The key step in the synthesis is the oxidative ring closure of an N-protected 3-(4-hydroxyindol-3-yl)-4-indol-3-ylmaleimide with DDQ/PPTS, which affords exclusively the desired arcyroxocin derivative. Attempts to obtain the arcyroxocin system from a 3-(4-hydroxyindolyl)-4-(2-oxoindolinyl)maleimide precursor were less successful and led to oxidative formation of a spiroindoline compound. [ABSTRACT FROM AUTHOR]

The interplay between catalyst and substrate control in crossed acyloin condensation reactions has been studied. It was found that a pentafluorophenyl-substituted triazolium ion derived catalyst was capable of catalyzing highly chemoselective processes between a range of aliphatic and aromatic aldehydes utilized in a 1:1 ratio. [ABSTRACT FROM AUTHOR]

Benzoin (and neither the Breslow intermediate nor the NHC–aldehyde tetrahedral adduct) has been unambiguously identified as the oxidised species in aerobic NHC-catalysed aldehyde esterifications. [ABSTRACT FROM AUTHOR]

A highly efficient, broad scope, additive-free mild protocol for the oxidative carbene-catalysed esterification of aldehydes (including the related aqueous oxidation to acids) has been developed. [ABSTRACT FROM AUTHOR]

The Cover Feature shows a machine that generates conjugated enynes and cyclic nitronates within a one‐pot reaction from simple nitroalkenes. The reaction towards both products shares a common pathway that deviates towards enynes or nitronates depending on the reaction conditions. By adjusting additive and base, the selectivity between enynes and nitronates can be controlled. NMR reaction monitoring in combination with theoretical calculations helped to elucidate the mechanism towards both products. This machine stands as a symbol for reaction flasks or NMR‐tubes in which the reactions were carried out. More information can be found in the Full Paper by R. M. Gschwind et al. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are the groups of Kirsten Zeitler and Evamarie Hey-Hawkins at the University of Leipzig. The image depicts the carborane catalyst being a result of a long hatching process that eventually provides the starting point of a new member of the NHC-catalyst family. Read the full text of the article at . [ABSTRACT FROM AUTHOR]

A new offspring of the organocatalyst family has hatched from the merger of covalent catalysis and a carborane as an aryl‐mimetic replacement: the novel zwitterionic triazolium based N‐heterocyclic carbene (NHC) precatalyst bears a 7,8‐dicarba‐nido‐undecaboranyl substituent (nidus (lat.)=nest) and offers excellent activity and broad applicability in a wide range of organocatalytic transformations. The straightforward synthesis and a detailed comparison to recent aryl‐based precatalysts provides useful insights to pave the way for further development of this unprecedented class of catalysts. More information can be found in the Full Paper by K. Zeitler et al. on page 7932. [ABSTRACT FROM AUTHOR]

The NHC-catalyzed oxidation of benzaldehyde (I) in the presence of alcohols (II) affords esters (III), whilst the analogous reaction in the presence of water leads to benzoic acid (IV). [ABSTRACT FROM AUTHOR]

The article presents diagrammatic representation of aromatic carbon rings which shows NHC-catalyzed aerobic aldehyde-esterifications with alcohols.

The easily available inorganic semiconductors (photocatalysts) can be simply removed and recycled. [ABSTRACT FROM AUTHOR]

Triazolium salt TRB in combination with K2CO3 is an efficient catalyst for the coupling reaction of aliphatic or aromatic/heteroaromatic aldehydes with α-ketoesters. [ABSTRACT FROM AUTHOR]