In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis.

Invited for the cover of this issue is Oliver Trapp and his co-workers at Ludwig-Maximilians-Universität München, the Max-Planck-Institute for Astronomy and Ruprecht-Karls-Universität Heidelberg. The image depicts a magic trick representing the autocatalytic process reported in the manuscript. Read the full text of the article at 10.1002/chem.202003260.

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis.

Chemical reactions that lead to a spontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interest in explaining the formation of a homochiral world. An outstanding example is Soai's asymmetric autocatalysis, in which small enantiomeric excesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine-5-carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high-resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formation of hemiacetal complexes, which can establish an autocatalytic cycle. We propose a mechanism that explains the autocatalytic amplification involving these hemiacetal complexes. Comprehensive kinetic experiments and modelling of the hemiacetal formation and the Soai reaction allow the precise prediction of the reaction progress, the enantiomeric excess as well as the enantiomeric excess dependent time shift in the induction period. Experimental structural data give insights into the privileged properties of the pyrimidyl units and the formation of diastereomeric structures leading to an efficient amplification of even minimal enantiomeric excesses, respectively.

Dinuclear thiazolylidene copper complex as highly active catalyst for azid-alkyne cycloadditions.

A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide-alkyne cycloaddition (CuAAC) "click" reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N-heterocyclic carbene, linker, sacrificial ligand, and counter ion.

Copper and Silver Carbene Complexes without Heteroatom-Stabilization: Structure, Spectroscopy, and Relativistic Effects.

Salts of a copper and a silver carbene complex were prepared from dimesityl diazomethane, made possible by the steric shielding of the N-heterocyclic carbene (NHC) ancillary ligand IPr**. The mint-green complex [IPr**Ag=CMes2 ](+) [NTf2 ](-) is the first isolated silver carbene complex without heteroatom donor substituents. Single-crystal X-ray diffraction provides evidence for a predominant carbenoid character, and supports the postulation of such reactive species as intermediates in silver-catalyzed C-H activation reactions. The greenish yellow copper carbene complex [IPr**Cu=CMes2 ](+) [NTf2 ](-) has spectroscopic properties in between the isostructural silver complex and the already reported emerald green gold carbene complex. A comparison in the Group 11 series indicates that relativistic effects are responsible for the strong σ bond and the significant π back-bonding in the gold carbene moiety.

A Fluxional Copper Acetylide Cluster in CuAAC Catalysis.

A molecularly defined copper acetylide cluster with ancillary N-heterocyclic carbene (NHC) ligands was prepared under acidic reaction conditions. This cluster is the first molecular copper acetylide complex that features high activity in copper-catalyzed azide-alkyne cycloadditions (CuAAC) with added acetic acid even at -5 °C. Ethyl propiolate protonates the acetate ligands of the dinuclear precursor complex to release acetic acid and replaces one out of four ancillary ligands. Two copper(I) ions are thereby liberated to form the core of a yellow dicationic C2-symmetric hexa-NHC octacopper hexaacetylide cluster. Coalescence phenomena in low-temperature NMR experiments reveal fluxionality that leads to the facile interconversion of all of the NHC and acetylide positions. Kinetic investigations provide insight into the influence of copper acetylide coordination modes and the acetic acid on catalytic activity. The interdependence of "click" activity and copper acetylide aggregation beyond dinuclear intermediates adds a new dimension of complexity to our mechanistic understanding of the CuAAC reaction.

Isolation of a non-heteroatom-stabilized gold-carbene complex.

Gold-carbene complexes are essential intermediates in many gold-catalyzed organic-synthetic transformations. While gold-carbene complexes with direct, vinylogous, or phenylogous heteroatom substitution have been synthesized and characterized, the observation in the condensed phase of electronically non-stabilized gold-carbenes has so far remained elusive. The sterically extremely shielded, emerald-green complex [IPr**Au=CMes2](+)[NTf2](-) has now been synthesized, isolated, and fully characterized. Its absorption maximum at 642 nm, in contrast to 528 nm of the red-purple carbocation [Mes2CH](+), clearly demonstrates that gold is more than just a "soft proton".

Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC's catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

Iodocyclization of o-alkynylbenzamides revisited: formation of isobenzofuran-1(3H)-imines and 1H-isochromen-1-imines instead of lactams.

The iodocyclization of o-alkynylbenzamides with various electrophiles has been reported to yield five- or six-membered lactams by nucleophilic attack of the amide nitrogen onto the triple bond. While the formation of an isobenzofuran-1(3H)-imine with two bulky substituents under Larock conditions was initially attributed to steric hindrance, we found out that cyclization via the amide oxygen is the rule rather than the exception. Thus, the structures of the products reported in the literature need to be revised.

A cationic gold complex cleaves BArF24.

A sterically shielded cationic NHC gold complex IPr**Au-BArF(24) without solvent coordination has been prepared in situ in CH(2)Cl(2). The monovalent transition metal electrophile, a "soft proton", heterolytically activates the C-B bond of the weakly coordinating counterion tetrakis[3,5-bis(trifluoromethyl)phenyl]borate at room temperature.

Iridium-catalyzed allylic substitutions with cyclometalated phosphoramidite complexes bearing a dibenzocyclooctatetraene ligand: preparation of (π-allyl)Ir complexes and computational and NMR spectroscopic studies.

(π-Allyl)Ir complexes derived from dibenzocyclooctatetraene and phosphoramidites by cyclometalation are effective catalysts for allylic substitution reactions of linear monosubstituted allylic carbonates. These catalysts provide exceptionally high degrees of regioselectivity and allow the reactions to be run under aerobic conditions. A series of (π-allyl)Ir complexes were prepared and characterized by X-ray crystal structure analyses. An allylic amination with aniline displayed different resting states depending on the presence of a strong base. DFT calculations were carried out on the mechanistic aspects of these reactions. The results suggest that for the (π-allyl)Ir complexes, the formation and reactions with nucleophiles proceed with comparable rates.

CO2 on a tightrope: stabilization, room-temperature decarboxylation, and sodium-induced carboxylate migration.

A sterically shielded 3-substituted zwitterionic N,N-dimethylisotryptammonium carboxylate has been synthesized by consecutive chemoselective double alkylation of indole. The carboxylate undergoes a quantitative and unusually facile decarboxylation in dimethyl sulfoxide (DMSO) or dimethyl formamide (DMF) at room temperature. The breaking of a nearly equidistant hydrogen bond by solvent molecules initiates heterolytic C-C cleavage. The decarboxylation rate decreases with increasing CO(2) partial pressure, proving the competitiveness of protonation and re-carboxylation of the carbanionic intermediate. Corresponding spiro compounds containing silylene and stannylene moieties show high thermal stability. Addition of an excess of methyllithium to the sodium salt triggers a reaction sequence comprising a deprotonation, carboxylate transfer, and nucleophilic trapping of the rearranged carboxylate by another equivalent of methyllithium. Hydrolytic work-up of the geminal diolate leads to an acetyl product. The role of the sodium counterion and the mechanism of the rearrangement have been unraveled by deuteration experiments.

Polyelectrolyte gels comprising a lipophilic, cost-effective aluminate as fluorine-free absorbents for chlorinated hydrocarbons and diesel fuel.

Superabsorbent polymers comprising a lipophilic, halogen-free, and cost-effective aluminate ("altebate") anion have been synthesized. The polyelectrolytes are based on octadecyl acrylate monomers, 0.8-1 mol % ethylene dimethacrylate cross-linker, and 5 mol % N-3-acroyloxypropyl trialkylammonium altebate. At 30 °C, swelling degrees of 70 (chlorobenzene), 102 (CHCl3), 130 (THF), 163 (ClCH2CH2Cl), 171 (dichlorobenzene), and 208 (CH2Cl2) have been determined. The polyelectrolyte absorbs reversibly diesel fuel with a swelling degree of 34, even in the presence of water. Swelling times and critical swelling temperatures have also been determined. The challenges for the development of oil absorbents are discussed.

A synthesis of pseudoconhydrine and its epimer via hydroformylation and dihydroxylation.

A synthesis of the alkaloid pseudoconhydrine and its epimer has been achieved using tandem hydroformylation-condensation to form the six-membered ring and stereoselective dihydroxylation to introduce oxygenation. The stereoselectivity of dihydroxylation can be explained by lipophilic and electrostatic effects, supported by DFT calculations. The alkaloids can be obtained either by regioselective dehydroxylation or by rearrangement, followed by reduction.

Highly diastereoselective arylations of substituted piperidines.

A highly diastereoselective methodology for the preparation of various substituted piperidines via Negishi cross-couplings with (hetero)aryl iodides was developed. Depending on the position of the C-Zn bond relative to the nitrogen (position 2 vs position 4), the stereoselectivity of the coupling can be directed toward either the trans- or cis-2,4-disubstituted products. Density functional theory calculations on the relative stabilities of the Zn and Pd intermediates were performed to explain the high diastereoselectivities obtained. A novel 1,2-migration of Pd further expands this method to the stereoselective preparation of 5-aryl-2,5-disubstituted piperidines.

Predicting the cis-trans dichloro configuration of group 15-16 chelated ruthenium olefin metathesis complexes: a DFT and experimental study.

Gradient-corrected (BP86) and hybrid (M06-L) density functional calculations were used to study the relative stability of cis and trans-dichloro X-chelated benzylidene ruthenium complexes (X = O, S, Se, N, P). Calculations in the gas phase differed from experimental results, predicting the trans-dichloro configuration as being more stable in every case. The addition of Poisson-Boltzmann (PBF) continuum approximation (dichloromethane) corrected the disagreement and afforded energies consistent with experimental results. Novel N, Se, and P chelated ruthenium olefin metathesis complexes were synthesized to evaluate calculation predictions. These findings reinforce the importance of including solvent corrections in DFT calculations of ruthenium metathesis catalysts and predict that stronger sigma donors as chelating atoms tend to electronically promote the unusual and less active cis-dichloro configuration.

Palladium-catalyzed cyclopropanation of alkenyl silanes by diazoalkanes: evidence for a Pd(0) mechanism.

Alkenyl silanes are efficiently converted to the corresponding silyl cyclopropanes in the presence of a slight excess of diazomethane (2-4 equiv) and a low loading of Pd(OAc)(2) (<0.5 mol %). Diazoethane and diazobutane can also be employed and yield silyl cyclopropanes with diastereoselectivities of up to 10:1 for the trans isomer. When conducted on a 4 g scale, the reaction only required a catalyst loading of 5x10(-3) mol %, which corresponds to a turnover frequency of 40,000 h(-1). Competition experiments revealed that vinyl silanes can be selectively cyclopropanated in the presence of an aliphatic terminal alkene and styrene. The complex [Pd(0) (2)(DVTMS)(3)] (38, DVTMS = divinyltetramethyldisiloxane) proved to be an exceptionally active catalyst for the cyclopropanation reaction, giving complete conversion at -35 degrees C in 1 min. Intermolecular and intramolecular competition experiments with DVTMS (36), both with Pd(OAc)(2) and 38, provided strong evidence for a Pd(0)(alkenyl silane)(3) resting state. Detailed density functional calculations on the reaction pathways for the cyclopropanation of trimethylvinylsilane and DVTMS by diazomethane with Pd(0) corroborated the experimental observations.

Oxygen donor-mediated equilibration of diastereomeric alkene-palladium(II) intermediates in enantioselective desymmetrizing Heck cyclizations.

This investigation examines the origin of enantioselection in the desymmetrization of an acyclic prochiral Heck cyclization precursor. High asymmetric induction (97-98% ee) is attributed to a temporary interaction of a Lewis basic oxygen donor with weakly Lewis acidic palladium(II). A series of control experiments combined with quantum-chemical model calculations provided sound evidence for a mechanism involving oxygen donor-mediated, rapid equilibration of diastereomeric alkene-palladium(II) complexes prior to the selectivity-determining ring-closing event, a Curtin-Hammett scenario. Our study also highlights the importance of the cationic pathway (triflate counter anions versus halido ligand) and alkene stereochemistry (E versus Z) in asymmetric Heck reactions.

mu-Acetylide and mu-alkenylidene ligands in "click" triazole syntheses.

In a computational investigation, dinuclear and tetranuclear copper acetylide complexes display both superior stability and higher reactivity in the CuAAC reaction than do mononuclear complexes due to favored dicopper(I,III) mu-alkenylidene fragments, instead of ring strain in a Cu=C=C intermediate.