Sandra Künzler

Two‐Faced Nucleophiles! We provide intuitive design rules to predict ambident reactivity for S_N2@C and S_N2@Si reactions, based on detailed quantum‐chemical activation strain analyses. Our approach overcomes issues that arise from the use of the widely employed HSAB principle and constitutes a more comprehensive predictive model.

Abstract

The ability to understand and predict ambident reactivity is key to the rational design of organic syntheses. An approach to understand trends in ambident reactivity is the hard and soft acids and bases (HSAB) principle. The recent controversy over the general validity of this principle prompted us to investigate the competing gas‐phase S_N2 reaction channels of archetypal ambident nucleophiles CN⁻, OCN⁻, and SCN⁻ with CH₃Cl (S_N2@C) and SiH₃Cl (S_N2@Si), using DFT calculations. Our combined analyses highlight the inability of the HSAB principle to correctly predict the reactivity trends of these simple, model reactions. Instead, we have successfully traced reactivity trends to the canonical orbital‐interaction mechanism and the resulting nucleophile–substrate interaction energy. The HOMO–LUMO orbital interactions set the trend in both S_N2@C and S_N2@Si reactions. We provide simple rules for predicting the ambident reactivity of nucleophiles based on our Kohn–Sham molecular orbital analysis.

Inspecting halogen bonding: Is it possible to predict halogen‐bonding strength accurately by a single DFT calculation and achieve better performance than that offered by the static σ‐hole depth?

Abstract

Halogen‐bond donors (halogen‐based Lewis acids) have now found various applications in diverse fields of chemistry. The goal of this study was to identify a parameter obtainable from a single DFT calculation that reliably describes halogen‐bonding strength (Lewis acidity). First, several DFT methods were benchmarked against the CCSD(T) CBS binding data of complexes of 17 carbon‐based halogen‐bond donors with chloride and ammonia as representative Lewis bases, which revealed M05‐2X with a partially augmented def2‐TZVP(D) basis set as the best model chemistry. The best single parameter to predict halogen‐bonding strengths was the static σ‐hole depth, but it still provided inaccurate predictions for a series of compounds. Thus, a more reliable parameter, Ω _σ*, has been developed through the linear combination of the σ‐hole depth and the σ*(C−I) energy, which was further validated against neutral, cationic, halogen‐ and nitrogen‐based halogen‐bond donors with very good performance.

Benchtop transformation: Nitrenium salts are investigated as Lewis acid catalysts in five organic transformations. Despite their weakly acidic character, these species prove competent catalysts in a number of benchmark transformations. The moisture‐stability of the salts allows for the reactions to be carried on the benchtop without the need for pre‐dried solvents.

Abstract

Molecular compounds featuring nitrogen atoms are typically regarded as Lewis bases and are extensively employed as donor ligands in coordination chemistry or as nucleophiles in organic chemistry. By contrast, electrophilic nitrogen‐containing compounds are much rarer. Nitrenium cations are a new family of nitrogen‐based Lewis acids, the reactivity of which remains largely unexplored. In this work, nitrenium ions are explored as catalysts in five organic transformations. These reactions are the first examples of Lewis acid catalysis employing nitrogen as the site of substrate activation. Moreover, these compounds are readily accessed from commercially available reagents and exhibit remarkable stability toward moisture, allowing for benchtop transformations without the need to pretreat solvents.

SiR, the NMe has surrendered: Benzylic ammonium salts can be transformed into the corresponding silanes by a copper‐catalyzed S_N2‐type displacement. The enantioenrichment of the precursors is completely retained in the α‐chiral silanes. A cyclopropyl group at the benzylic carbon atom remains intact, thereby supporting an ionic reaction mechanism.

Abstract

A method for the synthesis of benzylsilanes starting from the corresponding ammonium triflates is reported. Silyl boronic esters are employed as silicon pronucleophiles, and the reaction is catalyzed by copper(I) salts. Enantioenriched benzylic ammonium salts react stereospecifically through an S_N2‐type displacement of the ammonium group to afford α‐chiral silanes with inversion of the configuration. A cyclopropyl‐substituted substrate does not undergo ring opening, thus suggesting an ionic reaction mechanism with no benzyl radical intermediate.

Alterations in Zn2+ concentration are seen in normal tissues and in disease states, and for this reason imaging of Zn2+ is an area of active investigation. Herein, enriched [1‐13C]cysteine and [1‐13C2]iminodiacetic acid were developed as Zn2+‐specific imaging probes using hyperpolarized 13C magnetic resonance spectroscopy. [1‐13C]cysteine was used to accurately quantify Zn2+ in complex biological mixtures. These sensors can be employed to detect Zn2+ via imaging mechanisms including changes in 13C chemical shift, resonance linewidth, or T1.

“The unexpected facile switch between aromatic and non‐aromatic states of a germole anion that is initiated by complexation of the potassium counter cation is the central result of the here highlighted research.” Read more about the story behind the cover in the Cover Profile and about the research itself on page 10858 ff. (DOI: https://doi.org/10.1002/chem.20190223810.1002/chem.201902238).

Abstract

Invited for the cover of this issue is the group of Thomas Müller at the University of Oldenburg. The image depicts the switch between aromatic and non‐aromatic states of a potassium germacyclopentadienide triggered by complexation of the potassium cation. Read the full text of the article at https://doi.org/10.1002/chem.20190223810.1002/chem.201902238.

New phosphonium cations: Despite the bulky m‐terphenyl substituents that are needed to provide kinetic stabilization of this new compound class, various functional groups of different size and electronegativity may be chosen.

Abstract

Efforts to prepare an elusive donor‐free phosphenium ion, [R₂P]⁺, led us to synthesize functionalized fluorophosphonium cations of the type [R₂P(F)X]⁺ (X=SiEt₃, H, F), which were obtained from the related neutral fluorophosphines R₂PF and R₂PF₃ upon protonation and reaction with solvated [Et₃Si]⁺ ions (R=2,6‐Mes₂C₆H₃). The hypothetical reductive elimination of [R₂P(F)SiEt₃]⁺ and [R₂P(F)H]⁺ affording [R₂P]⁺, Et₃SiF and HF, respectively, was calculated to be endothermic by 40.1 and 190.6 kJ mol⁻¹.

Hydrogen-substituted silylium ions are long-sought reactive species. We report a protolysis strategy that chemoselectively cleaves either an Si–C(sp²) or an Si–H bond using a carborane acid to access the full series of [CHB₁₁H₅Br₆]^–-stabilized R₂SiH⁺, RSiH₂⁺, and SiH₃⁺ cations, where bulky tert-butyl groups at the silicon atom (R = tBu) were crucial to avoid substituent redistribution. The crystallographically characterized molecular structures of [CHB₁₁H₅Br₆]^–-stabilized tBu₂HSi⁺ and tBuH₂Si⁺ feature pyramidalization at the silicon atom, in accordance with that of tBu₃Si⁺[CHB₁₁H₅Br₆]^–. Conversely, the silicon atom in the H₃Si⁺ cation adopts a trigonal-planar structure and is stabilized by two counteranions. This solid-state structure resembles that of the corresponding Brønsted acid.

N→Si initiated non‐catalyzed hydrosilylation of C=N imine group in C,N‐chelated organohydrosilanes has been reported. The set of substituted C,N‐chelating ligands has been prepared for this study. It allows studying the influence of substituents on aryl ring, C=N imine group or silicon atom on this hydrosilylation process.

4‐Methoxy and 2,4‐di‐tBu substituted C,N‐chelating ligands 2‐[(2,6‐iPr₂‐C₆H₃)N=CH]‐4‐MeO‐C₆H₃}^– and {2‐[(2,6‐iPr₂‐C₆H₃)N=CH]‐4,6‐tBu₂‐C₆H₃}^– and also {2‐[(2,6‐Me₂‐C₆H₃)N=C(Me)]‐C₆H₄}^– and {2‐[(2,6‐iPr₂‐C₆H₃)N=C(Me)]‐5,6‐OCH₂O‐C₆H₂}^– containing Me substituted imine group were used for the preparation of intramolecularly coordinated organohydridosilanes L^1–4Ph_nSiH_4‐n and L¹SiHCl₂. The spontaneous hydrosilylation reaction occurs very quickly in L^1–4Ph_nSiH_4‐n and hydrosilylated products are formed. In contrast, the isolation of L¹SiHCl₂ allows us to study kinetics of the hydrosilylation.

Tales of the unexpected: Chemical‐exchange‐induced cross‐peaks can arise in even the simplest two‐dimensional NMR experiments. These peaks originate from exchange of magnetisation during chemical shift evolution and coherence transfer periods and may be useful both as a qualitative indicator of exchange in routine experiments, and for quantitative characterisation of exchange kinetics by lineshape fitting.

Abstract

Two‐dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small‐molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods. However, exchange occurring during chemical shift evolution periods can also influence the appearance of such spectra. While this is often exploited through one‐dimensional lineshape analysis (“dynamic NMR”), the analysis of exchange across multiple chemical shift evolution periods has received less attention. Here we report that chemical exchange‐induced cross‐peaks can arise in even the simplest two‐dimensional NMR experiments. These cross‐peaks can have highly distorted phases that contain rich information about the underlying exchange process. The quantitative analysis of such peaks, from a single 2D spectrum, can provide a highly accurate characterisation of underlying exchange processes.

In this work we describe the interaction between Lewis bases, especially N‐Heterocyclic Carbenes (NHCs), and hindered neutral silicon derivatives featuring high Lewis acid properties. It has been established that the formation of normal and abnormal Lewis adducts can be controlled by playing with the acidity of the corresponding tetravalent spiro organosilane. Some DFT calculations have been performed in order to gain insight into the thermodynamics of the NHC‐spirosilane interaction featuring various NHCs differing in size and σ‐donor capacity. In a second part, we have studied the possibility of introducing spirosilanes as new Lewis partners in FLP chemistry. Some FLP‐type reactivities are presented, notably the activation of formaldehyde that could occur with both hindered NHCs and phosphines.

Bond issue: Extension of recently introduced techniques for bonding analysis in position space permits characterization of the external polar‐covalent bonding of the Zintl‐type polyanion with respect to the (8−N)‐rule implemented in the Lewis model. This is exemplarily demonstrated for a series of intermetallic rare‐earth germanides with variable electron count around the ideal Zintl value using CaGe for comparison.

Abstract

A comparative chemical bonding analysis for the germanides La₂ MGe₆ (M=Li, Mg, Al, Zn, Cu, Ag, Pd) and Y₂PdGe₆ is presented, together with the crystal structure determination for M=Li, Mg, Cu, Ag. The studied compounds adopt the two closely related structure types oS72‐Ce₂(Ga_0.1Ge_0.9)₇ and mS36‐La₂AlGe₆, containing zigzag chains and corrugated layers of Ge atoms bridged by M species, with La/Y atoms located in the biggest cavities. Chemical bonding was studied by means of the quantum chemical position‐space techniques QTAIM (quantum theory of atoms in molecules), ELI‐D (electron localizability indicator), and their basin intersections. The new penultimate shell correction (PSC0) method was introduced to adapt the ELI‐D valence electron count to that expected from the periodic table of the elements. It plays a decisive role to balance the Ge−La polar‐covalent interactions against the Ge−M ones. In spite of covalently bonded Ge partial structures formally obeying the Zintl electron count for M=Mg²⁺, Zn²⁺, all the compounds reveal noticeable deviations from the conceptual 8−N picture due to significant polar‐covalent interactions of Ge with La and M ≠ Li, Mg atoms. For M=Li, Mg a formulation as a germanolanthanate M[La₂Ge₆] is appropriate. Moreover, the relative Laplacian of ELI‐D was discovered to reveal a chemically useful fine structure of the ELI‐D distribution being related to polyatomic bonding features. With the aid of this new tool, a consistent picture of La/Y−M interactions for the title compounds was extracted.

All at once: A copper‐catalyzed three‐component coupling of 1,3‐dienes, bis(pinacolato)diboron, and acylsilanes affords densely functionalized tertiary α‐silyl alcohols regioselectively in high yields as well as with excellent enantioselectivity (up to 99 % ee) and diastereoselectivity (d.r. >20:1). Subsequent transformations illustrate the versatility of these chiral building blocks.

Abstract

An efficient synthesis of functionalized tertiary α‐silyl alcohols by an enantio‐ and diastereoselective copper‐catalyzed three‐component coupling of 1,3‐dienes, bis(pinacolato)diboron, and acylsilanes is reported. The reaction proceeds well with different 1,3‐dienes and a broad range of aryl‐ as well as alkenyl‐ but also alkyl‐substituted acylsilanes. The target compounds are formed with high regio‐, diastereo‐, and enantioselectivity (up to 99 % ee and d.r. >20:1) and are highly versatile synthetic building blocks.

Faster and faster: A ¹⁹F MAS DNP enhanced NMR technique was developed by using an optimized polarizing solution of 12 mm AMUPol in trifluoroethanol‐d ₃ (with microcrystalline KBr), providing ¹⁹F signal enhancements of a factor of 118. Application to an active pharmaceutical ingredient and fluorinated materials yielded ¹⁹F and ¹⁹F–¹³C CP spectra with a saving time of a factor of up to 600.

Abstract

The introduction of high‐frequency, high‐power microwave sources, tailored biradicals, and low‐temperature magic angle spinning (MAS) probes has led to a rapid development of hyperpolarization strategies for solids and frozen solutions, leading to large gains in NMR sensitivity. Here, we introduce a protocol for efficient hyperpolarization of ¹⁹F nuclei in MAS DNP enhanced NMR spectroscopy. We identified trifluoroethanol‐d ₃ as a versatile glassy matrix and show that 12 mm AMUPol (with microcrystalline KBr) provides direct ¹⁹F DNP enhancements of over 100 at 9.4 T. We applied this protocol to obtain DNP‐enhanced ¹⁹F and ¹⁹F–¹³C cross‐polarization (CP) spectra for an active pharmaceutical ingredient and a fluorinated mesostructured hybrid material, using incipient wetness impregnation, with enhancements of approximately 25 and 10 in the bulk solid, respectively. This strategy is a general and straightforward method for obtaining enhanced ¹⁹F MAS spectra from fluorinated materials.

High five: A new aromatic [5,5]‐sigmatropic rearrangement reaction has been achieved by simply treating a mixture of an aryl sulfoxide and allyl nitrile with Tf₂O (Tf=trifluoromethanesulfonyl) and DABCO (1,4‐diazabicyclo[2.2.2]octane). The reaction features high chemo‐ and regioselectivity, which can be a challenge for conventional [5,5]‐sigmatropic rearrangement reactions.

Abstract

Aromatic [5,5]‐sigmatropic rearrangement is an appealing protocol for accessing 1,4‐substituted arenes. However, such a protocol has not been well utilized in organic synthesis because of the difficulties in the synthesis of the substrates, selectivity issues, and limited substrate scope. Described herein is a new [5,5]‐sigmatropic reaction utilizing readily available aryl sulfoxides and allyl nitriles. This reaction features mild reaction conditions, high chemo‐ and regioselectivity, excellent functional‐group compatibility, and broad substrate scope. Computational studies suggest that the success of the reaction can be attributed to the selective electrophilic assembly of the rearrangement precursors, in which a linear ‐C=C=N‐ linkage favors [5,5]‐sigmatropic rearrangement over the competitive [3,3]‐sigmatropic rearrangement.

New and robust! The reactivity of a cyclic(alkyl)(amino)carbene (CAAC) derivative with ZnMe₂ was investigated. Combining a CAAC with ZnMe₂ lead to unexpected reactivity (Me⁻ transfer, see Figure), but also afford robust (CAAC)ZnR⁺ and (CAAC)₂ZnR⁺ Lewis acidic cations, some of which could be applied in alkene, alkyne and CO₂ hydrosilylation catalysis.

Abstract

The reactivity of Zn^II dialkyl species ZnMe₂ with a cyclic(alkyl)(amino)carbene, 1‐[2,6‐bis(1‐methylethyl)phenyl]‐3,3,5,5‐tetramethyl‐2‐pyrrolidinylidene (CAAC, 1), was studied and extended to the preparation of robust CAAC‐supported Zn^II Lewis acidic organocations. CAAC adduct of ZnMe₂ (2), formed from a 1:1 mixture of 1 and ZnMe₂, is unstable at room temperature and readily undergoes a CAAC carbene insertion into the Zn−Me bond to produce the ZnX₂‐type species (CAAC‐Me)ZnMe (3), a reactivity further supported by DFT calculations. Despite its limited stability, adduct 2 was cleanly ionized to robust two‐coordinate (CAAC)ZnMe⁺ cation (5⁺ ) and derived into (CAAC)ZnC₆F₅ ⁺ (7⁺ ), both isolated as B(C₆F₅)₄ ⁻ salts, showing the ability of CAAC for the stabilization of reactive [ZnMe]⁺ and [ZnC₆F₅]⁺ moieties. Due to the lability of the CAAC−ZnMe₂ bond, the formation of bis(CAAC) adduct (CAAC)₂ZnMe⁺ cation (6⁺ ) was also observed and the corresponding salt [6][B(C₆F₅)₄] was structurally characterized. As estimated from experimental and calculations data, cations 5⁺ and 7⁺ are highly Lewis acidic species and the stronger Lewis acid 7⁺ effectively mediates alkene, alkyne and CO₂ hydrosilylation catalysis. All supporting data hints at Lewis acid type activation–functionalization processes. Despite a lower energy LUMO in 5⁺ and 7⁺ , their observed reactivity is comparable to those of N‐heterocyclic carbene (NHC) analogues, in line with charge‐controlled reactions for carbene‐stabilized Zn^II organocations.

A winning combination: The combination of ¹³C{¹H} REDOR, ¹³C chemical shift tensor and DFT calculation improve refinement of the positions of protons in hydrated materials.

Abstract

Solid‐state NMR measurements coupled with density functional theory (DFT) calculations demonstrate how hydrogen positions can be refined in a crystalline system. The precision afforded by rotational‐echo double‐resonance (REDOR) NMR to interrogate ¹³C–¹H distances is exploited along with DFT determinations of the ¹³C tensor of carbonates (CO₃ ²⁻). Nearby ¹H nuclei perturb the axial symmetry of the carbonate sites in the hydrated carbonate mineral, hydromagnesite [4 MgCO₃⋅Mg(OH)₂⋅4 H₂O]. A match between the calculated structure and solid‐state NMR was found by testing multiple semi‐local and dispersion‐corrected DFT functionals and applying them to optimize atom positions, starting from X‐ray diffraction (XRD)‐determined atomic coordinates. This was validated by comparing calculated to experimental ¹³C{¹H} REDOR and ¹³C chemical shift anisotropy (CSA) tensor values. The results show that the combination of solid‐state NMR, XRD, and DFT can improve structure refinement for hydrated materials.

Eliminate to activate: Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under mild conditions, starting from organometallic intermediates with fluorine substituents on the carbon atoms β or α to the metal centers, respectively. Recently, these elimination processes have been used in the development of a variety of methods for activating C−F bonds.

Abstract

The activation of carbon–fluorine (C−F) bonds is an important topic in synthetic organic chemistry. Metal‐mediated and ‐catalyzed elimination of β‐ or α‐fluorine proceeds under milder conditions than oxidative addition to C−F bonds. The β‐ or α‐fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations through these elimination processes (C−F bond cleavage), which are typically preceded by carbon–carbon (or carbon–heteroatom) bond formation, have been increasingly developed in the past five years as C−F bond activation methods. In this Minireview, we summarize the applications of transition‐metal‐mediated and ‐catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective with early studies and from a systematic perspective with recent studies.

Polymers go main group! This Review shows how the incorporation of the full range of available main‐group elements into polymers leads to new functional hybrid materials with potential use in diverse application fields ranging from advanced elastomers, responsive gels, biodegradable materials, to organic electronics, imaging agents, sensors, and supported catalysts.

Abstract

The past decade has witnessed tremendous advances in the synthesis of polymers that contain elements from the main groups beyond those found in typical organic polymers. Unique properties that arise from dramatic differences in bonding and molecular geometry, electronic structure, and chemical reactivity, are exploited in diverse application fields. Herein we highlight recent advances in inorganic backbone polymers, discuss how Lewis acid/base functionalization of polymers results in unprecedented reactivity, and survey conjugated hybrids with unique electronic structures for sensor and device applications.

Pd‐nanoparticle‐catalyzed dehydrogenative coupling between hydrosilanes and alcohols to give silyl ethers is described. High selectivity for the silylation of primary versus secondary and secondary versus tertiary alcohols in 1,2‐diols is observed. Tandem silylation/hydrogenation of the triple bond of alkynols to afford Z‐alkenols has also been achieved.

Abstract

Pd‐nanoparticle‐catalyzed dehydrogenative coupling between various hydrosilanes and alcohols was shown to provide silyl ethers in good and reproducible yields. The synthetic methodology is effective for a wide range of simple and bulky silanes and secondary alcohols, while keeping various other functional groups intact. The procedure also exhibits high selectivity for the silylation of primary versus secondary alcohols in 1,2‐diols, and allows the successive silylation of alkynols and hydrogenation of the triple bond to afford Z‐alkenols in good yields.