Substrate Photoswitching for Rate Enhancement of an Organocatalytic Cyclization Reaction

In this article, we report that applying in situ LED-NMR irradiation with appropriate wavelength resulted in the photoswitching of an α,β-unsaturated hydrazone C=N double bond configuration. This reaction was previously reported to be the first step in a chiral Brønsted acid-catalyzed cyclization reaction, where the minor but stable Z -isomer is the reactive intermediate. By enhancing the rate of the isomerization, we could show that the overall rate of the cyclization could be increased and followed directly by NMR kinetics. Exclusively light with a specific wavelength matching the isomerization process affected the cyclization. The light- and acid-mediated isomerization provide complementary pathways that can be exploited in synthetic applications to increase reaction rates of asymmetric transformations, especially in reactions requiring high loadings of elaborate chiral catalysts

Bidentate Substrate Binding in Brønsted Acid Catalysis: Structural Space, Hydrogen Bonding and Dimerization

BINOL derived chiral phosphoric acids (CPAs) are a prominent class of catalysts in the field of asymmetric organocatalysis, capable of transforming a wide selection of substrates with high stereoselectivities. Exploiting the Brønsted acidic and basic dual functionality of CPAs, substrates with both a hydrogen bond acceptor and donor functionality are frequently used as the resulting bidentate binding via two hydrogen bonds is expected to strongly confine the possible structural space and thus yield high stereoselectivities. Despite the huge success of CPAs and the popularity of a bidentate binding motif, experimental insights into their organization and origin of stereoinduction are scarce. Therefore, in this work the structural space and hydrogen bonding of CPAs and N-(ortho-hydroxyaryl) imines (19 CPA/imine combinations) was elucidated by low temperature NMR studies and corroborated by computations. The postulated bidentate binding of catalyst and substrate by two hydrogen bonds was experimentally validated by detection of trans-hydrogen bond scalar couplings. Counterintuitively, the resulting CPA/imine complexes showed a broad potential structural space and a strong preference towards the formation of [CPA/imine]2 dimers. Molecular dynamics simulations showed that in these dimers, the imines form each one hydrogen bond to two CPA molecules, effectively bridging them. By finetuning steric repulsion and noncovalent interactions, rigid and well-defined CPA/imine monomers could be obtained. NOESY studies corroborated by theoretical calculations revealed the structure of that complex, in which the imine is located in between the 3,3’-substituents of the catalyst and one site of the substrate is shielded by the catalyst, pinpointing the origin or stereoselectivity for downstream transformations

Photoinitiated Carbonyl-Metathesis: Deoxygenative Reductive Olefination of Aromatic Aldehydes via Photoredox Catalysis

Carbonyl-carbonyl olefination, known as McMurry reaction, represents a powerful strategy for the construction of olefins. However, catalytic variants that directly couple two carbonyl groups in a single reaction are less explored. Here, we report a photoredox-catalysis that uses B2Pin2 as terminal reductant and oxygen trap allowing for deoxygenative olefination of aromatic aldehydes under mild conditions. This strategy provides access to a diverse range of symmetrical and unsymmetrical alkenes with moderate to high yield (up to 83%) and functional-group tolerance. To follow the reaction pathway, a series of experiments were conducted including radical inhibition, deuterium labelling, fluorescence quenching and cyclic voltammetry. Furthermore, NMR studies and DFT calculations were combined to detect and analyze three active intermediates: A cyclic three-membered anionic species, an α-oxyboryl carbanion and a 1,1-benzyldiboronate ester. Based on these results, we propose a mechanism for the C=C bond generation involving a sequential radical borylation, “bora-Brook” rearrangement, B2Pin2-mediated deoxygenation and a boron-Wittig process

What is the Role of Acid-Acid Interactions in Asymmetric Phosphoric Acid Organocatalysis? A Detailed Mechanistic Study using Interlocked and Non-Interlocked Catalysts

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst-catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which react mainly as phosphoric acid dimers. For acyclic phosphoric acids, we found a strongly concentration dependent behavior, involving both monomeric and dimeric catalytic pathways. Based on a detailed experimental analysis, DFT-calculations and a direct NMR-based observation of the catalyst aggregates, we could demonstrate that intermolecular acid-acid interactions have a drastic influence on the reaction rate and stereoselectivity of the asymmetric transfer-hydrogenation catalyzed by chiral phosphoric acids

Highly Acidic N-Triflylphosphoramides as Chiral Brønsted Acid Catalysts: The Effect of Weak Hydrogen Bonds and Multiple Acceptors on Complex Structures and Aggregation

N-Triflylphosphoramides (NTPAs) represent an important catalyst class in asymmetric catalysis due to their multiple hydrogen bond acceptor sites and acidity, which is increased by several orders of magnitude compared to conventional chiral phosphoric acids (CPAs). Thus, NTPAs allow for several challenging transformations, which are not accessible with CPAs. However, detailed evidence on their hydrogen bonding situation, complex structures and aggregation is still lacking. Therefore, this study covers the hydrogen bonding behavior and structural features of binary NTPA/imine complexes compared to their CPA counterparts. Deviating from the single-well potential hydrogen bonds commonly observed in CPA/imine complexes, the NTPA/imine complexes exhibit a tautomeric equilibrium between two proton positions. Low-temperature NMR at 180 K supported by computer simulations indicate a OHN hydrogen bond between the phosphoramide oxygen and the imine, instead of the mostly proposed NHN H-bond. Furthermore, this study finds no evidence for the existence of dimeric NTPA/NTPA/imine complexes as previously suggested for CPA systems, both synthetically and through NMR studies

A Structural Diversity of Molecular Alkaline‐Earth‐Metal Polyphosphides: From Supramolecular Wheel to Zintl Ion

A series of molecular group 2 polyphosphides has been synthesized by using air‐stable [Cp*Fe(η(5)‐P(5))] (Cp*=C(5)Me(5)) or white phosphorus as polyphosphorus precursors. Different types of group 2 reagents such as organo‐magnesium, mono‐valent magnesium, and molecular calcium hydride complexes have been investigated to activate these polyphosphorus sources. The organo‐magnesium complex [((Dipp)BDI−Mg(CH(3)))(2)] ((Dipp)BDI={[2,6‐( i )Pr(2)C(6)H(3)NCMe](2)CH}(−)) reacts with [Cp*Fe(η(5)‐P(5))] to give an unprecedented Mg/Fe‐supramolecular wheel. Kinetically controlled activation of [Cp*Fe(η(5)‐P(5))] by different mono‐valent magnesium complexes allowed the isolation of Mg‐coordinated formally mono‐ and di‐reduced products of [Cp*Fe(η(5)‐P(5))]. To obtain the first examples of molecular calcium‐polyphosphides, a molecular calcium hydride complex was used to reduce the aromatic cyclo‐P(5) ring of [Cp*Fe(η(5)‐P(5))]. The Ca‐Fe‐polyphosphide is also characterized by quantum chemical calculations and compared with the corresponding Mg complex. Moreover, a calcium coordinated Zintl ion (P(7))(3−) was obtained by molecular calcium hydride mediated P(4) reduction

Brønstedsäure‐Katalyse – Kontrolle der Konkurrenz zwischen monomerem und dimerem Reaktionsweg erhöht Stereoselektivität

Chirale Phosphorsäuren (CPS) sind inzwischen ein bevorzugter Katalysatortyp in der Organokatalyse, jedoch bleibt die Auswahl der optimalen Katalysatorstruktur weiterhin eine Herausforderung. Zusätzlich können unbekannte konkurrierende Reaktionswege die maximale Stereoselektivität und das Potenzial von Vorhersagemodellen einschränken. Bei der CPS-katalysierten Transferhydrierung von Iminen haben wir für viele Systeme zwei Reaktionswege mit inverser Stereoselektivität gefunden, bei denen entweder eine monomere CPS oder ein Wasserstoffbrücken-verknüpftes Dimer als Katalysator fungiert. NMR-Messungen und DFT-Berechnungen offenbarten ein dimeres Intermediat mit einer stärkeren Substrataktivierung durch Kooperativitätseffekte. Beide Wege können separiert werden: Niedrige Temperaturen und hohe Katalysatoranteile begünstigen den dimeren Reaktionsweg (ee bis zu −98 %), während niedrige Temperaturen und reduzierte Katalysatoranteil den monomeren Reaktionsweg fördern und zu einem signifikant verbesserten ee führen (92–99 % ee; vorher 68–86 % bei höheren Temperaturen). Insgesamt wird eine große Auswirkung auf die CPS-Katalyse in Bezug auf Reaktionsoptimierung und Vorhersage erwartet

NMR‐Spectroscopic Detection of an Elusive Protonated and Coinage Metalated Silicide [NHC Dipp Cu(η 4 ‐Si 9 )H] 2− in Solution

A simultaneously protonated and functionalized silicide cluster [NHCDippCu(η4-Si9)H]2− was detected and characterized in liquid ammonia by NMR spectroscopy. Key NMR results were corroborated by theoretical calculations. 1H-NMR line-widths at variable temperatures revealed that proton hopping in the metalated complex [NHCDippCu(η4-Si9)H]2− is less pronounced than in the non-complexed silicide [HSi9]3−. Besides [HSi9]3− and [NHCDippCu(η4-Si9)H]2− also the unprotonated analogous cluster [NHCDippCu(η4-Si9)]3− was detected in solution. In addition, a new 29Si-NMR signal was obtained in the course of 29Si-NMR studies that we assigned to [NHCDippCu(η4-Si9)]3−. The isolation of crystals of (K[2.2.2]-crypt)2K0.48Rb3.52[NHCDippCu(η4-Si9)]2 prove the availability of the non-protonated NHCDippCu(η4-Si9) fragment in solution. To the best of our knowledge the detection of [NHCDippCu(η4-Si9)H]2− represents the first case of a protonated and coinage metalated group 14 Zintl cluster in solution so far

NMR Spectroscopic Characterization of Charge Assisted Strong Hydrogen Bonds in Brønsted Acid Catalysis

Hydrogen bonding plays a crucial role in Bronsted acid catalysis. However, the hydrogen bond properties responsible for the activation of the substrate are still under debate. Here, we report an in depth study of the properties and geometries of the hydrogen bonds in (R)-TRIP imine complexes (TRIP: 3,3'-Bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diylhydrogen phosphate). From NMR spectroscopic investigations H-1 and N-15 chemical shifts, a Steiner-Limbach correlation, a deuterium isotope effect as well as quantitative values of (1)J(NH), (2h)J(PH) and (3h)J(PN) were used to determine atomic distances (r(OH), r(NH), r(NO)) and geometry information. Calculations at SCS-MP2/CBS//TPSS-D3/def2-SVP-level of theory provided potential surfaces, atomic distances and angles. In addition, scalar coupling constants were computed at TPSS-D3/IGLO-III. The combined experimental and theoretical data reveal mainly ion pair complexes providing strong hydrogen bonds with an asymmetric single well potential. The geometries of the hydrogen bonds are not affected by varying the steric or electronic properties of the aromatic imines. Hence, the strong hydrogen bond reduces the degree of freedom of the substrate and acts as a structural anchor in the (R)-TRIP imine complex