RESUMO
The concept of hydrogen bonding for enhancing substrate binding and controlling selectivity and reactivity is central in catalysis. However, the properties of these key hydrogen bonds and their catalyst-dependent variations are extremely difficult to determine directly by experiments. Here, for the first time the hydrogen bond properties of a whole series of BINOL-derived chiral phosphoric acid (CPA) catalysts in their substrate complexes with various imines were investigated to derive the influence of different 3,3'-substituents on the acidity and reactivity. NMR 1H and 15N chemical shifts and 1 J NH coupling constants of these hydrogen bonds were used to establish an internal acidity scale corroborated by calculations. Deviations from calculated external acidities reveal the importance of intermolecular interactions for this key feature of CPAs. For CPAs with similarly sized binding pockets, a correlation of reactivity and hydrogen bond strengths of the catalyst was found. A catalyst with a very small binding pocket showed significantly reduced reactivities. Therefore, NMR isomerization kinetics, population and chemical shift analyses of binary and ternary complexes as well as reaction kinetics were performed to address the steps of the transfer hydrogenation influencing the overall reaction rate. The results of CPAs with different 3,3'-substituents show a delicate balance between the isomerization and the ternary complex formation to be rate-determining. For CPAs with an identical acidic motif and similar sterics, reactivity and internal acidity correlated inversely. In cases where higher sterical demand within the binary complex hinders the binding of the second substrate, the correlation between acidity and reactivity breaks down.
RESUMO
Despite the huge success of enantioselective Brønsted acid catalysis, experimental data about structures and activation modes of substrate/catalyst complexes in solution are very rare. Here, for the first time, detailed insights into the structures of imine/Brønsted acid catalyst complexes are presented on the basis of NMR data and underpinned by theoretical calculations. The chiral Brønsted acid catalyst R-TRIP (3,3'-bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate) was investigated together with six aromatic imines. For each investigated system, an E-imine/R-TRIP complex and a Z-imine/R-TRIP complex were observed. Each of these complexes consists of two structures, which are in fast exchange on the NMR time scale; i.e., overall four structures were found. Both identified E-imine/R-TRIP structures feature a strong hydrogen bond but differ in the orientation of the imine relative to the catalyst. The exchange occurs by tilting the imine inside the complex and thereby switching the oxygen that constitutes the hydrogen bond. A similar situation is observed for all investigated Z-imine/R-TRIP complexes. Here, an additional exchange pathway is opened via rotation of the imine. For all investigated imine/R-TRIP complexes, the four core structures are highly preserved. Thus, these core structures are independent of electron density and substituent modulations of the aromatic imines. Overall, this study reveals that the absolute structural space of binary imine/TRIP complexes is large and the variations of the four core structures are small. The high mobility is supposed to promote reactivity, while the preservation of the core structures in conjunction with extensive π-π and CH-π interactions leads to high enantioselectivities and tolerance of different substrates.
RESUMO
Hydrogen bonding plays a crucial role in Brønsted 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 1H and 15N chemical shifts, a Steiner-Limbach correlation, a deuterium isotope effect as well as quantitative values of 1JNH,2hJPH and 3hJPN were used to determine atomic distances (rOH, rNH, rNO) 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.
