Highly acidic N-triflylphosphoramides as chiral Brønsted acid catalysts: the effect of weak hydrogen bonds and multiple acceptors on complex structures and aggregation

Abstract

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 indicates 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.

Fig. 1. (A) Previously binary complexes between CPAs and imines have been studied proving the formation of strong, charge-assisted hydrogen bonds. For the CPA/imine complexes, two different orientations of each imine isomer (E and Z) inside the binary complex were detected. (B) The focus of this work was a hydrogen bond and a structural analysis of NTPA/imine complexes addressing the influence of increased acidity of the catalyst, multiple hydrogen bond acceptors and the missing C₂ symmetry.

Fig. 2. (a) NTPA catalyst 1 was selected due to its 3,3′-substituents, which provide the opportunity for ¹⁹F NMR measurements. (b) Structures of the imines 2–12 for the hydrogen bond analysis to cover a broad basicity range. Imine 2 was investigated in detail with NTPA 1 to gain structural insights into the binary NTPA/imine complexes. (c) The focus of this work was the NMR-spectroscopic investigation of the binary NTPA/imine complexes to clarify which of the several hydrogen bond acceptors is included in the weak hydrogen bond. The imine exists either as E- or Z-isomer.

Fig. 3. Plot of δ(OHN̲)_ref against δ(OH̲N) for various binary NTPA 1/imine and CPA/imine complexes. The ¹⁵N chemical shifts are referenced by δ(OHN̲)_ref = δ(OHN̲)_obs – 340.8 ppm. 340.8 ppm is the chemical shift of the free imine showing the strongest hydrogen bond in the previous work. Data points of phenols/carboxylic acids, tetrafluoroboric acid and the CPA TRIP are from previous studies (see ESI†). Binary E- and Z-complexes of NTPA 1 and imines 2–12 are depicted in red rectangles and show a deviation from the correlation curve. This is an indication for a double-well potential, which means the proton is either located at the proton acceptor or donor.

Fig. 4. (a) ¹H NMR spectra of the binary complexes between NTPA 1 and imine 2 at 180 K (600 MHz). Generally, the ¹H NMR spectra can be divided into an H-bond region, an aromatic region, and an aliphatic region. (b) ¹H,³¹P HMBC H-bond section of the NTPA 1/imine 2 complex at 180 K and 600 MHz in CD₂Cl₂. (1) Polarization transfer is mediated only by scalar coupling (2) and (3) polarization transfer is mediated by ¹H-CSA and ¹H,³¹P-DD cross relaxation. (4) Polarization transfer is mediated by the sum of scalar coupling and the ¹H-CSA and ¹H,³¹P-DD cross relaxation. (c) Binary complex of NTPA 1 and imine 2. ^2hJ_PH coupling was detected in a ¹H, ³¹P HMBC experiment, whereas neither the ^2hJ_NN coupling nor the ^1hJ_NH coupling could be detected in a 1D ¹⁵N or 2D ¹H,¹⁵N-HSQC spectrum.

Fig. 5. Structures for the oxygen-based H-binding motif of the binary E-complex: inter-atomic distances obtained from molecular dynamics simulations are consistent with the intense NOE contacts for the type I E₀ structure (for details and assignment of the substructures to the NOE signals see ESI†). No NOE contacts were found for the type II E₀ structure, obtained by rotating the imine leading to the exclusion of structure motif II.

Fig. 6. Low-temperature NMR at 180 K was used to investigate the presence of dimers in a 2 : 1 ratio of catalyst to imine. In the samples with a 2 : 1 ratio of NTPA to imine, no dimeric formation was identified. However, when employing a 2 : 1 ratio with CPA to imine, dimer formation became evident in the ¹H NMR spectrum.