Disulfonimides versus Phosphoric Acids in Brønsted Acid Catalysis: The Effect of Weak Hydrogen Bonds and Multiple Acceptors on Complex Structures and Reactivity

Abstract

In Brønsted acid catalysis, hydrogen bonds play a crucial role for reactivity and selectivity. However, the contribution of weak hydrogen bonds or multiple acceptors has been unclear so far since it is extremely difficult to collect experimental evidence for weak hydrogen bonds. Here, our hydrogen bond and structural access to Brønsted acid/imine complexes was used to analyze BINOL-derived chiral disulfonimide (DSI)/imine complexes. ¹H and ¹⁵N chemical shifts as well as ¹J_NH coupling constants revealed for DSI/imine complexes ion pairs with very weak hydrogen bonds. The high acidity of the DSIs leads to a significant weakening of the hydrogen bond as structural anchor. In addition, the five hydrogen bond acceptors of DSI allow an enormous mobility of the imine in the binary DSI complexes. Theoretical calculations predict the hydrogen bonds to oxygen to be energetically less favored; however, their considerable population is corroborated experimentally by NOE and exchange data. Furthermore, an N-alkylimine, which shows excellent reactivity and selectivity in reactions with DSI, reveals an enlarged structural space in complexes with the chiral phosphoric acid TRIP as potential explanation of its reduced reactivity and selectivity. Thus, considering factors such as flexibility and possible hydrogen bond sites is essential for catalyst development in Brønsted acid catalysis.

Figure 1

(a) Assumed catalytic cycle for the DSI-catalyzed asymmetric transfer hydrogenation of N-alkylimines 2 derived from that of CPAs. (b) The focus of this study was a hydrogen bond as well as a structural analysis of DSI/imine complexes regarding the influence of the weakened hydrogen bonds and the increased ion pair character. All results were compared to the previously investigated less acidic CPAs.^−, Finally, the internal acidity of these different classes of catalysts was correlated to the reactivity in the transfer hydrogenation. (c) In contrast to the CPAs, not only two but five possible hydrogen bond acceptors exist for the DSIs. (d) Investigated binary E-and Z-complexes are shown.

Figure 2

Binary complexes of different BINOL-derived Brønsted acids were analyzed. (a) While the phosphoric acids (CPAs) 1a–1d were the main focus of our previous works,^−, (b) in this study the binary complexes between with the disulfonimides catalysts (DSIs) 1e and 1f were investigated. (c) In addition, the sulfonic acid (BINSA) 1g was used for the reactivity analysis. (d) Hydrogen bond and structural analysis was done with imine 2a and 2b, whereas the reaction kinetics of imines 2a, 2c, and 2d were investigated. (e) Additionally, also the hydrogen bonds between the N-alkylimine 3a and CPA 1a as well as DSI 1e were investigated.

Figure 3

(a) With increasing acidity of the hydrogen bond donor, the proton is shifted toward the nitrogen of the hydrogen bond acceptor until an ion pair is formed. (b) Plot of δ_(OHN) against δ_(OHN) of the hydrogen-bonded complexes. The binary complexes of DSIs 1e and 1f with the imines 2a and 2b (green diamonds) are complemented with the binary imine complexes of HBF₄ (purple triangles), CPAs (pink cycles), and some carboxylic acids and phenols (orange triangles) from previous studies.^, All ¹⁵N chemical shifts are referenced [δ(OHN)_ref = δ(OHN)_exp – 340 ppm] (for details and exact values see the SI).

Figure 4

(a) Experimental ¹J_HN coupling constants are shown for E- and Z-imine 2a with the CPAs 1a–1d,^, HBF₄, and the DSIs 1e and 1f (for values, see the SI). Due to fast chemical exchange, the ¹J_HN of 1f/Z-2a could not be determined (marked by an asterisk). (b) The (green) ¹J_HN and trans-hydrogen bond scalar couplings (red ^1hJ_NH and ^2hJ_NN) were addressed.

Figure 5

Overlay of TRIP 1a (red) and (CF₃)₂-DSI 1e (blue) showing the differences of the binding pockets (oxygen, phosphorus and nitrogen atoms are marked in respective colors). Indeed, the binding pocket of DSI is just slightly larger, but the hydrogen-binding sites of the DSI (denoted with blue arrows) stick out of the binding pocket and are easily available for the substrate compared to TRIP. This in combination with the increased number of hydrogen bond acceptors may result in a higher mobility of the substrate.

Figure 6

Calculations predict for the DSI/imine 2a complexes the existence of (a) one stable structure where a hydrogen bond to the nitrogen of the DSI catalyst (type E_N), is formed and (b) several orientations with a hydrogen bond to one of the oxygens. The two most stable structures are shown. Type II E_o could be identified by the green NOE. All distances given in this figure were obtained from calculations.

Figure 7

¹H NMR spectra of the hydrogen bond region of the TRIP 1a/3a and DSI 1e/3a binary complexes in CD₂Cl₂ at 180 K, showing the presence of various hydrogen bonded species with TRIP. In contrast with the (CF₃)₂-DSI, only the major E and Z complexes were observed. On the left side of the Steiner–Limbach curve higher ¹H chemical shifts reveal increasing hydrogen bond strength, while smaller ¹H chemical shifts indicate an enhanced ion-pair character.