Neutral Chiral Tetrakis-Iodo-Triazole Halogen-Bond Donor for Chiral Recognition and Enantioselective Catalysis

Abstract

Halogen bonding represents a powerful tool in the field of noncovalent interactions. However, applications in enantioselective recognition and catalysis remain almost nonexistent, due in part to the distinct features of halogen bonds, including long covalent and noncovalent bond distances and high directionality. Herein, this work presents a novel chiral tetrakis-iodo-triazole structure as a neutral halogen bond donor for both chiral anion-recognition and enantioinduction in ion-pair organocatalysis. NMR-titration studies revealed significant differences in anion affinity between the halogen bonding receptor and its hydrogen bonding parent. Selective recognition of chiral dicarboxylates and asymmetric induction in a benchmark organocatalytic reaction were demonstrated using the halogen bond donor. Inversions in the absolute sense of chiral recognition, enantioselectivity, and chiroptical properties relative to the related hydrogen donor were observed. Computational modeling suggested that these effects were the result of distinct anion-binding modes for the halogen- versus hydrogen-bond donors.

Keywords: DFT; NMR titration; chiral anion recognition; halogen bonding; organocatalysis.

Figure 1

Novel neutral chiral XB‐donor 1 based on the pseudo‐helical HB‐donor tetrakistriazole backbone 2.

Scheme 1

Synthesis of chiral Tetrakis‐I‐Triazole XB‐donor 1.

Figure 2

CD‐spectra of the XB‐donor 1 [62.5 μm] and HB‐donor 2 [62.5 μm] in THF (a and b) and of 1 in MeCN (c). (d) isolated CD‐spectrum of 1 in THF upon addition of 1 equiv of TBACl. (e) Optimized structure including solvent effects (SMD model) and CD‐spectrum for a model XB‐1:TMACl complex in THF. (f) XB‐1:d and l‐tartrate‐(TMA)₂ complexes and calculated binding energies (BE=E[XB‐1:d‐ or l‐Tartrate‐(TMA)₂]–E[XB‐1]–E[d‐Tartrate‐(TMA)₂]) in kcal mol⁻¹, I−O distances and C‐I‐O angles. See Supporting Information for more details.