Bidentate Chiral Bis(imidazolium)-Based Halogen-Bond Donors: Synthesis and Applications in Enantioselective Recognition and Catalysis

Abstract

Even though halogen bonding-the noncovalent interaction between electrophilic halogen substituents and Lewis bases-has now been established in molecular recognition and catalysis, its use in enantioselective processes is still very rarely explored. Herein, we present the synthesis of chiral bidentate halogen-bond donors based on two iodoimidazolium units with rigidly attached chiral sidearms. With these Lewis acids, chiral recognition of a racemic diamine is achieved in NMR studies. DFT calculations support a 1:1 interaction of the halogen-bond donor with both enantiomers and indicate that the chiral recognition is based on a different spatial orientation of the Lewis bases in the halogen-bonded complexes. In addition, moderate enantioselectivity is achieved in a Mukaiyama aldol reaction with a preorganized variant of the chiral halogen-bond donor. This represents the first case in which asymmetric induction was realized with a pure halogen-bond donor lacking any additional active functional groups.

Keywords: chiral recognition; enantioselectivity; halogen bonding; haloimidazolium salts; organocatalysis.

Figure 1

Chiral bidentate XB donors based on 1,2,4‐triazolium or imidazolium moieties.

Scheme 1

Synthesis of chiral bis(imidazolium)‐based XB donors and X‐ray structural analysis of trans‐1 c⋅OTf (anions and hydrogen atoms omitted).14 BAr^F ₄=tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate anion, DCM=CH₂Cl₂, NIS=N‐iodosuccinimide, Tf=trifluoromethanesulfonyl.

Figure 2

Chiral substrates tested as XB acceptors.

Figure 3

Enantiodiscrimination of trans‐11 with 1 b⋅BAr^F ₄.

Figure 4

Structures of the adducts of 1 b⋅BAr^F ₄ with enantiomers of trans‐11, as obtained by DFT calculations (prepared with CYLview;17 for further details see the Supporting Information).

Figure 5

Determination of er of preformed mixtures of trans‐11 with 1 b⋅BAr^F ₄.

Figure 6

Kinetics of the Mukaiyama aldol reaction in the presence of various catalysts at 25 °C (based on ¹H NMR yields). TMS=trimethylsilyl.