Stereoselective Processes Based on σ-Hole Interactions

Abstract

The σ-hole interaction represents a noncovalent interaction between atoms with σ-hole(s) on their surface (such as halogens and chalcogens) and negative sites. Over the last decade, significant developments have emerged in applications where the σ-hole interaction was demonstrated to play a key role in the control over chirality. The aim of this review is to give a comprehensive overview of the current advancements in the use of σ-hole interactions in stereoselective processes, such as formation of chiral supramolecular assemblies, separation of enantiomers, enantioselective complexation and asymmetric catalysis.

Keywords: chalcogen bond; enantioselectivity; enantioseparation; halogen bond; noncovalent interaction; organocatalysis; recognition; σ-hole.

Figure 1

Halogen bond (XB) and chalcogen bond (ChB) as representative members of σ-hole interactions.

Figure 2

Representative examples of spontaneous resolution (XB is represented by blue dash lines): (a) Crystal structure of the chiral double helical structure formed by mixing 1, 2 and BaI₂^.2H₂O; (b) Crystal structure of the right-handed helix obtained by self-assembly of 3 (Reprinted/adapted with permission from Ref [37]. Copyright 2009, Wiley and from Ref [39]. Copyright 2018, Wiley).

Figure 3

Representative examples of chiral amplification: (a) Formation of single or double helices through self-organization of 4 and 5, respectively; (b) Formation of a chiral blade with increased chiroptical properties by combining 6 and 7.

Figure 4

Structures of 1,2-dibromohexafluoropropane 12 and (–)-sparteine hydrobromide 13.

Figure 5

Structures of the chiral selector 14 and 1-(4-halophenyl)ethylamines (halo = F, Cl, Br, I) 15.

Figure 6

Model for the interaction of iodine (PFIs 17 and 18) and Cl⁻ (SAX sorbent 16).

Figure 7

Structures of cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC), cellulose tris(3-chloro-4-methylphenylcarbamate) (CCMPC) and tris(3,5-dichlorophenylcarbamate) (CDCPC). V_S,min values for the carbonyl oxygens (DFT/B3LYP/6-311G*) are reported.

Figure 8

Halogenated 4,4′-bipyridines 19 (a), and V_S representations on electron density isosurfaces (0.002 au) for representative compounds 19a–c (b). For the V_S representations, colors toward red depict negative V_S, while colors toward blue depict positive V_S, and colors in between (orange, yellow, green) depict intermediate values.

Figure 9

Solvent- and CSP-dependent chromatographic profiles of derivative 19d.

Figure 10

Enantioseparation of ferrocenes 20a (a), 20b (b) and 20c (c) at variable temperatures on a CDMPC-based chiral column with n-hexane/2-PrOH 95:5 v/v as mobile phase and variation of the V_S,min and V_S,max values (au, atomic unit) (d–f) as the 1-halogen substituent changes in the series of 1-halo-2-(iodoethynyl)ferrocenes 20a–c (Reprinted/adapted with permission from Ref. [67]. Copyright 2022, Elsevier).

Figure 11

(a) Structure of mebroqualone (21); (b) MPLC chart of 21; (c) XB in the crystal packing of rac-21 (Reprinted/adapted with permission from Ref. [80]. Copyright 2017, Wiley).

Figure 12

(a) Structure of derivatives 22a and 22b; (b) comparative enantioseparation of compounds 22a and 22b (CDMPC, n-hexane/2-propanol) (Reprinted/adapted with permission from Ref. [80]. Copyright 2018, Elsevier).

Figure 13

Effect of XB on the enantioselective discrimination of chiral anions (Reprinted/adapted with permission from Ref. [90]. Copyright 2016, Royal Chemical Society).

Figure 14

Design of XB-based [2]-rotaxane 24 (a) and [3]-rotaxane 25 (b) for chiral recognition of anions (Reprinted/adapted with permission from Ref [92]. Copyright 2017, American Chemical Society and from Ref [93]. Copyright 2018, Wiley).

Figure 15

Structure of chiral hosts 26a–c.

Figure 16

Chiral recognition of trans-1,2-dibromocyclohexane in the diaxial conformation bound to the interior of 27 (Reprinted/adapted with permission from Ref [95]. Copyright 2017, American Chemical Society).

Figure 17

Structures of 28 and 29 and recorded ¹H NMR shifts in CDCl₃ for their 1:1 mixtures (Reprinted/adapted with permission from Ref [96]. Copyright 2017, Wiley).

Figure 18

XB-Catalyzed asymmetric Mukaiyama reaction.

Figure 19

XB-catalyzed asymmetric Reisser-type reaction.

Figure 20

XB-catalyzed asymmetric aza-Diels–Alder reaction.

Figure 21

XB/HB-catalyzed asymmetric additions to ketimines 44.

Figure 22

XB/HB-catalyzed asymmetric reactions with Cinchona alkaloid-derived chiral catalysts 47 involving iminoesters (a), imines (b) and vinyl phosphonates (c).

Figure 23

PnB-catalyzed asymmetric reduction in benzoxazines 55.

Figure 24

Stabilization of intermediate or catalyst through ChB in asymmetric reactions: (a) kinetic resolution of tertiary alcohols and (b) intramolecular C−H insertion into α-aryl-α-diazoacetates.