Frontiers in Halogen and Chalcogen-Bond Donor Organocatalysis

Abstract

Non-covalent molecular interactions on the basis of halogen and chalcogen bonding represent a promising, powerful catalytic activation mode. However, these "unusual" non-covalent interactions are typically employed in the solid state and scarcely exploited in catalysis. In recent years, an increased interest in halogen and chalcogen bonding has been awaken, as they provide profound characteristics that make them an appealing alternative to the well-explored hydrogen bonding. Being particularly relevant in the binding of "soft" substrates, the similar strength to hydrogen bonding interactions and its higher directionality allows for solution-phase applications with halogen and chalcogen bonding as the key interaction. In this mini-review, the special features, state-of-the-art and key examples of these so-called σ-hole interactions in the field of organocatalysis are presented.

Keywords: Chalcogen; Halogen-bonding; Non-covalent activation; Organocatalysis; Sigma-hole.

Figure 1

a) σ‐Holes that are predicted to increase with heavier atoms and a higher polarizability. b) Model structures candidates explored in catalysis.14

Scheme 1

Pioneer XB‐bond‐catalyzed reduction of quinolines by Bolm et al.

Scheme 2

XB‐bond‐catalyzed reduction of quinolines, pyridines and imines.

Scheme 3

Diels‐Alder reaction catalyzed by bidentate iodo‐imidazolium salts.

Scheme 4

XB‐donor‐catalyzed Michael additions by Huber and Breugst et al.

Scheme 5

Activation of benzaldehydes: CBr₄‐catalyzed Aldol and Knoevenagel condensation reactions.

Scheme 6

Cross‐enolate coupling catalyzed by monodentate XB‐donor 6.

Scheme 7

XB‐donor 7‐catalyzed aza‐Diels‐Alder reaction of imines and 2‐siloxy‐1,3‐butadienes.

Scheme 8

XB‐donor 8‐catalyzed aza‐Diels‐Alder reaction between imines and the Danishefsky's diene.

Scheme 9

Plausible reaction mechanism via a) a Mannich‐Michael or b) a [4+2]‐aza‐Diels‐Alder pathway.

Scheme 10

XB‐donor 9‐catalyzed aziridine synthesis.

Scheme 11

XB‐donor‐catalyzed, TMS‐I induced activation of alcohols.

Scheme 12

Iodoalkyne 11‐catalyzed benzoxazole formation.

Scheme 13

NBS‐catalyzed benzothiazole formation.

Scheme 14

Early XB‐donor‐mediated solvolysis of benzhydryl bromides.

Scheme 15

Stoichiometric hypervalent iodine(III) X‐donor 15 in the solvolysis of benzhydryl chloride.

Scheme 16

XB‐donor‐mediated Friedel‐Crafts alkylation of electron rich arenes.

Scheme 17

SN1‐type nucleophilic addition to 1‐chloroisochroman.

Scheme 18

XB‐donor‐mediated glycosylation using 3‐OTf as activating reagent.

Scheme 19

XB‐donor‐catalyzed controlled cationic polymerization reaction.

Scheme 20

[4+2]‐Cycloaddition of 2‐alkenylindoles catalyzed by C–I–π‐halogen‐bond‐interactions.

Scheme 21

Intramolecular Aldol lactonization for the enantioselective preparation of β‐lactones via a secondary Ch‐bonding stabilization.

Figure 2

Conformational stabilization of the isothiourea moiety.19, 23

Scheme 22

Organoselenides as Lewis basic organocatalysts.

Scheme 23

ChB‐donor‐catalyzed transfer hydrogenation reported by Matile et al.

Scheme 24

Carbon‐halogen bond activation by Se‐based Ch‐bonding reported by Huber et al.

Scheme 25

(a) ChB‐donor‐based BDS catalysts 26–27 developed by Matile et al. and (b) schematic illustration of chloride (green) bound to the BDS core showing an ideal bite angle of 45°.

Scheme 26

ChB‐donor‐catalyzed reaction of 1‐chloroisochroman with a silyl ketene acetal. TBS=tert‐butyldimethylsilyl.

Scheme 27

Chloride abstraction of 1‐chloroisochroman and Troc‐protected 1‐chloroisoquinoline by ChB‐catalysts 28 and 29.

Scheme 28

ChB‐donor‐catalyzed assembly of small molecules: Synthesis of fused N‐heterocycles via Michael/aldol/cyclization tandem reaction.