Activation of Glycosyl Halides by Halogen Bonding

Abstract

Halogen bonding is the formation of a non-covalent interaction between an electrophilic halogen substituent and a Lewis base, for instance, a halide. These kinds of relatively weak interactions have found applications in crystal engineering and initial applications in solution-phase chemistry are starting to appear. We report on the exploration of bis(iodoimidazolium) compounds as halogen-based Lewis acids in the activation of glycosyl halides. We show that these dicationic halogen-bond donors can be used to activate glycosyl halides if the carbohydrate core is sufficiently reactive enough. Furthermore, we provide comparison experiments which indicate that the mode of activation is indeed based on halogen bonding. This represents the first glycosylation reaction mediated by a (carbon-backbone-based) halogen-bond donor.

Halogen Bonding in Organic Synthesis and Organocatalysis

“…The concept of using imidazolium‐based Lewis acidic halogen‐bond donors in halide abstraction reactions was later also implemented by Codée and co‐workers in the activation of glycosyl halides . Based on the classic method for the activation of the latter by mercury or silver salts (Königs–Knorr glycosylation), the authors showed that it is possible to perform some of these reactions with imidazolium‐based halogen‐bond donors such as 18 .…”

Acceptor reactivity in glycosylation reactions

“…As a result, the acceptors used in these studies differ greatly in steric and electronic properties, making it difficult to establish clear structurereactivity relationships. 7 Unexpected stereoselectivities and/or poor yields, as a result of ill-understood acceptor reactivity, are continuously being reported, [8][9][10][11][12] and indicate the need for deeper insight into carbohydrate acceptor reactivity and its effect of the outcome of glycosylation reactions. At a time when the mechanism of the glycosylation reaction is understood better than ever before 13 and insight in and control over donor reactivity has taken shape it is clear that understanding and harnessing the reactivity of the glycosyl acceptor is crucial for the development of more general glycosylation methodology and to remedy the need for ill-defined and time consuming reaction optimization procedures, that have thwarted the field 4690 | Chem.…”

Koenigs–Knorr Glycosylation Reaction Catalyzed by Trimethylsilyl Trifluoromethanesulfonate

“…To advance the classical Koenigs-Knorr glycosylation, many activators including salts of mercury, [5][6][7][8] cadmium, [9][10][11] tin, [12,13] zinc, [14,15] indium, [16,17] silver [18][19][20][21][22][23][24][25][26] have emerged. [27] Nevertheless, these modifications failed to adequately enhance the reactiont hat continued to suffer from fair yields, poor reactivity of donors, substrate scope, and the requirement to use excess of toxic or expensive reagents.T his prompted the investigationo fo ther,n on-metallic activators andp romoters including halide ions, [28] iodine or IBr with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone/1,4-diazobicyclo[2.2.2]octane( DDQ/DABCO), [29,30] bromine, [31] and 3,3-difluoroxindole (HOFox), [32,33] diarylborinic acid, [34] iodonium ions, [35] halogen bonding, [36] supercriticalC O 2 , [37] and organocatalysis. [38][39] Many of these conditions still fail to glycosidate perbenzoylated bromides.…”