Towards High‐Performance Lewis Acid Organocatalysis

Abstract

The combination of Lewis acid organocatalysis and internal hydrogen-bond assistance was used to develop a new type of highly active disulfonimide catalyst. The increased Lewis acidity was documented by activity comparisons as well as theoretical investigations. Finally, the potential of the hydrogen-bond-assisted disulfonimide catalyst was demonstrated by its application in an enantioselective transformation.

Stronger Brønsted Acids: Recent Progress

“…Quite recently, List and co-workers reported the development of highperformance chiral disulfonimide derivatives. 217 The key to enhancing the catalytic activity of sulfonimide is the use of internal hydrogen bonds, and the bis[3,5-bis(trifluoromethyl)-phenyl]methyl carbinol unit was introduced as a suitable hydroxy moiety. They examined the catalytic activities in the Mukaiyama aldol reaction of benzophenone (217) with ketene silyl acetal.…”

“…217 The key to enhancing the catalytic activity of sulfonimide is the use of internal hydrogen bonds, and the bis[3,5-bis(trifluoromethyl)-phenyl]methyl carbinol unit was introduced as a suitable hydroxy moiety. They examined the catalytic activities in the Mukaiyama aldol reaction of benzophenone (217) with ketene silyl acetal. Dramatic enhancement of the reactivity was observed in the presence of simple disulfonimide.…”

Development and Applications of Disulfonimides in Enantioselective Organocatalysis

“…As such, novel (biaryl)hydroxyl acids (HYDRAs) were developed that exploit internal hydrogen bonding between the hydroxyl and disulfonimide motifs to increase the NH acidity. 42 This novel class of highly acidic catalyst 7 was accessed in a one-pot lithiation/alkylation sequence from the enantiomerically pure 3,3′-unsubstituted disulfonimide 8b, thus trapping the bis-lithiated species with appropriate benzophenone derivatives (Scheme 4).…”

Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction

“…Several DSI catalysts were then screened. The use of catalyst 3 b with 3,5‐di(trifluoromethyl)benzene substitution in the 3,3′‐position of the backbone gave us a hint about the nature of the “ideal” catalyst for this reaction, since all selectivity parameters were increased (Table , entry 4) . In fact, by simply modulating the CF 3 substitution on those aromatic moieties, we obtained catalyst 3 c with 2,5‐di(trifluoromethyl)benzene substitution, which afforded excellent enantioselectivity (97.5 : 2.5 e.r.)…”