An enantioconvergent halogenophilic nucleophilic substitution (S _N 2X) reaction

Abstract

Bimolecular nucleophilic substitution (SN2) plays a central role in organic chemistry. In the conventionally accepted mechanism, the nucleophile displaces a carbon-bound leaving group X, often a halogen, by attacking the carbon face opposite the C–X bond. A less common variant, the halogenophilic SN2X reaction, involves initial nucleophilic attack of the X group from the front and as such is less sensitive to backside steric hindrance. Herein, we report an enantioconvergent substitution reaction of activated tertiary bromides by thiocarboxylates or azides that, on the basis of experimental and computational mechanistic studies, appears to proceed via the unusual SN2X pathway. The proposed electrophilic intermediates, benzoylsulfenyl bromide and bromine azide, were independently synthesized and shown to be effective.

σ‐Hole Interactions in Catalysis

“…However, more detailed mechanistic investigations are difficult, as the non‐iodinated catalyst also shows a significant catalytic activity in the reaction between the 2‐thiophenyl‐substituted sulfoxide 7 and benzyl bromide (61 % ee for the non‐iodinated catalyst and 91 % ee for the iodinated catalyst C9 ). Very recently, the non‐halogenated pentanidium system was also employed in enantioconvergent halogenophilic nucleophilic substitution reactions . In these S N 2X‐type reactions, the leaving group (Br – ) forms a transient halogen bond to the thiocarboxylate nucleophile.…”

Iodonium salts as efficient iodine(iii)-based noncovalent organocatalysts for Knorr-type reactions

“…A covalent activation mode involves the formation of covalent bond(s) between a substrate and catalyst (such as amines, [1][2][3][4][5] heterocyclic carbenes, 1,6,7 or phosphines 8 ), whereas a noncovalent mode involves the activation of substrates through noncovalent linkages to the catalyst. 2,[9][10][11][12][13][14][15][16][17][18] For noncovalent catalysis, an organic catalyst typically interacts with a substrate through hydrogen bonding (HB), and many important results were achieved for the reactions based on such HB donors as ureas, 2,[19][20][21][22][23][24] squaramides, [24][25][26] and other Brønsted acids, [27][28][29][30][31] whereas catalytic reactions involving halogen (XB) 9,10,15,[32][33][34][35] or chalcogen bonding (ChB) 34,36,37 are far less explored. Although XB has been established as a valuable tool in solid-state chemistry and crystal engineering, …”

Advances in asymmetric organocatalysis over the last 10 years

“…Tan’s group made a further stride in 2019 employing a chiral cationic pentanidium catalyst, which involves a different catalytic process (Fig. 2a , reaction ii) 29 . While both methods share a similar key formation of stabilized chiral ion pair, in Tan’s work a halogenophilic S N 2X pathway with halogen leaving group is operative.…”