Organocatalytic Asymmetric Synthesis of Sulfoxides from Sulfenic Acid Anions Mediated by a Cinchona-Derived Phase-Transfer Reagent

Abstract

Preliminary results concerning a conceptually novel route to chiral sulfoxides based on the asymmetric alkylation of sulfenate salts with alkyl halides mediated by a chiral phase-transfer catalyst are described. As a representative example, o-anisyl methyl sulfoxide was produced in 96% yield and with an enantiomeric excess of 58% using commercial cinchonidinium derivative 2a.

Catalytic Enantioselective Alkylation of Sulfenate Anions to Chiral Heterocyclic Sulfoxides Using Halogenated Pentanidium Salts

“…It should be noted that benzyl bromides caused an erosion of the enantioselectivity in the previous report of a related reaction by Perrio group. [8] Moreover, commercially available PTCs were also tested and low enantioselectivity was obtained (below 15 % ee, SI, Table S5). The construction of stereogenic sulfoxides bearing allylic and propargylic substituents could also be achieved in a similar manner (entries 7-9).…”

“…[7a,c] Recent attempts with cinchona alkaloids as phase-transfer catalysts were reported by Perrio and co-workers; despite the high yields, the ee values did not exceed 60 %. [8] Asymmetric phase-transfer catalysis is a convenient, scalable and environmentally benign method to prepare compounds in high enantiopurity. [9] Despite the success of several reported phase-transfer catalysts (PTCs) in the literature, it is still meaningful to design new ones with a high level of stereocontrol.…”

Neue Entwicklungen bei asymmetrischen Phasentransferreaktionen

“…[78] 3. Konjugierte Addition Tan et al entwickelten den neuen chiralen Pentanidiumkatalysator 101 und verwendeten ihn erfolgreich in der enantioselektiven konjugierten Addition von Glycinbenzophenonimin-tert-butylester (7) an a,b-ungesättigte Carbonylverbindungen (Schema 59).…”

“…Perrio et al berichteten über einen konzeptionell neuen Zugang zu chiralen Sulfoxiden durch asymmetrische Phasentransferalkylierung mit dem Katalysator 2 c. Beispielsweise wurde o-Anisylmethylsulfoxid (99) durch asymmetrische Methylierung von 98 über die Zwischenstufe 100 mit mittlerer Enantioselektivität erhalten (Schema 58). [78] 3. Konjugierte Addition Tan et al entwickelten den neuen chiralen Pentanidiumkatalysator 101 und verwendeten ihn erfolgreich in der enantioselektiven konjugierten Addition von Glycinbenzophenonimin-tert-butylester (7) an a,b-ungesättigte Carbonylverbindungen (Schema 59).…”

A New Role for Sulfenate Anions: Organocatalysis

“…Sulfenates are prochiral and have been probed for their chemical reactivity, [4] organometallic chemistry [6] and nucleophilic chemistry, [7] the latter primarily taking the form of alkylation at sulfur to provide sulfoxide. Recent work has focussed on enantio- [8,9] and diastereoselective sulfoxide formation. [10] The sulfenic acid has a pK a of about 6-7, making the sulfenate a reasonable leaving group.…”