Organocatalyzed Asymmetric α-Thiocyanation of Oxindoles: Synthesis of Chiral Tertiary 3-Thiocyanatoxindoles

Abstract

An enantioselective thiocyanation of oxindoles has been developed for the first time using a bifunctional cinchona-derived organo-catalyst and N-thiocyanatophthalimide as the electrophilic thiocyanation source in the presence of 2-naphthol as the additive. Various enantioenriched 3,3′-disubstituted oxindoles with SCN-containing quaternary carbon stereocenters were synthesized under mild conditions in high yields (up to 99%) and good enantioselectivities (up to 6:94 er).

Organocatalyzed Asymmetric Tandem Intramolecular oxa‐Michael Addition/Electrophilic Thiocyanation: Synthesis of Chiral α‐Thiocyanato Flavanones

“…reported an asymmetric α‐ thiocyanation with the help of a chiral Evans auxiliary group [14] . Recently, our group successively developed a catalytic asymmetric electrophilic thiocyanation of β‐ ketoesters and oxindoles (Scheme 1B) [11d,15] . Based on our research interest in the field of cyano‐containing chemicals, [16] we disclosed the asymmetric tandem oxa‐Michael addition and electrophilic thiocyanation to produce functionalized flavanones in one‐pot step.…”

Design and Use of Electrophilic Thiocyanating and Selenocyanating Reagents: An Interesting Trend for the Construction of SCN‐ and SeCN‐Containing Compounds

“…One year later,t he same group reported an extension of their methodology to the a-thiocyanation of 3-substituted oxindoles 26 (Scheme 12). [20] Indeed, by using as imilar catalytic system and the 2-naphthol as ac o-catalyst, the expected thiocyanatedp roducts 27 were afforded in excellent yields (e.r.u p to 94:6). Note that the stereoselectivity outcome of the reaction was substrate-dependent.…”

Phosphoric Acid Catalyzed Electrophilic Thiocyanation of Indoles: Access to SCN‐Containing Aryl‐Indole Compounds

“…Recently, this research area has attracted increasing attention and several remarkable works have been reported [3] . Chen and coworkers developed a new reagent thiocyanatosaccharin (NTSc) and reported catalytic asymmetric α‐thiocyanations of cyclic β‐ketoesters and oxindoles, recently [3a–c] . In 2019, we designed and synthesized an electrophilic N‐thiocyanodibenzenesulfonimide (NTSI) reagent, which has been applied for thiocyano oxyfunctionalizations of alkenes and thiocyano semipinacol rearrangement of allylic alcohols [3d–e] .…”