Catalytic Asymmetric Electrophilic Cyanation of 3-Substituted Oxindoles

Abstract

The first example of catalytic asymmetric electrophilic cyanation of 3-substituted oxindoles has been achieved using readily accessible 4-acetylphenyl cyanate as the cyano source. Thus, a series of all-carbon quaternary center 3-aryl-3-cyano oxindoles were prepared using a zinc complex of a chiral pincer ligand as the catalyst in high yields (up to 95%) and excellent enantioselectivities (up to >99% ee) in the presence of 4 Å MS and 2,6-lutidine in THF at 0 °C.

Recent developments in enantioselective zinc-catalyzed transformations

“…In the same context, the first example of catalytic asymmetric cyanation of 3-aryl-substituted oxindoles 253 was disclosed by these authors using the same cyano source 247 (Scheme 85) [120]. Employing chiral pincer bisoxazoline 254 (12 mol%) in combination with Zn(BF 4 ) 2 (H 2 O) 6 as precatalyst (10 mol%) in the presence of 2,6-lutidine as a base in THF as solvent, a range of chiral 3aryl-3-cyano oxindoles 255 were synthesized with both good to high yields (65-95%) and enantioselectivities (78À>99% ee).…”

“…Scheme 85. a-Cyanation of 3-aryl-substituted oxindoles with p-acetylphenylcyanate in the presence of a bisoxazoline ligand [120].…”

Chiral Tridentate-Based Ligands

“…54 The same zinc complexes were also used in the asymmetric oxindole cyanation with 4-acetylphenyl cyanate as cyanide source (see Scheme 5.3, e)). 55 Scheme 5.3: some asymmetric reactions with Boxmi ligands.…”

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

“…[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. (Scheme 1C).…”

“…When an organic base such as DBU, DABCO, DMAP or Et 3 N used (Table 2, entries 12-15), to our delight, DABCO was found to greatly increase the yield to 84% with retained 90% ee (Table 2, entry 13). A combination of PhCF 3 and other non-polar solvents such as toluene, CH 2 Cl 2 , PhCl in a 9 : 1 v/v ratio was then evaluated using DABCO as the base (Table 2, entries [16][17][18]. The mixture of PhCF 3 and PhCl afforded the optimal catalyst performance in 92% yield and 96% ee (Table 2, entry 18 vs 19).…”