Efficient Catalytic Kinetic Resolution of Spiro‐epoxyoxindoles with Concomitant Asymmetric Friedel–Crafts Alkylation of Indoles

Abstract

An efficient process involving the catalytic kinetic resolution of racemic spiro‐epoxyoxindoles with the simultaneous enantioselective Friedel–Crafts alkylation of indoles has been realized using a chiral phosphoric acid catalyst. The reaction provides two useful intermediates in high yields and excellent enantioselectivities. Performing the catalysis on a gram scale led to (R)‐3‐(3‐indolyl)‐oxindole‐3‐methanol, which was used in the asymmetric formal total synthesis of (+)‐gliocladin C. Notably, the enantiomers (S)‐3‐(3‐indolyl)‐oxindole‐3‐methanol can be obtained easily by the reaction of the resolved spiro‐epoxyoxindole with indole.

Recent Advancements in Typical Friedel–Crafts Alkylation Reactions Focused on Targeting Arene Nucleophiles

“…Interestingly, Sun, Hong, Wang and co-workers reported a proficient enantioselective FC alkylation of indoles involving the catalytic kinetic resolution of racemic spiroepoxyoxindoles rac - 14 simultaneously by using chiral phosphoric acid catalyst 13 (Scheme 35 ) 186 This process not only afforded resolved spiroepoxyoxindoles ( R )- 14 , but also provided useful 3-(3-indolyl)-oxindole-3-methanols 16 in good to excellent yields and excellent enantioselectivities.…”

Cycloaddition Reaction of Spiro-Epoxy Oxindole with CO2 at Atmospheric Pressure Using Deep Eutectic Solvent

“…Therefore, developing a methodology for the facile synthesis of novel and unique small organic molecule is an intellectually challenging exercise. It is difficult to overstate the importance of the privileged spiro-skeletons since it represents a significant class of biologically and pharmaceutically active bicyclic compounds. − In spite of their widespread bioactivities, functionalities such as spiro-epoxy oxindoles have the potential to serve as a versatile synthon for generating new molecular entities. In chemical conversion of spiro-epoxy oxindoles, catalytic systems were recently developed for the ring-opening reaction of epoxides using various nucleophiles to form 3,3-disubstituted-oxindoles (Figure ).…”

Ni-Catalyzed Enantioconvergent Coupling of Epoxides with Alkenylboronic Acids: Construction of Oxindoles Bearing Quaternary Carbons

“…Spiroepoxyoxindole is an easily accessible and strained compound that has been used in organocatalytic kinetic resolutions previously. 74,75 Thus, this compound represents an ideal substrate for testing our proposal. We chose spiroepoxyoxindole 1 and styrenyl boronic acid 10a as the coupling partners to screen reaction conditions.…”

“…(5) With regards to the importance of chiral oxindole skeletons for the discovery of bioactive molecules [65][66][67] and our current work concerning Ni-catalyzed enantioselective reactions, [68][69][70][71] especially alkenylation, we sought to develop an enantioconvergent alkenylation of spiroepoxyoxindoles. [72][73][74][75] Hereby, we report a Ni-catalyzed enantioconvergent ring-opening alkenylation of spiroepoxyoxindoles with alkenylboronic acids for the construction of chiral oxindoles bearing a homoallylic alcohol moiety and quaternary carbon stereocenter, in good yields and ees, and with excellent regioselectivity (Scheme 1c).…”