Co(III)salen Catalyzed Enantioselective C3‐Indolylation of Spiro‐Epoxyoxindoles and Its Mechanistic Studies

Abstract

Catalytic asymmetric C3-indolylation of N-protected spiro-epoxyoxindoles has been developed for the access of 3-(3-indolyl)-oxindole methanols with excellent enantioselectivity (ee up to > 99%). The widespread substrate scope and easily accessible Co(III)-salen over 1,1'-Spirobiindane-7,7'-diol phosphoric acid prove our condition to be more beneficial than the chiral Brønsted acid-catalyzed reaction. Further, kinetic resolution of spiro-epoxides is achieved in high enantiomeric excess under certain conditions. The detailed mechanistic study endorses that the feedback inhibition played a key role which restricts the dynamic kinetic resolution process. Besides it also revealed the S N 2' mechanism for the Co(III)-salen catalysed C3-indolylation of spiro-epoxyoxindoles.

Enzymatic Kinetic Resolution of Bulky Spiro-Epoxyoxindoles via Halohydrin Dehalogenase-Catalyzed Enantio- and Regioselective Azidolysis

“…In general, the enzymatic kinetic resolution process works well toward a variety of spiro-epoxyoxindole substrates with good E values (145 → 200). Compared to the chemical satrategies, − the enzymatic method was performed under mild conditions and exhibited high catalytic efficiency, leading to catalytic kinetic resolution of spiro-epoxyoxindoles completion in several hours.…”

“…In addition, the spiro-epoxyoxindole 1m with C 4-substituted by electron-donating methyl group was also tolerated by the mutant 2-H6, giving ( R )- 2m in 46% isolated yield and 94% ee . Notably, these C 4-substituted spiro-epoxyoxindoles are usually absent in many chemical ring-opening methods. ,,,− …”

“…22,23 Very recently, Hajra's group has also achieved catalytic kinetic resolution of spiro-epoxyoxindoles via Co-(III)salen-catalyzed asymmetric C3-indolylation reactions (Figure 1b). 24,25 These elegant works feature broad substrate scope and mild conditions, which is a milestone for the asymmetric ring-opening of spiro-epoxyoxindoles and provides both chiral spiro-epoxyoxindoles and 3-substituted 3-hydroxyoxindoles. However, these methods suffer from the use of expensive catalysts, hazardous solvents and long reaction time.…”

“…Kinetic resolution of racemic spiro-epoxyoxindoles via enantio- and regiospecific ring-opening enables the straightforward formation of 3-substituted 3-hydroxy­oxindoles with remaining unresolved spiro-epoxyoxindoles in chiral forms. Although many efficient strategies have been developed for highly regioselective ring-opening of spiro-epoxyoxindoles to a diverse variety of 3-substituted 3-hydroxy­oxindoles, enantioselectivity control in these processes remains challenging. ,,− Several efforts have been devoted by Wang’s group to realize ring-opening of spiro-epoxyoxindoles in high enantio- and regioselectivity with indole or 1-naphthols (Figure a). , Very recently, Hajra’s group has also achieved catalytic kinetic resolution of spiro-epoxyoxindoles via Co­(III)­salen-catalyzed asymmetric C3-indolylation reactions (Figure b). , These elegant works feature broad substrate scope and mild conditions, which is a milestone for the asymmetric ring-opening of spiro-epoxyoxindoles and provides both chiral spiro-epoxyoxindoles and 3-substituted 3-hydroxy­oxindoles. However, these methods suffer from the use of expensive catalysts, hazardous solvents and long reaction time.…”

Recent trends in the direct oxyphosphorylation of C–C multiple bonds

“… 11,12 In this family of reactions, oxyfunctionalization of alkenes/alkynes, which installs a unique functional group and an oxo group in adjacent carbons simultaneously, offers a powerful strategy for the selective synthesis of β-substituted ketones. 13 In this context, direct oxyphosphorylation of C–C multiple bonds with P(O)–H compounds has gained a considerable amount of attention in the last couple of years in the preparation of numerous synthetically and biologically important β-phosphorylated ketones ( Fig. 1 ).…”