Kinetic Resolution of 2‐Substituted Indolines by N‐Sulfonylation using an Atropisomeric 4‐DMAP‐N‐oxide Organocatalyst

Abstract

Abstract:The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s = 2.6-19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl-4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model that accounts for the stereodiscrimination is proposed.

Understanding the Reactivity and Selectivity of Fluxional Chiral DMAP‐Catalyzed Kinetic Resolutions of Axially Chiral Biaryls

“…The biological relevance of chiral alcohols has driven the development of many methods for their kinetic resolution (KR), which have been subjected to numerous experimental and theoretical studies . Among available strategies for the KR of alcohols, chiral 4‐dimethylaminopyridine (DMAP) catalyzed KRs are particularly appealing due to their operational simplicity, high turnover, and environmental friendliness . Studying such reactions computationally not only enriches our understanding of these processes but also creates opportunities to improve their efficiency …”

Kinetic Resolution of 2‐Substituted Indolines by N‐Sulfonylation using an Atropisomeric 4‐DMAP‐N‐oxide Organocatalyst

“…[34] All three datasets led to (+)-4a being assigned the (Sa) configuration. [32] The VCD data was most compelling as the match in the 1000-1250 cm [32 ] For further details see Supporting Information.…”

Kinetic resolution of indolines by asymmetric hydroxylamine formation

“…The current nonenzymatic KR of secondary amines predominantly relies on asymmetric N -acylation strategy involving N–C bond formation, which typically requires the use of stoichiometric pre-prepared acylating agents involving lengthy reagent synthesis (Fig. 1a ) 12 – 18 . Development of a catalytic KR of secondary amines based on other elementary reaction bearing an economy-oriented mind-set would be highly desirable.…”