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

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Amonga vailables trategies for the KR of alcohols, chiral 4-dimethylaminopyridine (DMAP) catalyzed KRs are particularly appealingd ue to their operational simplicity,h igh turnover,a nd environmental friendliness. [14][15][16][17][18][19] Studying such reactions computationally not only enriches our understanding of thesep rocesses but also creates opportunities to improvetheir efficiency. [20][21][22][23][24][25][26][27] In continuationo fo ur efforts to understandt he stereoselectivity of organocatalyzed reactions, [29] particularly in the context of KRs, [30,31] we have examined the KR of axially chiral biaryls reported by Sibi and co-workersi n2 014 (Scheme 1).…”

Recent Advances in the Application of Vibrational Circular Dichroism Spectroscopy for the Characterization of Asymmetric Catalysts

“…Scheme 2), it has even been used to determine the AC of the novel asymmetric catalyst itself. [22] The exceptional sensitivity for conformational preferences and solvent-induced structural changes made VCD spectroscopy also an interesting tool for general conformational studies on known chiral catalysts. [23] Particularly noteworthy in this context are early works by Bürgi and co-workers on cinchonidine (derivatives like 9) [24] , which is frequently used as catalyst, auxiliary or as a general building block for more complex catalysts.…”

“…In the case of 8 (cf. Scheme ), it has even been used to determine the AC of the novel asymmetric catalyst itself . The exceptional sensitivity for conformational preferences and solvent‐induced structural changes made VCD spectroscopy also an interesting tool for general conformational studies on known chiral catalysts .…”

Axial chirality in biaryl N,N‐dialkylaminopyridine derivatives bearing an internal carboxy group

“…Chiral N , N ‐dimethylaminopyridine (DMAP) derivatives have attracted attention as asymmetric nucleophilic catalysts for stereoselective acylations in kinetic resolution of chiral alcohols and amines, as well as desymmetrization of meso ‐diols . DMAP derivatives possessing central chirality have been well developed; however, only a few DMAP derivatives bearing molecular asymmetry such as axial chirality, planer chirality, and other miscellaneous chirality have been investigated.…”