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Volumn 47, Issue 30, 2008, Pages 5661-5665

Asymmetric Brønsted acid catalyzed isoindoline synthesis: Enhancement of enantiomeric ratio by stereoablative kinetic resolution

Author keywords

Asymmetric catalysis; Aza Michael addition; Chiral Br nsted acids; Friedel Crafts reaction; Organocatalysis

Indexed keywords

CHEMICAL REACTIONS; FRIEDEL-CRAFTS REACTION; SYNTHESIS (CHEMICAL);

EID: 53549133122     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200801354     Document Type: Article
Times cited : (208)

References (83)
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    • Potassium carbonate and activated neutral alumina also facilitated the aza-Michael addition of the Friedel-Crafts adduct 12a in comparable yield and diastereoselectivity; however, the reaction times were longer
    • Potassium carbonate and activated neutral alumina also facilitated the aza-Michael addition of the Friedel-Crafts adduct 12a in comparable yield and diastereoselectivity; however, the reaction times were longer.
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    • 2, the reaction of the Friedel-Crafts adduct 12a and indole (8a) to form bis-indole 11a was slow (<5% conversion after 24 h). In chlorobenzene, the Friedel-Crafts adduct 12a, although only sparingly soluble, underwent reaction with indole (8a) to form the bis-indole 11a.
    • 2, the reaction of the Friedel-Crafts adduct 12a and indole (8a) to form bis-indole 11a was slow (<5% conversion after 24 h). In chlorobenzene, the Friedel-Crafts adduct 12a, although only sparingly soluble, underwent reaction with indole (8a) to form the bis-indole 11a.
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    • Racemic Friedel-Crafts adduct 12a was exposed to N-triflyl phosphoramide 7h in the absence of indole for 2 d. Following cyclization with DBU, isolindoline 10a was isolated in nearly quantitative yield and as a racemate. This provides further evidence that the enhancement of enantiomeric ratio is a result of a stereoablative nucleophilic displacement reaction: in the absence of a nucleophile, no enhancement occurs.
    • Racemic Friedel-Crafts adduct 12a was exposed to N-triflyl phosphoramide 7h in the absence of indole for 2 d. Following cyclization with DBU, isolindoline 10a was isolated in nearly quantitative yield and as a racemate. This provides further evidence that the enhancement of enantiomeric ratio is a result of a stereoablative nucleophilic displacement reaction: in the absence of a nucleophile, no enhancement occurs.


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