Synthesis of Chiral Bis(3-indolyl)methanes Bearing a Trifluoromethylated All-Carbon Quaternary Stereocenter via Nickel-catalyzed Asymmetric Friedel-Crafts Alkylation Reaction.

doi:10.1021/acs.joc.0c00336

Paper

Synthesis of Chiral Bis(3-indolyl)methanes Bearing a Trifluoromethylated All-Carbon Quaternary Stereocenter via Nickel-catalyzed Asymmetric Friedel-Crafts Alkylation Reaction.

Published Jul 6, 2020 · Wen-Jing Zhu, Jun-Fang Gong, Mao‐Ping Song

The Journal of organic chemistry

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Abstract

Bis(3-indolyl)methanes are well known natural products with a broad range of important biological functions including cancer cell growth inhibition and anti-microbial activity. Incorporation of a trifluoromethyl group is known to have a profound effect on the parent compound's biological activities. Here an efficient method for the synthesis of chiral trifluoromethylated bis(3-indolyl)methanes via a catalytic asymmetric Friedel-Crafts (F-C) alkylation reaction has been established. Both enantiomers of the catalysis products can be obtained by tuning the chiral substituents of the catalyst. With 5 mol% of the Ni(II)/(imidazoline-oxazoline) complex as the catalyst, the F-C reaction of indoles with β CF3 β-(3-indolyl)nitroalkenes proceeded well to afford a series of chiral bis(3-indolyl)methanes bearing a trifluoromethylated all-carbon quaternary stereocenter in generally good yields with excellent enantioselectivities (up to 98% yield and 94% ee). Furthermore, through interchanging the indole moieties of the two reactants, indole vs β CF3 β-(3-indolyl)nitroalkene in the F-C reaction, both enantiomers of a given trifluoromethylated bis(3-indolyl)methane were obtained with high enantioselectivities (89-94% ee) upon removal of the indole N-protecting group in the F-C products. The current work represents the first general catalytic enantioselective approach to the important class of trifluoromethylated bis(3-indolyl)methanes.

Study Snapshot

This study developed an efficient method for synthesis of chiral trifluoromethylated bis(3-indolyl)methanes with high enantioselectivity, potentially impacting biological functions like cancer cell growth inhibition and anti-microbial activity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Synthesis of Chiral Bis(3-indolyl)methanes Bearing a Trifluoromethylated All-Carbon Quaternary Stereocenter via Nickel-catalyzed Asymmetric Friedel-Crafts Alkylation Reaction.

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