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. 2018 Apr 25;8(28):15641-15651.
doi: 10.1039/c8ra02481b. eCollection 2018 Apr 23.

Diastereoselective construction of 4-indole substituted chromans bearing a ketal motif through a three-component Friedel-Crafts alkylation/ketalization sequence

Jiao-Mei Guo  1 , Wen-Bo Wang  1 , Jia Guo  1 , Yan-Shuo Zhu  1 , Xu-Guan Bai  1 , Shao-Jing Jin  1 , Qi-Lin Wang  1 , Zhan-Wei Bu  1
Affiliations

Diastereoselective construction of 4-indole substituted chromans bearing a ketal motif through a three-component Friedel-Crafts alkylation/ketalization sequence

Jiao-Mei Guo et al. RSC Adv. .

Abstract

The first TfOH-catalyzed three-component Friedel-Crafts alkylation/ketalization sequence of indoles, alcohols and ortho-hydroxychalcones was developed to afford a wide range of 4-indole substituted chromans bearing a ketal motif in 77-99% yields. Notably, only a simple filtration was needed to purify them. By altering methanol to CHCl3, 2,4-bisindole substituted chroman with the same indole substituent at the C2 and C4 positions was afforded. Moreover, 2,4-bisindole substituted chromans with different indole substituents could be obtained by treatment of 4-indole monosubstituted chromans with another indole molecule.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Selected biologically active compounds containing a chroman motif.
Scheme 1
Scheme 1. Our synthetic design for the construction of 4-indole substituted chromans bearing a ketal motif.
Scheme 2
Scheme 2. Synthesis of 2,4-bisindole substituted chroman 4 with the same indole substituents.
Scheme 3
Scheme 3. Assembly of chromans with two different indole substituents.
Scheme 4
Scheme 4. Gram-scale preparation of 3n.
Scheme 5
Scheme 5. Chemical conversions of 3n and 3v.
Scheme 6
Scheme 6. Plausible reaction mechanism.
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