Organocatalytic enantioselective dearomatization of thiophenes by 1,10-conjugate addition of indole imine methides

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmet...

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Bibliographic Details
Published in:Nature communications 2021-08, Vol.12 (1), p.4881-4881, Article 4881
Main Authors: Li, Xingguang, Duan, Meng, Yu, Peiyuan, Houk, K. N., Sun, Jianwei
Format: Article
Language:English
Subjects:
140/131
140/58
639/638/549/933
639/638/77/883
Aromatic compounds
Asymmetry
Catalysis
Conjugates
Construction
Context
Enantiomers
Furans
Humanities and Social Sciences
Hydrogen bonding
Indoles
multidisciplinary
Pesticides
Phosphoric acid
Science
Science (multidisciplinary)
Selectivity
Solvents
Substitutes
Thiophenes
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Summary:Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control. Catalytic asymmetric dearomatization is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. Here the authors show an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-021-25165-7