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Asymmetric 1,4‐Addition Reactions Catalyzed by N‐Terminal Thiourea‐Modified Helical l ‐Leu Peptide with Cyclic Amino Acids
Author(s) -
Sato Kazuki,
Umeno Tomohiro,
Ueda Atsushi,
Kato Takuma,
Doi Mitsunobu,
Tanaka Masakazu
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101252
Subject(s) - enantioselective synthesis , thiourea , chemistry , moiety , michael reaction , amide , catalysis , adduct , peptide , stereochemistry , malonate , dimethyl malonate , medicinal chemistry , yield (engineering) , alkyl , organic chemistry , biochemistry , materials science , metallurgy
N‐terminal thiourea‐modified l ‐Leu‐based peptide {(3,5‐diCF 3 Ph)NHC(=S)‐( l ‐Leu‐ l ‐Leu‐Ac 5 c) 2 ‐OMe} with five‐membered ring α,α‐disubstituted α‐amino acids (Ac 5 c) catalyzed a highly enantioselective 1,4‐addition reaction between β‐nitrostyrene and dimethyl malonate. The enantioselective reaction required only 0.5 mol % chiral peptide‐catalyst in the presence of i Pr 2 EtN (2.5 equiv.), and gave a 1,4‐adduct with 93 % ee of an 85 % yield. As Michael acceptors, various β‐nitrostyrene derivatives such as methyl, p ‐fluoro, p ‐bromo, and p ‐methoxy substituents on the phenyl group, 2‐furyl, 2‐thiophenyl, and naphthyl β‐nitroethylenes could be applied. Furthermore, various alkyl malonates and cyclic β‐keto‐esters could be used as Michael donors. It became clear that the length of the peptide chain, a right‐handed helical structure, amide N−Hs, and the N‐terminal thiourea moiety play crucial roles in asymmetric induction.