Asymmetric 1,4-Addition Reactions Catalyzed by N-Terminal Thiourea-Modified Helical l-Leu Peptide with Cyclic Amino Acids |
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Authors: | Kazuki Sato Dr Tomohiro Umeno Dr Atsushi Ueda Dr Takuma Kato Prof Mitsunobu Doi Prof Masakazu Tanaka |
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Institution: | 1. Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 8528521 Japan;2. Osaka Medical and Pharmaceutical University, Osaka, 5698686 Japan |
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Abstract: | N-terminal thiourea-modified l -Leu-based peptide {(3,5-diCF3Ph)NHC(=S)-(l -Leu-l -Leu-Ac5c)2-OMe} with five-membered ring α,α-disubstituted α-amino acids (Ac5c) 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 iPr2EtN (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. |
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Keywords: | α α-disubstituted α-amino acid conformation helix organocatalyst peptide |
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