Asymmetric 1,4‐Addition Reactions Catalyzed by N‐Terminal Thiourea‐Modified Helical L‐Leu Peptide with Cyclic Amino Acids
Asymmetric 1,4‐Addition Reactions Catalyzed by N‐Terminal Thiourea‐Modified Helical L‐Leu Peptide with Cyclic Amino Acids
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N-末端硫脲修饰的螺旋L-Leu肽与环状氨基酸催化的不对称1,4-加成反应
DOI：
10.1002/chem.202101252
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Tanaka Masakazu
中科院分区：
文献类型：
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作者：
Sato Kazuki;Umeno Tomohiro;Ueda Atsushi;Kato Takuma;Doi Mitsunobu;Tanaka Masakazu
N端硫脲修饰的l - Leu基肽{(3,5‐diCF3Ph)NHC（=S）‐（l‐Leu‐l‐Leu‐Ac5c）2‐OMe}与五元环α，α -二取代α -氨基酸（Ac5c）催化了β -硝基苯乙烯和丙二酸二甲酯之间的高度对映选择性1,4加成反应。对映选择性反应只需要0.5 mol %的手性肽催化剂，在fipr2etn的存在下（2.5等量），得到的1,4 -加合物的ee为93%，产率为85%。作为Michael受体，各种β -硝基苯乙烯衍生物，如甲基、对氟、对溴和苯基上的对甲氧基取代基、2 -呋喃基、2 -噻吩基和萘基β -硝基苯乙烯都可以应用。此外，各种丙二酸烷基酯和环β -酮酯可作为Michael供体。很明显，肽链的长度、右手螺旋结构、酰胺N - Hs和N端硫脲部分在不对称诱导中起着至关重要的作用。
N‐terminal thiourea‐modifiedl‐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 ofiPr2EtN (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, andp‐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.