Asymmetric Radical Cyclopropanation of Dehydroaminocarboxylates: Stereoselective Synthesis of Cyclopropyl α-Amino Acids.
Asymmetric Radical Cyclopropanation of Dehydroaminocarboxylates: Stereoselective Synthesis of Cyclopropyl α-Amino Acids.
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DOI：
10.1016/j.chempr.2021.03.002
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发表时间：
2021-06-10
期刊：
影响因子：
23.5
通讯作者：
Zhang XP
中科院分区：
文献类型：
--
作者：
Cindy Lee WC;Wang DS;Zhang C;Xie J;Li B;Zhang XP
研究了Co（II）基金属催化（MRC）脱氢氨基羧酸酯与原位生成α-芳基重氮甲烷的不对称环丙化反应。通过对d2对称手性酰胺卟啉平台作为支撑配体的环境进行微调，Co(II)-金属体系可以在温和的条件下有效激活各种α-芳基重氮甲烷，使不同的脱氢氨基羧酸酯环丙烷化，从而实现手性环丙基α-氨基酸衍生物的立体选择性合成。Co（II）催化的不对称自由基环丙烷化反应除了具有较高的产率和良好的对映选择性外，还表现出与非催化热反应相反的(Z)-非对映选择性。计算和实验相结合的研究支持Co（II）催化环丙化反应的逐步自由基机制。所得到的对映体富集(Z)-α-氨基-β-芳基环丙烷羧酸酯可用于二肽的高效合成，可作为设计和制备具有限制性构象的新型肽的独特的非蛋白质氨基酸构建块。钴基金属催化（MRC）成功地应用于脱氢氨基羧酸酯与原位生成的α-芳基重氮甲烷的不对称环丙化反应。该Co（II）基催化体系由最佳的2d对称手性酰胺卟啉配体支撑，适用于α-芳基重氮甲烷和脱氢氨基羧酸盐的广泛组合。Co（II）催化的不对称环丙化反应具有较高的产率和良好的对映选择性，与非催化的热反应不同，它能直接合成具有(Z)非对映选择性的α-氨基-β-芳基环丙烷羧酸酯。
A catalytic radical process has been developed for asymmetric cyclopropanation of dehydroaminocarboxylates with in situ-generated α-aryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the environments of D2-symmetric chiral amidoporphyrin platform as the supporting ligands, the Co(II)-metalloradical system can effectively activate various α-aryldiazomethanes to cyclopropanate different dehydroaminocarboxylates under mild conditions, enabling the stereoselective synthesis of chiral cyclopropyl α-amino acid derivatives. In addition to high yields and excellent enantioselectivities, the Co(II)-catalyzed asymmetric radical cyclopropanation exhibits (Z)-diastereoselectivity, which is the opposite of uncatalyzed thermal reaction. Combined computational and experimental studies support a stepwise radical mechanism for the Co(II)-catalyzed cyclopropanation reaction. The resulting enantioenriched (Z)-α-amino-β-arylcyclopropanecarboxylates, as showcased for the efficient synthesis of dipeptides, may serve as unique non-proteinogenic amino acid building blocks for the design and preparation of novel peptides with restricted conformations. Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for the development of a new catalytic radical process that is highly effective for asymmetric cyclopropanation of dehydroaminocarboxylates with in situ-generated α-aryldiazomethanes. Supported by an optimal D2-symmetric chiral amidoporphyrin ligand, the Co(II)-based catalytic system is applicable to broad combinations of α-aryldiazomethanes and dehydroaminocarboxylates. In addition to high yields and excellent enantioselectivities, the Co(II)-catalyzed asymmetric cyclopropanation enables direct synthesis of α-amino-β-arylcyclopropanecarboxylates with (Z)-diastereoselectivity, which is different from uncatalyzed thermal reaction.