Direct Access to N-Unprotected α- and/or β-Tetrasubstituted Amino Acid Esters via Direct Catalytic Mannich-Type Reactions Using N-Unprotected Trifluoromethyl Ketimines.
Direct Access to N-Unprotected α- and/or β-Tetrasubstituted Amino Acid Esters via Direct Catalytic Mannich-Type Reactions Using N-Unprotected Trifluoromethyl Ketimines.
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DOI：
10.1002/chem.201703516
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
Masanao Sawa;Kazuhiro Morisaki;Yutaka Kondo;H. Morimoto;T. Ohshima
中科院分区：
文献类型：
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作者：
Masanao Sawa;Kazuhiro Morisaki;Yutaka Kondo;H. Morimoto;T. Ohshima
直接催化C-C键形成n -无保护酮胺是合成n -无保护四取代胺的一种有效和直接的方法，消除了先前的保护/去保护步骤，使产物易于转化。然而，尽管有其优点，n -未保护的酮胺在C-C键形成反应中存在困难，与n -未保护的酮胺相比，只有有限数量的反应和底物被报道。本文以mannich型反应为模型，报道了n -无保护的三氟甲基氯胺酮对C-C键形成反应有效。我们证明Lewis酸催化可以有效地促进与各种n无保护的三氟甲基氯胺酮的反应，而硫脲有机催化可以有效地促进与各种羰基亲核试剂的高度对映选择性反应，从而直接获得各种n无保护的α-和/或β-四取代氨基酸酯。此外，还首次以高度对映选择性和非对映选择性的方式直接构建了邻四取代手性碳立体中心。这些结果证明了n -无保护酮胺作为底物适用于许多其他加成反应的潜力。
Direct catalytic C-C bond-forming addition to N-unprotected ketimines is an efficient and straightforward method of synthesizing N-unprotected tetrasubstituted amines that eliminates prior protection/deprotection steps and allows facile transformation of the products. Despite its advantages, however, N-unprotected ketimines have difficulties in C-C bond-forming reactions, and only a limited number of reactions and substrates are reported compared with their N-protected counterparts. Herein we report that N-unprotected trifluoromethyl ketimines are effective for C-C bond-forming reactions using Mannich-type reactions as a model case. We demonstrate that Lewis acid catalysis was effective for promoting reactions with various N-unprotected trifluoromethyl ketimines, and thiourea organocatalysis was effective for promoting highly enantioselective reactions with various carbonyl nucleophiles, providing direct access to various N-unprotected α- and/or β-tetrasubstituted amino acid esters. Furthermore, direct construction of vicinal tetrasubstituted chiral carbon stereocenters was achieved for the first time in a highly enantio- and diastereoselective manner. These results demonstrate the potential of N-unprotected ketimines as substrates applicable to many other addition reactions.