Catalytic Asymmetric Three-Component Synthesis of Homoallylic Amines
Catalytic Asymmetric Three-Component Synthesis of Homoallylic Amines
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DOI：
10.1002/anie.201209776
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
List, Benjamin
中科院分区：
文献类型：
--
作者：
Gandhi, Shikha;List, Benjamin
醛（1）、氨基甲酸酯（或胺; 2）和无毒烯丙基三甲基硅烷（3）的直接催化三组分偶联是制备高烯丙基胺衍生物4的非常有效的方法[Eq.（1）]。然而，尽管在过去的几十年中，它在手性含氮物质的实际合成和不对称催化方面取得了巨大的进展，但该反应的对映选择性版本一直是完全未知的。[1-3]在此，我们报告我们的发现，9-芴基甲基氨基甲酸酯的反应（Fmoc-NH_2）与各种醛（1）和硅烷（3）在一种新的手性二磺酰亚胺催化剂存在下，高对映选择性地合成了相应的产物（4）。作为甲硅烷基化亲核试剂与醛反应的高活性和对映选择性催化剂。[4]初步的机理研究表明，这些反应进行通过一个不对称的counteraniondirected刘易斯酸催化机制操作的原位硅烷化的手性二磺酰亚胺。[5]虽然我们的DSI催化剂活化其他亲电试剂如亚胺的能力尚未被探索，但我们推测它们在上述三组分反应中的潜在适用性。虽然机制的细节是目前未知的，我们试图假设，这和相关的过程涉及甲硅烷基转移机制，并意味着顺从我们的甲硅烷基不对称反阴离子定向催化（ACDC）活化策略。我们的方法已被证明特别适用于具有强甲硅烷基催化背景的反应，因此不容易被手性刘易斯酸催化。可能，这种非对映选择性背景反应阻碍了催化不对称的发展。
The direct catalytic three-component coupling of aldehydes (1), carbamates (or amines; 2), and nontoxic allyltrimethylsilane (3) is a very effective approach to homoallylic amine derivatives 4 [Eq.(1)]. However, despite its great potential for the practical synthesis of chiral nitrogenous substances and the enormous progress of asymmetric catalysis over the last few decades, an enantioselective version of this reaction has been entirely unknown.[1–3] Herein we report our finding that the reaction of 9-fluorenylmethyl carbamate (Fmoc-NH2) with a variety of aldehydes (1) and silane 3 in the presence of a new chiral disulfonimide catalyst furnishes the corresponding products 4 highly enantioselectively and in good yield.We have recently introduced chiral enantiomerically pure disulfonimides (DSI) as highly active and enantioselective catalysts for the reaction of silylated nucleophiles with aldehydes.[4] Preliminary mechanistic studies suggest that these reactions proceed through an asymmetric counteraniondirected Lewis acid catalysis mechanism operated by an in situ silylated chiral disulfonimide.[5] While the ability of our DSI catalysts to activate other electrophiles such as imines has not yet been explored, we speculated on their potential applicability in the above three-component reaction. Although mechanistic details are currently unknown, we were tempted to hypothesize that this and related processes involve a silyl-transfer mechanism, and implies amenability to our silyl asymmetric counteranion-directed catalysis (ACDC) activation strategy. Our approach has proven particularly suitable in reactions that have a strong silyl catalysis background and are hence not easily catalyzed by chiral Lewis acids. Possibly, such a non-enantioselective background reaction has hampered the development of a catalytic asym-