A simple, mild, catalytic, enantioselective addition of terminal acetylenes to aldehydes
A simple, mild, catalytic, enantioselective addition of terminal acetylenes to aldehydes
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DOI：
10.1021/ja016378u
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发表时间：
2001-10-03
影响因子：
15
通讯作者：
Carreira, EM
中科院分区：
文献类型：
--
作者：
Anand, NK;Carreira, EM
末端乙炔与醛1或酮2的对映选择性加成提供了直接获得光学活性的炔丙醇的途径，这是一种有用的、用途广泛的构建单元，在化学合成中得到了广泛的应用。进行这些对映体选择性加成反应的现有方法需要使用化学计量的金属化乙炔，其形式为硼基乙酰或最近原位生成的锌(II)乙酰胺。1-3在我们对开发温和、实用的不对称CC键形成方法的持续兴趣中，1e我们研究了末端乙炔的原位CH活化，以给出参与催化的醛的不对称选择性加成的亲核碳负离子。在这里，我们报道了末端乙炔与醛的不对称加成反应，该反应在金属和手性配体中都是催化的。这是第一次使用真正催化量的金属将锌碳负离子对映体选择性地加到醛上；在此之前，化学计量的R2锌一直被使用。3以较高的产率和良好的选择性分离了炔丙基加合物。此外，我们记录了第一个例子，在醛的基础上加成了炔基苯胺，它可以在1.0当量的醛和1.05当量的炔的情况下进行无溶剂反应。4因此，这种体积效率高的工艺体现了理想的原子经济性，6这不仅是因为两种反应物组成了产物，而且还因为它省去了溶剂的使用。
The enantioselective addition of terminal acetylenes to aldehydes1 or ketones2 affords direct access to optically active propargyl alcohols which are useful, versatile building blocks that enjoy wide application in chemical synthesis. The existing methods for carrying out these enantioselective addition reactions require the use of stoichiometric quantities of metalated acetylenes, which have taken the form of boryl acetylides or, more recently, in situ generated Zn (II) alkynilides. 1-3 In our continuing interest in the development of mild, practical methods for asymmetric CC bond-formation, 1e we have investigated the in situ CH activation of terminal acetylenes to give nucleophilic carbanions that participate in catalytic, enantioselective additions to aldehydes. Herein, we report the enantioselective addition of terminal acetylenes to aldehydes, which is catalytic in both metal and chiral ligand. This is the first time that Zn-carbanions have been added enantioselectively to aldehydes using truly catalytic amounts of metal; previously, stoichiometric R2Zn has always been employed. 3 The propargylic adducts are isolated in useful yields and excellent selectivities. Additionally, we document the first example of an alkynilide addition to an aldehyde that can be conducted solvent-free with 1.0 equiv of aldehyde and 1.05 equiv of alkyne. 4 As such, this volumetrically efficient5 process exemplifies ideal atom economy, 6 not only because the two reactants comprise the product but also since it obviates the use of solvent.