Stereoselective synthesis of isoxazolidines through pd-catalyzed carboetherification of N-butenylhydroxylamines
Stereoselective synthesis of isoxazolidines through pd-catalyzed carboetherification of N-butenylhydroxylamines
复制标题
DOI：
10.1002/anie.200701386
复制
发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Wolfe, John P.
中科院分区：
文献类型：
--
作者：
Hay, Michael B.;Wolfe, John P.
异恶唑烷经常被用作合成复杂分子的中间体，并且在一些有趣的生物活性化合物中被发现此外，异恶唑烷的NO键在还原条件下容易断裂，生成1,3 -氨基醇，也具有合成用途构建异恶唑烷最常用的方法是硝基酮和烯烃之间的1,3 -偶极环加成反应[4]，一步生成O1-C5键和C3-C4键[Eq.(1)]。虽然这些转化非常有用，但许多非活化烯烃的分子间环加成会产生区域异构体的混合物此外，主要的立体异构体通常是由烯烃较少阻碍面上的内加成产生的，而由外加成和/或加成到更多取代的烯烃面产生的立体异构体的选择性制备不能以直接的方式实现。[4]在本文中，我们描述了一种构建取代异恶唑烷的新方法，该方法涉及钯催化的n -丁烯基羟胺衍生物与芳基溴的碳醚化反应[Eq.(2)]。该方法是一种一步形成O1-C5键和C5 ' -Ar键的异恶唑烷环的新方法这些转化还提供了使用现有方法无法生成的异恶唑烷立体异构体的途径。这些反应似乎是通过分子内烯烃插入到先前前所未有的钯烷氧胺中间体中来进行的，这可能在其他pd催化的碳杂原子成键过程中有用。
Isoxazolidines are frequently used as intermediates in the synthesis of complex molecules,[1] and are found in several interesting biologically active compounds.[2] In addition, the isoxazolidine NO bond can be easily cleaved under reducing conditions to afford 1, 3-amino alcohols, which are also of synthetic utility.[3] The most commonly employed method for the construction of isoxazolidines involves 1, 3-dipolar cycloaddition reactions between nitrones and alkenes,[4] which generates the O1-C5 bond and the C3-C4 bond in one step [Eq.(1)]. Although these transformations are very useful, many intermolecular cycloadditions of unactivated alkenes generate mixtures of regioisomers.[4] Moreover, the major stereoisomers typically result from endo-addition on the less hindered face of the alkene, and the selective preparation of stereoisomers resulting from exo-addition and/or addition to the more substituted alkene face cannot be achieved in a straightforward manner.[4]In this communication, we describe a new approach to the construction of substituted isoxazolidines that involves palladium-catalyzed carboetherification reactions of N-butenyl hydroxylamine derivatives with aryl bromides [Eq.(2)]. This method represents a new strategy for construction of the isoxazolidine ring, in which the O1-C5 bond and a C5′-Ar bond are formed in one step.[5] These transformations also provide access to isoxazolidine stereoisomers that cannot be generated with currently available methods. The reactions appear to proceed via intramolecular alkene insertion into previously unprecedented palladium alkoxyamine intermediates, which may be of utility in other Pd-catalyzed carbon-heteroatom bond-forming processes.