Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation
Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation
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三氟化硼活化氨基二茂铁的不对称锂化：实验和计算研究
DOI：
10.1002/adsc.201000306
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发表时间：
2010
影响因子：
5.4
通讯作者：
K. Taban
中科院分区：
文献类型：
--
作者：
C. Metallinos;Josh Zaifman;T. Dudding;Lori Van Belle;K. Taban
在体积较大的手性1，2-二氨基环己烷配体存在下，与三氟化硼(BF3)络合的叔氨基二茂铁与烷基锂发生不对称锂化合反应。这是第一个BF3激活的前手性芳香胺的不对称锂化合反应，也是第一个由手性二胺(而不是(-)-司马豆碱)介导的这种转化。该方法提供了一系列富含对映体的2-取代-1-氨基二茂铁的快速途径，包括具有在催化中感兴趣的罕见取代模式的衍生物。该方法对映体选择性高(87：13~91：9 Er)，可将简单重结晶后的几种产物的单一对映体分离为游离氨基二茂铁或其氟硼酸铵盐。平面手性2-取代-L-氨基二茂铁产物的两个对极都是可接近的，两个相对立体化学相反的化合物的单晶X射线衍射分析证实了这一点。对该反应在M06-2X/6-311+g(2d，2p)水平上的32个不同过渡态进行了单点计算，得到了一个正确预测手性诱导的意义和程度的计算模型。在BF3络合叔氨基二茂铁的锂化反应中，有三个因素起着重要的作用：(I)保持一个高度有序的八元环过渡态；(Ii)存在一个强的Li···F接触，使手性二胺配体靠近二茂铁底物；(Iii)手性二胺添加剂中空间要求很高的N-烷基朝向或朝向氨基二茂铁和烷基锂。该模型可作为合理设计不对称锂离子新配体的预测工具。
Tertiary aminoferrocenes complexed to boron trifluoride (BF 3 ) are shown to undergo asymmetric lithiation with alkyllithiums in the presence of bulky chiral 1,2-diaminocyclohexane ligands. This reaction represents the first BF 3 -activated asymmetric lithiation of a prochiral aromatic amine and the first such transformation to be mediated by a chiral diamine other than (-)-sparteine. The process provides rapid access to a broad range of enantiomerically enriched 2-substituted-1-aminoferrocenes, including derivatives with uncommon substitution patterns that are of interest in catalysis. The enantioselectivity of the process is high enough (87:13 to 91:9 er) to allow for isolation of single enantiomers of several products after simple recrystallization as either the free aminoferrocenes or their ammonium fluoroborate salts. Both antipodes of the planar chiral 2-substituted-l-aminoferrocene products are accessible, as confirmed by single crystal X-ray diffraction analysis of two compounds with opposite relative stereochemistry. Single-point calculation of thirty-two different transition states of the reaction at the M06-2X/6-311+g(2d,2p) level produced a computational model that correctly predicted both the sense and extent of chiral induction. Three factors appeared to play important roles in determining enantioinduction during lithiation of BF 3 -complexed tertiary aminoferrocenes: (i) the maintenance of a highly organized eight-membered ring transition state; (ii) the existence of a strong Li···F contact which placed the chiral diamine ligand in close proximity to the ferrocene substrate; (iii) the orientation of the sterically demanding N-alkyl groups of the chiral diamine additives, either away or towards, the aminoferrocene and the alkyllithium. The model may serve as a predictive tool for the rational design of new ligands for this and related asymmetric lithiations.