Chemoenzymatic Synthesis and Application of Bicyclo[2.2.2]octadiene Ligands: Increased Efficiency in Rhodium-Catalyzed Asymmetric Conjugate Additions by Electronic Tuning
Chemoenzymatic Synthesis and Application of Bicyclo[2.2.2]octadiene Ligands: Increased Efficiency in Rhodium-Catalyzed Asymmetric Conjugate Additions by Electronic Tuning
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DOI：
10.1002/anie.200907033
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Carnell, Andrew J.
中科院分区：
文献类型：
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作者：
Luo, Yunfei;Carnell, Andrew J.
手性二烯是一类新的高效配体，由Hayashi和Carriera等人独立开发，其在铑和铱催化的反应的不对称催化领域中显示出巨大的前景。[1]利用C1-对称和C2-对称的二烯，已经实现了一系列合成上有用的转化，具有优异的产率和对映体过量。[2 - 10]然而，与膦配体和C1-对称二烯相比，最广泛使用的C2-对称[2.2. 2]二烯配体受到不灵活的合成路线的限制，并且最值得注意的是，二烯或其合成前体的拆分困难，这目前是使用二烯或后期中间体的手性HPLC分离实现的。[1b因此，这些配体中的电子效应对活性和对映选择性的影响尚未得到很好的研究。尽管已经用当前的双环框架进行了包括电子和空间变化的结构修饰，[2b，c，5，6d，7]，但结果表明空间因素占主导地位。Hayashi等人已经证明了C1-对称[2.2. 2]其中一个烯烃与酯基共轭的二烯使亚胺的芳基化反应速率显著增加。[6d]尽管与膦配体相比，手性二烯-Rh催化剂允许反应在较低温度下进行，在二烯-铑-用芳基硼酸催化的芳基化反应通常需要多于两当量的芳基硼酸以获得高产率，并且对于特别是无活性的底物多达5当量。[2h这归因于竞争性脱硼副反应[17]，并表明反应温度不是导致低原子效率的唯一因素。
Chiral dienes are a new class of highly effective ligands, developed independently by Hayashi and Carriera et al., that have shown great promise in the field of asymmetric catalysis for reactions catalysed by rhodium and iridium.[1] A range of synthetically useful transformations have been realized in excellent yield and enantiomeric excess using C1-symmetric and C2-symmetric dienes.[2–10] However, compared with phosphine ligands and C1-symmetric dienes, the accessibility and structural variation in the most widely employed C2-symmetric [2.2. 2] diene ligands has been limited by inflexible synthetic routes and, most notably, the difficulty in resolution of the dienes or their synthetic precursors, which is currently achieved using chiral HPLC separation of the diene or a late-stage intermediate.[1b, 2, 11–14] As a result, the electronic effects on activity and enantioselectivity in these ligands have not been well studied. Although structural modifications including both electronic and steric changes have been made with the current bicyclic frameworks,[2b, c, 5, 6d, 7] the results have shown that steric factors are dominant. Hayashi et al. have shown that C1-symmetric [2.2. 2] dienes in which one alkene was conjugated with an ester group gave a remarkable rate increase in arylation of imines.[6d] In this example it is believed that an electron withdrawing naphthyl ester substituent on one of the alkenes accelerates transmetallation to form a trans aryl–rhodium bond.Although the chiral diene–Rh catalyst allows reactions to be conducted at lower temperatures compared with phosphine ligands, in diene–rhodium-catalyzed arylations with aryl boronic acids generally more than two equivalents of the arylboronic acid are necessary in order to achieve a high yield, and for particularly inactive substrates as many as 5 equivalents.[2h, 15, 16] This is attributed to the competing protodeboronation side-reaction [17] and indicates that reaction temperature is not the only factor responsible for the low atom efficiency.