Full Chirality Transfer in the Conversion of Secondary Alcohols into Tertiary Boronic Esters and Alcohols Using Lithiation-Borylation Reactions
Full Chirality Transfer in the Conversion of Secondary Alcohols into Tertiary Boronic Esters and Alcohols Using Lithiation-Borylation Reactions
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DOI：
10.1002/anie.201001371
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发表时间：
2010-01-01
影响因子：
16.6
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Bagutski, Viktor;French, Rosalind M.;Aggarwal, Varinder K.
制备完全取代的碳原子（例如季立体中心[1]或叔醇[2]）的一般方法通常具有高的对映选择性（> 96%ee）和广泛的底物范围，是有机合成中最具挑战性的目标之一。[3]我们的研究小组最近描述了一种概念上的新方法，接近于满足这样的挑战（方案1）。[4]在该方法中，首先将容易获得的对映体富集的仲醇转化为氨基甲酸酯化合物。锂化和随后的反应与硼试剂，氧化后处理，叔醇具有高ee值。也许最有趣的方面，这种新的方法是，在所有情况下，反应发生时，基本上完全反转的配置时，硼烷，但几乎完全保留的配置时，使用硼酸酯。虽然该反应对于简单底物（> 90%ee）运行良好，但我们发现在氨基甲酸酯或硼酸酯中引入空间上更苛刻的基团或在氨基甲酸酯中引入吸电子芳族基团导致对映选择性的相当大的侵蚀。在本文中，我们为观察到的对映体选择性降低提供了理论依据，并且通过理解该过程的复杂性，我们还提出了一种解决问题的方案，该方案现在对所有测试的底物（即使是最苛刻的底物）都具有> 98%的ee。
A general method for the preparation of fully substituted carbon atoms (eg quaternary stereogenic centers [1] or tertiary alcohols [2]) that routinely gives high enantioselectivities (> 96% ee) with broad substrate scope is one of the most challenging goals in organic synthesis.[3] Our research group has recently described a conceptually new method that comes close to meeting such a challenge (Scheme1).[4] In this process, readily available enantioenriched secondary alcohols were first converted into carbamate compounds. Lithiation and subsequent reaction with boron reagents gave, after oxidative workup, tertiary alcohols with high ee values. Perhaps the most intriguing facet of this novel methodology was that in all cases the reactions occurred with essentially complete inversion of configuration when boranes were employed but almost complete retention of configuration when boronic esters were used. Although the reaction worked well for simple substrates (> 90% ee), we have found that the introduction of sterically more demanding groups in the carbamate or boronic ester or the introduction of electronwithdrawing aromatic groups in the carbamate resulted in a considerable erosion of enantioselectivity. Herein, we provide a rationale for the observed decrease in enantioselectivity and through understanding the intricacies of the process, we also present a solution to the problem that now results in> 98% ee for all the substrates tested, even the most demanding.