Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates
Synthesis of Enantioenriched Tertiary Boronic Esters by the Lithiation/Borylation of Secondary Alkyl Benzoates
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DOI：
10.1021/ja409100y
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发表时间：
2013-10-30
影响因子：
15
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Pulis, Alexander P.;Blair, Daniel J.;Aggarwal, Varinder K.
据报道，简单的2,4,6-三异丙基苯甲酸酯（TIB酯）和仲二烷基N，N-二异丙基氨基甲酸酯具有抗强碱去质子化的能力。我们发现，在-60℃的CPME中，sBuLi（1.6当量）和TMEDA（6当量）的组合可以使未活化的仲二烷基TIB酯去质子化，但不能使氨基甲酸酯去质子化。这些碳离子与一系列新戊基硼酯反应，经过1,2-金属酸盐重排和氧化，得到一系列收率高、普遍高的叔醇。进一步证明叔硼酯的官能团转化（转化为四元中心，c -叔胺），并将该方法应用于合成最简单的含四元中心的无支化烃(R)-4-乙基-4-甲基辛烷，验证了该方法的合成实用性。
Simple, secondary 2,4,6-triisopropyl benzoates (TIB esters) and secondary dialkyl N,N-diisopropyl carbamates have been reported to be resistant to deprotonation by strong bases. We have found that the combination of sBuLi (1.6 equiv) and TMEDA (6 equiv) in CPME at -60 degrees C enables deprotonation of unactivated secondary dialkyl TIB esters, but not the carbamates. These carbanions were reacted with a range of neopentyl boronic esters which, after 1,2-metalate rearrangement and oxidation, gave a range of tertiary alcohols in high yield and universally high er. Further functional group transformations of the tertiary boronic esters were demonstrated (conversion to quaternary centers, C-tertiary amines) together with application of the methodology to the synthesis of the simplest unbranched hydrocarbon bearing a quaternary center, (R)-4-ethyl-4-methyloctane, validating the synthetic utility of the methodology.