An experimental and computational investigation of the enantioselective deprotonation of Boc-piperidine
An experimental and computational investigation of the enantioselective deprotonation of Boc-piperidine
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DOI：
10.1021/ja012169y
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发表时间：
2002-03-06
影响因子：
15
通讯作者：
Wiberg, KB
中科院分区：
文献类型：
--
作者：
Bailey, WF;Beak, P;Wiberg, KB
本文用实验和计算方法研究了仲烷基锂与（-）-金雀花碱的1：1络合物对N-Boc-哌啶（3）的不对称去质子化反应。3与sec-BuLi-（-）-金雀花碱在-78 ℃下的锂化反应（这是比N-Boc-吡咯烷（1）的类似去质子化慢得多的过程，并且相对于sec-BuLi竞争性地加成到氨基甲酸酯中是较小的反应）以中等程度的选择性（er = 87：13）进行，以除去3的pro-S氢。N-Boc-4-甲苯磺酰氧基哌啶（6）与2摩尔当量sec-BuLi-（-）-金雀花碱的相关去质子化也涉及pro-S氢的优先转移。通过i-PrLi-（-）-金雀花碱对（3）的去质子化的计算研究发现，优先在三组分中间体复合物内转移的质子是3的化学上酸性最小的α-氢。计算3的不对称去质子化以较差的对映选择性进行，并且具有比N-Boc-吡咯烷（1）的去质子化计算的活化能高得多的活化能。实验结果与计算结果吻合较好。
The asymmetric deprotonation of N-Boc-piperidine (3) by the 1:1 complex of a sec-alkyllithium and (-)-sparteine has been investigated both experimentally and computationally. The lithlation of 3 with sec-BuLi-(-)-sparteine at -78 degreesC, which is a much slower process than is the analogous deprotonation of N-Boc-pyrrolidine (1) and a minor reaction relative to the competing addition of sec-BuLi to the carbamate, proceeds with a moderate degree of selectivity (er = 87:13) for removal of the pro-S hydrogen of 3. The related deprotonation of N-Boc-4-tosyloxypiperidine (6) with two molar equiv of sec-BuLi-(-)-sparteine also involves preferential transfer of the pro-S hydrogen. The computational study of the deprotonation of (3) by i-PrLi-(-)-sparteine found that the proton that is preferentially transferred within three-component intermediate complex is the thermodynamically least acidic alpha-hydrogen of 3. The asymmetric deprotonation of 3 is calculated to proceed with poor enantioselectivity and to have an activation energy considerably higher than that calculated for deprotonation of N-Boc-pyrrolidine (1). The experimental and computational results are in good agreement.