Centre for Synthesis and Chemical Biology, Trinity Biomedical Sciences Institute, School of Chemistry, The University of Dublin, Trinity College, Dublin 2, Ireland.
Org Biomol Chem. 2021 Jan 6;19(1):248-258. doi: 10.1039/d0ob02017f.
The enantioselective intermolecular crossed-benzoin condensation mediated by novel chiral N-heterocyclic carbenes derived from pyroglutamic acid has been investigated. A small library of chiral triazolium ions were synthesised. Each possessed a tertiary alcohol H-bond donor and a variable N-aryl substituent. It was found that increasing both the steric requirement and the electron-withdrawing characteristics of the N-aryl ring led to more chemoselective, efficient and enantioselective chemistry, however both quenching the reaction at different times and deuterium incorporation experiments involving the product revealed that this is complicated by product racemisation in situ (except in the case of benzoin itself), which explains the dependence of enantioselectivity on the electrophilicity of the reacting aldehydes common in the literature. Subsequent protocol optimisation, where one reacting partner was an o-substituted benzaldehyde, allowed a range of crossed-benzoins to be synthesised in moderate-good yields with moderate to excellent enantioselectivity.
新型手性吡咯烷酮衍生的氮杂环卡宾介导的对映选择性分子间交叉苯偶姻缩合反应已经被研究。合成了一系列手性三唑鎓盐。每个三唑鎓盐都具有叔醇氢键供体和可变的 N-芳基取代基。研究发现，增加 N-芳基环的空间位阻和吸电子特性会导致更具化学选择性、高效和对映选择性的化学，但同时也会在不同时间使反应猝灭，并且涉及产物的氘掺入实验表明，这会使产物在原位外消旋复杂化（苯偶姻本身的情况除外），这解释了文献中常见的反应性醛的亲电性对对映选择性的依赖性。随后的优化方案中，一个反应性亲电体是邻位取代的苯甲醛，这允许以中等至良好的收率合成一系列中等至优异对映选择性的交叉苯偶姻。
