Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, UK.
Chemistry. 2010 Apr 6;16(13):4082-90. doi: 10.1002/chem.200903059.
Proton abstraction of N-tert-butoxycarbonyl-piperidine (N-Boc-piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino-alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2-substituted piperidines, including (after Boc deprotection) the alkaloid (+)-beta-conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2-substituted seven-membered azepine ring derivatives.
用 sBuLi 和 TMEDA 对 N-叔丁氧羰基-哌啶（N-Boc-哌啶）进行质子抽提，得到外消旋的有机锂试剂，可以使用手性配体进行拆分。对映异构的有机锂试剂可以相互转化，从而发生动态拆分。在产物中促进对映选择性有两种可能的机制。缓慢加入三甲基硅氯等亲电试剂，可以在动力学控制下（DKR）进行动态拆分。这个过程具有高对映选择性，并且通过亚化学计量手性配体的催化（催化动态动力学拆分）成功。或者，这种有机锂试剂的两个对映异构体可以在热力学控制下进行良好的对映选择性拆分（动态热力学拆分，DTR）。发现的最佳配体基于手性二氨基烷氧基化物。使用 DTR，可以使用各种亲电试剂进行不对称合成对映体富集的 2-取代哌啶，包括（Boc 脱保护后）生物碱（+）-β-康定碱。该化学方法得到了扩展，尽管收率较低，但得到了相应的 2-取代的七元氮杂环庚烷衍生物。
