Departamento de Química Orgánica, Universidad de Valencia, Dr Moliner 50, E-46100, Burjassot, Valencia, Spain.
Org Biomol Chem. 2011 Oct 7;9(19):6616-22. doi: 10.1039/c1ob05609c. Epub 2011 Aug 15.
The role of Ti(Oi-Pr)(4) Lewis acid (LA) in the cooperative N-heterocyclic carbene (NHC)/LA catalyzed addition of enals to enones to yield cis-cyclopentenes has been investigated using DFT methods at the B3LYP/6-31G** computational level. Ti(IV) effectively catalyzes the reaction by formation of a complex with cinnamaldehyde 1, which favors the nucleophilic attack of NHC 5 on 1, and the subsequent proton abstraction to yield the extended Ti(IV)-Breslow intermediate 21. The nature of the metal involved in the LA catalyst plays a relevant role due to the more basic character of NHCs than aldehydes. Thus, strong LAs, such as Zn(OTf)(2), prevent the catalytic behavior of NHCs to form a very stable complex. The subsequent formation of a complex between chalcone 2 and the extended Ti(IV)-Breslow intermediate 21 favors the cis stereoselective C-C bond-formation. Analysis of the structures of Ti(IV)-complex precursors for the cis and trans C-C bond-formation steps allows for an explanation of the unexpected cis stereoselectivity.
采用 B3LYP/6-31G** 计算水平的密度泛函理论（DFT）方法，研究了 Ti(Oi-Pr)(4)路易斯酸（LA）在 N-杂环卡宾（NHC）/LA 协同催化烯醛与烯酮加成生成顺式环戊烯中的作用。Ti(IV) 通过与肉桂醛 1 形成配合物，有效地催化了反应，这有利于 NHC 5 对 1 的亲核进攻，以及随后质子的提取，生成扩展的 Ti(IV)-Breslow 中间体 21。LA 催化剂中金属的性质起着重要的作用，因为 NHCs 的碱性比醛更强。因此，像 Zn(OTf)(2) 这样的强 LA 会阻止 NHC 发挥催化作用，形成非常稳定的配合物。查尔酮 2 与扩展的 Ti(IV)-Breslow 中间体 21 之间形成配合物，有利于顺式立体选择性的 C-C 键形成。对顺式和反式 C-C 键形成步骤的 Ti(IV)-配合物前体的结构分析，解释了出乎意料的顺式立体选择性。
