Table 8. Houk-List Transition state analogues

The ten year old Houk-List model, for rationalising the origin of stereoselectivity in the organocatalysed intermolecular aldol addition, is revisited using a variety of computational techniques which have been introduced or improved since the original study. Even for such a relatively small system, the role of dispersion interactions is shown to be crucial, along with the use of basis sets where the superposition errors are low. Understanding the non covalent interactions (NCI) at play is highlighted as essential for the design of new synthetic routes and alternative reactants. An NCI analysis of the transition states enables the identification of non-covalent interactions that determine the reaction outcome, confirming the role of the electrostatic NCHᵟ+∙∙∙Oᵟ- interactions and highlighting new geometric schemes based on dispersion. Alternative mechanisms, such as proton-relays involving a water molecule or the Hajos-Parrish alternative, are shown to be higher in energy. The Amsterdam manifesto, which espouses the principle that scientific data should be citable, is followed here by using interactive data tables assembled via calls to the data DOI (digital-object-identifiers) held on a digital repository.

针对已有十年历史的Houk-List模型（Houk-List model），本研究借助自该原始研究问世以来新提出或优化的多种计算技术对其展开重新审视。该模型最初用于阐释有机催化分子间羟醛加成反应中立体选择性的起源。即便针对这类相对小型的反应体系，色散相互作用的作用仍被证实至关重要，同时需采用基组叠加误差较低的基组。明确反应体系中参与作用的非共价相互作用（non-covalent interactions, NCI），被视为设计全新合成路径与替代反应物的核心必要条件。对反应过渡态开展的NCI分析，可精准识别决定反应最终结果的非共价相互作用，验证了静电相互作用NCHδ+∙∙∙Oδ-的核心作用，并揭示了基于色散作用的新型几何作用模式。其他反应路径，例如涉及水分子的质子转移机制或Hajos-Parrish变体路径，均被证实具有更高的反应能垒。本文遵循《阿姆斯特丹宣言》（Amsterdam manifesto）所倡导的"科学数据可被引用"原则，通过调用数字仓储中存储的数字对象标识符（digital-object-identifiers, DOI）构建交互式数据表，实现了相关研究数据的可追溯与可复用。