The Soai reaction has profoundly impacted chemists’ perspective of autocatalysis, chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Here we describe the unprecedented observation of asymmetry-amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc alkoxides that incorporate specific structural mutations reveal a ‘pyridine-assisted cube escape’. The new tetrameric cluster functions as a catalyst that activates the substrate through a two-point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the nonlinear behaviour of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility—a central mechanistic aspect of this iconic transformation.

Soai反应深刻地影响了化学家的自催化，手性对称性断裂，绝对不对称合成及其在生物同手性起源中的作用的观点。在这里，我们描述了使用二异丙基锌在5-（三甲基甲硅烷基乙炔基）吡啶-3-甲醛烷基化反应中不对称扩增自催化作用的空前观察。用替代底物进行的动力学研究以及一系列掺入特定结构突变的烷氧基锌的光谱分析表明，存在“吡啶辅助的立方逃逸”。新的四聚体簇起催化剂的作用，该催化剂通过两点结合模式激活底物，并形成用于烷基转移的配位二异丙基锌部分。通过密度泛函理论计算验证了导致同手性和杂手性产物的过渡态模型。此外，杂手性配合物的实验和计算分析为该系统的非线性行为提供了明确的解释。我们对Soai系统的解构揭示了自动催化剂演变，功能和底物相容性的结构逻辑，这是该标志性转变的主要机制。