Ali Camran, Blackmond Donna G, Burés Jordi
Department of Chemistry, The University of Manchester, Manchester M13 9PL, U.K.
Scripps Research, Department of Chemistry, La Jolla, California 92037, United States.
ACS Catal. 2022 May 20;12(10):5776-5785. doi: 10.1021/acscatal.2c00783. Epub 2022 Apr 29.
Observations of nonlinear effects of catalyst enantiopurity on product enantiomeric excess in asymmetric catalysis are often used to infer that more than one catalyst species is involved in one or more reaction steps. We demonstrate here, however, that in the case of asymmetric catalytic cascade reactions, a nonlinear effect may be observed in the absence of any higher order catalyst species or any reaction step involving two catalyst species. We illustrate this concept with an example from a recent report of an organocatalytic enantioselective [10 + 2] stepwise cyclization reaction. The disruption of pre-equilibria (Curtin-Hammett equilibrium) in reversible steps occurring prior to the final irreversible product formation step can result in an alteration of the final product from what would be expected based on a linear relationship with the enantiopure catalyst. The treatment accounts for either positive or negative nonlinear effects in systems over a wide range of conditions including "major-minor" kinetics or the more conventional "lock-and-key" kinetics. The mechanistic scenario proposed here may apply generally to other cascade reaction systems exhibiting similar kinetic features and should be considered as a viable alternative model whenever a nonlinear effect is observed in a cascade sequence of reactions.
在不对称催化中，催化剂对映体纯度对产物对映体过量的非线性效应的观察结果常被用于推断在一个或多个反应步骤中涉及不止一种催化剂物种。然而，我们在此证明，在不对称催化级联反应的情况下，在不存在任何高阶催化剂物种或任何涉及两种催化剂物种的反应步骤时，也可能观察到非线性效应。我们以最近一篇关于有机催化对映选择性[10 + 2]逐步环化反应的报告中的一个例子来说明这一概念。在最终不可逆产物形成步骤之前发生的可逆步骤中，预平衡（柯廷-哈梅特平衡）的破坏可能导致最终产物与基于对映纯催化剂的线性关系所预期的产物有所不同。该处理方法适用于包括“主次”动力学或更传统的“锁钥”动力学在内的广泛条件下系统中的正或负非线性效应。这里提出的机理情况可能普遍适用于其他表现出类似动力学特征的级联反应系统，并且每当在反应的级联序列中观察到非线性效应时，都应将其视为一个可行的替代模型。
