How the Binding of Substrates to a Chiral Polyborate Counterion Governs Diastereoselection in an Aziridination Reaction: H-Bonds in Equipoise

The stereochemistry-determining step of the self-assembled chiral Brønsted acid-catalyzed aziridination reactions of MEDAM imines and three representative diazo nucleophiles has been studied using ONIOM(B3LYP/6-31G*:AM1) calculations. The origin of cis selectivity in the reactions of ethyldiazoacetate and trans selectivity in reactions of N-phenyldiazoacetamide can be understood on the basis of the difference in specific noncovalent interactions in the stereochemistry-determining transition state. A H-bonding interaction between the amidic hydrogen and an oxygen atom of the chiral counterion has been identified as the key interaction responsible for this reversal in diastereoselectivity. This hypothesis was validated when a 3° diazoamide lacking this interaction showed pronounced cis selectivity both experimentally and calculationally. Similar trends in diastereoselection were observed in analogous reactions catalyzed by triflic acid. The broad implications of these findings and their relevance to chiral Brønsted acid catalysis are discussed.

本研究采用ONIOM(B3LYP/6-31G*:AM1)计算方法，对MEDAM亚胺与三种代表性重氮亲核试剂的自组装手性布朗斯特酸（Brønsted acid）催化氮丙啶化反应的立体化学决定步骤展开了系统研究。对于重氮乙酸乙酯参与反应所呈现的顺式选择性，以及N-苯基重氮乙酰胺参与反应所表现出的反式选择性，其内在根源可通过立体化学决定过渡态中特定非共价相互作用的差异得到合理解释。研究证实，酰胺氢原子与手性反离子的氧原子之间形成的氢键相互作用，是引发非对映选择性反转的关键相互作用。当缺乏该相互作用的三级重氮酰胺在实验与计算研究中均表现出显著的顺式选择性时，这一假说得到了有效验证。在三氟甲磺酸（triflic acid）催化的同类反应体系中，同样观察到了类似的非对映选择性变化趋势。本研究进一步讨论了上述发现的广泛学术意义，以及其在手性布朗斯特酸催化领域的相关应用价值。