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亚胺与三类代表性重氮亲核试剂参与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进行了系统探究。重氮乙酸乙酯反应的顺式选择性与N-苯基重氮乙酰胺反应的反式选择性，其成因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以阐明。研究证实，酰胺氢与手性反离子的氧原子之间形成的氢键相互作用，是引发该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层面均表现出显著顺式选择性时，上述假说得到了有效验证。在三氟甲磺酸(triflic acid)催化的同类反应中，同样观测到了相似的非对映选择性变化趋势。本文讨论了本研究发现的广泛启示，及其在手性布朗斯特酸催化领域的研究价值。