Banik Steven M, Levina Anna, Hyde Alan M, Jacobsen Eric N
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Science. 2017 Nov 10;358(6364):761-764. doi: 10.1126/science.aao5894.
Small-molecule dual hydrogen-bond (H-bond) donors such as ureas, thioureas, squaramides, and guanidinium ions enjoy widespread use as effective catalysts for promoting a variety of enantioselective reactions. However, these catalysts are only weakly acidic and therefore require highly reactive electrophilic substrates to be effective. We introduce here a mode of catalytic activity with chiral H-bond donors that enables enantioselective reactions of relatively unreactive electrophiles. Squaramides are shown to interact with silyl triflates by binding the triflate counterion to form a stable, yet highly Lewis acidic, complex. The silyl triflate-chiral squaramide combination promotes the generation of oxocarbenium intermediates from acetal substrates at low temperatures. Enantioselectivity in nucleophile additions to the cationic intermediates is then controlled through a network of noncovalent interactions between the squaramide catalyst and the oxocarbenium triflate.
小分子双氢键（H键）供体，如脲、硫脲、方酰胺和胍离子，作为促进各种对映选择性反应的有效催化剂被广泛使用。然而，这些催化剂酸性较弱，因此需要高反应活性的亲电底物才能有效发挥作用。我们在此介绍一种手性H键供体的催化活性模式，它能使相对不活泼的亲电试剂发生对映选择性反应。研究表明，方酰胺通过与三氟甲磺酸根抗衡离子结合，与三氟甲磺酸硅相互作用，形成一种稳定但具有高路易斯酸性的配合物。三氟甲磺酸硅-手性方酰胺组合在低温下促进了缩醛底物生成氧鎓中间体。然后，通过方酰胺催化剂与三氟甲磺酸氧鎓之间的非共价相互作用网络，控制亲核试剂对阳离子中间体加成反应中的对映选择性。
