Urruzuno Iñaki, Mugica Odei, Zanella Giovanna, Vera Silvia, Gómez-Bengoa Enrique, Oiarbide Mikel, Palomo Claudio
Departamento de Química Orgánica I, Universidad del País Vasco UPV/EHU, Manuel Lardizabal 3, 20018, San Sebastián, Spain.
Chemistry. 2019 Jul 22;25(41):9701-9709. doi: 10.1002/chem.201901694. Epub 2019 Jul 3.
In this study, the unique capacity of bifunctional Brønsted bases to generate α-branched ketone dienolates and control both site- and stereoselectivity of their addition reactions to representative classes of carbon electrophiles (i.e., vinyl sulfones, nitroolefins, formaldehyde) is documented. We demonstrate that by using selected chiral tertiary amine/squaramide catalysts, the reactions of β,γ-unsaturated cycloalkanones proceed through the dienolate Cα almost exclusively and provide all-carbon quaternary cyclic ketone adducts in good yields with very high enantioselectivities. A minor amount (<5 %) of γ-addition is observed when nitroolefins are used as electrophiles. The parent acyclic ketone dienolates proved to be less reactive under these conditions, and thus still constitute a challenging class of substrates. Quantum chemical calculations correctly predict these differences in reactivity and explain the observed site-specificity and enantioselectivity.
在本研究中，记录了双功能布朗斯特碱生成α-支链酮烯醇化物并控制其与代表性碳亲电试剂（即乙烯基砜、硝基烯烃、甲醛）加成反应的位点选择性和立体选择性的独特能力。我们证明，通过使用选定的手性叔胺/方酰胺催化剂，β,γ-不饱和环烷酮的反应几乎完全通过烯醇化物的Cα进行，并以高对映选择性提供高收率的全碳季碳环酮加合物。当使用硝基烯烃作为亲电试剂时，观察到少量（<5%）的γ-加成。事实证明，在这些条件下，母体无环酮烯醇化物的反应活性较低，因此仍然是一类具有挑战性的底物。量子化学计算正确地预测了这些反应活性的差异，并解释了观察到的位点特异性和对映选择性。
