Department of Chemistry, The Hong Kong University of Science and Technology , Clearwater Bay, Kowloon, Hong Kong, China.
J Org Chem. 2014 Sep 19;79(18):8774-85. doi: 10.1021/jo501604e. Epub 2014 Sep 4.
Reactions of α,β-unsaturated aldehydes and cyclic 1,3-dicarbonyl compounds proceed primarily by cascade Knoevenagel condensation/six-π-electron electrocyclization (K6EC, formal [3 + 3] cycloaddition), while α,β-unsaturated ketones usually react with cyclic 1,3-dicarbonyl compounds in a 1,4-addition manner. This paper discloses our findings that under acidic conditions, α,β-unsaturated carbonyl compounds (ketones and aldehydes) with a tethered alcohol react with cyclic 1,3-dicarbonyl compounds in a highly regioselective 1,4-addition fashion via in situ generation of a hypothetical α-methylene cyclic oxonium ion as the reactive Michael acceptor. Our studies uncovered the important effect of the tethered alcohol on the reaction rate and/or efficiency and some new mechanistic aspects of the cascade Michael addition/cycloketalization. Finally, the substrate scope was examined, and 43 analogues of penicipyrone and tenuipyrone were prepared in good to excellent yields.
α,β-不饱和醛和环状 1,3-二羰基化合物的反应主要通过级联 Knoevenagel 缩合/六-π-电子电环化（K6EC，形式上为 [3 + 3] 环加成）进行，而 α,β-不饱和酮通常以 1,4-加成方式与环状 1,3-二羰基化合物反应。本文揭示了我们的发现，即在酸性条件下，带有连接醇的α,β-不饱和羰基化合物（酮和醛）与环状 1,3-二羰基化合物以高度区域选择性的 1,4-加成方式反应，通过原位生成假设的α-亚甲基环状氧鎓离子作为反应性迈克尔受体。我们的研究揭示了连接醇对反应速率和/或效率的重要影响，以及级联迈克尔加成/环缩酮化的一些新的机制方面。最后，考察了底物范围，以良好至优异的收率制备了 43 个类似品比啶酮和泰尼比啶酮。
