School of Chemistry and Materials Science, Guizhou Normal University, Guiyang 550001, China.
J Org Chem. 2020 Apr 17;85(8):5203-5219. doi: 10.1021/acs.joc.9b03164. Epub 2020 Apr 3.
A novel Michael/alkylation cascade reaction of -unprotected 3-bromooxindoles with α,β-unsaturated acyl phosphonates using DABCO as a robust catalyst followed by the derivatization of the acyl phosphonate intermediates has been developed. This scenario enables rapid access to a diverse set of highly functionalized spirocyclopropyl oxindoles in moderate yields with good to excellent diastereoselectivities, which are analogues of a high active non-nucleoside reverse transcriptase inhibitor against HIV-1. The synthetic potential of this tactic has been highlighted by a gram-scale reaction and Suzuki cross-coupling reactions of the product. Moreover, the reaction mechanism has been tentatively elucidated by control experiments and dynamic high-resolution mass spectrometry studies, which indicates that the Michael/alkylation cascade reaction involves DABCO-derived α-substituted ammonium ylides.
发展了一种新颖的 DABCO 作为强催化剂的 - 未保护的 3-溴代氧吲哚与α,β-不饱和酰基膦酸盐的迈克尔/烷基化级联反应，随后对酰基膦酸盐中间体进行衍生化。这种方案可以快速获得多种高度官能化的螺环丙基氧吲哚，产率中等，具有良好到优秀的非对映选择性，这些化合物是一种针对 HIV-1 的高活性非核苷逆转录酶抑制剂的类似物。通过克级反应和产物的 Suzuki 交叉偶联反应突出了这种策略的合成潜力。此外，通过对照实验和动态高分辨率质谱研究初步阐明了反应机理，表明迈克尔/烷基化级联反应涉及 DABCO 衍生的α-取代铵叶立德。
