Development of catalytic enantioselective amide allylation of isatins under mild conditions and its application to the synthesis of spirocyclic 2-oxindole lactones

2015 Fiscal Year Final Research Report

• Project/Area Number: 25410038
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Organic chemistry
• Research Institution: Shizuoka University
• Principal Investigator: Yoda Hidemi 静岡大学, 工学部, 教授 (20201072)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI MASAKI 静岡大学, 工学部, 教授 (30313935) ; SENGOKU TETSUYA 静岡大学, 工学部, 助教 (70451680)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: イサチン / アミドアリル化 / 不斉触媒 / 立体選択性 / 生理活性物質

Outline of Final Research Achievements

Novel catalytic asymmetric amide allylation of isatin derivatives with β-amido functionalized allylstannanes was investigated to develop an enantioselective synthesis of antineoplactic spirocyclic 2-oxindole lactones. As a result of our investigations, we found that indium-catalyzed amide allylation of isatins with N-(p-tolyl)-β-amidoallylstannane provided the corresponding homoallylic alcohols with both excellent enantioselectivities and chemical yields. Several mechanistic investigations demonstrated that the substrate-reagent hydrogen bond interaction plays a critical role in the formation of the key transition state resulting in enhanced catalytic reactions. Subsequent lactonization of the homoallylic alcohols followed by iodination gave the corresponding spirocyclic 2-oxindole lactones without loss of the stereochemical integrities.

Free Research Field

有機化学