利用一價銠金屬催化芳基硼酸對環狀α,β-不飽和β-酮酯進行不對稱1,4-加成反應：合成三尖杉鹼天然物

Abstract

本研究利用掌性雙環[2.2.1]雙烯配基L1與一價銠金屬形成的催化劑催化芳基硼酸28對環狀α,β-不飽和β-酮酯27和環狀α,β-不飽和β-醯胺酯27進行不對稱1,4-加成反應。在3.0 mol %的銠金屬和3.6 mol %的掌性雙[2.2.1]雙烯配基L催化下，可以得到加成產物產率17−82%、鏡像超越值75 −>99.5%的加成產物，且此加成產物也可進行一鍋化的烷基化反應(C-alkylation)，來建構出具有四級碳的產物，產物產率介於25−94%、鏡像超越值92−99%。此法可以應用在合成天然物(−)-Cephalotaxine以及抗憂鬱性質的藥物(−)-Paroxetine。

關鍵詞：銠金屬、1,4-加成反應、烷基化反應、芳基硼酸、雙烯配基

In this thesis, an enantioselective 1,4-addition of arylboronic acids 28 to cyclic α,β-unsaturated β-ketoesters 27 and cyclic α,β-unsaturated β-ketoamides 27 catalyzed by a Rh(I)-chiral diene catalyst is described. In the presence of 3.0 mol % of the catalyst generated in situ from a Rh(I) salt and diene L1, the asymmetric reaction afforded the desired adducts 26 in up to 82% yield (17–82% yield) and with up to >99.5% ee (75– >99.5% ee). In addition, this method can be applied in the one-pot alkylation reaction to afford products with a quaternary carbon in up to 94% yield (25–94% yield for two steps) and with 99% ee (92–99% ee). The method was applied in the synthesis of (−)-Cephalotaxine and (−)-Paroxetine.