利用銠金屬催化反應合成前列腺素以及阿普斯特片

Abstract

本論文研究以一價銠金屬形成之催化劑催化不對稱1，4-加成反應。分為兩部分:第一部分是合成阿普斯特片(Apremilast)，第二部分則是合成多種前列腺素。 一、 銠金屬(I)催化芳香族硼酸對β-酞醯亞胺烯基碸進行不對稱加成反應進而合成阿普斯特片 利用5 mol %銠金屬與6 mol %掌性雙烯配基L1或L10催化芳香基硼酸對-酞醯亞胺烯基碸化合物進行不對稱芳基加成反應，可以有效合成一系列具有高鏡像選擇性產物。總共有27個例子，產率為13–96%，鏡像超越值為94–99%，並且我們藉由配基的選擇可以控制產物的掌性中心。得到的加成產物經過一步反應後可以得到藥物阿普斯特片(18)。

二、 銠金屬(I)催化烯基芳香族硼酸對2-環戊烯酮進行不對稱加成反應並應用在合成前列腺素 此題目主要是探討利用一價銠金屬([RhCl(COD)]2)，以甲醇作為溶劑，催化量的氫氧化鉀作為添加劑，以低功率微波(50 W)在30 °C的條件下進行烯基硼酸對具有掌性中心的化合物(129)進行1,4-共軛加成反應，得到單一非鏡像異構物，並可進而合成F型前列腺素(Prostaglandins, PG) dinoprost以及tafluprost (zioptan)。

共軛加成反應,銠金屬, 掌性配基, 硼酸, 鏡像超越值

This thesis describes the employment of Rh(I)-catalyzed 1,4-addition reactions and is divided into two topics: the synthesis Apremilast and the preparation of various prostaglandins. 1. Rh-Catalyzed Enantioselective Arylation of β-Phthalimino Vinylsulfones: The Syntheisis of Apremilast. Enantioenriched -amino sulfones were prepared from the Rh-catalyzed asymmetric addition of a range of arylboronic acids to -phthalimide vinyl sulfones in the presence of Rh(I)-catalysts comprising chiral diene ligands L1 and L10 that gave (R) and (S) adduct, respectively. This asymmetric transformation sees its synthetic application in the synthesis of Apremilast.

2. Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a Cyclopentenone Useful for the Synthesis of Prostaglandins An efficient and trans-diastereoselective Rh(I)-catalyzed 1,4-conjugate addition reaction of alkenylboronic acids and a homochiral (R)-4-silyloxycyclopentenone useful for the synthesis of derivatives of prostaglandins E and F is described for the first time. The reaction functions under mild conditions and is particularly rapid under low power (50 W) microwave irradiation at 30 °C in MeOH in the presence of a catalytic amount of KOH. Under these conditions, 3 mol % of [RhCl(COD)]2 is typically required to produce high yields. This method demonstrats its utility in the synthesis of PGF2α (dinoprost) and tafluprost (zioptan).

conjugate addition, Rh(I)-catalyzed, chiral ligand, boronic acid, Enantioselective