利用一價銠金屬催化不對稱反應合成掌性天然生物鹼

Rhodium(I)-Catalyzed Enantioselective Transformations: Syntheses of Natural Occurring Alkaloids

李韋賢(Li Wei-Sian)

指導教授 ： 吳學亮

國立臺灣師範大學/理學院/化學系/博士(2020年)

https://doi.org/10.6345/NTNU202000935

摘要

本論文探討利用一價銠金屬與掌性雙環[2.2.1]雙烯配基所形成掌性催化劑催化不對稱加成反應，並藉由得到的掌性化合物來合成生物鹼。內容分為兩部分:
一、 藉由以一價銠金屬催化劑催化脂肪族醛亞胺進行具鏡像選擇性之烯丙基化反應以合成掌性高烯丙基脂肪胺化合物
以3.0 mol %一價銠金屬與掌性雙環[2.2.1]雙烯配基L1a所形成錯合物為催化劑，在含水的條件下，催化烯丙基三氟硼酸鉀鹽11對脂肪族醛亞胺10及53進行不對稱加成反應，生成一系列掌性高烯丙基脂肪胺化合物12、76、77及78，產物產率為21–95%，鏡像超越值為85–98%，非鏡像選擇性最高為13.5:1。此外，將掌性高烯丙基脂肪胺化合物經由數步反應可合成出(R)-Coniceine (13)、(−)-Indolizidine 167B (3)、(S)-Coninne (5)及(−)-Pelletierine (6)。

二、 利用一價銠金屬催化對3,4-二氫異喹啉胺鹽進行不對稱芳基化反應
利用3.0 mol %一價銠金屬與掌性雙環[2.2.1]雙烯配基L22f所形成之催化劑，催化四芳香基硼與具不同取代3,4-二氫異喹啉胺所形成的錯鹽133進行不對稱芳基化反應，得到一系列1號位具芳基取代的掌性1,2,3,4-四氫異喹啉15，產率為35–94%，鏡像超越值為75–97%。值得注意的是，利用四芳香基硼為配位離子不光可穩定起始物，且可當作芳基提供來源。另外可藉由此方法合成(R)-Cryptostylines I (ent-7)。

關鍵字

一價銠金屬催化 ； 脂肪族醛亞胺 ； 烯丙基加成反應 ； 掌性高烯丙基脂肪胺化合物 ； 3,4-二氫異喹啉 ； 不對稱加成 ； 掌性1,2,3,4-四氫異喹啉

並列摘要

This thesis describes the syntheses of natural occuring alkaoids from the enantioselective addition reactions catalyzed by Rh(I)-catalysts, which are in situ generated from [RhCl(C2H4)2]2 and the chiral bicyclo[2.2.1]heptadiene ligands. The content comprises two topics.
I. Syntheses of -Allyl Alkylamines by Enantioselective Rhodium(I)-Catalyzed Allylation of Aliphatic Imines
An enantioselective allylation of aliphatic aldimines was achieved, in the presence of 3.0 mol % of Rh(I)-catalyst in situ generated from the [RhCl(C2H4)2]2 and the chiral bicyclo[2.2.1]heptadiene ligand L1a, furnishing the desired homoallylic amines 12、76、77 and 78 bearing an -aliphatic side chain in 21–95% yields with 85–98% ee’s, and up to 13.5:1 diastereoselectivity under aqueous reaction conditions. Enantioselective syntheses of (R)-Coniceine (13), (−)-Indolizidine 167B (3), (S)-Coniine (5) and (−)-Pelletierine (6) were performed to prove the feasibility of this method.

II. Enantioselective Rhodium(I)-Catalyzed Arylation of 3,4-Dihydroisoquinolinium salts
An enantioselective arylation of 3,4-dihydroisoquinolinium salts was reported. In the presence of 3.0 mol % of the catalyst in situ generated from the [RhCl(C2H4)2]2 and the chiral bicyclo[2.2.1]heptadiene ligand L22f, the desired 1-aryl-tetrahydroisoquinolines 15 were afforded in 35–94% yields with 75–97% ee’s. Notably, the use of tetraarylborate counteranions not only enhance the stability of substrates but they also are nucleophilic aryl donor for such addition reaction. This method tolerates with various dihydroisoquinolinium tetraarylborates 133 to efficiently offer chiral 1-aryl-tetrahydroquinolines 15, demonstrated in the expedient synthesis of (−)-cryptostyline I (ent-7).

並列關鍵字

Rh(I)-catalyst ； enantioselective allylation of aliphatic aldimines ； enantioselective arylation of 3,4-dihydroisoquinolinium salts ； 1-aryl-tetrahydroisoquinolines

參考文獻

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