以掌性銠金屬雙烯錯合物催化不對稱1,4-加成反應合成掌性含氮分子

Syntheses of Chiral Nitrogen-containing Molecules via Asymmetric 1,4-Addition Reactions Catalyzed by Rhodium/Chiral Diene Complexes

方若嫙(Fang Jo-Hsuan)

指導教授 ： 吳學亮

國立臺灣師範大學/理學院/化學系/博士(2016年)

https://doi.org/10.6345/NTNU202203482

摘要

['壹、銠催化芳基硼酸與氮-特丁氧羰基保護的α,β-不飽和γ-內醯胺的不對稱1,4-加成反應：
我們運用由左旋醋酸冰片酯合成出的一系列掌性雙環[2.2.1]二烯配體L1與一價銠金屬形成之催化劑，催化各種芳基硼酸14與氮-特丁氧羰基保護的α,β-不飽和γ-內醯胺195a進行不對稱1,4-加成反應。在0.5 mol%的Rh(I)/L1f催化劑量下，本反應可生成高產率 （31–>99%） 及高鏡像選擇性（93–>99.5% ee）的加成產物(R)-197。此法可應用至苯基海人酸207以及MCHR1拮抗劑302的形式合成。

貳、銠催化芳基硼酸與α-取代的β-硝基丙烯酸酯的不對稱1,4-加成反應：
本部分內容綜述各種芳基硼酸14與α-取代的β-硝基丙烯酸酯361的不對稱共軛加成反應。以5.0 mol%的Rh(I)/L1e進行催化反應，並利用KHF2做為添加劑，可製備出加成產物(R)-362，產率最高可至63%，鏡像超越值高達99% ee。此方法可應用至具有光學活性的β2,2-胺基酸369，β-內醯胺375，以及α,β2,2,α-胜肽380的不對稱合成。
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關鍵字

鏡像選擇性 ； 掌性二烯配體 ； 銠催化 ； 不對稱合成 ； 共軛加成 ； 芳基硼酸 ； β-胜肽

並列摘要

['I.Rhodium-Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to N-Boc Protected α,β-Unsaturated γ-Lactam:
A family of chiral bicyclo[2.2.1]heptadiene ligands L1 synthesized from L-(−)-bornyl acetate were utilized in the Rh(I)-catalyzed enantio- selective 1,4-addition of various arylboronic acids 14 to N-Boc-protected α,β-unsaturated γ-lactam 195a. In the presence of 0.5 mol% of a Rh(I)/L1f catalyst, the corresponding adducts (R)-197 were isolated in high yields (31–>99%) and excellent enantioselectivities (93–>99.5% ee). This metho- dology was employed for the formal synthesis of phenylkainic acid 207 and MCHR1 antagonist 302.

II.Rhodium-Catalyzed Asymmetric 1,4-Addition of Arylboronic Acids to α-Substituted β-Nitroacrylates:
Asymmetric conjugate addition of various arylboronic acids 14 to α-substituted β-nitroacrylates 361 was described. The reaction, catalyzed by 5.0 mol% of Rh(I)/L1e, provided the conjugate adduct (R)-362 in up to 63% yield and up to 99% ee using KHF2 as an additive. This method are applied to the asymmetric synthesis of optically active β2,2-amino acid 369, β-lactam 375, and α,β2,2,α-peptide 380.
']

並列關鍵字

Enantioselective ； Chiral diene ligands ； Rhodium-catalyzed ； Asymmetric synthesis ； Conjugate addition ； Arylboronic acids ； β-Peptides

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