掌性銠金屬雙烯錯合物催化不對稱加成反應

Asymmetric Transformations Catalyzed by Rh(I)/Chiral Dienes

張瓊安(Chang Chiung-An)

指導教授 ： 吳學亮

國立臺灣師範大學/理學院/化學系/博士(2018年)

https://doi.org/10.6345/DIS.NTNU.DC.073.2018.B05

摘要

本論文探討銠金屬與掌性雙環[2.2.1]雙烯配基形成之催化劑催化不對稱加成反應。內容分成下列兩部分。

一、 一價銠金屬/掌性雙環[2.2.1]雙烯配基催化烯醇醚基三氟硼酸鉀鹽試劑對α,β-不飽和羰基化合物進行不對稱1,4-加成反應
利用一價銠金屬以及掌性雙環[2.2.1]雙烯配基L1及L6形成之催化劑催化烯醇醚基三氟硼酸鉀鹽試劑2對環狀及鏈狀之α,β-不飽和羰基化合物1進行不對稱1,4-加成反應，可得到最高>99%之產率(13–>99%)及>99.5%之鏡像選擇性(44–>99.5% ee)的加成產物3。加成產物3ha可經由水解反應得到具有掌性中心之1,5-雙羰基結構23a，改善傳統由醛進行麥可加成反應(Michael addition)時會遇到加成產物為外消旋混合物；以及易有醛醇反應(aldol reaction)副反應發生之缺點。

二、 銠金屬(I)/掌性雙環[2.2.1]雙烯配基催化芳基硼酸試劑對α-酮酯化合物進行不對稱1,2-加成反應：(S)-Flutriafol的合成
利用一價銠金屬以及掌性雙環[2.2.1]雙烯配基L6形成之催化劑催化芳基硼酸試劑10對α-酮酯化合物76進行不對稱1,2-加成反應。僅需使用0.5 mol %之低催化量的一價銠金屬催化劑，即可得到最高達99%之鏡像選擇性(90–99% ee)及最高>99%之產率(2–>99%)的加成產物78，並成功建立具有掌性四級碳中心之α-羥基酯結構。此研究提供一個更快速、更簡單且產率更高的(S)-Flutriafol ((S)-90)新合成方法。

關鍵字

共軛加成 ； 銠 ； 酮酯化合物 ； 硼酸 ； 三氟硼酸鉀鹽

並列摘要

This thesis describes the employment of chiral Rh(I)-catalysts, in situ generated from [RhCl(C2H4)2]2 and chiral bicyclo[2.2.1]heptadienes, in the enantioselective addition reactions. The content covers two parts.

I. Enantioselective 1,4-Addition Reactions of Potassium Enol Ether Trifluoroborates to α,β-Unsaturated Carbonyl Compounds Catalyzed by Rh(I)/Chiral Bicyclo[2.2.1] dienes.
An enantioselective 1,4-addition of potassium enol ether trifluoroborates 2 to α,β-unsaturated carbonyls is described. In the presence of 3.0 mol % of the catalysts generated in situ from the [RhCl(C2H4)2]2 pre-catalyst and diene L1 or L6, the asymmetric reaction afforded the desired adducts 3 in up to 99% yield (13–>99%) and with up to >99.5% ee (44–>99.5% ee). The method was applied to the synthesis of 1,5-dicarbonyl 23a via a microwave-assisted acid hydrolysis that overcomes those existed in the conventional addition of aldehydes to α,β-unsaturated carbonyl compounds.

II. Enantioselective Arylation of α-Ketoesters: Total Synthesis of (S)-Flutriafol
A highly enantioselective addition of arylboronic acids 10 to α-ketoesters 76 catalyzed by a Rh(I)-chiral diene catalyst is reported. This transformation proceeds regioselectively in the presence of as low as 0.5 mol % of the catalyst generated in situ from a Rh(I) salt and diene L6 to afford tertiary chiral α-hydroxy esters 78 with high stereoselectivities (90–99% ee) and in good chemical yields (2–>99%). The method provides a new, expeditious and enantioselective approach to the synthesis of the fungicide (S)-Flutriafol ((S)-90).

並列關鍵字

conjugate addition ； rhodium ； ketoester ； boronic acid ； potassium enol ether trifluoroborate

參考文獻

參考文獻

1. (a) Shallenberger, R. S. J. Food Science 1963, 28, 584–589. (b) Shallenberger, R. S. Nature 1967, 216, 480–482.

2. (a) Franks, M. E.; Macpherson, G. R.; Figg, W. D. The Lancet 2004, 363, 1802–1811. (b) Moghe, V. V.; Kulkarni, U.; Parmar, U. I. Bombay Hosp. J. 2008, 50, 472–476. (c) Landesman-Dwyer, S. Appl. Res. Ment. Retard. 1982, 3, 241–263. (d) Kelsey F. O. J. Dent. Res. 1967, 46, 1201–1205.

3. (a) Van Caillie-Bertrand, M.; Degenhart, H. J.; Luijendijk, I.; Bouquet, J.; Sinaasappel, M. Arch. Dis. Child. 1985, 60, 652–655. (b) Aronson, J. K. Meyler's Side Effects of Analgesics and Anti- inflammatory Drugs. 1st edn (Elsevier, 2009)

4. Libershteyn, Y. Optometey. Vision. Sci. 2016, 93, 211–217.