樟腦衍生之掌性β-胺基醇及β-胺基硫醇在催化不對稱加成反應之研究

Asymmetric Addition Reactions Catalyzed by Camphor-Derived Chiral β-Amino Alcohols and β-Amino Thiols

黃偉銘(Huang, Wei Ming)

指導教授 ： 汪炳鈞

國立清華大學/理學院/化學系/博士(2015年)

摘要

因申請專利緣故，資料延後公開 本論文在討論樟腦衍生之掌性β-胺基醇及β-胺基硫醇催化不對稱加成反應之研究。論文共分三部份，第一部份探討一系列β-胺基醇12a–l為催化劑，促進烷基鋅對芳香亞胺的不對稱加成反應。最後以10 mol%的催化劑12a在添加1.8當量的甲醇添加劑條件下，得到60–92%產率的二級芐胺及84–96%的鏡像選擇性。 第二部份探討一系列β-胺基醇31a–42e、43和44，將其應用在不對稱亨利反應。最後以2 mol%的催化劑35e在添加2當量的硼酸三乙酯添加劑條件下，得到21–>99%產率的硝基醇產物及82–96%的鏡像選擇性。値得注意的是，額外添加34 mol%的去離子水，可進一步提升對位-氯苯甲醛之加成物的產率。 第三部份探討β-胺基硫醇30為催化劑，促進重氮乙酸乙酯對苯甲醛的不對稱加成反應，以建立具光學活性的α-重氮-β-羥基酸乙酯，得到92%的產率和66%的鏡像超越值。

關鍵字

樟腦 ； 不對稱加成反應 ； 二烷基鋅 ； 亨利反應 ； 亞胺 ； 重氮乙酸乙酯

並列摘要

因申請專利緣故，資料延後公開
This thesis reports the application of camphor-derived chiral β-amino alcohols and β-amino thiols in asymmetric addition reactions. In the first part, a series of chiral amino alcohols 12a–l has been synthesized and used in the enantioselective addition of dialkylzinc to aromatic aldimines. Application of the optimal chiral ligand 12a (10 mol%) with methanol (1.8 equiv.) as the additive to activate the reaction of aromatic aldimines with diethylzinc and dimethylzinc resulted in high yields (60–92%) and enantioselectivities (84–96% ee).
In the second part, a series of chiral amino alcohols 31e–42e, 43 and 44 has been synthesized and used in asymmetric Henry reaction. Application of the optimal chiral ligand 35e (2 mol%) with triethyl borate (2 equiv.) as the additive to activate the reaction of aldehyde with nitromethane and nitroethane resulted in yields (21–>99%) and enantioselectivities (82–96% ee). Notably, the addition of extra 34 mol% H2O could improve the adduct yield of para-chlorobenzaldehyde.
The third part reports the application of β-amino thiol 30 catalyzed asymmetric addition of ethyl diazoacetate to benzaldehyde to give β-hydroxy a-diazo ester in good yield (92%) and with moderate enantioselectivity (66% ee).

並列關鍵字

camphor ； asymmetric addition reactions ； dialkylzinc ； Henry reaction ； aldimines ； diazo ester

參考文獻

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