樟腦-吡咯烷衍生之有機催化劑在羰基化合物不對稱α-胺化反應之研究

Catalytic Asymmetric α-Amination of Aldehydes and Ketones by Camphor-pyrrolidinyl Derived Organocatalysts

劉邦民(Pang-Min Liu)

指導教授 ： 陳焜銘

國立臺灣師範大學/理學院/化學系/博士(2010年)

摘要

合成高光學純度胺基酸衍生物，是合成化學中重要的研究課題，藉由偶氮化合物（dialkyl azodicarboxylate）進行醛、酮化合物α-胺化反應是有效合成胺基酸的方法之一。利用本實驗室開發的新型樟腦-吡咯烷催化劑，成功的運用在醛類不對稱α-胺化反應，在低催化量作用下，反應在短時間內完成，得到高產率（up to 97%）與高鏡像超越值（up to >99% ee）的胺化產物。另一方面，將α-胺化反應用於β-氨基-γ-丁酸內酯的合成，經五步合成反應，得到總產率56 %與鏡像超越值88% ee，絕對立體組態為(R)-form之β-氨基-γ-丁酸內酯衍生物；此外，(S)-香茅醛在樟腦-吡咯烷催化劑的作用下，進行一鍋化α-胺化、烯反應，接著，經三步合成反應，可得到單一非鏡相異構物的六圓環產物。另外，利用本實驗室所製備的雙功能樟腦-硫尿素-L-脯胺酸衍生物，催化環己酮進行不對稱α-胺化反應，可得到產率66% yield與鏡像超越值26% ee的胺化產物。然而，所得結果雖不甚理想，但證明了樟腦-硫尿素-L-脯胺酸衍生之催化劑對反應的光學環境控制有一定之作用。

關鍵字

胺化反應 ； 有機催化

並列摘要

Asymmetric synthesis of optically pure amino acid derivetives is an important subject in synthetic chemistry. The directly α-amination of aldehydes and ketones with dialkyl azodicarboxylate (DAAD) is one of the most useful methods. Novel organocatalysts, camphor-pyrrolidinyl derivatives designed by our group, have been used successfully in asymmetric α-amination of aldehydes. With low catalyst loading, the amination can be performed in very short time, and give high yields (up to 97%) with excellent enantioselectivities (up to >99% ee). The synthetic utility of the organocatalyticα-amination has been shown in the synthesis of -amino--butyrolactones( 56% yield in five steps and 88% ee of aminated lactone). On the other hand, camphor-pyrrolidine catalyzedα-amination of (S)-citronellal (93) and the subsequent ene reaction is proceeded smoothly in one pot. After several steps, a highly substituted cyclohexane product was obtained in 33% yield, and the absolute confinguration of aminated product was confirmed as (1R, 2R, 3R, 6S) via 2D-NMR. Besides, the use of bifunctional camphor-thiourea-L-proline derivetives in organocatalytic enantionselective α-aminations gives desired aminated products in 66% yield and 26% ee. Although unsatisfied results were obtained, the stereo-control of new organocatalysts has been proven by the investigation of enantio-rich products.

並列關鍵字

amination ； organocatalysis

參考文獻

5. Duron, S. G.; Gin, D. Y. Org. Lett. 2001, 3, 1551.

8. Najera, C.; Sansano, J. M. Chem. Rev. 2007, 107, 4584.

13. Rueping, M.; Sugimoto, E.; Azap, C. Angew. Chem., Int. Ed. 2006, 45, 2617.

16. Palomo, C.; Oiarbide, M.; Halder, R.; Laso, A.; Lo ́pez, R. Angew. Chem., Int. Ed. 2006, 45, 117.

17. Fini, F.; Sagarzani, V.; Pettersen, D.; Herrera, R. P.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005, 44, 7975.