利用兩類具矽基酮官能基的分子進行自由基環化反應之研究

The Study of Free Radical Cyclizations with Two Different Types of Acylsilane Derivatives

陳駿騰(Gyun-Teng Chen)

指導教授 ： 蔡蘊明

國立臺灣大學/理學院/化學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.02805

摘要

本篇論文中探討了兩類具有矽基酮的分子進行自由基環化之反應，在A部分中，我們利用烯基自由基與矽基酮的環化反應，嘗試連繼性環化反應的可能性；在B部分中，我們利用具有矽基酮官能基的環合前驅物進行自由基環化反應合成哌啶(piperidine)類化合物。
本實驗室之前的研究顯示出烯基自由基與矽基酮具有連繼性自由基環化反應的可能。這部分我們利用烯基碘產生烯基自由基，環化後所得到的β-矽基烷氧自由基經過Brook重排，產生因共振而穩定的烯丙自由基。希望透過共振而有自由基性質的三號碳與末端炔基進行第二次環化反應。研究過程中，成功的改善先前製備烯基碘的低產率問題，另外，也找到一個適當條件合成矽基酮官能基。在最後一步的環化反應結果不如預期，只得到一個五員環的單環產物。
另一部分，我們利用L-絲胺酸當掌性模板，建立一個具有光學活性的矽基酮當作自由基環合前趨物，並在氮上引入Boc保護基，由於A1,3 strain的關係迫使氮鄰位上的酯基位於軸向上，在這部份我們選擇使用立體障礙較大的第三丁基酯，當自由基與矽基酮進行分子內環化及重排後產生的矽氧基自由基要抓取氫原子時，會有1,3雙軸排斥的效應，使得反應傾向從赤道向抓取氫原子，而得到具有順式為主的產物。研究過程中，成功找到了引入苯硒基的適當條件，接著透過甲苯磺酸選擇性的去除氮上的Boc保護基，而不影響第三丁基酯。在最後進行自由基環化反應後，得到含有氮的六員環。總共經過九步得到總產率41%的哌啶甲酸酯，但與苄基酯體系的比較，順反式的選擇性反而從先前的3.6：1下降到2.2：1。

關鍵字

自由基 ； 矽基酮 ； 連繼性環化反應 ； 絲胺酸 ； 哌啶甲酸

並列摘要

We studied the free radical cyclizations of two different types of acylsilane derivatives in this thesis. In part A, we tested the possibility of tandem radical cyclizations of acylsilane with vinyl radical. In part B, we synthesized piperidine derivatives by radical cyclization of the precursor containing acylsilane.
According to previous research in our laboratory, tandem radical cyclizations of acylsilane with vinyl radical are feasible. We used vinyl iodide as vinyl radical precursor, the β-silyl alkoxy radical obtained from radical cyclization underwent a radical Brook-rearrangement to afford a resonance stabilized allylic radical. We expected that this radical could perform a second cyclization with a terminal alkyne and designed a tandem radical cyclization system. During our research, we synthesized a suitable acylsilane to examine the idea. Contrary to our expectation, this system gave only a monocyclic product after the cyclization reaction.
In another direction, we used L-serine as a chiral template to synthesize a chiral acylsilane as radical cyclization precursor. We used a “Boc” group for the protection of amino group. Because of Ａ1,3 strain, the neighboring bulky tert-butyl ester group was pushed into an axial position in the radical cyclization chair transition state. After intramolecular radical cyclization and Brook-rearrangement, the resulting silyloxy substituted cyclohexyl radical preferred to abstract H atom from equatorial position to avoid the axially oriented ester group, so that we obtained the cis isomer as major product. During our research, we found a suitable condition to prepare the phenyl selenenyl group containing amino acid from L-serine, and successfully deprotected Boc group selectively in the presence of tert-butyl ester by p-toluenesulfonic acid. Eventually, we successfully produced tert-butyl pipecolate with 41% yield in nine steps. However, comparing with the system of benzyl ester, the cis-trans selectivity was descended from 3.6:1 to 2.2:1.

並列關鍵字

radical ； acylsilan ； tandem cyclization ； serine ； pipecolic acid

參考文獻

1.Gomberg, M. Chem. Ber. 1900, 33, 3150.

2.Gomberg, M. J. Am. Chem. Soc. 1900, 22, 757.

3.Beckwith, A. L. J.; Hay, B. P. J. Am. Chem. Soc. 1989, 111, 230.

4.Beckwith, A. L. J.; Hay, B. P. J. Am. Chem. Soc. 1989, 111, 2674.

5.Jung, M. E.; Gervay, J. J. Am. Chem. Soc. 1991, 113, 224.