本論文主要分成兩個部分，首先利用本實驗室所開發之新穎氮轉移試劑，來合成出具對掌輔助(Chiral auxiliary)修飾之胺基酸酯類重氮化合物，並進一步對其進行N-H卡賓(Carbene)插入反應，藉此探討對掌輔助結構在重氮化合物進行不對稱合成之影響。
過去文獻在探討N-H插入反應時，多使用昂貴且合成難度高的配體或光學試劑，以達到高光學選擇性，因此我們提出在重氮化合物修飾上對掌輔助劑，預期提高N-H插入反應的光學選擇性。首先我們對天然樟腦化合物進行不同位相之官能基修飾，再與苯丙胺酸經由三步驟合成路徑，得到多種具對掌輔助結構之重氮化合物。最後將化合物與鄰氨基苯甲醚(o-Anisidine)進行N-H插入反應，想藉由鄰位的甲醚官能基探討非鏡像異構物的比例(diastereomeric ratio)。
實驗結果顯示，僅使用具對掌輔助修飾之重氮化合物，對N-H插入反應並沒有顯著的選擇性差異，故我們嘗試搭配相較容易合成的光學磷酸試劑，在對掌輔助劑與光學磷酸試劑的共同作用下， N-H插入反應的不對稱合成選擇性可以提高至三成，不同的對掌輔助結構也提供不同光學選擇性的結果。此外，我們用烏爾曼反應(Ullmann reaction)合成L型標準品，以確認產物是否為自然界鮮少的D型胺基酸結構。並且也嘗試使用容易除去的胺類或醯胺類保護基來進行N-H插入反應的探討，同時發現實驗步驟的先後順序對產率與選擇性的影響性。
於本研究中，我們原先預期利用對掌輔助劑之立體障礙與光學磷酸試劑的作用，應可對平面分子的重氮官能基進行N-H插入反應，製備出具高光學選擇性的非天然界胺基酸。雖然我們成功地合成出多樣性的對掌輔助劑重氮化合物且製備出不同的光學磷酸試劑，在兩者搭配下有不錯的產率，儘管可惜地是反應結果僅有達到三成的光學選擇性，但我們仍能製備的特殊具對掌輔助劑的重氮結構，或許在未來是可以朝向對分子內的N-H插入反應來探討其選擇性。

D-amino acid is of certain importance to many organisms, but it is not easily available in the biological world. However, a nitrogen-transfer reagent which was developed in our laboratory was carried out to synthesize substituted diazo ester with a chiral auxiliary from daily essential amino acids to explore the selectivity of asymmetric N-H insertion and the synthesis of D-amino acids.
We firstly modified the camphor compounds on to the amino acid structure which was confirmed by 2D-NMR spectrum (NOESY), and applied the result onto other eight different chiral auxiliaries. During the process, we found that the chiral auxiliary of the phenol compound was not successful. Therefore, we only obtained five different chiral auxiliaries of diazo compounds in the end.
We also tried to improve the selectivity of asymmetric N-H insertion reaction by combining with optical phosphoric acid reagents. The authentic standard of L-form amino acid was prepared by the Ullmann reaction and was used to the comparison of the synthesized L-from product. Furthermore, instead of the aniline group, we also explored the N-H insertion process with other amines or amides which were protected by easily removable protecting groups. One of the important factors affecting the selectivity was unexpectedly found that the adding order of the reagents did affect the yields and stereoselectivity of the products.
Under the combination of a variety of chiral auxiliary diazo compounds and different optical phosphoric acid reagents, we could obtained good yields of N-H insertion products. Unfortunately, these reactions resulted only up to 30% optical purity. In conclusion, we could still prepare a special diazo compounds with chiral auxiliary, which might be useful towards to the N-H intramolecular insertion reaction with good stereoselectivity in the future.

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