一、對掌樟腦架構衍生之α-重氮羰基輔助劑於不對N-H鍵嵌入反應之探討 二、有機催化Michael加成反應在製備掌性四級碳化合物之探討
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2010
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本論文共分兩大部分：第一部分探討非鏡像選擇性之胺化反應，第二部分則探討鏡像1,4-加成反應。第一部分以本實驗室合成之對掌輔助劑110進行修飾，製備α-重氮羰基對掌輔助劑起始物123，在室溫下，以二氯甲烷為作為反應溶劑，與各種胺類受質124及5 mol%之二價銠金屬催化劑進行不對稱N-H鍵嵌入反應，可得到最佳產率(65%)及非鏡像選擇性(88:12)，產物分子經由核磁共振光譜分析及X光單晶繞射確定新建構之立體中心構形為R。另外，可成功將對掌輔助劑110切除回收，得到98%之對掌輔助劑及80%的胺基醇化合物131e。
第二部分利用本實驗室所開發之含有樟腦分子架構之L-脯胺酸有機催化劑230催化β-硝基苯乙烯類起始物136、147及α,α-不同取代之醛類起始物198、228進行不對稱Michael加成反應，篩選出以-硝基苯乙烯136及4當量的2-苯基丙醛228為起始物，在室溫下，以甲醇為反應溶劑，以20 mol%的催化劑進行反應時，得到最佳之產率(62%)、非鏡像選擇性（88:12）及鏡像超越值(52%)。
This dissertation was divided into two parts, they are as follows: The first part represents to study the chiral auxiliary mediated diastereoselective N-H insertion by using the modified derivative from N-phenyl camphorpyrazolindione (110). The reaction was carried out in CH2Cl2 at ambient temperature, by using the α-diazocarbonyl compound (123) as the starting material and catalytic amount of rhodium acetate (5 mol%) generate metallocarbene intermediate. This was followed by addition of amine source (124). In this process N-H insertion products were obtained in high yield up to 65% yield and with up to 88:12 diastereoselectivity. The newly generated chiral center of the major product shows R configuration was confirmed by H-NMR studies and X-ray crystallographic data. On the other hand, the chiral auxiliary was successfully removed, and the recovered yield of 110 up to 98% and amino alcohol 131e was obtained in 80% yield. In the second part, the Michael additoion ofα,α-disubstituted aldehydes (198, 228) to β-nitroalkenes (136, 147) have been developed. The Michael addition is efficiently catalyzed by the pyrrolidin-camphor derivative (230) as bifunctional organocatalyst producing Michael adduct in moderate to good yield and stereoselectivities. The reaction was carried out in MeOH under room temperature by using β-nitrostyrene and 4 equivalents of donor aldehyde as starting material and 20 mol% of catalyst 230. The Michael adduct achieved with best result is 62% yield with 88:12 diastereoselectivity and 52% enantioselectivity.
This dissertation was divided into two parts, they are as follows: The first part represents to study the chiral auxiliary mediated diastereoselective N-H insertion by using the modified derivative from N-phenyl camphorpyrazolindione (110). The reaction was carried out in CH2Cl2 at ambient temperature, by using the α-diazocarbonyl compound (123) as the starting material and catalytic amount of rhodium acetate (5 mol%) generate metallocarbene intermediate. This was followed by addition of amine source (124). In this process N-H insertion products were obtained in high yield up to 65% yield and with up to 88:12 diastereoselectivity. The newly generated chiral center of the major product shows R configuration was confirmed by H-NMR studies and X-ray crystallographic data. On the other hand, the chiral auxiliary was successfully removed, and the recovered yield of 110 up to 98% and amino alcohol 131e was obtained in 80% yield. In the second part, the Michael additoion ofα,α-disubstituted aldehydes (198, 228) to β-nitroalkenes (136, 147) have been developed. The Michael addition is efficiently catalyzed by the pyrrolidin-camphor derivative (230) as bifunctional organocatalyst producing Michael adduct in moderate to good yield and stereoselectivities. The reaction was carried out in MeOH under room temperature by using β-nitrostyrene and 4 equivalents of donor aldehyde as starting material and 20 mol% of catalyst 230. The Michael adduct achieved with best result is 62% yield with 88:12 diastereoselectivity and 52% enantioselectivity.
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不對稱合成, 重氮, diazo