本論文主要分成兩部分：第一部分報導還原去氰反應在有機合成上的應用，其再分成兩小節。第一節探討以萘化鋰為還原試劑與不同的雙取代的雜環芳基乙腈化合物如26、55及68進行還原去氰反應，接著再與各類的親電子基試劑進行烷化/加成反應，藉由控制反應的溫度及時間，可成功製備一系列具三級取代基的雜環芳香化合物如34及64；新型的丙二烯系化合物58及2,3-及2,5-雙取代的噻吩化合物75a及75b。第二節中主要利用丙二腈的次烷基衍生物如化合物90與親二烯基進行Diels-Alder反應可生成環化加成產物98，接著與萘化鋰試劑進行還原取代及還原消去反應，可成功將氰基轉換成酮基及建立具環外雙鍵的化合物108及120。因此丙二腈的次烷基衍生物可以有效的作為乙烯酮對等物及丙二烯對等物應用在Diels-Alder反應上。

第二部分報導抗癌化合物D-501036的合成研究。利用化合物128與化合物134進行Suzuki耦合反應，可成功獲得耦合產物139，接著將醛基保護及引入二羥硼基可生成化合物141，再利用化合物128與化合物141進行第二次Suzuki耦合反應可製備關鍵中間物129。最後，化合物129經由引入醛基及還原反應可完成D-501036之合成。

The research projects described in this thesis are involved in the fields of synthetic organic chemistry methodology development and the total synthesis of an antineoplastic agent. In the first area, the use of the reductive alkylation protocol of nitriles previously developed in this laboratory towards the generation of structural motifs not readily attained via conventional methodologies is discussed. Specifically, starting with compounds 26 and 55, reductive decyanation as achieved by treatment with lithium naphthalenide followed by the addition of methyl iodide (26□34) or n-butyl iodide (55□64) yielded the desired tetrasubstituted methylene product. Interestingly, when thiophene 55 was subjected to the same process but trapping with benzaldehyde, the predicted product was not isolated. Instead, substituted thiophenes 75a and 75b as well as ring opened thioether 58 resulted. In addition to this, the use of malononitrile derivative 90 in the Diels-Alder cycloaddition reaction was explored. Reacting dienophile 90 with 2-methyl-1,3-butadiene allowed for the facile formation of highly substituted cyclohexene 98. Upon reductive acylation of this with lithium naphthalenide followed by benzaldehyde, alcohol 107 was obtained, the hydroxyl of which was readily converted to the methyl ether. Subsequent reductive decyanation of this intermediate with lithium naphthalenide resulted in an overall E2 elimination process to yield cyclohexene 108. Likewise, reductive decyanation of 98 followed by trapping of the ensuing anion with oxygen and reduction of the resulting endoperoxide gave tertiary alcohol 113, base treatment of which allowed for the isolation of cyclohexenone 120. Overall, dienophile 90 has been demonstrated as a versatile reagent in the Diels-Alder cycloaddition process, effectively functioning as, in the first case, an 1,3-disubstituted allene equivalent and, in the latter case, monosubstituted ketene equivalent.

In the total synthesis area, the total synthesis of D-501036, a recently discovered highly potent 126 antineoplastic agent is detailed. Suzuki coupling of boronic acid 134 and iodoselenophene 128 gave the expected aldehyde 139. The aldehyde functionality of compound 139 was protected and the resulted intermediate was converted readily to boronic acid 141. This was followed by a second Suzuki coupling reaction with iodide 128, the product of which was readily converted to the target molecule.

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