The Study of Radical Cyclization Reactions with Acylsilanes Derived from Carbohydrate Templates

在本論文第一部分中，探討具矽基酮的六碳醣衍生物，進行自由基環化反應效率不佳原因。我們利用2-去氧葡萄糖為起始物，預期去除矽基酮二號碳上captodative effect，抑制分子內1,5-氫轉移競爭反應的發生，提升環化效率，因此，利用不改變其立體化學的合成步驟，將還原端轉換成矽基酮官能基，非還原端轉換成溴基，其它二級羥基皆保護成甲醚，製備出自由基環合前驅物，並進行自由基環化反應；接著我們利用重氫三丁基錫烷作為自由基環化試劑，證明2-去氧葡萄糖體系的分子內1,5-氫轉移反應仍然是個嚴重的問題；接著探討環化產物結構鑑定與自由基環化中間體抓氫立體位向問題；再結合之前葡萄糖及甘露糖研究結果，最後我們推測推拉電子效應及不同六碳醣分子上的取代基立體位向不同，對於自由基環化效率的影響。 論文第二部分中，我們利用具丙縮酮保護基的矽基酮核糖衍生物，預期藉由丙縮酮鎖住分子構形，進行具有高度立體選擇性的自由基環化反應；我們利用核糖為起始物，利用不改變其立體化學的合成步驟，將二號及三號碳上羥基利用丙縮酮為保護基，四號碳上羥基保護成甲醚，還原端轉換成矽基酮官能基，非還原端轉換成溴基，製備出自由基環合前驅物，此系統的確能進行具高度立體選擇性的自由基環化反應，得到單一立體化學的環化產物；接著我們探討環化產物結構鑑定及丙縮酮保護基對於自由基環化中間體抓氫立體位向選擇性的影響。另外，環合產物結構上具有三種不同保護基，便於作進一步的衍生合成。In the first part of this thesis, we wanted to understand why the radical cyclization was not efficient using acylsilanes derived from hexoses. We used 2-deoxy-D-glucose as a chiral template to synthesize a related acylsilane as a radical cyclization precursor. Our method conserved the orginal stereochemistry of 2-deoxy-D-glucose. The reducing end was converted to an acylsilane functionality whereas the non-reducing end was transformed into a halide. All the secondary hydroxyl groups were protected as methyl ethers. We expected captodative stabilization of a radical on C(2) of acylsilane could be avoided when using this acylsilane. By using tributyltin deuteride as reagent, we found the presence of severe 1,5-hydrogen shift in this system thus disproved the importance of captodative effect. We identified cyclization products, and discussed the stereoselectivity. Combining previous research in D-glucose and D-mannose systems, we concluded that the crucial factor controlling the ratio of radical cyclization and 1,5-hydrogen transfer is the conformation in transition state. In the second part of this thesis, we used D-ribose as a chiral template to synthesize a related acylsilane as a radical cyclization precursor. Our method conserved the orginal stereochemistry of D-ribose. We protected hydroxyl groups on C(2) and C(3) as acetonide, and that on C(4) with methyl ether. Due to the acetonide, the molecular structure is locked in a puckerd form, and highly stereoselective origin of radical cyclization was realized. We identified cyclization product, and discussed the stereoselectivity. Furthermore, the cyclization product with three different types of protecting groups could enable us to futher functionalize the structure