多取代螺環環己烷結構化合物之1,6/1,4/1,2有機催化連鎖反應
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2017
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藉由三單元有機催化連鎖反應，進行多取代螺環環己烷產物之生成。本實驗以乙醯乙酸酯與吡唑啉酮雙烯，加入20 mol%苯胺硫尿素氫鍵催化劑，並添加20 mol%的 1,4-二氮雜二環[2,2,2]辛烷，在二乙基醚為溶劑及常溫條件下，進行1,6-/Michael/aldol 三步驟連鎖反應，得到多取代螺環環己烷，此反應具有中等的產率(24-66%)及高非鏡像選擇性(up to > 20:1 dr)；透過單晶繞射X-ray 分析，獲得產物相對立體化學組態。本實驗亦透過高級量反應，確定此反應穩定性，在大量合成產物的條件下，產率與非鏡像選擇性皆沒有差異。本實驗亦選定不同親核試劑，確定此反應對羰基酯類親核試劑具有較顯著的反應性；在反應機構部分，確定此反應機構在1,6-/Michael反應步驟，具有顯著誘導效應；本實驗成功以三步驟連鎖反應，生成6個鏡像立體中心，並具有多取代基結構，未來將繼續發展鏡像選擇性，並希望此新穎有機催化連鎖反應，可應用在藥物合成、染料開發，與有機合成領域。
A novel 3-component organocatalytic cascade reaction to form a multisubstituted spirocyclohexane product was presented. This reaction occur with 5-methyl-2-phenyl-4-(-3-phenylallylidene)-2,4-dihydro-3H-pyrazol-3-one and β-keto esters using a catalytic amount of benzyl amine derived thiourea hydrogen-bond catalyst (20 mol%) and DABCO (20 mol%) in diethyl ether at ambient temperature, to promote the 3-step 1,6-/Michael/aldol cascade process with medium chemical yield and excellent diastereoselectivities (up to > 20:1 dr). The structure of the product is ensured by using single crystal X-ray analysis and to realize the relative stereochemistry. This reaction is treated in high-scale to promise the steability of yield and diastereoseletivity. Besides, with different nucleophiles substrate scope, this study find that β-keto esters are the suitable nucleophile of this electrophile. About the mechanism, it's considered that 1,6-addtion will trigger the Michael addition in the cascade reaction. This reaction successfully synthesize the multisubstituted spirocyclohexane product via a 3-step cascade reaction, constructed 6 chiral centers, and the prodcut bears multiple functional groups. To improve the enantioselectivity is the study, and hope this creative organocascade reaction shall be applied in pharmaceutical methodology, dye development, and organosynthesis in the future.
A novel 3-component organocatalytic cascade reaction to form a multisubstituted spirocyclohexane product was presented. This reaction occur with 5-methyl-2-phenyl-4-(-3-phenylallylidene)-2,4-dihydro-3H-pyrazol-3-one and β-keto esters using a catalytic amount of benzyl amine derived thiourea hydrogen-bond catalyst (20 mol%) and DABCO (20 mol%) in diethyl ether at ambient temperature, to promote the 3-step 1,6-/Michael/aldol cascade process with medium chemical yield and excellent diastereoselectivities (up to > 20:1 dr). The structure of the product is ensured by using single crystal X-ray analysis and to realize the relative stereochemistry. This reaction is treated in high-scale to promise the steability of yield and diastereoseletivity. Besides, with different nucleophiles substrate scope, this study find that β-keto esters are the suitable nucleophile of this electrophile. About the mechanism, it's considered that 1,6-addtion will trigger the Michael addition in the cascade reaction. This reaction successfully synthesize the multisubstituted spirocyclohexane product via a 3-step cascade reaction, constructed 6 chiral centers, and the prodcut bears multiple functional groups. To improve the enantioselectivity is the study, and hope this creative organocascade reaction shall be applied in pharmaceutical methodology, dye development, and organosynthesis in the future.
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有機催化反應, 有機連鎖反應, 吡唑啉酮, 1, 6-加成反應, 1, 4-加成反應, 螺環環己烷, Organocatalysis, organocascade reactions, pyrazolone, 1, 6- addtion, 1, 4- addition, spirocyclohexane