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Andrew D. Mesecar et al. J. Mol. Biol. (2009) 386, 1038–1053.
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有机催化
有机小分子作为不对称催化剂,还具有许多特殊的优点。 直接不对称羟醛缩合反应具有操作简单和原子经济性的显著优点。
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二肽磺酰胺11a 在产率和ee 值方面表现出最好的结果。
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水 相 反 应
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syn-1,2-Diol 结构特征——水溶性
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寻求能够高效高选择性地催化不对称直 接aldol反应的催化体系正日渐成为有机化 学的一项新课题。
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参考文献: [1] Yamaoka, M,; Nakazaki, A.; Kobayashi, S. Rate enhancement by water in a TiCl4-mediated stereoselective vinylogous Mukaiyama aldol reaction. Tetrahedron Lett. 51 (2010) 287–289. [2] Yamaoka, M.; Fukatsu, Y.; Nakazaki, A.; Kobayashi, S. Synthetic study of fomitellic acids:construction of the AB ring moiety. Tetrahedron Lett. 2009, 50,3849– 3852. [3] Mitsutaka Iwata, Ryo Yazaki, Yuta Suzuki, Naoya Kumagai, Masakatsu Shibasaki. Direct Catalytic Asymmetric Aldol Reactions of Thioamides: Toward a Stereocontrolled Synthesis of 1,3-Polyols. J. AM. CHEM. SOC. 9 VOL. 131, NO. 51, 2009 18245. [4] Scott D. Pegan, Kamolchanok Rukseree, Scott G. Franzblau and Andrew D. Mesecar. Structural Basis for Catalysis of a Tetrameric Class IIa Fructose 1,6Bisphosphate Aldolase from Mycobacterium tuberculosis. J. Mol. Biol. (2009) 386, 1038–1053. [5] S. S. V. Ramasastry, Klaus Albertshofer, Naoto Utsumi, and Carlos F. Barbas III. Water-Compatible Organocatalysts for Direct Asymmetric syn-Aldol Reactions of Dihydroxyacetone and Aldehydes. Org. Lett., Vol. 10, No. 8, 2008。1621-1624 [6] Evaggelia Tsandi, Christoforos G. Kokotos, Sofia Kousidou, Valentine Ragoussis, George Kokotos. Sulfonamides of homoproline and dipeptides as organocatalysts for Michael and aldol reactions Tetrahedron 65 (2009) 1444–1449. 23
谢谢！
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Kobayashi et al. Tetrahedron Letters 51 (2010) 287–289.5在天然产物全合成中的 Nhomakorabea用6
Yamaoka, M.; Fukatsu, Y.; Nakazaki, A.; Kobayashi, S. Tetrahedron Lett. 2009, 50, 3849–3852
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模拟Ⅱ类醛缩酶催化不对称直接Aldol反应
The class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since it is upregulated in latent TB.
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生物催化
• 在生物体内广泛存在的醛缩酶是不对称直 接Aldol反应的高效催化剂。迄今为止已有 30余种醛缩酶被鉴别，根据催化机理的不 同，它们被分为两大类：I类醛缩酶，II类醛 缩酶。 • List等认为可以把L-脯氨酸看作是一类“微 型醛缩酶”(micro-aldolase）
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模拟Ⅰ类醛缩酶催化不对称直接Aldol反应
Tol： 77 h， 77% yield Tol+5 mol% H2O： 55 h，76% yield Tol+10 mol% H2O： 40 h，74% yield Tol+20 mol% H2O： 26 h，69% yield
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是否是此类反应的特征？
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Although the specific role of water in the VMAR remains unclear, they tentatively propose the following two possibilities: (i)water might coordinate to TiCl4 and result in partial dissociation of TiCl4 aggregates, and (ii) both the proton and TiCl4 of a plausible hydrated TiCl4 might coordinate to the carbonyl oxygen, resulting in double activation.
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配位催化
DMF， -20℃， 100h 62（14）% yield 87% ee X = 10 Calculated pKa value of hydrogen was 12.3. Experimentally determined pKa of 2-methoxyphenol is reported as 9.90 (calculated as 9.62), thus lithium salt of 2,2,5,7,8 pentamethylchromanol is much stronger base than lithium salt of 2-methoxyphenol
X=3 DMF， -60℃， 40h 91（trace） % yield
91% ee
x = 10 ， 95% ee
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底物范围
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合成应用
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• Future work will be dedicated to applying the present protocol to the asymmetric synthesis of natural products bearing a 1,3-polyol motif.
不对称aldol 反应
黄海 有机化学 200920102003
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Aldol反应被认为是最有效的形成C—C键的反应之一。
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手性辅基 金属配合物催化 生物催化 有机分子催化 参考文献
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手性辅基举例
Vinylogous Mukaiyama aldol reaction 二氯甲烷：产率低；甲苯：反应极慢，无法反复生产。