Roskamp-馮小明反應

1989年，Roskamp首先報道了利用氯化亞錫催化乙基重氮乙酸乙酯和醛反應制備β-酮酯的反應【J. Org. Chem., 1989, 54, 3258】。經過二十多年的發展各種路易斯酸（Sc(OTf)3，BF3, GeCl2）都可用于此反應。2011年，四川大學化學學院馮小明教授，以手性氮氧–Sc(OTf)3絡合物催化劑實現了首例催化不對稱Roskamp反應。

他所設計合成的具柔性直鏈烷基鏈接的C2對稱雙氮氧酰胺化合物，是一類新型的全能型“優勢手性配體”。

重氮乙酸乙酯和醛在路易斯酸及手性配體催化下，伴隨著氫的遷移和N2的離去生成手性β-酮酯的反應被稱為Roskamp-Feng反應。

反應機理

重氮乙酸乙酯的α碳負離子在路易斯酸和手性配體催化下首先對醛進行親核加成，然后氫遷移，氮氣離去，生成產物。

反應實例

Preparation of L3-Sc(OTf)3 catalyst solution

To a 1 mL volumetric flask , L3 (0.01 mmol, 7.1 mg), Sc(OTf)3 (0.012 mmol, 6.0 mg) and THF (1.0 mL) were added to afford L3-Sc(OTf)3 catalyst solution (0.01 M in THF). The catalyst solution (0.01 M in THF) was stored at room temperature under N2 atmosphere, and used for asymmetric reactions. The activity and selectivity of the catalyst solution remained unchanged at least for one month. General procedure for the racemic Roskamp reaction

To a test tube, Sc(OTf)3 (2.5 mg, 0.005 mmol) and 3 ? molecular sieves (10.0 mg) were added. Then 0.5 mL CH2Cl2 was added and stirred at room temperature for 10 min. Subsequently, aldehyde (0.1 mmol) and α-alkyl-α-diazoester (0.1 mmol) were added, and the reaction mixture was stirred for 1 h under room temperature. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate = 30/1) to afford the desired product. (F) General procedure for the catalytic asymmetric Roskamp reaction

To a test tube, 10.0 mg 3 ? molecular sieves and 50.0 μL L3-Sc(OTf)3 catalyst solution (0.01 M in THF) were added, and then THF was removed under reduced pressure. After that, 0.2 mL CH2Cl2 was added under N2 atmosphere, and the mixture was stirred at 35 o C for 1 h. Subsequently, aldehyde (1.0 mmol) and α-alkyl-α-diazoester (1.0 mmol) were added at -20 o C. When the α-alkyl-α-diazoester was consumed, 2 mL CH2Cl2 was added, the solution was purified by flash filtration with a thin silica gel (scheme 1) and washed with 8 mL CH2Cl2 to afford the desired product. To get the exact yield, the S6 product was further purified by a flash chromatography on silica gel。

【J. Am. Chem. Soc., 2010, 132 (25), pp 8532–8533】

To a stirred solution of N-diazoacyl-(–)-camphorsultam (0.20 mmol) and aldehyde (0.24 mmol) in dichloromethane (2.0 mL) was added BF3·OEt2 (5.1 μL, 0.040 mmol) at —78 °C under argon. The reaction mixture was stirred at the same temperature for 30 min. The mixture was quenched with aqueous NaHCO3 and extracted with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography on silica gel (eluting with hexane/ethyl acetate = 10:1~3:1) to give the corresponding α-substituted β-keto amide.

【J. Am. Chem. Soc., 2009, 131 (32), pp 11280–11281】

【J. Am. Chem. Soc., 2007, 129 (5), pp 1048–1049】

參考文獻

一、《Organic Syntheses Based on Name Reactions》，P408

二、http://www.x-mol.com/news/1441