Roskamp-Feng反应

1989年，Roskamp首先报道了利用氯化亚锡催化乙基重氮乙酸乙酯和醛反应制备β-酮酯的反应【J. Org. Chem., 1989, 54, 3258】。经过二十多年的发展各种路易斯酸（Sc(OTf)3，BF3, GeCl2）都可用于此反应。2011年，四川大学化学学院冯小明教授，以手性氮氧–Sc(OTf)3络合物催化剂实现了首例催化不对称Roskamp反应。

他所设计合成的具柔性直链烷基链接的C2对称双氮氧酰胺化合物，是一类新型的全能型“优势手性配体”。

重氮乙酸乙酯和醛在路易斯酸及手性配体催化下，伴随着氢的迁移和N2的离去生成手性β-酮酯的反应被称为Roskamp-Feng反应。

反应机理

重氮乙酸乙酯的α碳负离子在路易斯酸和手性配体催化下首先对醛进行亲核加成，然后氢迁移，氮气离去，生成产物。

反应实例

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 (1.0mL) were added to afford L3-Sc(OTf)3 catalyst solution (0.01 M in THF). The catalyst solution (0.01 Min THF) was stored at room temperature under N2 atmosphere, and used for asymmetric reactions. Theactivity 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 Å molecular sieves (10.0 mg) were added. Then0.5 mL CH2Cl2 was added and stirred at room temperature for 10 min. Subsequently, aldehyde (0.1mmol) and α-alkyl-α-diazoester (0.1 mmol) were added, and the reaction mixture was stirred for 1 hunder room temperature. The residue was purified by flash chromatography on silica gel (petroleumether/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 Å molecular sieves and 50.0 µL L3-Sc(OTf)3 catalyst solution (0.01 M inTHF) were added, and then THF was removed under reduced pressure. After that, 0.2 mL CH2Cl2 wasadded under N2 atmosphere, and the mixture was stirred at 35 oC for 1 h. Subsequently, aldehyde (1.0mmol) and α-alkyl-α-diazoester (1.0 mmol) were added at -20 oC. When the α-alkyl-α-diazoester wasconsumed, 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 S6product 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 (0.24mmol) in dichloromethane (2.0 mL) was added BF3·OEt2 (5.1 µL, 0.040 mmol) at —78 °Cunder argon. The reaction mixture was stirred at the same temperature for 30 min. Themixture was quenched with aqueous NaHCO3 and extracted with ethyl acetate. Thecombined organic layers were dried over anhydrous Na2SO4 and concentrated. The residuewas 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】

参考文献

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

二、http://www.x-mol.com/news/1441