Takemoto手性催化剂是由手性二胺和苯胺制备得到的手性硫脲。Takemoto课题组，在2003年报道了此类催化剂，此类催化剂对含有硝基或羰基等强吸电子基团的烯烃进行不对称Michael加成反应，具有较高的选择性和产率。

【T. Okino, Y. Hoashi, T. Fukukawa, X. Xu, Y. Takemoto, J. Am. Chem. Soc., 2005, 7, 119-125】

反应机理

在手性框架下对亲核碳负离子化合物和亲电共轭体系进行同时活化。

反应操作

催化剂的制备

1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-(amino)cyclohexyl]thiourea (4). 

To 1 (280 mL,410 mg, 1.82 mmol) and pyridine (160 mL, 157 mg, 1.99 mmol) in DCM (6 mL) was added phenyl chlorothioformate 2 (250 mL, 312 mg, 1.81 mmol) at r.t. and the mixture was stirred for 2 h. To this was added dropwise (1R,2R)-1,2-diaminocyclohexane 3 (207 mg, 1.81 mmol) in DCM (1 mL) and DIPEA (300 mL, 234 mg, 1.81 mmol). After 15 min, the mixture was refluxed and sat NaHCO3 (7 mL) was added. The aq phase was extracted with DCM and the combined organic layers were worked up and chromatographed (CHCl3:MeOH, 7:1) to afford 4 (50%), mp 69 ℃.

Methylation of (4). Zn powder (102 mg, 1.56 mmol), AcOH (180 mL, 187 mg, 3.12 mmol), and aq formaldehyde (37%, 95 mL, 1.17 mmol) were added to 4 (150 mg, 389 mmol) in dioxane (0.5 mL) at r.t. After the mixture was stirred for 72 h, NH4OH (500 mL) was added and the aq phase was extracted with DCM. Usual workup and chromatography (CHCl3:MeOH, 7:1) afforded 117 mg (73%) of solid 5.

【Berkessel A， Synthesis， 2009， 2113】

Ketothioester (8). To a stirred mixture of chalcone 6 (0.1 mmol) and thiourea 5 (10 mol %) in ether (0.5 mL) was added thioacetic acid (0.2 mmol) and after 3 h stirring at r.t., chromatography (silica gel, EA/hexane1:20–1:3) gave 8 (95%, 58% ee).

【Wang W, Tet Lett., 2006, 47, 3145】

相关文献

1* Takemoto Y J Am Chem Soc 2003 125 12672

2* Takemoto Y J Am Chem Soc 2005 127 119

3* Berkessel A Angew Chem Int 2005 44 7466

4* Wang W Tet Lett 2006 47 3145

5* Berkessel A Synthesis 2009 2113

6* Takemoto Y Chem Pharm Bull 2010 58 593

编译自：Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 479.