常用烷基化試劑----Meerwein鹽

Meerwein鹽也稱為Meerwein試劑，是指三甲基氧鎓四氟硼酸鹽 (Me3OBF4)或是三乙基氧鎓四氟硼酸鹽 (Et3OBF4)。此試劑以其發(fā)現(xiàn)者Hans Meerwein的名字命名，此烷氧鎓鹽是很強(qiáng)的烷基化試劑，可以對各種雜原子親核試劑進(jìn)行烷基化，如酰胺，內(nèi)酰胺（O-烷基化），胺（可以N-烷基化到季銨鹽），α-吡啶酮（N-或O-烷基化），芳香氮雜環(huán)（N-烷基化后形成鎓鹽），硫代羰基化合物（S-烷基化）。

【 J. Chem. Ber., 1956, 89, 2060； Can. J. Chem. , 1977, 5, 1433 】

在水相中Meerwein 鹽能作用于羧酸實(shí)現(xiàn)酯化反應(yīng)，在這一反應(yīng)條件下，酰胺基團(tuán)不會(huì)發(fā)生O-烷基化反應(yīng)。而在非質(zhì)子溶劑和不存在堿的條件中，羧酸酰胺化合物只會(huì)發(fā)生O-烷基化反應(yīng)。

O -烷基化的酰胺，可以還原制備胺，也可以水解制備酯。

常見的烷基化試劑強(qiáng)弱按照以下順序排列：

Me2Cl(SbF6) > (MeO)2CHBF4> Me3OBF4> Et3OBF4> MeOTf >MeOSO2F > (MeO)2SO2> MeI

試劑的制備：

【 (a) Meerwein, H. Org. Synth.; Coll. Vol. V 1973, 1080. Triethyloxonium tetrafluoroborate. (b) Curphey, T. J. Org. Synth.; Coll. Vol. VI, 1988, 1019. Trimethyloxonium tetrafluoroborate. 】

反應(yīng)實(shí)例

【 J. Organomet. Chem. 1983 , 247, 187–201 】

【 J. Am. Chem. Soc. , 1993, 115, 30 】

【Tetrahedron Lett. 1996, 37, 5679】

To a stirred mixture of 163 mg 6-nitro-1Hindazole (1 mmol) and 3 mL EtOAc was added 192 mg trimethyloxonium tetraflfluoroborate (1.3 mmol). The mixture was stirred at room temperature for 5 h under nitrogen and then diluted with 20 mL EtOAc and washed with 20 mL saturated NaHCO 3 solution. The organic layer was separated, and the aqueous layer was extracted with EtOAc (20 mL × 2). The combined organic layers were dried over anhydrous MgSO 4 , fifiltered, and evaporated. The residue was purifified by column chromatography (1:1, EtOAc/hexane) to afford 154 mg 2-methyl-6-nitro-2 H - indazole as a yellow solid, in a yield of 87%, mp 158–16 0 ? C (EtOAc).

【 J. Org. Chem. , 2003 , 68 , 4093 】

To a solution of 300 mg gluconothiolactam (0.54 mmol) in 13 mL dry CH2Cl2 at 0℃ was added 112 mg triethyloxonium tetraflfluoroborate (0.59 mmol). The mixture was stirred at 0 ℃ for 1.5 h, then the solvent was removed under vacuum to afford 298 mg ethyl 2,3,4,6-tetra- O -benzyl-D-gluconoiminothioether, in a yield of 95%.

【 J. Am. Chem. Soc. , 2004 , 126 , 1971 】

【 J. Fluorine Chem. 2006, 127, 1261–1264 】

【 J. Org. Chem. 2008, 73, 6816–6823. 】

【J. Org. Chem., 2016, 81, 3470-3472】

相關(guān)文獻(xiàn)

1. (a) Meerwein, H.; Hinz, G.; Hofmann, P.; Kroning, E.; Pfeil, E. J. Prakt. Chem. 1937, 147, 257–285. (b) Meerwein, H.; Bettenberg, E.; Pfeil, E.; Willfang, G. J. Prakt. Chem. 1939, 154, 83–156.

2. (a) Meerwein, H. Org. Synth.; Coll. Vol. V 1973, 1080. Triethyloxonium tetrafluoroborate. (b) Curphey, T. J. Org. Synth.; Coll. Vol. VI, 1988, 1019. Trimethyloxonium tetrafluoroborate.

3. Chen, F. M. F.; Benoiton, N. L. Can. J. Chem. 1977, 55, 1433–1435.

4. D?tz, K. H.; M?hlemeier, J.; Schubert, U.; Orama, O. J. Organomet. Chem. 1983, 247, 187–201.

5. Downie, I. M.; Heaney, H.; Kemp, G.; King, D.; Wosley, M. Tetrahedron 1992, 48, 4005–4016.

6. Kiessling, A. J.; McClure, C. K. Synth. Commun. 1997, 27, 923–937.

7. Pichlmair, S. Synlett 2004, 195-196. (Review).

8. Egashira, M.; Yamamoto, Y.; Fukutake, T.; Yoshimoto, N.; Morita, M. J. Fluorine Chem. 2006, 127, 1261–1264.

9. Delest, B.; Nshimyumukiza, P.; Fasbender, O.; Tinant, B.; Marchand-Brynaert, J.; Darro, F.; Robiette, R. J. Org. Chem. 2008, 73, 6816–6823.

10. Perst, H.; Seapy, D. G. Triethyloxonium Tetrafluoroborate In Encyclopedia of Reagents for Organic Synthesis Wiley: New York, 2008,

11. Hari, D. P., K?nig, B. Angew. Chem. Int. Ed. 2013, 52, 4734–4743. (Review).

參考資料：

一、Name Reactions （A Collection of Detailed Reaction Mechanisms）, Jie Jack Li, Meerwein’s salt，page 384-385.

二、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，P1877-1879.

三、《現(xiàn)代有機(jī)合成試劑——性質(zhì)、制備和反應(yīng)》，胡躍飛等編著