Noji Masahiro, Ohno Tomoko, Fuji Koji, Futaba Noriko, Tajima Hiroyuki, Ishii Keitaro
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
J Org Chem. 2003 Nov 28;68(24):9340-7. doi: 10.1021/jo034255h.
The combination of a secondary benzyl alcohol and a metal triflate (e.g., La, Yb, Sc, and Hf triflate) in nitromethane was a highly effective secondary-benzylation system. Secondary benzylation of carbon (aromatic compounds, olefins, an enol acetate), nitrogen (amide derivatives), and oxygen (alcohols) nucleophiles was carried out with a secondary benzyl alcohol and 0.01-1 mol % of a metal triflate in the presence of water. Secondary benzyl alcohols and nucleophiles bearing acid-sensitive functional groups (e.g., tert-butyldimethylsilyloxy and acetoxy groups and methyl and benzyl esters) could be used for alkylation. Hf(OTf)4 was the most active catalyst for this alkylation, and trifluoromethanesulfonic acid (triflic acid, TfOH) was also a good catalyst. The catalytic activity of metal triflates and TfOH increased in the order La(OTf)3 < Yb(OTf)3 < TfOH < Sc(OTf)3 < Hf(OTf)4. A mechanistic study was also performed. The reaction of 1-phenylethanol (4a) in the presence of Sc(OTf)3 in nitromethane gave an equilibrium mixture of 4a and bis(1-phenylethyl) ether (54). Addition of a carbon nucleophile to the equilibrium mixture gave alkylated product in high yield.
在硝基甲烷中，仲苄醇与金属三氟甲磺酸盐（如镧、镱、钪和铪的三氟甲磺酸盐）的组合是一种高效的仲苄基化体系。在水存在下，使用仲苄醇和0.01 - 1 mol%的金属三氟甲磺酸盐对碳（芳香族化合物、烯烃、烯醇醋酸酯）、氮（酰胺衍生物）和氧（醇）亲核试剂进行仲苄基化反应。带有酸敏感官能团（如叔丁基二甲基硅氧基、乙酰氧基以及甲酯和苄酯）的仲苄醇和亲核试剂可用于烷基化反应。Hf(OTf)₄是该烷基化反应中活性最高的催化剂，三氟甲磺酸（三氟乙酸，TfOH）也是一种良好的催化剂。金属三氟甲磺酸盐和TfOH的催化活性按La(OTf)₃ < Yb(OTf)₃ < TfOH < Sc(OTf)₃ < Hf(OTf)₄的顺序增加。还进行了机理研究。1 - 苯乙醇（4a）在硝基甲烷中Sc(OTf)₃存在下反应生成4a和双（1 - 苯乙基）醚（54）的平衡混合物。向该平衡混合物中加入碳亲核试剂可高产率得到烷基化产物。
