Benzylic Aroylation of Toluenes Mediated by a LiN(SiMe3)2/Cs+ System

Yuanyun Gu, Zhen Zhang, Yan-En Wang, Ziteng Dai, Yaqi Yuan, Dan Xiong, Jie Li, Patrick J. Walsh,* and Jianyou Mao

aTechnical Institute of Fluorochemistry (TIF), Institute of Advanced Synthesis, Schoolof Chemistry and Molecular Engineering, Nanjing Tech University, 30 South Puzhu

Road, Nanjing 211816, P.R. China

Abstract:Chemoselective deprotonative functionalization of benzylicC−H bonds is challenging, because the arene ring contains multiplearomatic C(sp 2 )−H bonds, which can be competitively deprotonated andlead to selectivity issues. Recently it was found that bimetallic[MN(SiMe₃)₂M = Li, Na]/Cs+ combinations exhibit excellent benzylicselectivity. Herein, is reported the first deprotonative addition of toluenesto Weinreb amides mediated by LiN(SiMe₃)₂/CsF for the synthesis of a diverse array of 2-arylacetophenones. Surprisingly, simplemethyl benzoates also react with toluenes under similar conditions to form 2-arylacetophenones without double addition to givetertiary alcohol products. This finding greatly increases the practicality and impact of this chemistry. Some challenging substrateswith respect to benzylic deprotonations, such as fluoro and methoxy substituted toluenes, are selectively transformed to 2-arylacetophenones. The value of benzylic deprotonation of 3-fluorotoluene is demonstrated by the synthesis of a key intermediate in thepreparation of Polmacoxib.

J. Org. Chem/ 2022, 87, 1, 406–418(2021年影响因子4.198)

论文链接：https://pubs.acs.org/doi/full/10.1021/acs.joc.1c02446