Uchiyama Masanobu, Kobayashi Yuri, Furuyama Taniyuki, Nakamura Shinji, Kajihara Yumiko, Miyoshi Tomoko, Sakamoto Takao, Kondo Yoshinori, Morokuma Keiji
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Am Chem Soc. 2008 Jan 16;130(2):472-80. doi: 10.1021/ja071268u. Epub 2007 Dec 20.
We present full details of our new methods for preparing functionalized benzynes with lithium di-alkyl(2,2,6,6-tetramethylpiperidino)zincate (R2Zn(TMP)Li) through deprotonative zincation as a key reaction. In this system, by choosing appropriate ligands for the zincate, either regioselective zincation of functionalized haloaromatics or the generation of substituted benzynes can be controlled in good yields with excellent chemoselectivity, using the same substrate. Zincation with (t)Bu2Zn(TMP)Li followed by electrophilic trapping or zincation with Me2Zn(TMP)Li followed by nucleophilic or diene trapping is shown to be a powerful tool for the chemoselective preparation of 1,2,3-/1,2,4-trisubstituted benzene derivatives. These methods offer far greater generality than previous methods for the synthesis of multifunctionalized benzenes. Computational/theoretical studies of the reaction mechanism of this unique benzyne formation indicated that preferential coordination of the dialkylzinc moiety of zincate to halogen is the reason for the reduced activation energy of the elimination, that is, for the formation of the benzyne. The role of the ligands on Zn in accelerating/decelerating the elimination is also discussed.
我们详细介绍了通过去质子锌化反应（这是关键反应），利用二烷基（2,2,6,6 - 四甲基哌啶基）锌酸锂（R2Zn(TMP)Li）制备功能化苯炔的新方法。在该体系中，通过为锌酸盐选择合适的配体，使用相同的底物，既可以实现功能化卤代芳烃的区域选择性锌化，也能够以良好的产率和出色的化学选择性生成取代苯炔。用(t)Bu2Zn(TMP)Li进行锌化随后进行亲电捕获，或者用Me2Zn(TMP)Li进行锌化随后进行亲核或二烯捕获，被证明是化学选择性制备1,2,3 - /1,2,4 - 三取代苯衍生物的有力工具。这些方法比以往合成多官能化苯的方法具有更高的通用性。对这种独特苯炔形成反应机理的计算/理论研究表明，锌酸盐中二烷基锌部分与卤素的优先配位是消除反应活化能降低的原因，也就是形成苯炔的原因。还讨论了锌上配体在加速/减速消除反应中的作用。
