Iida Asumi, Matsuoka Mizuki, Hasegawa Hiroshi, Vanthuyne Nicolas, Farran Daniel, Roussel Christian, Kitagawa Osamu
Department of Applied Chemistry (QOL Improvement and Life Science Consortium) , Shibaura Institute of Technology , 3-7-5 Toyosu , Kohto-ku , Tokyo 135-8548 , Japan.
School of Pharmacy , Tokyo University of Pharmacy and Life Sciences , 1432-1, Horinouchi , Hachioji , Tokyo 192-0392 , Japan.
J Org Chem. 2019 Mar 15;84(6):3169-3175. doi: 10.1021/acs.joc.8b03043. Epub 2019 Feb 21.
The fluorine atom is the second smallest atom; nevertheless, the ortho-fluoro group may lead to stable N-aryl atropisomers when the steric demand of the flanking substituents is large enough. 2-Alkyl-3-(2-fluorophenyl)quinazolin-4-ones and 3-(2-fluorophenyl)-4-methylthiazoline-2-thione were found to be the first N-aryl axially chiral compounds bearing an ortho-fluoro group whose enantiomers were isolated at ambient temperature. The reaction of alkyl halides with the anionic species prepared from 2-ethyl-3-(2-fluorophenyl)quinazolin-4-one presenting an N-C axial chirality provided a model reaction for quantitative evaluation of the steric discrimination (slight difference of steric factor) between hydrogen and fluorine atoms. In the case of low steric demand (allylation reaction) no diastereoselectivity was detected, while in the case of high steric demand (isopropylation reaction) the diastereoselectivity became significant.
氟原子是第二小的原子；然而，当两侧取代基的空间需求足够大时，邻氟基团可能导致稳定的N-芳基阻转异构体。2-烷基-3-(2-氟苯基)喹唑啉-4-酮和3-(2-氟苯基)-4-甲基噻唑啉-2-硫酮被发现是首批带有邻氟基团的N-芳基轴手性化合物，其对映体在室温下被分离出来。卤代烃与由具有N-C轴手性的2-乙基-3-(2-氟苯基)喹唑啉-4-酮制备的阴离子物种的反应，为定量评估氢原子和氟原子之间的空间识别（空间因子的微小差异）提供了一个模型反应。在空间需求较低的情况下（烯丙基化反应），未检测到非对映选择性，而在空间需求较高的情况下（异丙基化反应），非对映选择性变得显著。
