Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St., Catharines, ON L2S 3A1, Canada.
Department of Chemistry and Institute of Chemical Biology, Vanderbilt University Nashville, Tennessee, 37235, USA.
Chemistry. 2023 Apr 25;29(24):e202204066. doi: 10.1002/chem.202204066. Epub 2023 Mar 20.
The fluorine atom is a powerful, yet enigmatic influence on chemical reactions. True to form, fluorine was recently discovered to effect diastereodivergence in an enantioselective aza-Henry reaction, resulting in a very rare case of syn-β-amino nitroalkane products. More bewildering was the observation of an apparent hierarchy of substituents within this substrate-controlled behavior: Ph>F>alkyl. These cases have now been examined comprehensively by computational methods, including both non-fluorinated and α-fluoro nitronate additions to aldimines catalyzed by a chiral bis(amidine) [BAM] proton complex. This study revealed the network of non-covalent interactions that dictate anti- (α-aryl) versus syn-selectivity (α-alkyl) using α-fluoronitronate nucleophiles, and an underlying secondary orbital interaction between fluorine and the activated azomethine.
氟原子对化学反应有着强大而神秘的影响。最近发现，氟原子在对映选择性的aza-Henry 反应中影响非对映异构体的发散，导致非常罕见的顺式-β-氨基硝基烷产物。更令人困惑的是，在这种受底物控制的行为中，观察到取代基的明显顺序：Ph>F>烷基。现在已经通过计算方法全面研究了这些情况，包括手性双（脒基）[BAM]质子配合物催化的醛亚胺的非氟化和α-氟代硝酮的加成。该研究揭示了使用α-氟代硝酮亲核试剂决定反式（α-芳基）与顺式选择性（α-烷基）的非共价相互作用网络，以及氟原子和活化的亚甲胺之间的潜在次级轨道相互作用。
