Secondary Orbital Effect Involving Fluorine is Responsible for Substrate‐Controlled Diastereodivergence in the Catalyzed syn‐aza‐Henry Reaction of α‐Fluoronitroalkanes

Abstract

AbstractThe 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.