Kinetic Control in the Synthesis of a Möbius Tris((ethynyl)[5]helicene) Macrocycle Using Alkyne Metathesis

Abstract

The synthesis of conjugated Möbius molecules remains elusive since twisted and macrocyclic structures are low-entropy species sporting their own synthetic challenges. Here we report the synthesis of a Möbius macrocycle in 84% yield via alkyne metathesis of 2,13-bis(propynyl)[5]helicene. MALDI-MS, NMR spectroscopy, and X-ray diffraction indicated a trimeric product of twofold symmetry with <i>PPM</i>/<i>MMP</i> configurations in the helicene subunits. Alternatively, a threefold-symmetric <i>PPP/MMM</i> structure was determined by DFT calculations to be more thermodynamically stable, illustrating remarkable kinetic selectivity for this alkyne metathesis cyclooligomerization. Computational studies provided insight into the kinetic selectivity, demonstrating a difference of 15.4 kcal/mol between the activation barriers for the <i>PPM</i>/<i>MMP</i> and <i>PPP</i>/<i>MMM</i> diastereodetermining steps. Computational (ACID and EDDB) and experimental (UV-vis and fluorescence spectroscopy and cyclic voltammetry) studies revealed weak conjugation between the alkyne and adjacent helicene groups as well as the lack of significant global aromaticity. Separation of the <i>PPM</i> and <i>MMP</i> enantiomers was achieved via chiral HPLC at the analytical scale.