On the Origin of Diastereoselectivity in [2 + 2 + 2]
Cycloisomerization of Chiral Triynes: Controlling Helicity of
Helicene-like Compounds by Thermodynamic Factors
posted on 2008-03-21, 00:00authored byPetr Sehnal, Zuzana Krausová, Filip Teplý, Irena G. Stará, Ivo Starý, Lubomír Rulíšek, David Šaman, Ivana Císařová
Diastereoselective CoI-mediated [2 + 2 + 2] cycloisomerization of CH3O-substituted optically pure
aromatic triynes to obtain nonracemic functionalized helicene-like compounds (comprising a penta-, hexa-,
and heptacyclic helical scaffold) was studied. The stereochemical outcome of the reaction at 140 °C
using CpCo(CO)2 was controlled by thermodynamic factors yielding diastereomeric ratios up to 91:9.
Using CpCo(ethylene)2 at room temperature, a kinetic control took place leading to the loss of
stereoselectivity. Barriers to epimerization for selected helicene-like compounds were measured indicating
their lower configurational stability in comparison to the parent carbohelicenes. Free energy differences
between corresponding pairs of diastereomers (calculated at the DFT B3LYP/TZV+P level) were in
excellent agreement with the experimental data and allowed for the prediction of the stereochemical
outcome of the reaction. An optically pure hexacyclic helicene-like alcohol was prepared on a multigram
scale. Its X-ray structure confirmed the previous helicity assignments being based on 1H−1H correlations
in ROESY 1H NMR spectra.