On the Origin of Diastereoselectivity in [2 + 2 + 2] Cycloisomerization of Chiral Triynes: Controlling Helicity of Helicene-like Compounds by Thermodynamic Factors

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.

本研究针对甲氧基（CH3O）取代的光学纯芳香三炔，开展了一价钴（Co(I)）介导的[2+2+2]环异构化反应，以制备非外消旋官能化类螺旋烯化合物（涵盖五环、六环及七环螺旋骨架）。当使用二羰基环戊二烯基钴（CpCo(CO)2）于140 ℃下反应时，反应的立体化学结果由热力学因素主导，所得非对映异构体比例最高可达91:9。改用二乙烯基环戊二烯基钴（CpCo(ethylene)2）在室温下反应时，则以动力学控制为主，导致立体选择性丧失。对选定的类螺旋烯化合物的差向异构化能垒进行了测定，结果表明其构型稳定性相较于母体碳螺旋烯更低。对应非对映异构体对之间的自由能差（在密度泛函理论（DFT）B3LYP/TZV+P理论水平下计算得到）与实验数据吻合极佳，可用于预测该反应的立体化学结果。研究人员以多克级规模制备了光学纯的六环类螺旋烯醇，其X射线晶体结构验证了此前基于旋转坐标系核奥弗豪泽增强谱（ROESY）1H核磁共振谱中1H-1H相关性所做出的螺旋构型指认。