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

Abstract

Diastereoselective CoI-mediated [2 + 2 + 2] cycloisomerization of CH(3)O-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 degrees 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 (1)H-(1)H correlations in ROESY (1)H NMR spectra.

An organometallic route to long helicenes

“…Recently, we have proven that constructing helicene scaffolds by using triyne [2 ϩ 2 ϩ 2] cycloisomerization constitutes a robust and flexible methodology for the synthesis of helically chiral aromatics (22)(23)(24)(25)(26). Conceptually, the advantage of this methodology consists in the formation of 3 rings of a helicene backbone in a single step.…”

“…We have recently developed an asymmetric synthesis of pentato-heptacyclic helicene-like compounds, which is based on a diastereoselective [2 ϩ 2 ϩ 2] cycloisomerization of chiral triynes (25,28). Therefore, we decided to follow this paradigm to prepare [11]helicene-like molecule 16 in a nonracemic form (Scheme 2).…”

“…Since suitable crystals for a single-crystal analysis were not obtained, the helicity of the major diastereomer (ϩ)-(P,S,S)-16 ( Fig. S1) was assigned by interpreting its ROESY 1 H NMR spectrum (for details, see SI Text) in accord with our earlier observations (25,28).…”

“…Although we could not prove the occurrence of the intermediate (M,S,S)-15 or (P,S,S)-15, the explanation of the diastereoselectivity relies on the assumption of their occurrence as well as the supporting calculations using the DFT(B3LYP)/TZVϩP method and conductor-like screening model (COSMO) to account for the solvation. We have recently found that the diastereoselectivity of [2 ϩ 2 ϩ 2] cycloisomerization of related triynes at elevated temperature is governed by the thermodynamic factors (25). Indeed, the reaction produced the more stable diastereomer (ϩ)-(P,S,S)-16, which was expected to be formed from the more stable intermediate (P,S,S)-15 (Table 1).…”

Racemic and Optically Pure Heptahelicene‐2‐carboxylic Acid: Its Synthesis and Self‐Assembly into Nanowire‐Like Aggregates

“…We had previously found [28] that this method for the demethylation of methoxyhelicenes can be superior to the more commonly used treatment with BBr 3 . By transforming 7 into the corresponding triflate 8 in an almost quantitative yield, a reactive [7]helicene derivative was prepared that allowed the desired functional group manipulation.…”