Chirality in the Absence of Rigid Stereogenic Elements: The Design of Configurationally Stable C₃‐Symmetric Propellers

Abstract

Residual stereoisomerism is a form of stereoisomerism scarcely considered so far for applicative purposes, though extremely interesting, since the production of stereoisomers does not involve classical rigid stereogenic elements. In three-bladed propeller-shaped molecules, a preferred stereomerization mechanism, related to the correlated rotation of the rings, allows the free interconversion of stereoisomers inside separated sets (the residual stereoisomers) that can interconvert through higher energy pathways. In light of possible future applications as chiral ligands for transition metals in stereoselective processes, some C(3)-symmetric phosphorus-centered propellers, which could exist as residual enantiomers, are synthesized and the possibility of resolving their racemates into residual antipodes is explored. While the tris(aryl)methanes are configurationally stable at room temperature, only selected tris(aryl)phosphane oxides display a configurational stability high enough to allow resolution by HPLC on a chiral stationary phase (CSP HPLC) at a semipreparative level at room temperature. Stability was evaluated through different techniques (circular dichroism (CD) signal decay, dynamic CSP HPLC (CSP DHPLC), dynamic NMR analysis (DNMR)) and the results compared and discussed. Phosphanes were found much less stable than the corresponding phosphane oxides, for which preliminary calculations suggest that the three-ring-flip enantiomerization mechanism (M(0)) would be easier than phosphorus pyramidal inversion. The parameters affecting the configurational stability of the residual enantiomers of C(3)-symmetric propellers are discussed.

Chirality in the Absence of Rigid Stereogenic Elements: The Absolute Configuration of Residual Enantiomers of C3‐Symmetric Propellers

“…Previous theoretical calculations showed that the M 0 mechanism racemisation barrier is significantly lowered on passing from phosphane oxide 3 b to the corresponding phosphane. [4] However, since the XRD data show that blade gearing is very similar in phosphanes and phosphane oxides, we cannot exclude that phosphorus inversion, a racemisation mechanism only possible in the case of phosphanes, could contribute to such a fast racemisation. We found that there is a relationship between the electronic availability at the phosphorus atom of phosphanes, measured by CV experiments, and their configurational stability, that is, the more electron-poor the phosphorus atom, the higher the racemisation barrier.…”

“…[4] On the basis of the XRD data, showing that the engagement of the blades is very similar in the couples 4 a/4 b and 5 a/5 b, one could suggest that such a large difference in configurational stability is due to phosphorus inversion, even though theoretical calculations at the DFT-B3 LYP/ccpVDZ level carried out for the tris[3-(2-ethyl-1-methyl)indolyl]phosphane [4] (the phosphane corresponding to phosphane oxide 3 b) showed that the barrier of the M 0 mechanism is about 13 kcal mol À1 lower than in 3 b. In any case, we are forced to consider the possibility that the phosphorus inversion process is responsible for the modest configurational stability of phosphanes in view of the fact that, to the best of our knowledge, no data on the inversion barrier is available in the literature for tris-…”

Chirality in the Absence of Rigid Stereogenic Elements: Steric and Electronic Effects on the Configurational Stability of C3 Symmetric Residual Tris‐Aryl Phosphanes

“…The phosphane‐oxides were easily synthesized by hydrogen peroxide oxidation of the corresponding phosphanes and were completely characterized by X‐ray diffraction analysis . The examination of the crystal structures gave us a basic idea about the level of the gearing of the blades.…”

Helical Phosphorus Derivatives

“…The synthesis of tris(benzimidazolyl) phosphine oxide 98 was accomplished similarly by reaction of 2-methylbenzimidazole 97 with phosphorus oxybromide in 60% yield (09CEJ94). When compared to the indole derivatives 96, compound 98 showed a peculiar behavior and had a temperature of enantiomerization higher than 50 C (Scheme 26).…”