Synthesis, Chiral Resolution, and Absolute Configuration of Dissymmetric 4,15-Difunctionalized [2.2]Paracyclophanes

Abstract

Despite the fact that functionalized planar chiral [2.2]paracyclophanes have received a lot of attention, the chemistry of pseudo-meta 4,15-distubstituted [2.2]paracyclophanes is largely unexplored. This is mainly due to the fact that the 4,5-dibromo-functionalized [2.2]paracyclophane is much less prone to halogen-metal exchange reactions than its constitutional pseudo-ortho or pseudo-para isomers. Here, we give an account of an efficient protocol to achieve this, which allows the synthesis of a broad variety of 4,15-disubstituted [2.2]paracyclophanes. Furthermore, we were able to resolve several of the racemic compounds via chiral HPLC and assign the absolute configurations of the isolated enantiomers by X-ray diffraction and/or by the comparison of calculated and measured CD-spectra.

Diastereoselective Self‐Assembly of a Neutral Dinuclear Double‐Stranded Zinc(II) Helicate via Narcissistic Self‐Sorting

“…Several conformers with different torsion angles around the C2/C8−N(imine) single bonds were considered for this purpose (see Computational Details). A shift of −0.45 eV was applied to the computed vertical excitation energies, which is typical for this functional/basis set in combination with the sTD‐DFT approach . Interestingly, the assignment made here is in perfect agreement with our empirical observation that ( R , R )‐configurated Tröger's base derivatives generally elute first from an ( S , S )‐Whelk O1 stationary phase .…”

Preparation and Synthetic Applications of [2.2]Paracyclophane Trifluoroborates: An Efficient and Convenient Route to Nucleophilic [2.2]Paracyclophane Cross‐Coupling Building Blocks

“…Inspired by the work on iterative cross‐coupling methodology developed by Burke et al, we then set out to synthesize PCP halotrifluoroborates. The required monolithiation of dibromo PCPs exploits the following finding: The two‐fold metal‐halogen exchange of pseudo‐ ortho and pseudo‐ para dibromo[2.2]paracyclophane ( 5 and 7 ) has been described as tedious and requires tert‐ butyllithium or large excess of n ‐butyllithium in THF . Thus, the synthesis of unexplored halotrifluoroborates containing a bromide substituent for further transformation was achieved in good yield for the pseudo‐ para and pseudo‐ ortho derivatives 6 and 8 (Scheme ).…”

Influencing the Self‐Sorting Behavior of [2.2]Paracyclophane‐Based Ligands by Introducing Isostructural Binding Motifs

“…However, CHN analyses could only be conducted with fluorine‐free compounds. ( rac )‐4,15‐diiodo[2.2]paracyclophane, ( rac )‐4,15‐diamino‐[2.2]paracyclophane and the enantiomerically pure diamines and [(dppp)Pd(OTf) 2 ] were prepared according to literature procedures. Numbering schemes for all compounds are included in the Supporting Information.…”

“…We obtained the ligand L nit by an alternative route achieving higher yields. Specifically, we performed the already reported bromine–lithium exchange in THF at −78 °C first by using t BuLi and then by quenching the dilithiated species with iodine to access the diiodinated [2.2]paracyclophane 3 in 80 % yield . Next, we synthesized L nit by palladium‐catalyzed cyanation reaction providing the desired product in 85 % yield.…”

“…Enantiomerically pure L iso crystallizes in the same orthorhombic space group P 2 1 2 1 2 1 upon evaporation of solvent from a solution in dichloromethane. As L iso was prepared from enantiomerically pure building blocks 4 its stereochemistry was already known, but the XRD analysis of its single crystals as well as of its coordination complex further confirmed the stereochemical assignment. As anticipated, a dihedral angle of 117.94° between the coordinating isonitrile groups and the centers of the phenyl rings in the paracyclophane backbone was found (vide supra).…”