Mechanically axially chiral catenanes and noncanonical mechanically axially chiral rotaxanes

Abstract

Chirality typically arises in molecules because of a rigidly chiral arrangement of covalently bonded atoms. Less generally appreciated is that chirality can arise when molecules are threaded through one another to create a mechanical bond. For example, when two macrocycles with chemically distinct faces are joined to form a catenane, the structure is chiral, although the rings themselves are not. However, enantiopure mechanically axially chiral catenanes in which the mechanical bond provides the sole source of stereochemistry have not been reported. Here we re-examine the symmetry properties of these molecules and in doing so identify a straightforward route to access them from simple chiral building blocks. Our analysis also led us to identify an analogous but previously unremarked upon rotaxane stereogenic unit, which also yielded to our co-conformational auxiliary approach. With methods to access mechanically axially chiral molecules in hand, their properties and applications can now be explored.

Figure 1. Schematic depictions of the mechanical stereogenic units of chiral catenanes and rotaxanes (stereolabels are arbitrary).

(a) The mechanical topological and planar chiral stereogenic units of catenanes and rotaxanes are related by a notional ring opening process. (b) The minimal schematic representation of a mechanically axially chiral catenane suggests that there is no analogous axially chiral rotaxane. (c) Semi-structural representations of axially chiral catenanes reveal that such molecules can display co-conformational covalent chirality alongside the fixed mechanical stereogenic unit. (d) The semi-structural representation reveals that rotaxanes display a related but previously unrecognized form of stereochemistry.

Figure 2. Proposed co-conformational auxiliary approach for the synthesis of axially chiral catenanes.

If the prochiral substituents and blocking groups are large enough to prevent co-conformational isomerism, the diastereomers can be separated and then converted into enantiomeric axially chiral catenanes.

Figure 3. Synthesis and analysis of enantiopure axially chiral catenane 6.

(a) Synthesis and separation of catenane diastereomers 3 from (R)-1 by route A or route B (Fig. 2) with opposite diastereoselectivity. Reagents and conditions: i. [Cu(MeCN)₄]PF₆, NⁱPr₂Et, CH₂Cl₂, rt, 16 h; ii. IBX, NEt₄Br, CHCl₃-H₂O (99 : 1), rt, 16 h. (b) Conversion of catenane 3 to enantiomeric catenanes 6. Reagents and conditions: CF₃CO₂H, CH₂Cl₂, 0 °C, 1 h. (c) The solid-state structure of rac-(S_ma,R_co-c)-3 allowed the major products of routes a and b to be assigned. (d) The solid-state structure of rac-6 contains rac-(S_ma,R_co-c)-6 as the major co-conformational diastereomer. Analysis of (R_ma)-6 (purple) and (S_ma)-6 (orange) by (e) chiral-stationary-phase high-performance liquid chromatography and (f) circular dichroism spectroscopy respectively confirmed their enantiopurity and their chiral nature. IBX = 2-iodoxybenzoic acid. R = CO₂Me.

Figure 4. Synthesis of mechanically axially chiral rotaxane 10.

(a) Synthesis of diastereomeric mechanically axially chiral rotaxanes 9 by route A or B gives separable rotaxanes 9 that are converted to 10 by removal of the Boc group. Reagents and conditions: i. macrocycle 2 (route A) or macrocycle 4 (route B), [Cu(MeCN)₄]PF₆, NⁱPr₂Et, CH₂Cl₂, rt, 16 h; ii. IBX, NEt₄Br, CHCl₃-H₂O (99 : 1), rt, 16 h; iii. CF₃CO₂H, CH₂Cl₂, rt, 16 h. (b) SCXRD analysis of (R_ma,R_co-c)-9allowed the major products of routes a and b to assigned. Analysis of (R_ma)-10 (purple) and (S_ma)-10 (orange) by (c) chiral-stationary-phase high-performance liquid chromatography and (d) circular dichroism spectroscopy respectively confirmed their enantiopurity and their chiral nature. IBX = 2-iodoxybenzoic acid.

Figure 5. Assignment and further analysis of the mechanical axial stereogenic unit.

Methods to assign the stereogenic units of mechanically axially chiral (a) catenanes and (b) rotaxanes by specifying the relative orientation of prochiral moieties. (c) The two diastereomers identified in catenanes containing one prochiral and one fixed covalent stereogenic center. (d) The four diastereomers identified in catenanes containing a covalent stereogenic center in both rings whose structures can be specified using either a mechanical topological or axial stereodescriptor. (e) Selective symmetrization of the in-plane or out of plane substituents of one diastereomers of (d) gives a topologically or axially chiral catenane respectively. R = CO₂Me.