A chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes

Abstract

Rotaxanes can display molecular chirality solely due to the mechanical bond between the axle and encircling macrocycle without the presence of covalent stereogenic units. However, the synthesis of such molecules remains challenging. We have discovered a combination of reaction partners that function as a chiral interlocking auxiliary to both orientate a macrocycle and, effectively, load it onto a new axle. Here we use these substrates to demonstrate the potential of a chiral interlocking auxiliary strategy for the synthesis of mechanically planar chiral rotaxanes by producing a range of examples in high enantiopurity (93–99% e.e.), including so-called ‘impossible’ rotaxanes whose axles lack any functional groups that would allow their direct synthesis by other means. Intriguingly, by varying the order of bond-forming steps, we can effectively choose which end of an axle the macrocycle is loaded onto, enabling the synthesis of both hands of a single target using the same reactions and building blocks.

Distinctive features and challenges in catenane chemistry

“…New strategies to direct the orientation of directional macrocycles, such as the use of chiral auxiliaries for enantioselective mechanical interlocking developed by Goldup, will be necessary. 99 …”

Conformational Control of [2]Rotaxane by Hydrogen Bond

“…The formation of the hydrogen bond between the acidic triazole proton and the amine moiety in [2]rotaxane has been postulated by several research groups. 22 , 23…”

“…The chemical shift of H y would also be strongly affected by the presence of the macrocycle because H y would form a hydrogen bond with the phenanthroline moiety. The formation of the hydrogen bond between the acidic triazole proton and the amine moiety in [2]­rotaxane has been postulated by several research groups. , …”

Mechanically interlocked molecules in metal–organic frameworks

“…For example, the utilization of interlocked catalysts [159][160][161][162][163] as ligands of MOFs would open new possibilities in heterogeneous catalysis. 11 Very likely, recent developments on the preparation of enantiopure MIMs incorporating novel chirality motifs [164][165][166] would allow significant advances in the construction of coherent chiral MOFs which can be employed in asymmetric catalysis. Other applications of intertwined molecules that have been widely studied in solution, in the context of molecular sensing 167 or ring-activated transformations, 168 could play an interesting role in the operability and usability of MOF-based materials.…”