Goldberg Active Template Synthesis of a [2]Rotaxane Ligand for Asymmetric Transition-Metal Catalysis

Abstract

We report on the active template synthesis of a [2]rotaxane through a Goldberg copper-catalyzed C-N bond forming reaction. A C2-symmetric cyclohexyldiamine macrocycle directs the assembly of the rotaxane, which can subsequently serve as a ligand for enantioselective nickel-catalyzed conjugate addition reactions. Rotaxanes are a previously unexplored ligand architecture for asymmetric catalysis. We find that the rotaxane gives improved enantioselectivity compared to a noninterlocked ligand, at the expense of longer reaction times.

Chiral Catenanes and Rotaxanes: Fundamentals and Emerging Applications

“…Leigh and co‐workers have since reported on a number of chiral rotaxanes for asymmetric catalysis . For instance, an active metal template synthesized rotaxane possessing a chiral C 2 symmetric trans ‐cyclohexanediamine macrocycle, for use in enantioselective nickel‐catalyzed conjugate addition reactions (Figure ) .…”

“…[50][51][52] For instance, an active metal template synthesized rotaxanep ossessing ac hiral C 2 symmetric trans-cyclohexanediaminem acrocycle, for use in enantioselective nickel-catalyzedc onjugate addition reactions ( Figure 22). [50] In comparison to an analogous acyclic ligand, rotaxane( R,R)-38 exhibited am uch better enantiomeric ratio of product (93:7 compared to 68:32), but considerably slower reaction times (27 vs. 2days for full conversion as determined by 1 HNMR spectroscopy). These observations are consistent with the rotaxanei mproving expression of chirality arising from the two stereogenic carbon atoms (by reducing degrees of freedom),b ut also restricting access to the cation (since it is buriedw ithin the rotaxane structure while coordinated to the nitrogen amine atoms), thusreducing the rate of reaction.…”

An Introduction to the Mechanical Bond

“…C-S couplings, 332 Cadiot-Chodkiewicz alkyne heterocouplings, 335 as well as Pd-and Ni-mediated homocouplings, 336,337 Ni-catalyzed sp 3 -sp 3 homocoupling of unactivated alkyl bromides, 307,338 oxidative Heck cross-couplings, 339 Michael additions, 340 Diels-Alder reactions, 341 and Goldberg amidations. 342 See Section 2.4 for a review of active template strategies. This new method of making mechanical bonds is undeniably versatile and elegant.…”

Heterobifunctional Rotaxanes for Asymmetric Catalysis

“…For an application in asymmetric catalysis, a number of chiral mechanically interlocked molecules (MIMs) have been developed . In transition‐metal catalysis, Leigh used rotaxanes with chiral diamine‐based macrocycles for Ni‐catalyzed enantioselective Michael additions, while Goldup employed mechanically planar‐chiral rotaxane ligands for Au‐mediated cyclopropanations . In the realm of organocatalysis, Leigh and Berna developed rotaxanes featuring nucleophilic secondary amines on the axle.…”