title: Stepwise, Protecting Group Free Synthesis of [4]Rotaxanes.
abstract: Despite significant advances in the last three decades towards high yielding syntheses of rotaxanes, the preparation of systems constructed from more than two components remains a challenge. Herein we build upon our previous report of an active template copper-catalyzed azide-alkyne cycloaddition (CuAAC) rotaxane synthesis with a diyne in which, following the formation of the first mechanical bond, the steric bulk of the macrocycle tempers the reactivity of the second alkyne unit. We have now extended this approach to the use of 1,3,5-triethynylbenzene in order to successively prepare [2]-, [3]- and [4]rotaxanes without the need for protecting group chemistry. Whilst the first two iterations proceeded in good yield, the steric shielding that affords this selectivity also significantly reduces the efficacy of the active template (AT)-CuAAC reaction of the third alkyne towards the preparation of [4]rotaxanes, resulting in severely diminished yields.
authors.affiliation: Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK. jem.lewis@soton.ac.uk.
authors.forename: James E M
authors.initials: JE
authors.lastname: Lewis
authors.affiliation: School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK. joby.winn@googlemail.com.
authors.forename: Joby
authors.initials: J
authors.lastname: Winn
authors.affiliation: Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK. s.goldup@soton.ac.uk.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Goldup
mesh_terms: D000480:Alkynes / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D001555:Benzene Derivatives / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D061565:Cycloaddition Reaction / Q000379:methods*; D053280:Diynes / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D043862:Rotaxanes / Q000138:chemical synthesis*
chemical_list: D000480:Alkynes; D001386:Azides; D001555:Benzene Derivatives; D053280:Diynes; D043862:Rotaxanes; C516768:1,3,5-triethylbenzene; D003300:Copper
keywords: CuAAC; active template; copper-catalyzed azide-alkyne cycloaddition; mechanically interlocked; rotaxane