Stepwise, protecting group free synthesis of [4]rotaxanes

James E.M. Lewis; Joby Winn; Stephen M. Goldup

doi:10.3390/molecules22010089

Stepwise, protecting group free synthesis of [4]rotaxanes

James E.M. Lewis, Joby Winn, Stephen M. Goldup^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	89
Journal	Molecules
Volume	22
Issue number	1
DOIs	https://doi.org/10.3390/molecules22010089
Publication status	Published - Jan 2017

Bibliographical note

Funding Information:
The authors are grateful to Fluorochem for the gift of reagents. This work was supported financially by the Royal Society, the European Commission, the EPSRC (EP/J01981X/1) and the University of Southampton. This project has received funding from the European Commission's Horizon 2020 research and innovation programmed under the Marie Skłodowska-Curie grant agreement No. 660731. JEML is an EC Marie Skłodowska-Curie Fellow. SMG is a Royal Society Research Fellow.

Publisher Copyright:
© 2017 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

Active template
Copper-catalyzed azide-alkyne cycloaddition
CuAAC
Mechanically interlocked
Rotaxane

ASJC Scopus subject areas

Analytical Chemistry
Chemistry (miscellaneous)
Molecular Medicine
Pharmaceutical Science
Drug Discovery
Physical and Theoretical Chemistry
Organic Chemistry

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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.",

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N2 - 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.

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Stepwise, protecting group free synthesis of [4]rotaxanes

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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