A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions

Illya Zalessky; Jack M Wootton; Jerry K F Tam; Dominic E Spurling; William C Glover-Humphreys; James R Donald; Will E Orukotan; Lee C Duff; Ben J Knapper; Adrian C Whitwood; Theo F N Tanner; Afjal H Miah; Jason M Lynam; William P Unsworth

doi:10.1021/jacs.4c00659

A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions

Illya Zalessky, Jack M Wootton, Jerry K F Tam, Dominic E Spurling, William C Glover-Humphreys, James R Donald, Will E Orukotan, Lee C Duff, Ben J Knapper, Adrian C Whitwood, Theo F N Tanner, Afjal H Miah, Jason M Lynam, William P Unsworth

Chemistry

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

Abstract

Macrocycles and medium-sized rings are important in many scientific fields and technologies but are hard to make using current methods, especially on a large scale. Outlined herein is a strategy by which functionalized macrocycles and medium-sized rings can be prepared using cyclization/ring expansion (CRE) cascade reactions, without resorting to high dilution conditions. CRE cascade reactions are designed to operate exclusively via kinetically favorable 5-7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization reactions are avoided. A modular synthetic approach has been developed to facilitate the simple assembly of the requisite linear precursors, which can then be converted into an extremely broad range of functionalized macrocycles and medium-sized rings using one of nine CRE protocols.

Original language	English
Number of pages	10
Journal	Journal of the American Chemical Society
Early online date	19 Feb 2024
DOIs	https://doi.org/10.1021/jacs.4c00659
Publication status	E-pub ahead of print - 19 Feb 2024

Bibliographical note

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10.1021/jacs.4c00659Licence: CC BY

A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions
© 2024 The Authors.
Final published version, 2.76 MBLicence: CC BY

Cite this

Zalessky, I., Wootton, J. M., Tam, J. K. F., Spurling, D. E., Glover-Humphreys, W. C., Donald, J. R., Orukotan, W. E., Duff, L. C., Knapper, B. J., Whitwood, A. C., Tanner, T. F. N., Miah, A. H., Lynam, J. M., & Unsworth, W. P. (2024). A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions. Journal of the American Chemical Society. Advance online publication. https://doi.org/10.1021/jacs.4c00659

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title = "A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions",

abstract = "Macrocycles and medium-sized rings are important in many scientific fields and technologies but are hard to make using current methods, especially on a large scale. Outlined herein is a strategy by which functionalized macrocycles and medium-sized rings can be prepared using cyclization/ring expansion (CRE) cascade reactions, without resorting to high dilution conditions. CRE cascade reactions are designed to operate exclusively via kinetically favorable 5-7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization reactions are avoided. A modular synthetic approach has been developed to facilitate the simple assembly of the requisite linear precursors, which can then be converted into an extremely broad range of functionalized macrocycles and medium-sized rings using one of nine CRE protocols.",

author = "Illya Zalessky and Wootton, {Jack M} and Tam, {Jerry K F} and Spurling, {Dominic E} and Glover-Humphreys, {William C} and Donald, {James R} and Orukotan, {Will E} and Duff, {Lee C} and Knapper, {Ben J} and Whitwood, {Adrian C} and Tanner, {Theo F N} and Miah, {Afjal H} and Lynam, {Jason M} and Unsworth, {William P}",

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Zalessky, I, Wootton, JM, Tam, JKF, Spurling, DE, Glover-Humphreys, WC, Donald, JR, Orukotan, WE, Duff, LC, Knapper, BJ, Whitwood, AC, Tanner, TFN, Miah, AH, Lynam, JM & Unsworth, WP 2024, 'A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions', Journal of the American Chemical Society. https://doi.org/10.1021/jacs.4c00659

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T1 - A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions

AU - Zalessky, Illya

AU - Wootton, Jack M

AU - Tam, Jerry K F

AU - Spurling, Dominic E

AU - Glover-Humphreys, William C

AU - Donald, James R

AU - Orukotan, Will E

AU - Duff, Lee C

AU - Knapper, Ben J

AU - Whitwood, Adrian C

AU - Tanner, Theo F N

AU - Miah, Afjal H

AU - Lynam, Jason M

AU - Unsworth, William P

PY - 2024/2/19

Y1 - 2024/2/19

N2 - Macrocycles and medium-sized rings are important in many scientific fields and technologies but are hard to make using current methods, especially on a large scale. Outlined herein is a strategy by which functionalized macrocycles and medium-sized rings can be prepared using cyclization/ring expansion (CRE) cascade reactions, without resorting to high dilution conditions. CRE cascade reactions are designed to operate exclusively via kinetically favorable 5-7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization reactions are avoided. A modular synthetic approach has been developed to facilitate the simple assembly of the requisite linear precursors, which can then be converted into an extremely broad range of functionalized macrocycles and medium-sized rings using one of nine CRE protocols.

AB - Macrocycles and medium-sized rings are important in many scientific fields and technologies but are hard to make using current methods, especially on a large scale. Outlined herein is a strategy by which functionalized macrocycles and medium-sized rings can be prepared using cyclization/ring expansion (CRE) cascade reactions, without resorting to high dilution conditions. CRE cascade reactions are designed to operate exclusively via kinetically favorable 5-7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization reactions are avoided. A modular synthetic approach has been developed to facilitate the simple assembly of the requisite linear precursors, which can then be converted into an extremely broad range of functionalized macrocycles and medium-sized rings using one of nine CRE protocols.

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