The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers

Tengfei Kang; Justin O'Yang; Kevin Kasten; Samuel S. Allsop; Toby Lewis-Atwell; Elliot H. E. Farrar; Martin Juhl; David B. Cordes; Aidan P. McKay; Matthew N. Grayson; Andrew D. Smith

doi:10.1038/s41557-025-02022-4

The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers

Tengfei Kang, Justin O'Yang, Kevin Kasten, Samuel S. Allsop, Toby Lewis-Atwell, Elliot H. E. Farrar, Martin Juhl, David B. Cordes, Aidan P. McKay, Matthew N. Grayson^*, Andrew D. Smith^*

^*Corresponding author for this work

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

Abstract

The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.

Original language	English
Number of pages	11
Journal	Nature Chemistry
Volume	AOP
Early online date	6 Jan 2026
DOIs	https://doi.org/10.1038/s41557-025-02022-4
Publication status	E-pub ahead of print - 6 Jan 2026

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10.1038/s41557-025-02022-4Licence: CC BY

Kang_2026_NC_Catalytic-Wittig-rearrangement-allylic-ethers_CC
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1 Finished
1 Active

Allan Watson Programme Grant: Boron: Beyond the Reagent
Watson, A. (PI), Morris, R. (CoI), Smith, A. (CoI) & Zysman-Colman, E. (CoI)
UK Research and Innovation
1/05/23 → 30/04/28
Project: Standard
Exploiting Chalcogen Bonding and Non: Exploiting Chalcogen Bonding and Non-Covalent Interactions in Isochalcogenourea Catalysis: Catalyst Preparation, Mechanistic Studies and Applications
Smith, A. (PI)
1/11/20 → 31/10/23
Project: Standard

The Catalytic Enantioselective [1,2]-Wittig Rearrangement of Allylic Ethers (dataset)
Smith, A. D. (Creator), Kang, T. (Owner), O'Yang, J. (Creator), Kasten, K. (Creator), Cordes, D. B. (Creator), McKay, A. (Creator), Juhl, M. (Creator), Grayson, M. (Creator), Farrar, E. (Creator) & Allsop, S. (Creator), University of St Andrews, 14 Aug 2024
DOI: 10.17630/5b5778a0-f337-4cbe-b336-c2afac22693b
Dataset

File
update to dataset 295983644 with updated title ""The Catalytic Enantioselective [1,2]-Wittig Rearrangement Cascade of Allylic Ethers"
Smith, A. D. (Creator), Kasten, K. (Owner) & O'Yang, J. (Owner), University of St Andrews, 10 Jun 2025
DOI: 10.17630/6424d442-e1bc-4834-9456-6cfb7296580f
Dataset

File

Cite this

@article{5cd64e9a8a864b578751962566511b88,

title = "The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers",

abstract = "The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.",

author = "Tengfei Kang and Justin O'Yang and Kevin Kasten and Allsop, \{Samuel S.\} and Toby Lewis-Atwell and Farrar, \{Elliot H. E.\} and Martin Juhl and Cordes, \{David B.\} and McKay, \{Aidan P.\} and Grayson, \{Matthew N.\} and Smith, \{Andrew D.\}",

note = "Funding: The research leading to these results has received funding from the Royal Society (Newton Fellowship to T.K.), EPSRC (T.K., K.K., EP/T023643/1; A.D.S., K.K., EP/W007517; E.H.E.F., EP/R513155/1; E.H.E.F., M.N.G., EP/W003724/1), UKRI (T.L.-A., ART-AI CDT, EP/S023437/1), The Carlsberg Foundation (M.J.) and the EaSI-CAT Centre for Doctoral Training (J.O'Y.).",

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doi = "10.1038/s41557-025-02022-4",

language = "English",

volume = "AOP",

journal = "Nature Chemistry",

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T1 - The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers

AU - Kang, Tengfei

AU - O'Yang, Justin

AU - Kasten, Kevin

AU - Allsop, Samuel S.

AU - Lewis-Atwell, Toby

AU - Farrar, Elliot H. E.

AU - Juhl, Martin

AU - Cordes, David B.

AU - McKay, Aidan P.

AU - Grayson, Matthew N.

AU - Smith, Andrew D.

N1 - Funding: The research leading to these results has received funding from the Royal Society (Newton Fellowship to T.K.), EPSRC (T.K., K.K., EP/T023643/1; A.D.S., K.K., EP/W007517; E.H.E.F., EP/R513155/1; E.H.E.F., M.N.G., EP/W003724/1), UKRI (T.L.-A., ART-AI CDT, EP/S023437/1), The Carlsberg Foundation (M.J.) and the EaSI-CAT Centre for Doctoral Training (J.O'Y.).

PY - 2026/1/6

Y1 - 2026/1/6

N2 - The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.

AB - The catalytic enantioselective [1,2]-Wittig rearrangement of allylic ethers constitutes a recognized synthetic challenge as it is traditionally considered to arise from a non-concerted reaction pathway via formation and recombination of radical pairs. Here we show a catalytic enantioselective solution to this challenge, demonstrating that [1,2]-Wittig products are generated via an alternative reaction cascade to traditional dogma. The developed process employs a chiral bifunctional iminophosphorane catalyst to promote an initial enantioselective [2,3]-sigmatropic rearrangement. A subsequent base-promoted, stereoconvergent, fragmentation–recombination process that proceeds with high enantiospecificity and retention of configuration, formally equivalent to a Woodward–Hoffmann forbidden thermal [1,3]-sigmatropic rearrangement, generates [1,2]-Wittig products in up to 97:3 enantiomeric ratio. Supported by extensive quantum chemistry calculations, this chirality transfer process will have broad implications for fundamental stereocontrol in organic transformations.

U2 - 10.1038/s41557-025-02022-4

DO - 10.1038/s41557-025-02022-4

M3 - Article

SN - 1755-4330

VL - AOP

JO - Nature Chemistry

JF - Nature Chemistry

ER -

The catalytic enantioselective [1,2]-Wittig rearrangement cascade of allylic ethers

Abstract

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Projects

Allan Watson Programme Grant: Boron: Beyond the Reagent

Exploiting Chalcogen Bonding and Non: Exploiting Chalcogen Bonding and Non-Covalent Interactions in Isochalcogenourea Catalysis: Catalyst Preparation, Mechanistic Studies and Applications

Datasets

The Catalytic Enantioselective [1,2]-Wittig Rearrangement of Allylic Ethers (dataset)

update to dataset 295983644 with updated title ""The Catalytic Enantioselective [1,2]-Wittig Rearrangement Cascade of Allylic Ethers"

Cite this