Compatibility assessment of unactivated internal alkynes in rhodium-catalyzed [2+2+2] cycloadditions

John Halford-McGuff; Aidan McKay; Allan John Bell Watson

doi:10.1055/a-2285-0007

Compatibility assessment of unactivated internal alkynes in rhodium-catalyzed [2+2+2] cycloadditions

John Halford-McGuff, Aidan McKay, Allan John Bell Watson^*

^*Corresponding author for this work

School of Chemistry

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

Abstract

Functionalized 1,2,4,5-tetrasubstituted benzenes are synthetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cycloaddition of a diyne and internal alkyne offers a seemingly straightforward route to these scaffolds; however, this has been largely restricted to alkynes bearing activating (coordinating) functional groups, with very few examples of unactivated alkynes. In this work, we disclose an assessment of Rh-catalyzed [2+2+2] cycloadditions employing unactivated internal alkynes, focusing on the structural diversity and compatibility of both alkyne and diyne components. The limitations of this method are disclosed, with exceptionally bulky alkynes and specific functional groups undergoing side reactions. Furthermore, the practicalities of gram-scale reactions and catalyst recovery/reuse are demonstrated.

Original language	English
Pages (from-to)	2128-2132
Number of pages	5
Journal	Synlett
Volume	35
DOIs	https://doi.org/10.1055/a-2285-0007
Publication status	Published - 28 Mar 2024

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Halford-McGuff_2024_Synlett_Compatibility-assessment_CCBY
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1 Finished
1 Active

Allan Watson Programme Grant: Boron: Beyond the Reagent
Watson, A. J. B. (PI), Morris, R. E. (CoI), Smith, A. D. (CoI) & Zysman-Colman, E. (CoI)
UK Research and Innovation
1/05/23 → 30/04/28
Project: Standard
A biochemical boron tagging stategy: A biochemical boron tagging strategy for biomolecule visualisation and profiling
Watson, A. J. B. (PI)
The Leverhulme Trust
1/09/22 → 31/08/24
Project: Fellowship

Dataset underpinning "Compatibility Assessment of Unactivated Internal Alkynes in Rhodium-Catalyzed [2+2+2] Cycloadditions"
Halford-McGuff, J. (Creator), McKay, A. (Creator) & Watson, A. J. B. (Creator), University of St Andrews, 29 May 2024
DOI: 10.17630/019f4d4d-d107-41d8-ad7f-3ddb244e1b3c
Dataset

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Cite this

@article{1187b7ab144747a99891cbb065a0840b,

title = "Compatibility assessment of unactivated internal alkynes in rhodium-catalyzed [2+2+2] cycloadditions",

abstract = "Functionalized 1,2,4,5-tetrasubstituted benzenes are synthetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cycloaddition of a diyne and internal alkyne offers a seemingly straightforward route to these scaffolds; however, this has been largely restricted to alkynes bearing activating (coordinating) functional groups, with very few examples of unactivated alkynes. In this work, we disclose an assessment of Rh-catalyzed [2+2+2] cycloadditions employing unactivated internal alkynes, focusing on the structural diversity and compatibility of both alkyne and diyne components. The limitations of this method are disclosed, with exceptionally bulky alkynes and specific functional groups undergoing side reactions. Furthermore, the practicalities of gram-scale reactions and catalyst recovery/reuse are demonstrated.",

author = "John Halford-McGuff and Aidan McKay and Watson, {Allan John Bell}",

note = "Funding: J.M.H.-M. thanks the EaSI-CAT Centre for Doctoral Training for a PhD Studentship. A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF 2022-014) and the EPSRC Programme Grant {\textquoteleft}Boron: Beyond the Reagent{\textquoteright} (EP/W0077517/1) for support.",

year = "2024",

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day = "28",

doi = "10.1055/a-2285-0007",

language = "English",

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pages = "2128--2132",

journal = "Synlett",

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T1 - Compatibility assessment of unactivated internal alkynes in rhodium-catalyzed [2+2+2] cycloadditions

AU - Halford-McGuff, John

AU - McKay, Aidan

AU - Watson, Allan John Bell

N1 - Funding: J.M.H.-M. thanks the EaSI-CAT Centre for Doctoral Training for a PhD Studentship. A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF 2022-014) and the EPSRC Programme Grant ‘Boron: Beyond the Reagent’ (EP/W0077517/1) for support.

PY - 2024/3/28

Y1 - 2024/3/28

N2 - Functionalized 1,2,4,5-tetrasubstituted benzenes are synthetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cycloaddition of a diyne and internal alkyne offers a seemingly straightforward route to these scaffolds; however, this has been largely restricted to alkynes bearing activating (coordinating) functional groups, with very few examples of unactivated alkynes. In this work, we disclose an assessment of Rh-catalyzed [2+2+2] cycloadditions employing unactivated internal alkynes, focusing on the structural diversity and compatibility of both alkyne and diyne components. The limitations of this method are disclosed, with exceptionally bulky alkynes and specific functional groups undergoing side reactions. Furthermore, the practicalities of gram-scale reactions and catalyst recovery/reuse are demonstrated.

AB - Functionalized 1,2,4,5-tetrasubstituted benzenes are synthetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cycloaddition of a diyne and internal alkyne offers a seemingly straightforward route to these scaffolds; however, this has been largely restricted to alkynes bearing activating (coordinating) functional groups, with very few examples of unactivated alkynes. In this work, we disclose an assessment of Rh-catalyzed [2+2+2] cycloadditions employing unactivated internal alkynes, focusing on the structural diversity and compatibility of both alkyne and diyne components. The limitations of this method are disclosed, with exceptionally bulky alkynes and specific functional groups undergoing side reactions. Furthermore, the practicalities of gram-scale reactions and catalyst recovery/reuse are demonstrated.

U2 - 10.1055/a-2285-0007

DO - 10.1055/a-2285-0007

M3 - Article

SN - 0936-5214

VL - 35

SP - 2128

EP - 2132

JO - Synlett

JF - Synlett

ER -

Compatibility assessment of unactivated internal alkynes in rhodium-catalyzed [2+2+2] cycloadditions

Abstract

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Projects

Allan Watson Programme Grant: Boron: Beyond the Reagent

A biochemical boron tagging stategy: A biochemical boron tagging strategy for biomolecule visualisation and profiling

Datasets

Dataset underpinning "Compatibility Assessment of Unactivated Internal Alkynes in Rhodium-Catalyzed [2+2+2] Cycloadditions"

Cite this