CC BY 4.0 · Synlett 2024; 35(18): 2128-2132
DOI: 10.1055/a-2285-0007
letter

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

John M. Halford-McGuff
,
Aidan P. McKay
,
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.


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.

Supporting Information



Publication History

Received: 13 February 2024

Accepted after revision: 11 March 2024

Accepted Manuscript online:
11 March 2024

Article published online:
28 March 2024

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