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. 2023 Oct 20;25(41):7584-7588.
doi: 10.1021/acs.orglett.3c03071. Epub 2023 Oct 9.

Palladium-Catalyzed Decarbonylative Coupling of (Hetero)Aryl Boronate Esters with Difluorobenzyl Glutarimides

Alexander Bunnell  1 , Naish Lalloo  1 , Conor Brigham  1 , Melanie S Sanford  1
Affiliations

Palladium-Catalyzed Decarbonylative Coupling of (Hetero)Aryl Boronate Esters with Difluorobenzyl Glutarimides

Alexander Bunnell et al. Org Lett. .

Abstract

This report describes the Pd-catalyzed decarbonylative coupling of difluorobenzyl glutarimides with (hetero)aryl boronate esters to yield difluorobenzyl-substituted (hetero)arene products. The use of PAd2Bu as the phosphine ligand in combination with neopentylboronate ester nucleophiles proved critical for the selective formation of the decarbonylative coupling product versus analogous difluorobenzyl ketone. This transformation is effective for electronically diverse (hetero)aryl boronate esters and substituted difluorobenzyl glutarimides.

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Figures

Scheme 1.
Scheme 1.
(a) Pd-catalyzed Suzuki coupling with fluoroalkyl glutarimides to form fluoroalkyl ketones. (b) Pd-catalyzed decarbonylative difluoromethylation with difluomethylacetyl fluoride. (c) This work: decarbonylative fluoroalkylation of (hetero)arylboronate esters with fluoroalkyl glutarimides.
Scheme 2.
Scheme 2.
Proposed catalytic cycles for (I) fluoroalkyl arene formation versus (II) fluoroalkyl ketone formation. Reactivity of intermediate A towards transmetalation (TM) versus CO de-insertion (De-I) is proposed to dictate product selectivity.
Scheme 3.
Scheme 3.
Scope of boronate ester nucleophiles in decarbonylative difluorobenzylation. NMR yield (isolated yield).
Scheme 4.
Scheme 4.
Scope of fluoroalkyl electrophiles in decarbonylative fluoroalkylation. NMR yield (isolated yield). a10 mol % Pd[P(otol)3]2, 20 mol % SPhos, Ar–B(OR)2, toluene, 100 °C, 18 h
See this image and copyright information in PMC

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