Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones.

Yi Liu,Bruce A Arndtsen,Angela M Kaiser

doi:10.1039/d0sc03129a

Yi Liu, Bruce A Arndtsen + Show 1 more

Open Access

https://doi.org/10.1039/d0sc03129a

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Journal: Chemical Science	Publication Date: Jan 1, 2020
Citations: 8	License type: CC BY 3.0

Affiliation: Toronto General Hospital, McGill University

Abstract

We describe here the design of a palladium catalyzed route to generate aryl ketones via the carbonylative coupling of (hetero)arenes and aryl- or vinyl-triflates. In this, the use of the large bite angle Xantphos ligand on palladium provides a unique avenue to balance the activation of the relatively strong C(sp2)–OTf bond with the ultimate elimination of a new class of potent Friedel–Crafts acylating agent: N-acyl pyridinium salts. The latter can be exploited to modulate reactivity and selectivity in carbonylative arene functionalization chemistry, and allow the efficient synthesis of ketones with a diverse array of (hetero)arenes.

Highlights

The design of catalytic methods for the efficient and selective functionalization of aromatic C–H bonds represents an important current thrust in synthetic chemistry.[1]
We turned to bidentate ligands, as these have been demonstrated to allow the oxidative addition of aryl tri ates in traditional carbonylations.[14]. Many of these were ineffective, which may re ect the difficult reductive elimination of the reactive aroyl tri ates from palladium.8e We considered using steric effects to balance the electronic needs of oxidative addition with the ultimate reductive elimination of a reactive acyl electrophile.[8]
While aryl tri ates react under these conditions to form a mixture of products (Fig. S3†), the carbonylation of a more reactive vinyl tri ate leads to the formation of the N-acyl pyridinium salt 1a (Fig. 3a).9n,18 The formation of 1a provides a rationale for the signi cant role of the pyridine base in the chemistry, where the more nucleophilic pyridine can presumably favor reductive elimination relative to the potential build-up of a labile acyl tri ate

Summary

Introduction

The design of catalytic methods for the efficient and selective functionalization of aromatic C–H bonds represents an important current thrust in synthetic chemistry.[1]. The reactivity of these electrophiles offers an efficient route to form ketones from broadly available (hetero)arenes, aryl/vinyl tri ates and carbon monoxide, and do so without the need for stoichiometric metal additives or expensive reagents.

Results

Conclusion