N-Acylphthalimides: Efficient Acyl Coupling Reagents in Suzuki–Miyaura Cross-Coupling by N–C Cleavage Catalyzed by Pd–PEPPSI Precatalysts

Md Rahman,Jonathan Buchspies,Michal Szostak

doi:10.3390/catal9020129

Md Rahman, Jonathan Buchspies + Show 1 more

Open Access

https://doi.org/10.3390/catal9020129

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Abstract

We report a general, highly selective method for Suzuki–Miyaura cross-coupling of N-acylphthalimides via N–C(O) acyl cleavage catalyzed by Pd–PEPPSI-type precatalysts. Of broad synthetic interest, the method introduces N-acylphthalimides as new, bench-stable, highly reactive, twist-controlled, amide-based precursors to acyl-metal intermediates. The reaction delivers functionalized biaryl ketones by acylative Suzuki–Miyaura cross-coupling with readily available boronic acids. Studies demonstrate that cheap, easily prepared, and broadly applicable Pd–PEPPSI-type precatalysts supported by a sterically demanding IPr (1,3-Bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) ancillary ligand provide high yields in this reaction. Preliminary selectivity studies and the effect of Pd–N-heterocyclic carbenes (NHC) complexes with allyl-type throw-away ligands are described. We expect that N-acylphthalimides will find significant use as amide-based acyl coupling reagents and cross-coupling precursors to acyl-metal intermediates.

Highlights

The cross-coupling of amides by transition metal-catalyzed N–C acyl cleavage has emerged as a powerful method for the construction of C–C and C–X bonds, enabling the utilization of traditionally inert amide derivatives in cross-coupling reactions of broad synthetic importance [1,2,3,4,5,6,7,8]
The present study provides one of the first experimental observations into the ligand effect in the cross-coupling of acyl electrophiles by the Pd–N-heterocyclic carbenes (NHC) catalysis platform
We were primarily interested in developing a cross-coupling method using readily available Pd–PEPPSI-type precatalysts, we considered it important to compare the reactivity of Pd–NHC precatalysts bearing pyridine throw-away ligands with allyl-type throw-away ligands (Scheme 5) [51]

Summary

Introduction

The cross-coupling of amides by transition metal-catalyzed N–C acyl cleavage has emerged as a powerful method for the construction of C–C and C–X bonds, enabling the utilization of traditionally inert amide derivatives in cross-coupling reactions of broad synthetic importance [1,2,3,4,5,6,7,8]. N-acylphthalimides [27,28,29] which are widely used as acylating reagents in organic synthesis, relying on the versatile phthalimide ring typically associated with the classical Gabriel synthesis [30,31,32], are yet to be reported in the cross-coupling of amides by N–C(O) bond cleavage. The development of new catalyst systems has generated major advancements in the field of acyl cross-coupling of bench-stable electrophiles [1]. N-acylphthalimides as new, benchhighly reactive, twist-controlled, amide-based precursors to acyl metal intermediates; (2). The reaction stable, highly reactive, twist-controlled, to acyl cross-coupling metal intermediates; The delivers functionalized biaryl ketones amide-based by acylative precursors. Pd–PEPPSI-type choice in to examining the reactivity using Pd–NHC reported date in diverse cross-couplings [42,43,44].catalysts

Pd–PEPPSI-IPr

Structures

Discussion

Materials and Methods