Abstract
Although the palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl esters has received significant attention, there is a lack of methods that utilize cheap and readily accessible Pd-phosphane catalysts, and can be routinely carried out with high cross-coupling selectivity. Herein, we report the first general method for the cross-coupling of pentafluorophenyl esters (pentafluorophenyl = pfp) by selective C–O acyl cleavage. The reaction proceeds efficiently using Pd(0)/phosphane catalyst systems. The unique characteristics of pentafluorophenyl esters are reflected in the fully selective cross-coupling vs. phenolic esters. Of broad synthetic interest, this report establishes pentafluorophenyl esters as new, highly reactive, bench-stable, economical, ester-based, electrophilic acylative reagents via acyl-metal intermediates. Mechanistic studies strongly support a unified reactivity scale of acyl electrophiles by C(O)–X (X = N, O) activation. The reactivity of pfp esters can be correlated with barriers to isomerization around the C(acyl)–O bond.
Highlights
The recent emergence of Suzuki-Miyaura cross-coupling of amide and ester electrophiles by selective C(acyl)–X cleavage represents one of the most promising approaches to functionalization of the traditionally inert amide and ester bonds in organic synthesis [1,2,3]
We have reported a general method for the cross-coupling of both esters and amides at room temperature [15]
Given the established capacity of pentafluorophenyl esters as acyl transfer reagents in nucleophilic addition reactions [20,21,22], we recently questioned whether the ground-state-destabilization principle might enable facile cross-coupling of pentafluorophenyl esters under chemoselective conditions that are inaccessible to the current-stateof-the-art phenolic esters [1,2,3]
Summary
The recent emergence of Suzuki-Miyaura cross-coupling of amide and ester electrophiles by selective C(acyl)–X cleavage represents one of the most promising approaches to functionalization of the traditionally inert amide and ester bonds in organic synthesis [1,2,3]. Given the established capacity of pentafluorophenyl esters as acyl transfer reagents in nucleophilic addition reactions [20,21,22], we recently questioned whether the ground-state-destabilization principle might enable facile cross-coupling of pentafluorophenyl esters under chemoselective conditions that are inaccessible to the current-stateof-the-art phenolic esters [1,2,3]. In this Special Issue on Amide Bond Activation, we report the successful realization of this approach, and report the first general method for the cross-coupling of pentafluorophenyl esters by selective C–O acyl cleavage.
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