Pd-Catalyzed Suzuki-Miyaura Cross-Coupling of Pentafluorophenyl Esters

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.

Recent Advances in Acyl Suzuki Cross-Coupling

“…The pyridine "throw-away" family of ligands render this class of Pd-NHC precatalysts an attractive method due to simplicity of synthesis and high reactivity in C(acyl)-O insertion. Later, we demonstrated that the cross-coupling is effectively promoted at remarkably mild room temperature conditions (Scheme 17C), while supporting various Pd-NHC precatalysts as well as Pd(II)-NHC hydroxide dimers ( Figure 2) In 2018, to further explore the reactivity of phenolic esters in the acyl Suzuki cross-coupling reaction, we have reported the Pd-phosphine-catalyzed cross-coupling of pentafluorophenyl esters (pfp) (Scheme 19) [52]. Due to the activating effect of the fluorine substituents, a mild Pd2(dba)3/PCy3 catalyst was able to effectively activate the C(acyl)-O bond giving products in high yields without the need for a more reactive, albeit less selective, Pd-NHC precatalyst.…”

“…Due to the activating effect of the fluorine substituents, a mild Pd2(dba)3/PCy3 catalyst was able to effectively activate the C(acyl)-O bond giving products in high yields without the need for a more reactive, albeit less selective, Pd-NHC precatalyst. In 2018, to further explore the reactivity of phenolic esters in the acyl Suzuki cross-coupling reaction, we have reported the Pd-phosphine-catalyzed cross-coupling of pentafluorophenyl esters (pfp) (Scheme 19) [52]. Due to the activating effect of the fluorine substituents, a mild Pd2(dba)3/PCy3 catalyst was able to effectively activate the C(acyl)-O bond giving products in high yields without the need for a more reactive, albeit less selective, Pd-NHC precatalyst.…”

“…In 2018, to further explore the reactivity of phenolic esters in the acyl Suzuki cross-coupling reaction, we have reported the Pd-phosphine-catalyzed cross-coupling of pentafluorophenyl esters (pfp) (Scheme 19) [52]. Due to the activating effect of the fluorine substituents, a mild Pd 2 (dba) 3 /PCy 3 catalyst was able to effectively activate the C(acyl)-O bond giving products in high yields without the need for a more reactive, albeit less selective, Pd-NHC precatalyst.…”

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

“…As expected, these reagents are more selective than "fully perpendicular" (τ = 88.6 • ) N-acyl-glutarimides (Scheme 4A). Importantly, full selectivity in the cross-coupling of N-acylphthalimides in the presence of electronically activated pfp esters (pfp = pentafluorophenyl) was observed (Scheme 4B) [50]. This further confirms the unique activation platform of the amide bond, wherein the selectivity is tuned by both sterics and electronics of N-substituents, which, for obvious reasons, is not possible with other acyl electrophiles.…”

Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Aryl Chlorobenzoates with Alkyl Grignard Reagents

“…We became interested in developing the iron-catalyzed cross-coupling of aryl chlorobenzoates as part of our program in iron catalysis [36][37][38][39][40][41][42][43] and the cross-coupling of C(acyl)-X (X = N, O) electrophiles [44,45]. Recently, several groups have reported methods for the nickel and palladium-catalyzed C(acyl)-O bond activation of aryl benzoates, leading to the selective formation of acyl-metal intermediates (Scheme 2, box) [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64]. While aryl benzoates have long been established as electrophiles in nucleophilic addition to the ester bond via tetrahedral intermediates owing to the increased electrophilicity of the ester bond due to O lp to Ar conjugation [65], the recent advances in accessing acyl metals from aryl benzoates significantly expand the utility of this class of carboxylic acid derivatives in organic synthesis.…”