Rapidly Activating Pd-Precatalyst for Suzuki–Miyaura and Buchwald–Hartwig Couplings of Aryl Esters

Abstract

Esters are valuable electrophiles for cross-coupling due to their ubiquity and ease of synthesis. However, harsh conditions are traditionally required for the effective cross-coupling of ester substrates. Utilizing a recently discovered precatalyst, Pd-catalyzed Suzuki-Miyaura and Buchwald-Hartwig reactions involving cleavage of the C(acyl)-O bond of aryl esters that proceed under mild conditions are reported. The Pd(II) precatalyst is highly active because it is reduced to the Pd(0) active species more rapidly than previous precatalysts.

Mechanistic Study of Suzuki–Miyaura Cross‐Coupling Reactions of Amides Mediated by [Pd(NHC)(allyl)Cl] Precatalysts

“…It is worthwhile to note that from amides 1a-1c,m ost syntheticallyu seful are amides 1c (N,N = Ph,Boc) due to ease of preparation from secondary benzamides in as ingle, operationally simple andh igh-yielding step. The observed order of reactivity with [Pd(IPr*)(cin)Cl] (1a> 1c> 1b)f ollows the reactivity order determined earlier using [Pd(IPr)(cin)Cl], [14] albeit at much lower conversions.…”

“…However,r ecent computational studies have shown that the more plausible pathway is the boronate one. Therefore, in this study,w eh ave only focused in the boronatep athway using potassium carbonate as ab ase in THF,c onditions employedb yt he Szostak group, [14] and potassium carbonate as ab ase (Figure 7). The transmetalation begins from intermediate I6 and the organoboronate compound.…”

“…[17] As a key insight, we show that water helps to activate the Pd-NHC catalytic system,w hich can then enabler oom temperature cross-coupling of ab road range of amides through selective NÀCb onds cissionu nder the mildestc onditions reportedt o date. [9][10][11][12][13][14] The use of sterically -hindered [Pd(IPr*)(cin)Cl] reported herein for the first time in the amide cross-couplingi ndicates that increasing flexible steric bulk of the isopropyl wingtip groups of the NHC ligand [15] provides am odular scaffold for promoting the amide cross-coupling in high yields. In light of the past experimentsw here it was demonstrated that terminal substitution of the allyl scaffold in [Pd(NHC)(allyl)Cl] complexes results in am ore facile activation of the complex to afford the catalytic species, [14,21] the precatalytic pathway of both NHC ligands as well as the catalytic pathway that starts from the Pd 0 speciesa re discussed.…”

“…[9][10][11][12][13][14] The use of sterically -hindered [Pd(IPr*)(cin)Cl] reported herein for the first time in the amide cross-couplingi ndicates that increasing flexible steric bulk of the isopropyl wingtip groups of the NHC ligand [15] provides am odular scaffold for promoting the amide cross-coupling in high yields. In light of the past experimentsw here it was demonstrated that terminal substitution of the allyl scaffold in [Pd(NHC)(allyl)Cl] complexes results in am ore facile activation of the complex to afford the catalytic species, [14,21] the precatalytic pathway of both NHC ligands as well as the catalytic pathway that starts from the Pd 0 speciesa re discussed. The mechanistic details provide the basis to understandt he amide bond twist (distortion) that leads to NÀCc ross-coupling reactions [6,[9][10][11][12][13] and that is required for the efficient NÀCb ond activation.…”

“…[9][10][11][12][13] In 2017, Szostak et al described the first method for the Pd-NHC catalyzedc ross-coupling of amides by highly selectiveN À Ci nsertion. [14] Within this catalytic manifold, it is known that Pd-NHCcomplexes provide the most active catalytic system reportedt od ate. [15] Strong s-donation by the ligand facilitates oxidative addition and flexible steric bulk stabilizes the active catalysta nd promotes reductive elimination.…”