Role of the Base in Buchwald–Hartwig Amination

Abstract

The Buchwald-Hartwig amination has been investigated theoretically and experimentally to examine the scope of possible bases under different reaction conditions. Nonpolar solvents resist the formation of new charges. Therefore, the base should be anionic to be able to deprotonate the neutral palladium-amine complex and/or expel the anionic leaving group (bromide). The calculated barrier for the organic base DBU was found to be prohibitively high. In polar solvent, dissociation of bromide becomes possible, but here the base will instead form a complex with palladium, creating an overly stable resting state. The conclusions for both solvent classes hold for both a hindered monodentate phosphine and the labile bidentate ligand BINAP. The computational studies were supported by experimental testing of a range of bases using BINAP in two different solvents, toluene and DMF.

Rate and Computational Studies for Pd‐NHC‐Catalyzed Amination with Primary Alkylamines and Secondary Anilines: Rationalizing Selectivity for Monoarylation versus Diarylation with NHC Ligands

“…increasing the length of the alkyl chains of the N-aryl moiety on the NHC has an initial positive effect on rate, but then slows the reactionf or Pd-PEPPSI-IHept (13). Selectivity for monoarylationo ft hese same catalysts increases significantly as the catalystg ains stericb ulk from lengthening the N-aryl alkyl chains.…”

“…The chemical shifts for 1 H-NMR spectra are given in parts per million (ppm) referenced to the residual proton signal of the deuterated solvent;c oupling constants are expressed in Hertz (Hz). 13 C-NMR spectra were referenced to the carbon signal(s) of the deuterated solvent. The following abbreviations are used to describe peak multiplicities:s = singlet, br s = broad singlet, d = doublet, t = triplet, q = quartet, quint = quintet, dd = doublet of doublets, tt = triplet of triplets, qt = quartet of triplets, qd = quartet of doublets, and m = multiplet.…”

“…[11,12] The catalytic cycle for Pd-mediated amination has been proposed to follow one of two paths (Figure 1). [13,14] Oxidativea ddition (OA) of an Ar-X to Pd 0 (6)createsintermediate 1.Coordination of an amine to 1 in Pathway Ic reates amine complex 2, which followingi ntermolecular deprotonation leads to metal amido complex 3.C onversely,l igand exchange of 1 with tertbutoxide leads to 7 (PathwayI I), which after amine coordination (8), can now undergo an intramolecular proton transfer to deliver 3.R eductive elimination( RE) of the amide and aryl partner via transition state 4 delivers the product (5), while reducing Pd II back to Pd 0 (6), thus completing the cycle. As the understanding of the role(s) played by ancillary ligandso n each step in this transformation has become clearer,s ignificant advances in the overall process have been realized.…”

Recyclable NHC Catalyst for the Development of a Generalized Approach to Continuous Buchwald–Hartwig Reaction and Workup

“…2 The use of soluble organic bases to avoid these issues has been assessed on a number of occasions, 3,4 however, a recent study stemming from this work has revealed them to be an unviable option in all but the minority of cases. 5 Other strategies to avoid this issue have included use of biphasic systems to solublise the inorganic base, particularly in combination with packed-bed reactors to combat the mixing issues inherent in running such systems in continuous flow mode. Our vision for developing this reaction into a continuous system takes a different approach to the perceived issues highlighted above: develop a reactor capable of dealing with the solid salt formation inherent in the reaction; incorporate a recycle of a suitably stable catalyst in situ, and thereby create a generic reaction system, incorporating a continuous work-up that allows for the reuse of the catalyst and ultimately has the potential to be applicable beyond this immediate project.…”

Sulfonated salicylidene thiadiazole complexes with Co (II) and Ni (II) ions as sustainable corrosion inhibitors and catalysts for cross coupling reaction

“…Whereas, both ethanol and in the aqueous water‐ethanol binary mixture are the optimized solvents for C―N coupling of 3‐chloroaniline with 2‐bromopyridine or 2‐chloropyridine (entries 17–24). This is probably caused by the higher stability of aryl amines in water for the C―N coupling reactions . Both C―C and C―N coupling reaction deigned respectable yields of the target products (as recorded in Table , entries1–4 and in Table , entries 1–4 and 13–17) with Ni‐Sanp and Co‐Sanp.…”