Ueber eine neue Darstellungsweise von Phenyläthersalicylsäure

The copper-mediated aromatic nucleophilic substitution reactions developed by Fritz Ullmann and Irma Goldberg required stoichiometric amounts of copper and very high reaction temperatures. Recently, it was found that addition of relatively cheap ligands (diamines, aminoalcohols, diketones, diols) made these reactions truly catalytic, with catalyst amounts as low as 1 mol% or even lower. Since these catalysts are homogeneous, it has opened up the possibility to investigate the mechanism of these modified Ullmann reactions. Most authors agree that Cu(I) is the true catalyst even though Cu(0) and Cu(II) catalysts have also shown to be active. It should be noted however that Cu(I) is capable of reversible disproportionation into Cu(0) and Cu(II). In the first step, the nucleophile displaces the halide in the LnCu(I)X complex forming LnCu(I)ZR (Z = O, NR¢, S). Quite a number of mechanisms have been proposed for the actual reaction of this complex with the aryl halide: 1. Oxidative addition of ArX forming a Cu(III) intermediate followed by reductive elimination; 2. Sigma bond metathesis; in this mechanism copper remains in the Cu(II) oxidation state; 3. Single electron transfer (SET) in which a radical anion of the aryl halide is formed (Cu(I)/Cu(II)); 4. Iodine atom transfer (IAT) to give the aryl radical (Cu(I)/Cu(II)); 5. p-complexation of the aryl halide with the Cu(I) complex, which is thought to enable the nucleophilic substitution reaction. Initially, the radical type mechanisms 3 and 4 where discounted based on the fact that radical clock-type experiments with ortho-allyl aryl halides failed to give the cyclised products. However, a recent DFT study by Houk, Buchwald and co-workers shows that the modified Ullmann reaction between aryl iodide and amines or primary alcohols proceeds either via an SET or an IAT mechanism. Van Koten has shown that stalled aminations can be rejuvenated by the addition of Cu(0), which serves to reduce the formed Cu(II) to Cu(I); this also corroborates a Cu(I)/Cu(II) mechanism. Thus the use of radical clock type experiments in these metal catalysed reactions is not reliable. DFT calculations from Hartwig seem to confirm a Cu(I)/Cu(III) type mechanism for the amidation (Goldberg) reaction, although not all possible mechanisms were calculated.

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“…Gaunt recently showed that treatment of anilides with catalytic Cu(OTf) 2 and Ph 2 IOTf resulted in meta-arylation of acetanilide.…”

Section: -150mentioning

confidence: 99%

The mechanism of the modified Ullmann reaction

et al. 2010

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“…Modern Ullmann coupling reactions [1][2][3][4] (Scheme-I) are widely used in organic synthesis and C-hetero atom bond formation [5]. These reactions are essential tool in modern laboratories and industries for the synthesis of bio-active drugs, agro-chemicals and polymers [5,[6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Theoretical Investigations on Deactivation of Copper Catalytic Species in Ullmann Cross Coupling Reactions

Gurjar¹,

Sharma²

2018

Asian J. Chem.

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Copper mediated reactions require higher loading of copper salt and ligand. After few hours, copper active species becomes inactive and further loading of copper salt requires. Various hypothesis proposed in literature, were investigated. DFT studies were performed on more than 20 intermediate species. In present computational studies, it was found that ligation of carbonate base to active copper species is actual reason for deactivation. Carbonate and nucleophile are competitive ligand in these reactions.

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“…The classical Ullmann reaction for diaryl ether synthesis often requires extremely harsh reaction conditions, i.e. high temperatures (200-300 o C), strong polar and toxic solvents and the use of stoichiometric quantities of copper, and generally gives low yields [10], so a number of other methodologies for the synthesis of diaryl ethers have been developed in recent years [11]. Meanwhile, the fact that the strategic use of protective groups is a necessary and time-consuming tactic in organic synthesis is well-known, so a merging of protective group chemistry with other transformations that can shorten a reaction sequence and improve synthetic efficiency and convenience is always of great interest.…”

Section: Introductionmentioning

confidence: 99%