Catalytic Decarboxylative Cross‐Ketonisation of Aryl‐ and Alkylcarboxylic Acids using Magnetite Nanoparticles

Abstract

In the presence of catalytic amounts of magnetite nanopowder, mixtures of aromatic and aliphatic carboxylic acids are converted selectively into the corresponding aryl alkyl ketones. As byproducts, only carbon dioxide and water are released. This catalytic cross-ketonisation allows the regioselective acylation of aromatic systems and, thus, represents a sustainable alternative to FriedelCrafts acylations.Keywords: aryl alkyl ketones; catalysis; cross-ketonisation; decarboxylation; iron Aryl alkyl ketones are among the most important synthons in the industrial manufacture of commodities, [1] fine chemicals, and pharmaceuticals.[2] Simple derivatives, at early stages of the chemical value creation chain, are synthesised almost exclusively via FriedelCrafts acylation of arenes, because the low cost of this reaction is unrivalled to date.[3] However, two main issues are associated with this approach. Its low regioselectivity leads to the co-manufacture of large amounts of isomeric by-products, and the use of acyl chlorides as starting materials activated with superstoichiometric amounts of salt mediators (e.g., AlCl 3 ) is responsible for the formation of enormous quantities of salt waste.Regioselective and less waste-intensive acylations, e.g., cross-couplings [4] of sensitive arylmetal reagents with either preformed [5] or in situ-generated [6] carboxylic acid derivatives are widely used to access highervalue synthetic intermediates. However, their high cost precludes their application in the manufacture of base chemicals. This is also the case for alternative approaches, such as Heck-type reactions, [7] or the Pdcatalysed decarboxylative cross-coupling of a-oxocarboxylate salts with aryl halides.[8] Thus, a clear need remained for a broadly applicable, regioselective and waste-minimised aryl alkyl ketone synthesis starting from simple, inexpensive, and widely available chemicals.As a solution to this long-standing problem, we envisioned a catalytic process in which an aromatic and an aliphatic carboxylic acid are cross-coupled under release of CO 2 and water, to selectively give the aryl alkyl ketone (Scheme 1). In such a decarboxylative cross-ketonisation, the carboxylate groups would predefine the position of bond formation, potentially allowing a selective synthesis of any desired regioisomer. If mediated by catalytic amounts of an inexpensive metal with high selectivity for hetero-over homocoupling, the overall process would be advantageous both from economical and ecological standpoints.The decarboxylative homoketonisation of aliphatic carboxylic acids is an established strategy for the preparation of symmetrical dialkyl ketones or cyclic alkanones.[9] State-of-the-art protocols involve gasphase transformations at temperatures above 350 8C at solid catalysts, for example, CaO, ZnO, MgO, [10] TiO 2 , [11] ZrO 2 , [12] MnO, [13] Fe 2 O 3 , [14] or rare earth metal oxides [15] on SiO 2 -, Al 2 O 3 -, or pumice-based supports. However, if equimolar mixtures of aromatic and aliphatic carboxylic acids ar...

Cross-selectivity in the catalytic ketonization of carboxylic acids

“…This is the case for aromatic acids [14], pivalic acid, and other acids missing alpha protons. In some cases, enolization may be severely disfavored, such as iiiiii See Fig.…”

“…It has been rediscovered several times [8]. The literature on ketonization reactions has been extensively reviewed [9][10][11], but the discussion of the cross-selectivity was limited to just a few cases [14][15][16]. The interest to ketonization has been recently revived in connection with the bio-oil upgrading [17].…”

Ketonic Decarboxylation Reaction Mechanism: A Combined Experimental and DFT Study

“…It has been observed that ketonic decarboxylation takes place over a wide range of metal oxide catalysts (such as MgO, BaO, CeO 2 , ZrO 2 , or TiO 2 , and mixtures thereof among others), [13,15,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] although a preferred catalyst cannot be identified. Therefore, it is of paramount interest for the further development of biomass transformations to optimize the catalytic process for the conversion of acids into ketones and to select the most suitable metal oxide catalyst.…”

Arylacetic Acids in Organic Synthesis

“…Especially, nucleophilic methylenes, Friedel‐Crafts reaction, nucleophilic acids and electrophilic acids have been used in total synthesis of (−)‐pauciflorol F, moxaverine, (−)‐6‐O‐desmethylantofine and (+)‐6‐O‐desmethylantofine, derivate of salvianolic acid B, communesin F and perophoramidine, (+)‐O‐methylthalibrine, sparstolonin B, lennoxamine, chilenine, fumaridine, 8‐Oxypseudoplamatine, 2‐O‐methyloxyfagaronine, (S)‐equol, xiamenmycin A and (±)‐glabridin . However, challenges still existed: (1) C−N and C−X (X=F, Cl, Br, I) bond may be constructed simultaneously during one procedure by the aid of decarboxylation and formation of radicals; (2) Decarboxylative cross coupling or tandem applications with boron reagent, diazonium salt, 1,3‐dicarbonyls were anticipated; (3) The ketones from reactions of arylacetic acids with aryl acids may function as useful intermediates in tandem reactions and show their significances in construction of diverse heterocycles.…”

“…The Gooßen group described a decarboxylative cross‐ketonisation 12.1 of aryl acids by employing magnetite nanoparticles (17–28 nm) as the catalyst (Eq. 12‐1).…”