Arylacetic alkylation

Andrus MB, Harper KC, Christansen MA, Binkley MA. Phase-transfer catalyzed asymmetric arylacetate alkylation. Tetrahedron Lett. 2009 50(31) 4541-4544. 

Alkyl aryl ketones can be converted to arylacetic acid derivatives in an entirely different manner. The reaction consists of treatment of the substrate with silver nitrate and I2 or Br2, ° or with thallium nitrate, MeOH, and trimethyl orthoformate adsorbed on Montmorillonite K-10 clay, an acidic clay. ... 

The methylation of arylacetic acid derivatives is chosen as a model reaction for the mechanistic discussion. Experimental evidence of DMC-mediated alkylation of A1CH2X (X = CN, C02Me) with DMC supports the hypothesis that the reaction does not proceed through a 8 2 displacement of the ArCH X nucleophile on DMC (Bai2 mechanism).Rather, the selectivity arises from consecutive... 

A new perspective for safe and highly selective mono-N-and mono-C-alkylations Selective Mono-Methylation of Arylacetoni-triles and Methyl Arylacetates by Dimethylcarbonate... 

Methyla-arylacetates. These esters have been obtained by oxidative rearrangement of alkyl aryl ketones with thallium(III) nitrate in acidic methanol or trimethyl orthoformate (4,496 5, 656 7, 362). A new method, which avoids the toxic TTN, is based on the Woodward version of the Prevost reaction. Thus, treatment of the ketone with iodine (or bromine) and silver nitrate (2 equiv.) in refluxing methanol containing trimethyl orthoformate results in methyl a-arylacetates in 90% yield from simple substrates. Yields are lowered by electron-withdrawing substituents on the aromatic group and by a-branching in the alkyl group.2... 

Diastereoselective a-alkylation of arylacetic acids.1 The binaphthyl ester (1) of phenylacetic acid undergoes highly diastereoselective methylation on treatment of... 

H. Weber, H. Spahn, E. Mutschler, and W. Moehrke, Activated-alkyl-arylacetic acid enantiomers for stereoselective thin-layer chromatographic and high-performance liquid chromatographic determination of chiral amines, J. Chromatogr., 307 145 (1984). 

The dianions of arylacetic acids 997 undergo alkylation reactions with l-bromo-3-chloropropane, with the resulting 5-chloropentanoic acids 998 cyclizing upon treatment with DBU providing a one-pot preparation of 3-aryltetrahy-dropyran-2-ones 999 (Scheme 259) <2003TL365>. 

In the previous sections, the reactions of nucleophilic alkyl and acyl radicals with electron-deficient aromatics via SOMO-LUMO interaction have been described. At this point, we introduce the reactions of electrophilic alkyl radicals and electron-rich aromatics via SOMO-HOMO interaction, though the study is quite limited. Treatment of ethyl iodoacetate with triethylborane in the presence of electron-rich aromatics (36) such as pyrrole, thiophene, furan, etc. produces the corresponding ethyl arylacetates (37) [50-54]. 

Chromium tricarbonyl complexes of arylacetic esters can be alkylated by the use of phase-transfer catalysis or sodium hydride in Af, /V-dimethyl-formamide (77). However, the yields obtained by the latter method are as good as or superior to those realized using phase-transfer techniques. Both methods give similar stereochemical results (e.g., 68 — 69 and 70). 

In an industrial asymmetric synthesis en route to the antiinflammatory agent naproxen, the dimethyl L-tartrate acetals of ethyl aryl ketones are brominated in high yield and selectivity to give the corresponding a-bromo derivatives. Subsequent stereospecific Ag -promoted 1,2-aryl migration provides the 2-alkyl-2-arylacetic acid after hydrolysis of the tartrate auxiliary, which is recovered (e.g. eq 4). 

M. Ahmar, C. Girard, and R. Bloch, Enzymatic resolution of methyl 2-alkyl-2-arylacetates, Tefratedron, Lett., 30 7053 (1989). 

The PTC carbonylation of substituted benzyl chlorides with Co2(CO)g gives a mixture of products [111, 115]. In all cases, arylacetic acids prevail. These are the sole products when R = H, CF3. Double carbonylation with subsequent alkylation producing ketoacids is observed in the case of methyl-substituted benzyl chlorides. 2,4,6-Trimethylbenzyl chloride yields mesitylacetic and mesitylpyruvic acid in equal amounts [115]. 

Tetracarbonylcobaltate anion, generated under PTC conditions, catalyzes the reaction of aryl halides with excess methyl iodide under a CO atmosphere [122]. The reaction produces aryl methyl ketones and carboxylic acids as the main products. Stoichiometric or catalytic iron pentacarbonyl can also be used for the carbonylation of organohalides under PTC conditions [123-128]. For example, reactions of alkyl and arylalkyl halides with CO in aqueous-organic systems using catalytic amounts of Fe(CO)5 and a PT agent afford alkyl- and arylacetic acids as the main products [127]. 

Canicio, J. A. Ginebreda, A. Canela, R., A New Direct a-Alkylation of Arylacetic Acids by Solid-Liquid Phase-Transfer Catalysis Synthesis of 2-Arylalkanoic Acids. An. Quint. 1985, 81, 181. 

JR)- and (S)-binaphthols 1.44 [230-235] have sometimes been used as chiral auxiliaries. Examples include reduction of y-ketoester 1.45 [236], nucleophilic substitution of binaphthol ethers (G = binaphthol) 1.46, by organomagnesium reagents, organocuprate additions to binaphthol monodnnamates [237], and alkylations of arylacetic or crotonic esters [238,239]. 

A benzylic alkyl group of o-bromoarylacetonitriles or the corresponding arylacetic esters is either dehydrogenated with one hydrogen atom to replace the bromine atom, or engaged in ring formation. The catalyst system to effect the transformation(s) consists of Pd(OAc)2 and tris(m-fluorophenyl)phosphine. ... 

Alkyl arylacetates react with Tf20 to give a cation which in the presence of a nitrile affords isoquinoline derivatives via cychza-tion of the intermediate nitrilium cation (eq 27). ... 

Arylthallium bis(trifluoroacetate)s are converted by successive treatment with KF and BF3 into aryl fluorides.Thallium(iii) nitrate (TTN) readily oxidizes dialkyl sulphides and selenides to the corresponding sulphoxides or selenoxides, and 2-(alkylthio)-l-arylethanones (37) into compounds (38) in methanolic solution.In a modification of the TTN oxidative conversion of aryl alkyl ketones into arylacetic acids, enol ethers derived from the ketones are used instead of the ketones themselves. This reduces the formation of side products. Cyclic aralkyl ketones (39) may be ring-expanded and alkylated to give compounds (40) via treatment of their Wittig-derived alkenes with TTN/ an extrapolation of the basic reaction discovered previously. 

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