Transition‐Metal‐Free Formal Decarboxylative Coupling of α‐Oxocarboxylates with α‐Bromoketones under Neutral Conditions: A Simple Access to 1,3‐Diketones

Abstract

A transition-metal-free formal decarboxylative coupling reaction between a-oxocarboxylates and a-bromoketones to synthesize 1,3-diketone derivatives is presented. In this reaction, a broad scope of substrates can be employed, and neither a metal-based reagent nor an additional base is required. DFT calculations reveal that this reaction proceeds through a coupling followed by decarboxylation mechanism and the a-bromoketone unprecedentedly serves as a nucleophile under neutral conditions. The rate-determining step is an unusual hydrogen-bond-assisted enolate formation by thermolysis.

Synthesis of 1,3-Diketones and β-Keto Thioesters via Soft Enolization

“…We began our study on the development of a procedure for the synthesis of 1,3-diketones and β-keto thioesters using crude acid chlorides as acylating agents by treating a solution of 2methylpropionic acid (1) in DMF and CH 2 Cl 2 with oxalyl chloride. The solvent was removed after 12 h, and the resulting residue was dissolved in CH 2 Cl 2 , and combined with MgBr 2 • OEt 2 , i-Pr 2 NEt, and acetophenone (8). Gratifyingly, this led to the formation of 1,3-diketone 11 in excellent yield (94%).…”

Iron-Catalyzed Transfer Hydrogenation in Aged N-Methyl-2-pyrrolidone: Reductive Ring-Opening of 3,5-Disubstituted Isoxazoles and Isoxazolines

“…The 1 H NMR spectral data are in good agreement with the literature data. 20 (Z)-1-Hydroxy-4,4-dimethyl-1-phenylpent-1-en-3-one (4a). The starting material was 5-(tert-butyl)-3-phenyl-4,5-dihydroisoxazol-5-ol.…”

“…The 1 H NMR spectral data are in good agreement with the literature data. 20 (Z)-3-Hydroxy-1-(3-methoxyphenyl)-3-phenylprop-2-en-1-one (4d). The crude product was purified by flash column chromatography on silica gel (eluent: 5:1 hexanes/ethyl acetate), and this product was obtained as a yellow oil (82.6 mg, 65% yield): 1 H NMR (400 MHz, CDCl 3 ) δ 16.85 (s, 1H), 7.97−8.00 (m, 2H), 7.47−7.57 (m, 5H), 7.40 (t, J = 7.8 Hz, 1H), 7.09−7.11 (m, 1H), 6.84 (s, 1H), 3.89 (s, 3H).…”

“…The 1 H NMR spectral data are in good agreement with the literature data. 20 Methyl (Z)-4-(1-Hydroxy-4,4-dimethyl-3-oxopent-1-en-1-yl)benzoate (4e). The crude product was purified by flash column chromatography on silica gel (eluent: 5:1 hexanes/ethyl acetate), and this product was obtained as a yellow solid (103.…”

Catalytic N‐Acylation of Cyclic Amines by Arylglyoxylic Acids via Radical‐Radical Cross‐Coupling

“…The pioneering discovery of redox-neutral decarboxylative acylation by has opened up new avenues to the synthetic community for utilizing α-oxo acids as an acyl surrogate primarily for C-based coupling partners. [3][4][5] However, the decarboxylative acylation of heteroatom systems is limited to only a handful of protocols, largely involving acyl radical intermediates formed from α-oxo acids. [6] For instance, the decarboxylative CÀ S coupling of α-oxo acids with disulfides or thiols to give thioesters proceeded in the presence of a strong oxidant including peroxysulfates.…”