Synthesis of Diketones, Ketoesters, and Tetraketones by Electrochemical Oxidative Decarboxylation of Malonic Acid Derivatives: Application to the Synthesis of cis-Jasmone

Abstract

Disubstituted malonic acid derivatives are smoothly converted into diketones and ketoesters in good to excellent yield (68% to 91%) under electrochemical conditions. The scope can be extended to transform trisubstituted bis-malonic acids into tetraketones in 77% to 86% yield. The new method was applied to the total synthesis of cis-jasmone.

Anodic Oxidation as an Enabling Tool for the Synthesis of Natural Products

“…173 A double decarboxylative reaction induced by electric current has also been applied in the total synthesis of naturally occurring cis-jasmone. 174 Scheme 21 Application of the Kolbe electrolysis in the formal total synthesis of prostaglandin F 2 (117) An interesting, electrochemically initiated, ring-expanding rearrangement was described by Little and Park in the total synthesis of daucene (121). 175 Here, housane 118 was subjected to an anodic oxidation under constant potential conditions mediated by the tris-(4-bromophenyl)aminium radical cation to generate intermediate 119.…”

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

“…[1,2] With the introduction of more readily available electrosynthesis equipment, [3,4] electrosynthesis has experienced ar esurgence in interest, [5][6][7][8][9][10][11][12] and has proven to possess diverse applications such as the allylic oxidation of alkenes, [9] fluorination of sp 3 carbon centres, [11] cathodic radical deoxygenation, [12] electrochemical methoxymethylation, [6] and oxidative decarboxylation. [8] Furthermore,t hese electrochemical transformations have been successfully transposed to an industrial scale. [9,13] Compounds containing g-butyrolactone fragments exhibit varied uses,f or example as fungicidal, [14] antibiotic, [15,16] and anticancer agents, [17,18] and therefore are of particular interest in the pharmaceutical industry.…”

Economical, Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

“…Electrochemistry has long been au seful synthetic tool in organic chemistry,with examples as early as 1832. [1,2] With the introduction of more readily available electrosynthesis equipment, [3,4] electrosynthesis has experienced ar esurgence in interest, [5][6][7][8][9][10][11][12] and has proven to possess diverse applications such as the allylic oxidation of alkenes, [9] fluorination of sp 3 carbon centres, [11] cathodic radical deoxygenation, [12] electrochemical methoxymethylation, [6] and oxidative decarboxylation. [8] Furthermore,t hese electrochemical transformations have been successfully transposed to an industrial scale.…”

“…[1,2] With the introduction of more readily available electrosynthesis equipment, [3,4] electrosynthesis has experienced ar esurgence in interest, [5][6][7][8][9][10][11][12] and has proven to possess diverse applications such as the allylic oxidation of alkenes, [9] fluorination of sp 3 carbon centres, [11] cathodic radical deoxygenation, [12] electrochemical methoxymethylation, [6] and oxidative decarboxylation. [8] Furthermore,t hese electrochemical transformations have been successfully transposed to an industrial scale. [9,13] Compounds containing g-butyrolactone fragments exhibit varied uses,f or example as fungicidal, [14] antibiotic, [15,16] and anticancer agents, [17,18] and therefore are of particular interest in the pharmaceutical industry.…”

“…Ester-functionalised lactones were also synthesised (8,9) with no undesired electrochemical overoxidation observed by 1 HNMR spectroscopy.More notably,itwas possible to install halogen-terminated alkyl chains into these systems (10), which are rarely tolerated by more conventional radical methodologies owing to the ease of competitive halide radical abstraction. Similarly,the synthesis of lactones using asecondary co-acid was successful (7)a lbeit in slightly lower yields, which is unsurprising given the ease with which secondary alkyl radicals are usually anodically overoxidised to give the corresponding carbocations.…”