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.

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N -Acetylamino Malonic Acid Derivatives

“…However, only a handful of reports exist on electrochemical decarboxylation of malonic acid derivatives (Figure B). Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals (Figure B, eq 1) . Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2) .…”

“…Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals ( Figure 1 B, eq 1). 12 Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2). 13 The above-mentioned electrolyses proceeded in alcoholic media and required the addition of an external base.…”

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N -Acetylamino Malonic Acid Derivatives

“…However, only a handful of reports exist on electrochemical decarboxylation of malonic acid derivatives (Figure B). Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals (Figure B, eq 1) . Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2) .…”

“…Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals ( Figure 1 B, eq 1). 12 Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2). 13 The above-mentioned electrolyses proceeded in alcoholic media and required the addition of an external base.…”

Electrosynthesis Using Carboxylic Acid Derivatives: New Tricks for Old Reactions

“…Not only are previously reported methods being improved, but new procedures formerly believed to be implausible by conventional means are becoming more widely available through the use of electrochemistry. Indeed, electrosynthesis has proven to possess a wide range of applications including cathodic radical deoxygenation, oxidative decarboxylation, allylic oxidation of alkenes, electrochemical methoxymethylation, , and decarboxylative etherification . Moreover, these transformations have also shown promise at an industrial scale. , The case studies reported herein demonstrate the versatility of synthetic electrochemistry, alongside its potential to provide a greener and more economical alternative to more traditional procedures, the majority of which rely on the use of toxic transition metals, inherently unstable intermediates, or harsh reaction conditions.…”

“…Similarly, the use of graphite electrodes to promote multielectron transfer processes has resulted in the development of both batch and continuous-flow approaches toward the synthesis of a wide variety of methoxymethyl ethers, thus reducing our reliance on procedures that necessitate the use of highly carcinogenic reagents. , Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies …”

“…9,10 Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies. 7 The growing impetus of the chemical community for the development of greener alternatives to classical reactions and the increasing availability of electrochemical equipment means that electrosynthesis is on its way to becoming a "classic" method to activate molecules.…”

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N -Acetylamino Malonic Acid Derivatives

“…However, only a handful of reports exist on electrochemical decarboxylation of malonic acid derivatives (Figure B). Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals (Figure B, eq 1) . Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2) .…”

“…Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals ( Figure 1 B, eq 1). 12 Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2). 13 The above-mentioned electrolyses proceeded in alcoholic media and required the addition of an external base.…”

Electrosynthesis Using Carboxylic Acid Derivatives: New Tricks for Old Reactions

“…Not only are previously reported methods being improved, but new procedures formerly believed to be implausible by conventional means are becoming more widely available through the use of electrochemistry. Indeed, electrosynthesis has proven to possess a wide range of applications including cathodic radical deoxygenation, oxidative decarboxylation, allylic oxidation of alkenes, electrochemical methoxymethylation, , and decarboxylative etherification . Moreover, these transformations have also shown promise at an industrial scale. , The case studies reported herein demonstrate the versatility of synthetic electrochemistry, alongside its potential to provide a greener and more economical alternative to more traditional procedures, the majority of which rely on the use of toxic transition metals, inherently unstable intermediates, or harsh reaction conditions.…”

“…Similarly, the use of graphite electrodes to promote multielectron transfer processes has resulted in the development of both batch and continuous-flow approaches toward the synthesis of a wide variety of methoxymethyl ethers, thus reducing our reliance on procedures that necessitate the use of highly carcinogenic reagents. , Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies …”

“…9,10 Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies. 7 The growing impetus of the chemical community for the development of greener alternatives to classical reactions and the increasing availability of electrochemical equipment means that electrosynthesis is on its way to becoming a "classic" method to activate molecules.…”

Electrochemical Synthesis of Unnatural Amino Acids via Anodic Decarboxylation of N -Acetylamino Malonic Acid Derivatives

“…However, only a handful of reports exist on electrochemical decarboxylation of malonic acid derivatives (Figure B). Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals (Figure B, eq 1) . Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2) .…”

“…Thus, Markò and Ma et al disclosed electrochemical oxidative decarboxylation of disubstituted malonic acids under constant current electrolysis in methanol as a solvent to furnish dimethyl ketals ( Figure 1 B, eq 1). 12 Anodic decarboxylation of N -acylamino malonic acid monoesters in alcoholic solvents to afford α-alkoxy α-amino acid derivatives was also reported by Iwasaki and Matsumoto et al in the late 1970s (eq 2). 13 The above-mentioned electrolyses proceeded in alcoholic media and required the addition of an external base.…”

Electrosynthesis Using Carboxylic Acid Derivatives: New Tricks for Old Reactions

“…Not only are previously reported methods being improved, but new procedures formerly believed to be implausible by conventional means are becoming more widely available through the use of electrochemistry. Indeed, electrosynthesis has proven to possess a wide range of applications including cathodic radical deoxygenation, oxidative decarboxylation, allylic oxidation of alkenes, electrochemical methoxymethylation, , and decarboxylative etherification . Moreover, these transformations have also shown promise at an industrial scale. , The case studies reported herein demonstrate the versatility of synthetic electrochemistry, alongside its potential to provide a greener and more economical alternative to more traditional procedures, the majority of which rely on the use of toxic transition metals, inherently unstable intermediates, or harsh reaction conditions.…”

“…Similarly, the use of graphite electrodes to promote multielectron transfer processes has resulted in the development of both batch and continuous-flow approaches toward the synthesis of a wide variety of methoxymethyl ethers, thus reducing our reliance on procedures that necessitate the use of highly carcinogenic reagents. , Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies …”

“…9,10 Furthermore, similar conditions have also been found to be extremely useful for the synthesis of 1,4-dicarbonyl compounds, which typically require umpolung strategies. 7 The growing impetus of the chemical community for the development of greener alternatives to classical reactions and the increasing availability of electrochemical equipment means that electrosynthesis is on its way to becoming a "classic" method to activate molecules.…”