Mild electrochemical decarboxylative alkyl-alkyl coupling and decarboxlative olefination enabled by rapid alternating polarity

Patent metadata

Field	Value
Publication number	US-2025320172-A1
Application number	US-202318868825-A
Country	US
Kind code	A1
Filing date	Jun 14, 2023
Priority date	Jun 14, 2022
Publication date	Oct 16, 2025
Grant date	—

Abstract

Rapid Alternating Polarity (rAP) is a new electrolysis mode for synthetic organic electrochemistry. As described herein, AC waveforms, particularly rAP, can profoundly alter the reaction outcome of the reduction of carbonyl groups and arenes, exhibiting unprecedented levels of chemoselectivity that is absent when DC is used under otherwise identical reaction conditions. Herein, disclosed are new applications of rAP electrolysis, such as i) rAP-Kolbe electrolysis for the decarboxylative coupling of carboxylic acids; and ii) rAP electrolysis for the decarboxylative olefination of carboxylic acids; both under mild electrochemical conditions.

First claim

What is claimed is:

1 . A method of decarboxylative coupling of carboxylic acids, wherein a carboxylic acid substrate is subjected to rapid Alternating Polarity (rAP)-Kolbe electrolysis.

2 . The method of claim 1 , wherein the rAP-Kolbe electrolysis occurs according to either reaction scheme (i) or reaction scheme (ii):

wherein each of R, R 1 , and R 2 is independently selected from H, saturated or unsaturated acyclic or cyclic aliphatic groups, each optionally including one or more heteroatoms and each optionally substituted with alkyl, alkenyl, ester, amino, halo, hydroxy, keto, formyl, aryl, heteroaryl, cycloalkyl or heterocyclic moieties, and aromatic or heteroaromatic ring systems, each optionally substituted with alkyl, alkenyl, ester, amino, halo, hydroxy, keto, formyl, aryl, heteroaryl, cycloalkyl or heterocyclic moieties.

3 . The method of decarboxylative coupling of carboxylic acids of either claim 1 or claim 2 , wherein the alternating frequency is 1 MHz-0.01 Hz.

4 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-3 , wherein the electrodes are composed of Pt, Pd, Ni, Rh, Ti, Pb, conductive metal oxides, or a carbon-based material with surface modification or coating.

5 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-4 , wherein the carboxylic acid substrate contains 2-100 carbon atoms.

6 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-5 , wherein the carboxylic acid substrate contains heteroatoms.

7 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-6 , wherein the carboxylic acid substrate is unsaturated, partially unsaturated, or aromatic.

8 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-7 , wherein the carboxylic acid substrate contains a C—N bond.

9 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-8 , wherein the carboxylic acid substrate contains alkenyl, ester, amino, free hydroxy, cycloalkyl, ketone, aryl, or heterocycloalkyl moieties.

10 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-9 , wherein a supporting electrolyte is added.

11 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-10 , wherein the supporting electrolyte is an ammonium salt.

12 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-11 , wherein the decarboxylative coupling of carboxylic acids occurs in the presence of a base.

13 . The method of decarboxylative coupling of carboxylic acids of claim 12 , wherein the amount of base is approximately 0.01 mol % to approximately 200 mol % to the overall amount of the carboxylic acid substrate.

14 . The method of decarboxylative coupling of carboxylic acids of claim 13 , wherein the amount of the base is approximately 10 to approximately 30 mol % to the overall amount of the carboxylic acid substrate.

15 . The method of decarboxylative coupling of carboxylic acids of any one of claims 12-14 , wherein the base is NR 4 OH, NH 4 OH, NaOH, or KOH and R is (C 1 -C 6 )alkyl.

16 . The method of decarboxylative coupling of carboxylic acids of claim 15 , wherein the base is NR 4 OH and R is (C 1 -C 6 )alkyl.

17 . The method of decarboxylative coupling of carboxylic acids of claim 16 , wherein the amount of NR 4 OH is approximately 10 mol % to the overall amount of the carboxylic acid substrate.

18 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-17 , wherein the solvent has a relative dielectric constant of more than 5.

19 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-18 , wherein the solvent contains a carbonyl moiety.

20 . The method of decarboxylative coupling of carboxylic acids of claim 19 , wherein the carbonyl moiety is a (C 3 -C 15 )ketone.

21 . The method of decarboxylative coupling of carboxylic acids of claim 20 , wherein the (C 3 -C 15 )ketone is acetone.

22 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-21 , wherein the alternating frequency is approximately 10 Hz.

23 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-22 , wherein the current is set at 1-1000 mA/mmol.

24 . The method of decarboxylative coupling of carboxylic acids of claim 23 , wherein the current is set at approximately 60 mA/mmol.

25 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-24 , wherein the amount of charge is set at 1-20 F/mol.

26 . The method of decarboxylative coupling of carboxylic acids of claim 25 , wherein the amount of charge is set at approximately 8-10 F/mol.

27 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-26 , wherein the electrodes are RVC electrodes.

28 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-27 , wherein the carboxylic acid substrate comprises one carboxylic acid or two carboxylic acids.

29 . The method of decarboxylative coupling of carboxylic acids of claim 28 , wherein the carboxylic acid substrate comprises one carboxylic acid.

30 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-29 , wherein the rAP-Kolbe electrolysis occurs according to the following reaction scheme:

wherein R 1 is (C 1 -C 20 )alkyl or cycloalkyl, optionally substituted with aryl, heteroaryl, O, N, or halo.

31 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-29 , wherein the rAP-Kolbe electrolysis occurs according to the following reaction scheme:

wherein R 1 is (C 1 -C 20 )alkyl or cycloalkyl, optionally substituted with aryl, heteroaryl, O, N, or halo; and
R 2 is (C 1 -C 6 )alkyl or cycloalkyl.

32 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-29 , wherein the rAP-Kolbe electrolysis occurs according to the following reaction scheme:

wherein A is (C 3 -C 20 )cycloalkyl; and
R 1 is (C 1 -C 20 )alkyl or (C 3 -C 20 )cycloalkyl, optionally substituted with aryl, heteroaryl, O, N, or halo.

33 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-29 , wherein the rAP-Kolbe electrolysis occurs according to the following reaction scheme:

wherein R 1 is (C 1 -C 20 )alkyl, cycloalkyl, or alkyl, optionally substituted with aryl, heteroaryl, O, N, or halo; and
PG is a protecting group including, but not limited to Boc and Cbz.

34 . The method of decarboxylative coupling of carboxylic acids of any one of claims 1-29

Assignees

• Scripps Research Inst

Inventors

• Kawamata Yu
• Hioki Yuta
• Baran Phil S

Classifications

• C07C227/18

  by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters · CPC title

• C07C29/147

  of carboxylic acids or derivatives thereof · CPC title

• C25B3/11

  Halogen containing compounds · CPC title

• C25B3/09

  Nitrogen containing compounds · CPC title

• C25B3/07

  Oxygen containing compounds · CPC title