Directed β-C(sp3)#H iodination and arylation of ketones

Patent metadata

Field	Value
Publication number	US-10875822-B2
Application number	US-201816639401-A
Country	US
Kind code	B2
Filing date	Aug 13, 2018
Priority date	Aug 16, 2017
Publication date	Dec 29, 2020
Grant date	Dec 29, 2020

Abstract

This invention discloses the first example of palladium(II)-catalyzed β-C(sp 3 )-H iodination or arylation of a wide range of ketones by using a commercially available aminooxyacetic acid auxiliary. This L, X-type directing group overcomes the limitation of the transient directing group approach for -βC(sp 3 )-H functionalization of ketones. Practical advantages of this method include simple installation of the auxiliary without chromatography, exceptional tolerance of a-functional groups, double bonds and triple bonds and rapid access to diverse sterically hindered quaternary centers.

First claim

What is claimed is:

1. A method of β-C(sp 3 )-H iodination of a ketone having a p-hydrogen substituent, comprising:
contacting the ketone and an aminooxyacetic acid in pyridine solvent to provide the corresponding oxime;

then,
contacting the oxime with iodine in the presence of a palladium(II) salt and phenyliodoniumacetate, in an aprotic solvent; then,
hydrolyzing the oxime group under acidic conditions to provide the product β-C(sp 3 )-iodoketone.

2. The method of claim 1 wherein the aminooxyacetic acid is aminooxyacetic acid or 2,2-dimethylaminooxyacetic acid.

3. The method of claim 1 wherein the palladium(II) salt is palladium(II) acetate or palladium(II)trifluoroacetate.

4. The method of claim 1 wherein the aprotic solvent is dioxane or 1,1,1,3,3,3-hexafluoroisopropanol.

5. The method of claim 1 wherein the oxime group is hydrolyzed in a solution of concentrated hydrochloric acid in dioxane.

6. A method of β-C(sp 3 )-H arylation of a ketone having a β-hydrogen substituent, comprising:
contacting the ketone and an aminooxyacetic acid in pyridine solvent to provide the corresponding oxime;

then,
contacting the oxime with an aryl iodide and silver trifluoroacetate in the presence of a palladium(II) salt, in an aprotic solvent; then,
hydrolyzing the oxime group under acidic conditions to provide the product β-C(sp 3 )-arylketone.

7. The method of claim 6 wherein the aminooxyacetic acid is aminooxyacetic acid or 2,2-dimethylaminooxyacetic acid.

8. The method of claim 6 wherein the palladium(II) salt is palladium(II) acetate or palladium(II)trifluoroacetate.

9. The method of claim 6 wherein the aprotic solvent is dioxane or 1,1,1,3,3,3-hexafluoroisopropanol.

10. The method of claim 6 wherein the oxime group is hydrolyzed in a solution of concentrated hydrochloric acid in dioxane.

Assignees

• Scripps Research Inst

Inventors

• Yu Jin-Quan
• Zhu ru-yi

Classifications

• C07C249/12

  by reactions not involving the formation of oxyimino groups · CPC title

• C07C2602/42

  the bicyclo ring system containing seven carbon atoms · CPC title

• C07C49/233

  containing six-membered aromatic rings · CPC title

• B01J2531/824

  Palladium · CPC title

• C07C45/42 Primary

  by hydrolysis · CPC title