Catalytic C—H bond activation

Patent metadata

Field	Value
Publication number	US-9416080-B2
Application number	US-201314405663-A
Country	US
Kind code	B2
Filing date	Jun 14, 2013
Priority date	Jun 15, 2012
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

Disclosed is a method for the transition metal-mediated oxidation of C—H bonds to form C—O or C—S bonds. The methods are useful for the formation of ethers (R—OR′) from alcohols, R′OH, and sp3-hybridized C—H bonds in substrates, R—H. Aryl or heteroaryl acetates may also be used for C—H to C—OAr bond formation. The methods are also useful in the preparation of C—S bonds from acetyl-protected thiols, MeC(O)SR, and disulfides, RSSR. Advantageously, the methods minimize reaction steps, the handling of oxidized intermediates, and environmental impact.

First claim

We claim:

1. A method of forming an ether, comprising:
combining a substrate comprising a reactive C—H bond, an alcohol, a peroxide, and a copper-containing catalyst, thereby forming an ether;

wherein:
the substrate comprising the reactive C—H bond is represented by:

wherein:
R 3 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
R 4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; or R 3 and R 4 taken together are oxo;
R 5 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; and
the substrate is optionally substituted with 1-3 substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro, amide, phosphonate, carboxyl, silyl, ether, sulfonyl, ester, fluoroalkyl, trifluoromethyl, and cyano; and

the copper-containing catalyst is represented by Formula I or an enantiomer, stereoisomer or diastereomer thereof:

wherein:
R 11 to R 19 are independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, halogen, cyano, nitro and trifluoromethyl;
X 1 to X 4 are independently selected from the group consisting of hydrogen, halogen, alkyl, perhaloalkyl, and aryl; and
L is absent or a Lewis base.

2. The method of claim 1 , wherein the alcohol is an aliphatic alcohol.

3. The method of claim 1 , wherein the peroxide is tert-butyl peroxide.

4. The method of claim 1 , wherein R 17 -R 19 represent independently for each occurrence hydrogen, methyl, trifluoromethyl, phenyl, or tert-butyl.

5. The method of claim 1 , wherein R 17 and R 18 represent tert-butyl.

6. The method of claim 1 , wherein R 17 and R 18 represent trifluoromethyl.

7. The method of claim 1 , wherein R 19 is hydrogen.

8. The method of claim 1 , wherein X 1 to X 4 are independently for each occurrence halogen or perfluoroalkyl.

9. The method of claim 8 , wherein X 1 to X 4 are independently for each occurrence Cl, I, Br, or CF 3 .

10. The method of claim 9 , wherein X 1 to X 4 are Cl.

11. The method of claim 9 , wherein X 1 to X 4 are CF 3 .

12. The method of claim 1 , wherein L is aromatic.

13. The method of claim 12 , wherein L is benzene.

14. The method of claim 1 , wherein the copper-containing catalyst is selected from the group consisting of:

15. The method of claim 1 , wherein the copper-containing catalyst is:

16. The method of claim 1 , wherein the copper-containing catalyst is:

17. A method of forming an ether, comprising:
combining a substrate comprising a reactive C—H bond, an aryl acetate, a peroxide, and a copper-containing catalyst, thereby forming an ether;

wherein:
the substrate comprising the reactive C—H bond is represented by:

wherein:
R 3 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
R 4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; or R 3 and R 4 taken together are oxo;
R 5 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; and
the substrate is optionally substituted with 1-3 substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro, amide, phosphonate, carboxyl, silyl, ether, sulfonyl, ester, fluoroalkyl, trifluoromethyl, and cyano; and

the copper-containing catalyst is represented by Formula I or an enantiomer, stereoisomer or diastereomer thereof:

wherein:
R 11 to R 19 are independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, halogen, cyano, nitro and trifluoromethyl;
X 1 to X 4 are independently selected from the group consisting of hydrogen, halogen, alkyl, perhaloalkyl, and aryl; and
L is absent or a Lewis base.

18. A method of forming a thioether, comprising
combining a substrate comprising a reactive C—H bond, an acetyl-protected thiol, a peroxide, and a copper-containing catalyst, thereby forming a thioether;

wherein:
the substrate comprising the reactive C—H bond is represented by:

wherein:
R 3 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
R 4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; or R 3 and R 4 taken together are oxo;
R 5 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; and the substrate is optionally substituted with 1-3 substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro, amide, phosphonate, carboxyl, silyl, ether, sulfonyl, ester, fluoroalkyl, trifluoromethyl, and cyano; and

the copper-containing catalyst is represented by Formula I or an enantiomer, stereoisomer or diastereomer thereof:

wherein:
R 11 to R 19 are independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, halogen, cyano, nitro and trifluoromethyl;
X 1 to X 4 are independently selected from the group consisting of hydrogen, halogen, alkyl, perhaloalkyl, and aryl; and
L is absent or a Lewis base.

19. A method of forming a thioether, comprising
combining a substrate comprising a reactive C—H bond, a disulfide, a peroxide, and a copper-containing catalyst, thereby forming a thioether;

wherein:
the substrate comprising the reactive C—H bond is represented by:

wherein:
R 3 is alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
R 4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether; or R 3 and R 4 taken together are oxo;
R 5 is hydrogen, alkyl, alkenyl, a

Assignees

• Univ Georgetown

Inventors

• Warren Timothy H
• Sapiezynski Nicholas G

Classifications

• C07C41/05 Primary

  by addition of compounds to unsaturated compounds · CPC title

• C07C2101/16

  Chemistry & Metallurgy · mapped topic

• C07C43/184

  to a carbon atom of a non-condensed ring · CPC title

• C07C2101/14

  Chemistry & Metallurgy · mapped topic

• C07C43/205

  the aromatic ring being a non-condensed ring · CPC title