Silicon-based cross coupling agents and methods of their use

Patent metadata

Field	Value
Publication number	US-9499660-B2
Application number	US-201314405587-A
Country	US
Kind code	B2
Filing date	Jun 7, 2013
Priority date	Jun 8, 2012
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

Compositions and methods using silicon-based cross-coupling agents in the formation of carbon-carbon and carbon-nitrogen bonds are described.

First claim

What is claimed:

1. A compound of formula I:

wherein
Y is CH or N;
R 1 and R 2 are independently methyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert butyl, n-pentyl, iso-pentyl, or n-hexyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl;
R 3 is H;
aryl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
heteroaryl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
C 1-10 straight or branched-chain alkyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl;
a polymer; or
a resin support;

or R 1 and R 2 are each ethyl and R 3 is
H;
aryl substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
heteroaryl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
C 1-10 straight or branched-chain alkyl substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl;
C 2-10 straight or branched-chain alkyl;
a polymer; or
a resin support;

R 3a is H or C 1-6 alkyl optionally substituted with one or more halogen; and
at least one R 4 , wherein each R 4 is independently hydrogen, halogen, nitro, C 1-6 alkoxy, C 1-6 alkyl, aryl, or a resin support.

2. The compound of claim 1 , wherein Y is CH.

3. The compound of claim 1 , wherein Y is N.

4. The compound of claim 1 , wherein R 1 and R 2 are independently methyl, propyl, or isopropyl.

5. The compound of claim 4 , wherein R 1 and R 2 are independently methyl, or isopropyl.

6. The compound of claim 4 , wherein R 1 and R 2 are each methyl.

7. The compound of claim 4 , wherein R 1 and R 2 are each isopropyl.

8. The compound of claim 1 , wherein R 1 and R 2 are each ethyl.

9. The compound of claim 1 , wherein R 1 and R 2 are independently methyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert butyl, n-pentyl, iso-pentyl, or n-hexyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl; and R 3 is C 1-6 straight or branched-chain alkyl optionally substituted with one or more C 1-6 alkoxy.

10. The compound of claim 9 , wherein R 3 is C 1-4 straight or branched-chain alkyl optionally substituted with one or more C 1-6 alkoxy.

11. The compound of claim 1 , wherein R 1 and R 2 are independently methyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert butyl, n-pentyl, iso-pentyl, or n-hexyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl; and R 3 is C 1-4 straight or branched-chain alkyl.

12. The compound of claim 11 , wherein R 3 is n-butyl, isobutyl, or tert-butyl.

13. The compound of claim 11 , wherein R 3 is n-butyl.

14. The compound of claim 1 , wherein R 3 is C 1-4 straight or branched-chain alkyl substituted with one or more halogen.

15. The compound of claim 14 , wherein R 3 is —CF 3 .

16. The compound of claim 1 , wherein R 1 and R 2 are independently methyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert butyl, n-pentyl, iso-pentyl, or n-hexyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl; and R 3 is phenyl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl.

17. The compound of claim 16 , wherein R 3 is phenyl optionally substituted with one or more diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl.

18. The compound of claim 16 , wherein R 3 is phenyl.

19. The compound of claim 1 , wherein R 3 is pyridyl.

20. The compound of claim 1 , wherein R 3 is a polymer.

21. The compound of claim 1 , wherein R 3a is H.

22. The compound of claim 1 , wherein R 3a is —CF 3 .

23. The compound of claim 1 , wherein R 4 is hydrogen, C 1-6 alkoxy, C 1-6 alkyl, or aryl.

24. The compound of claim 23 , wherein R 4 is hydrogen, C 1-6 alkoxy, or C 1-6 alkyl.

25. The compound of claim 23 , wherein R 4 is hydrogen.

26. The compound of claim 1 that is

wherein n is about 150 to about 300,

wherein n is 20 to 200,

wherein

is a resin support moiety.

27. A method of cross-coupling a compound of formula NuLi with a compound of formula E-X to form a compound of formula Nu-E comprising
contacting the compound of formula NuLi with the compound of formula E-X in the presence of a compound of Formula I, catalyst or catalyst system, and an ethereal solvent;

wherein
Y is CH or N;
R 1 and R 2 are independently C 1-10 straight or branched-chain alkyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl;
R 3 is H;
aryl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
heteroaryl optionally substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl;
C 1-10 straight or branched-chain alkyl optionally substituted with one or more halogen, nitro, C 1-6 alkoxy, or aryl;
a polymer; or
a resin support;

R 3a is H or C 1-6 alkyl optionally substituted with one or more halogen; and
at least one R 4 , wherein each R 4 is independently hydrogen, halogen, nitro, C 1-6 alkoxy, C 1-6 alkyl, aryl, or a resin support;
for a time and under conditions sufficient to produce the compound of formula Nu-E;
wherein Nu is an aryl compound or an alkenyl compound; E is an aryl compound or an alkenyl compound; and X is iodo, chloro, or bromo.

28. The method of claim 27 , wherein the solvent is tetrahydrofuran.

29. The method of claim 27 , wherein the catalyst system comprises palladium, copper, or a mixture thereof.

30. The method of claim 27 , wherein the catalyst system comprises PdCl 2 , dpca, and CuI.

31. The method of claim 27 , wherein the catalyst system comprises dpca and CuI.

32. The method of claim 27 , wherein the catalyst system comprises CuI and Johnphos.

33. The method of claim 27 , wherein the catalyst system comprises Pd(OAc) 2 and XPhos.

34. The method of claim 27 , wherein the compound of claim 1 is

wherein n is about 150 to about 300,

wherein n is 20 to 200,

Assignees

• Univ Pennsylvania

Inventors

• Hoye Adam T
• Kim Won-Suk
• Martinez-Solorio Dionicio
• Smith Iii Amos B
• Sanchez Luis
• Tong Rongbiao
• Nguyen Minh Huu
• Melillo Bruno

Classifications

• C07D295/033 Primary

  with the ring nitrogen atoms directly attached to carbocyclic rings · CPC title

• C08G61/02 Primary

  Macromolecular compounds containing only carbon atoms in the main chain of the macromolecule, e.g. polyxylylenes · CPC title

• C07F7/1844

  Chemistry & Metallurgy · mapped topic

• C08G2261/3324

  derived from norbornene · CPC title

• C07F7/1852

  Chemistry & Metallurgy · mapped topic