Silicon-based cross coupling agents and methods of their use

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,

wherein

is a resin support moiety.

35. 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 a disubstituted amine; and X is —O-benzoyl.

36. The method of claim 35 , wherein the compound of claim 1 is not

37. The method of claim 35 , wherein the solvent is tetrahydrofuran.

38. The method of claim 35 , wherein the catalyst system comprises palladium, copper, or a mixture thereof.

39. The method of claim 35 , wherein the catalyst system comprises dpca and CuI.

40. The method of claim 35 , wherein the catalyst system comprises PdCl 2 , dpca, and CuI.

41. The method of claim 35 , wherein the catalyst system comprises Pd(OAc) 2 and XPhos.

42. The method of claim 35 , wherein the catalyst system comprises CuI and Johnphos.

43. The method of claim 35 , wherein the compound of claim 1 is

wherein n is about 150 to about 300,

wherein n is 20 to 200,

wherein

is a resin support moiety.

44. The compound of claim 1 , wherein R 1 and R 2 are each ethyl; and R 3 is phenyl substituted with one or more nitro, diC 1-6 alkylamino, C 1-6 alkoxy, or C 1-6 alkyl.

45. The compound of claim 1 , wherein R 1 and R 2 are each ethyl; and R 3 is C 2-4 straight or branched-chain alkyl.

46. The compound of claim 1 , wherein R 1 and R 2 are each ethyl; and R 3 is C 1-6 straight or branched-chain alkyl substituted with one or more C 1-6 alkoxy.

47. A compound that is

48. The compound of claim 27 that is

wherein n is about 200.

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

wherein n is about 200.

50. The method of claim 43 , wherein the compound of claim 1 is:

wherein n is about 200.