Silicon-based cross coupling agents and methods of their use
Compositions and methods using silicon-based cross-coupling agents in the formation of carbon-carbon and carbon-nitrogen bonds are described.
1. 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 catalyst system consisting of palladium and a phosphate ligand, an ethereal solvent, and a compound of Formula I
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, diC1 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, a heteroaryl compound, or an alkenyl compound;
E is an aryl compound, a heteroaryl compound, or an alkenyl compound; and X is iodo, chloro, or bromo.
2. The method of claim 1 , wherein the compound of Formula I is
3. The method of claim 1 , wherein the compound of Formula I is
4. The method of claim 1 , wherein the solvent is tetrahydrofuran.
5. The method of claim 1 , wherein the palladium is Pd(OAc) 2 .
6. The method of claim 1 , wherein the phosphate ligand is XPhos, DavePhos, Johnphos, or SPhos.
7. The method of claim 6 , wherein the phosphate ligand is XPhos.
8. The method of claim 1 , wherein the phosphate ligand is Second Generation Buchwald Precatalyst, Third Generation Buchwald Precatalyst, or Fourth Generation Buchwald Precatalyst.
9. The method of claim 1 , wherein the catalyst system comprises Pd(OAc) 2 and XPhos.
10. The method of claim 1 , wherein Nu is phenyl.
11. The method of claim 1 , wherein Nu is pyridyl.
12. The method of claim 1 , wherein E is phenyl substituted with one or two of C 1-6 alkyl, —OC 1-6 alkyl, halogen, —C(O) 1-6 alkyl, —COOC 1-6 alkyl, —CN.
13. The method of claim 1 , wherein E is quinolinyl or benzoxazolyl.
14. The method of claim 1 , wherein X is iodo or chloro.
15. The method of claim 1 , wherein X is chloro.
16. The method of claim 1 , further comprising the step of recovering the compound of Formula I.