Silicon-based cross coupling agents and methods of their use

Patent metadata

Field	Value
Publication number	US-9850261-B2
Application number	US-201515326069-A
Country	US
Kind code	B2
Filing date	Jul 16, 2015
Priority date	Jun 8, 2012
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

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 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.

Assignees

• Univ Pennsylvania

Inventors

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

Classifications

• C07F7/20

  Purification, separation · CPC title

• C07D295/023

  Preparation; Separation; Stabilisation; Use of additives · CPC title

• C07C1/328

  the hetero-atom being an alkali metal atom · CPC title

• C07C41/30

  by increasing the number of carbon atoms, e.g. by oligomerisation · CPC title

• C07B43/00

  Formation or introduction of functional groups containing nitrogen · CPC title