Slow release of organoboronic acids in cross-coupling reactions

Patent metadata

Field	Value
Publication number	US-9845317-B2
Application number	US-201615142418-A
Country	US
Kind code	B2
Filing date	Apr 29, 2016
Priority date	Sep 26, 2008
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

A method of performing a chemical reaction includes reacting a compound selected from the group consisting of an organohalide and an organo-pseudohalide, and a protected organoboronic acid represented by formula (I) in a reaction mixture:

R 1 —B-T  (I);

where R 1 represents an organic group, T represents a conformationally rigid protecting group, and B represents boron having sp 3 hybridization. When unprotected, the corresponding organoboronic acid is unstable by the boronic acid neat stability test. The reaction mixture further includes a base having a pK B of at least 1 and a palladium catalyst. The method further includes forming a cross-coupled product in the reaction mixture.

First claim

What is claimed is:

1. A method of performing a chemical reaction, comprising:
reacting in a reaction mixture
a compound selected from the group consisting of an organohalide and an organo-pseudohalide, and
a protected organoboronic acid represented by formula (IV):

where
R 1 represents a 2-heterocyclic group, wherein the 2-heterocyclic group is an optionally substituted 3- to 10-membered heterocyclic group comprising 1 to 3 heteroatoms selected from O, N, and S; and one heteroatom is at the 2-position in the heterocyclic group,
B represents boron having sp 3 hybridization,
R 20 , R 21 , R 22 , R 23 , and R 24 independently are selected from the group consisting of hydrogen and an organic group, wherein the organic group is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, and a heteroaryl group,
a corresponding unprotected organoboronic acid is unstable by the boronic acid neat stability test, and
the reaction mixture further comprises a base having a pK B of at least 1, and a palladium catalyst; and

forming a cross-coupled product in the reaction mixture.

2. The method of claim 1 , wherein R 1 represents a 2-heterocyclic group.

3. The method of claim 2 , wherein R 1 represents a 2-heterocyclic group, and the 2-heterocyclic group is a 2-heteroaryl group.

4. The method of claim 1 ,
where R 21 , R 22 , R 23 , and R 24 independently are selected from the group consisting of hydrogen and an alkyl group; and
R 20 is an alkyl group.

5. The method of claim 4 , further comprising forming the protected organoboronic acid represented by formula (IV) by reacting the corresponding unprotected boronic acid with a N-substituted imino-di-carboxylic acid.

6. The method of claim 1 , where the protected organoboronic acid is represented by formula (V):

7. The method of claim 1 , where the compound is selected from the group consisting of an aryl halide, a heteroaryl halide, an aryl pseudohalide, and a heteroaryl pseudohalide.

8. The method of claim 7 , where the compound is selected from the group consisting of an unactivated aryl chloride and an unactivated heteroaryl chloride.

9. The method of claim 4 , where the compound is selected from the group consisting of an aryl halide, a heteroaryl halide, an aryl pseudohalide, and a heteroaryl pseudohalide.

10. The method of claim 9 , where the compound is selected from the group consisting of an unactivated aryl chloride and an unactivated heteroaryl chloride.

11. The method of claim 6 , where the compound is selected from the group consisting of an aryl halide, a heteroaryl halide, an aryl pseudohalide, and a heteroaryl pseudohalide.

12. The method of claim 11 , where the compound is selected from the group consisting of an unactivated aryl chloride and an unactivated heteroaryl chloride.

13. The method of claim 1 , where the base has a pK B of at least 1.5.

14. The method of claim 1 , where the base has a pK B of at least 3.

15. The method of claim 1 , where the base comprises an anion selected from the group consisting of [PO 4 ] 3− , [C 6 H 5 O] − , [CO 3 ] 2− , and [HCO 3 ] − .

16. A method of performing a chemical reaction, comprising: deprotecting in a reaction mixture a protected organoboronic acid represented by formula (IV):

where
R 1 represents a 2-heterocyclic group, wherein the 2-heterocyclic group is an optionally substituted 3- to 10-membered heterocyclic group comprising 1 to 3 heteroatoms selected from O, N, and S, and wherein one heteroatom is at the 2-position in the heterocyclic group,
B represents boron having sp 3 hybridization,
R 20 , R 21 , R 22 , R 23 , and R 24 independently are selected from the group consisting of hydrogen and an organic group, wherein the organic group is selected from the group consisting of an alkyl group, a heteroalkyl group, an alkenyl group, a heteroalkenyl group, an alkynyl group, a heteroalkynyl group, an aryl group, and a heteroaryl group, and

the reaction mixture further comprises a base and a palladium catalyst,
to form a corresponding unprotected organoboronic acid that is unstable by the boronic acid neat stability test;
reacting in the reaction mixture the unprotected organoboronic acid and a compound selected from the group consisting of an organohalide and an organopseudohalide; and
forming a cross-coupled product in the reaction mixture;
where the time required for at least 90% of the protected organoboronic acid to be deprotected in the reaction mixture is at least equal to the time required for 90% of the cross-coupled product to be formed in the reaction mixture.

Assignees

• Univ Illinois

Inventors

• Burke Martin D
• Knapp David M
• Gillis Eric P

Classifications

• C07D333/16

  by oxygen atoms · CPC title

• C07D263/56

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2 · CPC title

• C07D207/34

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07C41/30

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

• C07D307/80

  Radicals substituted by oxygen atoms · CPC title