Slow release of organoboronic acids in cross-coupling reactions

Patent metadata

Field	Value
Publication number	US-9328102-B2
Application number	US-201514686502-A
Country	US
Kind code	B2
Filing date	Apr 14, 2015
Priority date	Sep 26, 2008
Publication date	May 3, 2016
Grant date	May 3, 2016

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 an organic group selected from the group consisting of a 2-pyrollyl group, a 2-indolyl group, and a vinyl 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,
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 , where R 1 is selected from the group consisting of a 2-(N-butoxycarbonyl-pyrollyl) group and a 2-(N-phenylsulfonate-indolyl) group.

3. The method of claim 1 , where R 1 represents a vinyl group.

4. The method of claim 1 , where R 20 is an organic 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 4 , 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 1 , where the base has a pK B of at least 1.5.

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

11. 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 ] − .

12. 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 an organic group selected from the group consisting of a 2-pyrollyl group, a 2-indolyl group, and a vinyl 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, 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

• C07C2601/02

  with a three-membered ring · CPC title

• C07C2531/12

  containing organo-metallic compounds or metal hydrides · CPC title

• C07D213/57

  Nitriles · 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

• C07D209/30

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring · CPC title