Slow release of organoboronic acids in cross-coupling reactions
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.
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 l represents an organic group selected from the group consisting of a 2-furyl group, a 2-benzofuryl group, and a 2-thienyl 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 20 ° is an organic group.
3. The method of claim 2 , 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.
4. The method of claim 2 , where the protected organoboronic acid is represented by formula (V):
5. 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.
6. The method of claim 5 , where the compound is selected from the group consisting of an unactivated aryl chloride and an unactivated heteroaryl chloride.
7. The method of claim 1 , where the base has a pK B of at least 1.5.
8. The method of claim 1 , where the base has a pK B of at least 3.
9. 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 ] − .
10. The method of claim 9 , where the base is K 3 PO 4 .
11. The method of claim 1 , where the forming the cross-coupled product in the reaction mixture comprises maintaining the reaction mixture at a temperature of from 25° C. to 150° C. for a time of from 2 hours to 72 hours.
12. The method of claim 1 , where the forming the cross-coupled product in the reaction mixture comprises maintaining the reaction mixture at a temperature of from 50° C. to 120° C. for a time of from 4 hours to 48 hours.
13. A method of performing a chemical reaction, comprising:
deprotecting in a reaction mixture a protected organoboronic acid represented by formula (IV):
where
R l represents an organic group selected from the group consisting of a 2-furyl group, a 2-benzofuryl group, and a 2-thienyl group,
B represents boron having sp 3 hybridization, R 20 , R 21 ,R 22 , R 23 , 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 organo-pseudohalide; 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.
14. The method of claim 13 , where the time required for at least 90% of the protected organoboronic acid to be deprotected in the reaction mixture is at least twice the time required for 90% of the cross-coupled product to be formed in the reaction mixture.
15. The method of claim 13 , where the time required for at least 90% of the protected organoboronic acid to be deprotected in the reaction mixture is at least three times the time required for 90% of the cross-coupled product to be formed in the reaction mixture.
16. The method of claim 13 , where, when the unprotected organoboronic acid is subjected to the boronic acid neat stability test, the number of moles of the unprotected boronic acid measured in a second NMR analysis is at most 80% of the number of moles of the unprotected boronic acid measured in a first NMR analysis.
17. The method of claim 13 , where the compound is selected from the group consisting of an unactivated aryl chloride and an unactivated heteroaryl chloride.
18. The method of claim 13 , where the base has a pK B of at least 1.
19. The method of claim 13 , where the forming the cross-coupled product in the reaction mixture comprises maintaining the reaction mixture at a temperature of from 25° C. to 150° C. for a time of from 2 hours to 72 hours.