Cyclopropyl MIDA boronate
View Patent ↗This disclosure concerns a protected cyclopropylboronic acid comprising a substituted cyclopropyl group and a boronic ester group having a protecting group. The protecting group is an N-methyliminodiacetic acid (MIDA) group or MIDA-based group.
1. A protected organoboronic acid of the formula I:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a , R 2b , R 2c , and R 2d are independently selected from hydrogen, alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl,
wherein at least one of R 2a , R 2b , R 2c , and R 2d is not hydrogen.
2. The protected organoboronic acid of claim 1 , wherein R 1 is alkyl.
3. The protected organoboronic acid of claim 1 , wherein R 1 is methyl.
4. The protected organoboronic acid of claim 1 , wherein one of R 2a , R 2b , R 2c , and R 2d is substituted alkyl and the others are hydrogen.
5. The protected organoboronic acid of claim 1 , wherein one of R 2a , R 2b , R 2c , and R 2d is trifluoromethyl and the others are hydrogen.
6. The protected organoboronic acid of claim 1 , wherein the protected organoboronic acid is of the formula II:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a and R 2c are independently selected from hydrogen, alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl.
7. The protected organoboronic acid of claim 1 , wherein the protected organoboronic acid is of the formula III:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a is selected from alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl.
8. The protected organoboronic acid of claim 1 , wherein the protected organoboronic acid is of the formula IV:
9. The protected organoboronic acid of claim 8 , wherein the protected organoboronic acid has a trans stereochemistry with respect to the cyclopropyl ring.
10. A method of performing a chemical reaction comprising:
contacting a protected organoboronic acid of formula I:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a , R 2b , R 2c , and R 2d are independently selected from hydrogen, alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl, wherein at least one of R 2a , R 2b , R 2c , and R 2d is not hydrogen;
with an organohalide or organo pseudohalide and a metal catalyst, in the presence of a base to provide a cross-coupled product.
11. The method of claim 10 , wherein R 1 is alkyl.
12. The method of claim 10 , wherein R 1 is methyl.
13. The method of claim 10 , wherein one of R 2a , R 2b , R 2c , and R 2d is substituted alkyl and the others are hydrogen.
14. The method of claim 10 , wherein one of R 2a , R 2b , R 2c , and R 2d is trifluoromethyl and the others are hydrogen.
15. The method of claim 10 , further comprising removing MIDA group from the boron to form an organoboronic acid, and contacting the organoboronic acid and organohalide or organo pseudohalide with a metal catalyst, to provide a cross-coupled product.
16. The method of claim 15 , wherein the removing the MIDA group or MIDA-based group and the contacting the organoboronic acid and an organohalide or organo pseudohalide with a metal catalyst are performed simultaneously in the presence of a base.
17. The method of claim 15 , wherein the removing the MIDA group or MIDA-based group is performed prior to the contacting the organoboronic acid and an organohalide or organo pseudohalide with a metal catalyst.
18. The method of claim 10 , wherein the protected organoboronic acid is of formula II:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a and R 2c are independently selected from alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl.
19. The method of claim 10 , wherein the protected organoboronic acid of formula III:
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a is selected from alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl.
20. The method of claim 10 , wherein the protected organoboronic acid of formula IV:
with an organohalide or organo pseudohalide and a metal catalyst, in the presence of a base to provide a cross-coupled product.
21. A method of forming a compound of formula III
wherein
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, and heteroaryl; and
R 2a is selected from alkyl, substituted alkyl, halogen, hydroxyl, cyano, phosphate, alkoxy, substituted alkoxy, carboxyl, carboxyl ester, heterocyclyl, substituted heterocyclyl, alkenyl, substituted alkenyl, amino, substituted amino, acyl, acylamino, aminoacyl, alkoxycarbonylamino, thiol, alkylthiol, substituted thioalkoxy, and sulfonyl;
comprising reacting a compound of formula 1a:
with a compound of formula 1b:
in the presence of a metal catalyst.
22. The method of claim 10 , wherein the metal catalyst is selected from palladium, ruthenium, rhenium and rhodium.
23. The method of claim 10 , wherein the metal catalyst is selected from palladium(II)acetate, palladium on activated charcoal, tetrakis(triphenylphosphine)palladium (0), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II).
24. The method of claim 21 , wherein the metal catalyst is selected from palladium, ruthenium, cobalt, copper, iron, osmium, rhenium and rhodium.