Methods for forming protected organoboronic acids
Described are methods of forming protected boronic acids that provide in a manner that is straightforward, scalable, and cost-effective a wide variety of building blocks, such as building blocks containing complex and/or pharmaceutically important structures, and/or provide simple or complex protected organoboronic acid building blocks. A first method includes reacting an imino-di-carboxylic acid and an organoboronate salt. A second method includes reacting a N-substituted morpholine dione and an organoboronic acid.
1. A method, comprising:
combining a compound of formula A and a compound of formula B under conditions sufficient to form a compound of formula C;
wherein:
formula A is represented by:
formula B is represented by:
formula C is represented by:
R 10 is alkyl;
R 11 , R 12 , R 13 and R 14 are independently selected from the group consisting of hydrogen and alkyl;
R 21 and R 22 , independently for each occurrence, are alkyl;
n is an integer from 1 to 100;
X is a halide; and
the conditions sufficient to form a compound of formula C comprises a transition metal catalyst;
represents a trans or cis double bond; and
the stereochemistry of each double bond in the compound of formula A and the compound of formula B is conserved in the compound of formula C.
2. The method of claim 1 , wherein R 10 is methyl.
3. The method of claim 1 , wherein R 11 , R 12 , R 13 , and R 14 are hydrogen.
4. The method of claim 1 , wherein each R 21 is independently (C 1 -C 6 )alkyl.
5. The method of claim 4 , wherein R 21 is butyl.
6. The method of claim 1 , wherein each R 22 is independently (C 1 -C 6 )alkyl.
7. The method of claim 6 , wherein R 22 is ethyl.
8. The method of claim 1 , wherein n is an integer from 1 to 16.
9. The method of claim 1 , wherein X is iodide.
10. The method of claim 1 , wherein the transition metal catalyst is a palladium catalyst.
11. The method of claim 1 , further comprising combining the compound of formula C and I 2 to form a compound of formula D,
wherein the stereochemistry of each double bond in the compound of formula C is conserved in the compound of formula D.
12. The method of claim 11 , further comprising combining the compound of formula D and R 30 —B(OH) 2 under conditions sufficient to form a compound of formula E,
wherein R 30 is an organic group;
the conditions sufficient to form a compound of formula E comprises a second transition metal catalyst; and
the stereochemistry of each double bond in the compound of formula D is conserved in the compound of formula E.
13. The method of claim 12 , wherein the second transition metal catalyst is a palladium catalyst.
14. The method of claim 1 , wherein the compound of formula A is represented by formula A′:
the compound of formula B is represented by formula B′:
and
the compound of formula C is represented by formula C 1 :
15. The method of claim 1 , wherein the compound of formula A is represented by formula A′:
the compound of formula B is represented by formula B″:
and
the compound of formula C is represented by formula C 2 :
16. The method of claim 1 , wherein the compound of formula A is represented by formula A″:
the compound of formula B is represented by formula B′:
and
the compound of formula C is represented by formula C 3 :
17. The method of claim 1 , wherein the compound of formula A is represented by formula A″:
the compound of formula B is represented by formula B″:
and
the compound of formula C is represented by formula C 4 :