Difluoromethyl and difluoromethylene transfer reagents
View Patent ↗Disclosed herein are borazine, borate, and azaborinine compounds and compositions, methods of making said compounds and compositions, and methods of forming aromatic difluorocarbon compounds and difluorocarbon compounds.
1. A compound of Formula (I):
having a structure of:
wherein:
the dashed lines indicate optional double bonds;
R 1 is C 6-20 aryl or C 1-15 heteroaryl, and the heteroaryl comprises 1-5 ring heteroatoms selected from N, O, and S;
each R 2 and R 3 is independently OH, N(R 4 ) 2 , C 1-6 alkyl, C 3-8 cycloalkyl, OC 1-6 alkyl, or OC 3-8 cycloalkyl; or adjacent R 2 and R 3 , taken together with the atoms to which they are attached, form an optionally substituted 5-7 membered ring;
each R 4 is independently C 1-6 alkyl or C 3-8 cycloalkyl;
each R 5 is independently C 1-6 alkyl, C 3-8 cycloalkyl; or
each R 5 taken together with the atoms to which they are attached form an optionally substituted 5-7 membered ring;
each R 6 is independently C 1-6 alkyl, C 3-8 cycloalkyl, OC 1-6 alkyl, or OC 3-8 cycloalkyl; and
M comprises a counterion.
2. The compound of claim 1 , wherein R 1 is C 6-20 aryl.
3. The compound of claim 1 , wherein R 1 is C 1-15 heteroaryl.
4. The compound of claim 1 , wherein R 1 is selected from the group consisting of:
and
X is H, F, Cl, Br, I, CHs, OH, NH 2 , NO 2 , C 1-4 alkyl, OC 1-4 alkyl, CO 2 H, CHO, CF 3 , or CN.
5. The compound of claim 1 , wherein at least one R 2 or R 3 is methyl.
6. The compound of claim 1 having a structure selected from the group consisting of:
7. A composition comprising the compound of claim 1 and a crown ether.
8. A method for preparing the compound of claim 1 , comprising contacting H—CF 2 R 1 with a Lewis acid, a base, and optionally a crown ether under conditions sufficient to form the compound, wherein the Lewis acid has a structure:
9. The method of claim 8 , wherein the H—CF 2 R 1 is selected from the group consisting of:
and
X is H, F, Cl, Br, I, CHs, OH, NH 2 , NO 2 , C 1-4 alkyl, OC 1-4 alkyl, CO 2 H, CHO, CF 3 , or CN.
10. A method of forming an aromatic difluorocarbon compound comprising admixing the compound of claim 1 , with an electrophile under conditions sufficient to couple the electrophile and CF 2 R 1 to form the aromatic difluorocarbon compound.
11. A compound of Formula (III)
wherein:
the dashed lines indicate optional double bonds;
R 1 is H, C 6-20 aryl, or C 1-15 heteroaryl, and the heteroaryl comprises 1-5 ring heteroatoms selected from N, O, and S;
R 2 and R 3 are independently OH, N(R 4 ) 2 , C 1-6 alkyl, C 3-8 cycloalkyl, OC 1-6 alkyl, or OC 3-8 cycloalkyl, or R 2 and R 3 , taken together with the atoms to which they are attached, form an optionally substituted 5-7 membered ring;
each R 4 is independently C 1-5 alkyl or C 3-8 cycloalkyl;
each R 7 is independently H, C 1-6 alkyl, C 3-8 cycloalkyl, or at least one adjacent R 7 pair, taken together with the atoms to which they are attached, form an optionally substituted 5-7 membered ring; and
M comprises a counterion.
12. The compound of claim 11 , selected from the group consisting of:
13. The compound of claim 11 , wherein R 1 is H.
14. The compound of claim 11 , wherein R 1 is C 6-20 aryl.
15. The compound of claim 11 , wherein R 1 is C 1-15 heteroaryl.
16. The compound of claim 11 , wherein R 1 is selected from the group consisting of:
and
X is H, F, Cl, Br, I, CH 3 , OH, NH 2 , NO 2 , C 1-4 alkyl, OC 1-4 alkyl, CO 2 H, CHO, CF 3 , or CN.
17. The compound of claim 11 , wherein at least one of R 2 and R 3 is methyl.
18. A composition comprising the compound of claim 11 and a crown ether.
19. A method for preparing the compound of claim 11 , comprising contacting H—CF 2 R 1 with a Lewis acid, a base, and optionally a crown ether under conditions sufficient to form the compound, wherein the Lewis acid has a structure:
20. A method of forming a difluorocarbon compound comprising admixing the compound of, claim 11 , with an electrophile under conditions sufficient to couple the electrophile and CF 2 R 1 to form the aromatic difluorocarbon compound.