Fluorination of organic compounds

Patent metadata

Field	Value
Publication number	US-9024093-B2
Application number	US-200913130033-A
Country	US
Kind code	B2
Filing date	Nov 20, 2009
Priority date	Nov 20, 2008
Publication date	May 5, 2015
Grant date	May 5, 2015

Abstract

Methods for fluorinating organic compounds are described herein.

First claim

What is claimed is:

1. A method of fluorinating an organic compound, the method comprising providing an organic compound selected from the group consisting of aryl and heteroaryl tin species; vinyl, aryl, and heteroaryl boron species; and vinyl, aryl, and heteroaryl silicon species; a silver salt; and an organic, electrophilic fluorinating agent selected from the group consisting of N-fluoropyridinium triflate, N-fluoro-2,4,6-trimethylpyridinium triflate, N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate, N-fluoro-2,6-dichloropyridinium tetrafluoroborate, N-fluoro-2,6-dichloropyridinium triflate, N-fluoropylidinium pyridine heptafluorodiborate, N-fluoropyridinium tetrafluoroborate, N-fluoropyridinium triflate, an N-fluoroarylsulfonimide, N-chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate), and N-chloromethyl-N′-fluorotriethylenediammonium bis(hexafluorophosphate), under conditions sufficient to fluorinate the organic compound, thereby providing a fluorinated organic compound.

2. The method of claim 1 , wherein the tin species comprises an organostannane, wherein the organostannane comprises a trialkyltin moiety.

3. The method of claim 1 , wherein the boron comprises a boron substituent of the formulae:

wherein G 1 , G 2 and G 3 are, independently, —OH, —OR, or —R;
each R is, independently, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;
or G 1 and G 2 are joined to form an optionally substituted 5- to 8-membered ring having at least one O atom directly attached to B, wherein the ring is comprised of carbon atoms and optionally one or more additional heteroatoms independently selected from the group consisting of N, S, and O; and
wherein A ⊕ is a metal cation or ammonium.

4. The method of claim 1 , wherein the silicon species is a trialkoxysilane.

5. The method claim 1 , wherein the silver salt is selected from the group consisting of silver(I) fluoride, silver(I) acetate, silver(I) tetrafluoroborate, silver(I) perchlorate, silver(I) nitrate, silver(I) carbonate, silver(I) cyanide, silver(I) benzoate, silver(I) triflate, silver(I) hexafluorophosphate, silver(I) hexafluoroantimonate, silver(I) oxide, silver(I) nitrite and silver(I) phosphate.

6. The method of claim 1 , wherein the method comprises a catalytic amount of the silver salt relative to the organic compound.

7. The method of claim 1 , wherein the fluorinating agent comprises 18 F or 19 F.

8. The method of claim 1 , wherein the method further comprises a base selected from NaOH, KOH, BaO, MgO, NaHCO 3 , KHCO 3 , Na 2 CO 3 and Ba(OH) 2 .

9. The method of claim 1 , wherein the method further comprises a triflate salt in addition to the silver salt.

10. The method of claim 9 , wherein the salt is sodium triflate.

11. The method of claim 1 , wherein the organic compound is immobilized on a solid support.

12. The method of claim 1 , wherein the silver salt and the fluorinating agent are added to the organic compound.

13. The method of claim 8 , wherein the silver salt and the base are added to the organic compound, resulting in an intermediate product and wherein the intermediate product is isolated and the fluorinating agent and the silver-containing compound are added thereto, resulting in formation of the fluorinated organic compound.

14. A method of fluorinating an aryl or heteroaryl tin species, the method comprising combining silver(I) triflate, an aryl or heteroaryl tin species, a base, and N-chloromethyl-N′-fluorotriethylenediammonium bis(hexafluorophosphate), under conditions sufficient to fluorinate the aryl or heteroaryl tin species, thereby providing a fluorinated aryl or heteroaryl compound.

15. A method of fluorinating a vinyl, aryl, or heteroaryl boron species, the method comprising combining silver(I) triflate, a vinyl, aryl, or heteroaryl boron species, a base, and N-chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate), under conditions sufficient to fluorinate the vinyl, aryl, or heteroaryl boron species, thereby providing a fluorinated vinyl, aryl, or heteroaryl compound.

16. A method of fluorinating a vinyl, aryl, or heteroaryl silicon species, the method comprising combining silver(I) oxide, a vinyl, aryl, or heteroaryl silicon species, a base and N-chloromethyl-N′-fluorotriethylenediammonium bis(tetrafluoroborate), under conditions sufficient to fluorinate the vinyl, aryl, or heteroaryl silicon species, thereby providing a fluorinated vinyl, aryl, or heteroaryl organic compound.

Assignees

• Ritter Tobias
• Furuya Takeru
• Tang Pingping
• Harvard College

Inventors

• Ritter Tobias
• Furuya Takeru
• Tang Pingping

Classifications

• C07C22/08

  containing fluorine · CPC title

• C07C43/225

  containing halogen · CPC title

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title

• C07C41/22

  by introduction of halogens; by substitution of halogen atoms by other halogen atoms · CPC title

• C07D311/72

  3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols · CPC title