Nickel fluorinating complexes and uses thereof

1. A method of producing a fluorinated organic compound, the method comprising mixing a nickel comprising complex of formula (I):

wherein:

Ar 1 is aryl or heteroaryl substituted with n occurrences of R 1 ;

Ar 2 is aryl or heteroaryl substituted with m occurrences of R 2 ;

A 1 is C 1-6 alkyl, C 1-6 alkoxy, C 3-7 cycloalkyl, C 2-6 alkenyl, C(O)—R 6 , C(O)OR 6 , —NH 2 , —NHR 7 , —N(R 7 ) 2 , NO 2 , —OH, —OR 6 , aryl, heteroaryl or heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, alkenyl, aryl, heteroaryl or heterocyclyl can be further substituted with o occurrences of R 3 ;

A 2 is an N-heterocyclic carbene, phosphine, phosphate or heteroaryl substituted with p occurrences of R 4 ;

S is a substrate wherein the substrate is linked through an aryl, heteroaryl or alkenyl moiety present in the substrate;

each R 1 , R 2 , R 3 and R 4 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, C 3-7 cycloalkyl, C 2-6 alkenyl, C(O)—R 6 , C(O)OR 6 , —NH 2 , —NHR 7 , —N(R 7 ) 2 , NO 2 , —OH, —OR 6 , aryl, heteroaryl or heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, alkenyl, aryl, heteroaryl or heterocyclyl can be further substituted with 0-3 occurrences of R 8 ;

R 6 is C 1-6 alkyl, C 1-6 alkenyl, C 3-7 cycloalkyl, —C(O)O—C 1-6 alkyl, aryl, heteroaryl or heterocyclyl;

each R 7 is independently C 1-6 alkyl, C 1-6 alkenyl, C 3-7 cycloalkyl, —C(O)—C 1-6 alkyl, —C(O)O—C 1-6 alkyl, aryl, heteroaryl or heterocyclyl;

each R 8 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkenyl, C 3-7 cycloalkyl, C 1-6 alkyl-amine, —C(O)—C 1-6 alkyl, —C(O)O—C 1-6 alkyl, C 0-6 alkyl—NHR 7 , aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl or wherein two adjacent R 8 moieties, taken together with the atoms to which they are attached, form a C 3-7 cycloalkyl, aryl, heteroaryl or heterocyclyl group, wherein each alkyl, alkoxy, alkenyl, cycloalkyl, aryl; and

m, n, o and p are each independently an integer from 0-5;

with a source of fluorine and an organic compound under conditions sufficient to fluorinate the organic compound, thereby providing a fluorinated organic compound.

2. The method of claim 1 , wherein the source of fluorine is a fluoride source comprising water or a fluorinating agent.

3. The method of claim 1 , wherein source of fluorine comprises 18 F or 19 F.

4. The method of claim 1 , wherein the nickel complex of formula (I) is a complex of formula (II):

5. The method of claim 4 , wherein A 1 is aryl substituted with o occurrences of R 3 .

6. The method of claim 1 , wherein the nickel complex of formula (I) is a complex of formula (III):

7. The method of claim 6 , wherein A 2 is heteroaryl substituted with p occurrences of R 4 .

8. The method of claim 1 , wherein the nickel complex of formula (I) is a complex of formula (IV):

9. The method of claim 1 , wherein the nickel complex of formula (I) is a complex of formula (V):

10. The method of claim 1 , wherein S is an optionally substituted aryl comprising substrate an optionally substituted heteoaryl or an optionally substituted C 2-6 alkenyl.

11. The method of claim 10 , wherein S is selected from one of the following:

12. The method of claim 1 , wherein the complex of formula (I) is selected from the following:

13. The method of claim 1 , further comprising an oxidant, wherein the oxidant is a compound of formula (IX):

wherein

X is a halogen

A 3 is an aryl or heteroaryl group;

Cy taken together with the nitrogen atom to which it is attached forms a heterocyclyl or heteroaryl ring;

each occurrence of R F is independently halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; —OR″; —C(═O)R″; —CO 2 R″; —CN; —SCN; —SR″; —SOR″; —SO 2 R″; —NO 2 ; —N(R″) 2 ; —NHC(O)R″; or —C(R″) 3 ; wherein each occurrence of R″ is independently a hydrogen, a protecting group, an aliphatic moiety, a heteroaliphatic moiety, an aryl moiety; a heteroaryl moiety; alkoxy; aryloxy; alkylthio; arylthio; amino, alkylamino, dialkylamino, heteroaryloxy; or heteroarylthio moiety; and

Z is an anion.

14. The method of claim 13 , wherein the oxidant is selected from the following:

15. The method of claim 1 , wherein the fluorinated organic compound is selected from the following:

16. The method of claim 1 , wherein the method further comprises adding a salt to the source of fluorine.

17. The method of claim 1 , wherein the method further comprises adding a salt to the nickel comprising complex.

18. The method of claim 1 , wherein the method further comprises including a salt in the mixture containing the nickel comprising complex and source of fluorine.

19. A method of making a nickel complex of formula (I), the method comprising treating an organic compound of formula (VI):

S—X   (VI),

with tetramethylethylenediamine and bis( 1 , 5 -cyclooctadiene)nickel to provide a nickel complex of formula (VII):

the method further comprising, treating a nickel complex of formula (VII) with a silver compound of formula (VIII) and A 2 :

to provide a nickel complex of formula (I), wherein

X is a leaving group; and

Ar 1 , Ar 2 , A 1 , A 2 , A 3 , R 1 , R 2 , R 3 , R 4 , R 6 , R 7 , R 8 , m, n, o and p are as defined for formula (I).

20. A nickel complex of formula (I):

wherein:

Ar 1 is aryl or heteroaryl substituted with n occurrences of R 1 ;

Ar 2 is aryl or heteroaryl substituted with m occurrences of R 2 ;

A 1 is C 1-6 alkyl, C 1-6 alkoxy, C 3-7 cycloalkyl, C 2-6 alkenyl, C(O)—R 6 , C(O)O—R 6 , —NH 2 , —NHR 7 , —N(R 7 ) 2 , NO 2 , —OH, —OR 6 , aryl, heteroaryl or heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, alkenyl, aryl, heteroaryl or heterocyclyl can be further substituted with o occurrences of R 3 ;

A 2 is an N-heterocyclic carbene, phosphine, phosphate or heteroaryl substituted with p occurrences of R 4 ;

S is a substrate wherein the substrate is linked through an aryl, heteroaryl or alkenyl moiety present in the substrate;

each R 1 , R 2 , R 3 and R 4 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, C 3 - 7 cycloalkyl, C 2-6 alkenyl, C(O)—R 6 , C(O)OR 6 , —NH 2 , —NHR 7 , —N(R 7 ) 2 , NO 2 , —OH, —OR 6 , aryl, heteroaryl or heterocyclyl, wherein each alkyl, alkoxy, cycloalkyl, alkenyl, aryl, heteroaryl or heterocyclyl can be further substituted with 0-3 occurrences of R 8 ;

R 6 is C 1-6 alkyl, C 1-6 alkenyl, C 3-7 cycloalkyl, —C(O)O—C 1-6 alkyl, aryl, heteroaryl or heterocyclyl;

each R 7 is independently C 1-6 alkyl, C 1-6 alkenyl, C 3-7 cycloalkyl, —C(O)—C 1-6 alkyl, —C(O)O—C 1-6 alkyl, aryl, heteroaryl or heterocyclyl;

each R 8 is independently halo, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkenyl, C 3-7 cycloalkyl, C 1-6 alkyl-amine, —C(O)—C 1-6 alkyl, —C(O)O—C 1-6 alkyl, C 0-6 alkyl—NHR 7 , aryl, aryloxy, aralkyl, heteroaryl, heteroaralkyl, heterocyclyl or heterocyclylalkyl or wherein two adjacent R 8 moieties, taken together with the atoms to which they are attached, form a C 3-7 cycloalkyl, aryl, heteroaryl or heterocyclyl group, wherein each alkyl, alkoxy, alkenyl, cycloalkyl, aryl; and

m, n, o and p are each independently an integer from 0-5.