Method for preparation of fluoro, chloro and fluorochloro alkylated compounds by homogeneous catalysis

1. A method for the preparation of a fluoro, chloro or fluorochloro alkylated compound by a reaction of a compound COMPSUBST with a compound FCLALKYLHALIDE by homogeneous catalysis using a catalyst CAT

in the presence of BuPAd 2 and

in the presence of TEMPO and

in the presence of a compound BAS,

BAS is selected from the group consisting of Cs 2 CO 3 , CsHCO 3 , NEt 3 , and mixtures thereof;

FCLALKYLHALIDE is a compound of formula (III);

R3—X   (III)

X is Cl, Br or I;

R3 is C 1-20 alkyl or a C 1-20 alkyl, wherein in the alkyl chain at least one of the hydrogens is substituted by F or Cl;

CAT is selected from the group consisting of Pd(OAc) 2 , Pd(TFA) 2 , and mixtures thereof;

COMPSUBST is selected from the group consisting of a compound COMPSUBST-I, ethene, cyclohexene, ethine, and polystyrene;

the ethene and the cyclohexene being unsubstituted or substituted by 1, 2 or 3 substituents selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl, naphthyl and morpholine;

the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl and naphthyl;

COMPSUBST-1 contains a ring RINGA;

RINGA is an unsaturated or aromatic, 5 or 6 membered carbocyclic or heterocyclic ring,

when RINGA is a heterocyclic ring, then RINGA has 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S,

when RINGA is a 5 membered ring, then RINGA is unsubstituted or substituted by 1, 2, 3 or 4 identical or different substituents,

when RINGA is a 6 membered ring then RINGA is unsubstituted or substituted by 1, 2, 3, 4 or 5 identical or different substituents,

any of said substituents of RINGA is independently from any other of said substituent of RINGA selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, N(R10)R11, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C═C—R24, benzyl, phenyl and naphthyl;

RINGA can be condensed with a ring RINGB, RINGB is a 5 or 6 membered carbocyclic or heterocyclic ring,

when RINGB is a heterocyclic ring, is contains 1, 2 or 3 identical or different endocyclic heteroatoms independently from each other selected from the group consisting of N, O and S;

RINGB is unsubstituted or substituted with 1, 2 or 3 in case of RINGB being a 5 membered ring, with 1, 2, 3 or 4 in case of RINGB being a 6 membered ring, identical or different substituents independently from each other selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, N(R17)R18, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) n —C(O)Y2, S(O) 2 R51, CH═C(H)R38, C≡C-R34 benzyl, phenyl and naphthyl;

any of said C 1-10 alkyl substituent of RINGA or RINGB is unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, OH, O—C(O)—C 1-5 alkyl, O—C 1-10 alkyl, S—C 1-10 alkyl, S(O)—C 1-10 alkyl, S(O 2 )-C 1-10 alkyl, O—C 1-6 alkylen-O—C 1-6 alkyl, C 3-8 cycloalkyl and 1,2,4-triazolyl;

any of said benzyl, phenyl and naphthyl substituent of RINGA or RINGB is independently from each other unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, C 1-4 alkoxy, NO 2 and CN;

m, n and q are identical or different and independently from each other 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;

Y1, Y2 and R13 are identical or different and independently from each other selected from the group consisting of H, OH, C(R14)(R15)R16, C 1-6 alkyl, O—C 1-6 alkyl, phenyl, benzyl, O-phenyl, O—C 1-6 alkylen-O—C 1-6 alkyl and N(R19)R20;

R14, R15 and R16 are identical or different and independently from each other selected from the group consisting of H, F, Cl and Br;

R10, R11, R17, R18, R19 and R20 are identical or different and are independently from each other H or C 1-6 alkyl, or R10 and R11, R17 and R18 or R19 and R20 represent together a tetramethylene or a pentamethylene chain;

R50 and R51 are identical or different and independently from each other selected from the group consisting of OH, C 1-6 alkyl and C 1-6 alkoxy;

R24, R34, R28 and R38 are identical or different and independently from each other selected from the group consisting of H, C 1-10 alkyl, C(R25)(R26)—O—R27;

R25, R26 and R27 are identical or different and independently from each other selected from the group consisting of H and C 1-10 alkyl.

2. The method according to claim 1 , wherein

COMPSUBST is selected from the group consisting of compound COMPSUBST-I, ethene, cyclohexene, ethine, and polystyrene;

the ethene and the cyclohexene being unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of C 1-10 alkyl, C 3-6 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, benzyl, phenyl, naphthyl and morpholine;

the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C 1-10 alkyl, C 3-6 cycloalkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, benzyl, phenyl and naphthyl;

with COMPSUBST-I being selected from the group consisting of

with COMPSUBST-I being unsubstituted or substituted

by 1, 2, 3 or 4 in case of COMPSUBST-I being a monocyclic compound with 5 endocyclic atoms,

by 1, 2, 3, 4 or 5 in case of COMPSUBST-I being a monocyclic compound with 6 endocyclic atoms,

by 1, 2, 3, 4, 5 or 6 in case of COMPSUBST-I being a bicyclic compound wherein a 5-membered and a 6-membered ring are ortho-fused,

by 1, 2, 3, 4, 5, 6 or 7 in case of COMPSUBST-I being a bicyclic compound wherein two 6-membered rings are ortho-fused,

identical or different substituents independently from each other selected from the group consisting of C 1-10 alkyl, C 3-8 cycloalkyl, C 1-4 alkoxy, OH, C(H)═O, N(R10)R11, CN, NH—OH, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50, CH═C(H)R28, C≡C—R24, benzyl, phenyl and naphthyl;

said C 1-10 alkyl substituent of COMPSUBST-I is unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, OH, O—C(O)—C 1-5 alkyl, O—C 1-10 alkyl, S—C 1-10 alkyl, S(O)—C 1-10 alkyl, S(O 2 )—C 1-10 alkyl, O—C 1-6 alkylen-O—C 1-6 alkyl, C 3-8 cycloalkyl and 1,2,4-triazolyl;

said benzyl, phenyl and naphthyl substituent of COMPSUBST-I is independently from each other unsubstituted or substituted with 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of halogen, C 1-4 alkoxy, NO 2 and CN.

3. The method according to claim 1 , wherein m, n and q are identical or different and independently from each other 0, 1, 2, 3 or 4.

4. The method according to claim 1 , wherein

COMPSUBST is selected from the group consisting of benzene, pyrazole,

compound of formula (VI), ethene, cyclohexene, ethine, and polystyrene;

Y is C 1-6 alkyl;

the ethene and the cyclohexene being unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of C 1-10 alkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, benzyl, phenyl and morpholine;

the ethine being unsubstituted or substituted by 1 substituent selected from the group consisting of C 1-10 alkyl, C 1-4 alkoxy, N(R10)R11, CN, F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, benzyl and phenyl;

wherein

R44 is selected from the group consisting of C 1-10 alkyl, C 1-4 alkoxy, OH, N(R10)R11, CN, NO, NO 2 , F, Cl, Br, I, CF 3 , (CH 2 ) m —C(O)Y1, S(O) 2 R50.

5. The method according to claim 1 , wherein X is Br or I.

6. The method according to claim 1 , wherein X is Br.

7. The method according to claim 1 , wherein compound FCLALKYLHADLIDE is a perfluoroalkyl halide, F 2 HC—Cl or F 2 HC—Br.

8. The method according to claim 1 , wherein

X is Cl, Br or I, and

R3 is perfluoro C 1-20 alkyl, or

FCLALKYLHADLIDE is F 2 HC—Cl or F 2 HC—Br.

9. The method according to claim 1 , wherein

FCLALKYLHALIDE is selected from the group consisting of F 21 C 10 —I, F 17 C 8 —I, F 13 C 6 —I, F 9 C 4 —I, F 3 C—I, F 3 C—Br, F 3 C—Cl, F 2 HC—Cl, and F 2 HC—Br.

10. The method according to claim 1 , wherein

the reaction is done in the presence of a compound COMPSALT;

COMPSALT is selected from the group consisting of NaI, KI, CsI and N(R30)(R31)(R32)R33I;

R30, R31, R32 and R33 are identical or different and independently from each other selected from the group consisting of H and C 1-10 alkyl.

11. The method according to claim 10 , wherein R30, R31, R32 and R33 are identical or different and independently from each other selected from the group consisting of H and C 2-6 alkyl.

12. The method according to claim 10 , wherein COMPSALT is selected from the group consisting of NaI and (n-Bu) 4 NI.

13. The method according to claim 1 , wherein CAT is Pd(OAc) 2 .