Method for preparation of fluoro alkylated compounds by homogeneous Ni catalysis

A method for preparation of a mono-fluoro alkylated compound FACOMPSUBST that is mono-fluoroalkylated at a sp2 carbon, by a reaction of a compound COMPSUBST with a fluoro alkyl halide FAHALIDE by homogeneous catalysis using a Ni catalyst NICAT in the presence of a base BAS;

• wherein
• NICAT is Ni-cat1 or Ni-cat2;
• Ni-cat1 is a combination of a nickel salt NISALT with a ligand LIG
• NISALT is NiCl2 or Ni(NO3)2;
• LIG is selected from the group consisting of compound of formula (DPEPhos), compound of formula (dppb) and Ph3P;
• Ni-cat2 is compound of formula (Ni-cat2);
• BAS is selected from the group consisting of Cs2CO3, CsHCO3, K3PO4, NaH and NaOtBu;
• FAHALIDE is selected from the group consisting of perfluoro C1-20 alkyl-X1, and Br—(CF2)n3—Br;
• wherein X1 is Br or I;
• with n3 being an integer of 2 to 10;
• COMPSUBST is selected from the group consisting of a compound COMPSUBST-I, ethene, and polystyrene;
• the ethene being substituted by 1 substituent selected from the group consisting of C1-10 alkyl;
• COMPSUBST-I is a compound of formula (COMPSUBST-I);
• RINGA(COMPSUBST-I)
• RINGA is a 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 the substituents of RINGA is independently from any other of the substituents of RINGA selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, OH, N(R10)R11, CN, NH—OH, NO, NO2, F, Cl, Br, I, CF3, (CH2)m—C(O)Y1, S(O)2R50, CH═C(H)R28, CC—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;
• when RINGB is a 5 membered ring, then RINGB is unsubstituted or substituted by 1, 2 or 3 identical or different substituents,
• when RINGB is a 6 membered ring then RINGB is unsubstituted or substituted by 1, 2, 3 or 4 identical or different substituents,
• any of the substituents of RINGB is independently from any other of the substituents of RINGB selected from the group consisting of C1-10 alkyl, C3-8 cycloalkyl, C1-4 alkoxy, OH, N(R17)R18, CN, NH—OH, NO, NO2, F, Cl, Br, I, CF3, (CH2)n—C(O)Y2, S(O)2R51, CH═C(H)R38, CC—R34, benzyl, phenyl and naphthyl;
• any of the C1-10 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)—C1-5 alkyl, O—C1-10 alkyl, S—C1-10 alkyl, S(O)—C1-10 alkyl, S(O2)—C1-10 alkyl, O—C1-6 alkylen-O—C1-6 alkyl, C3-8 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, C1-4 alkoxy, NO2 and CN;
• m and n are identical or different and independently from each other 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
• Y1 and Y2 are identical or different and independently from each other selected from the group consisting of H, OH, C(R14)(R15)R16, C1-6 alkyl, O—C1-6 alkyl, phenyl, benzyl, O-phenyl, O—C1-6 alkylen-O—C1-6 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 C1-6 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, C1-6 alkyl and C1-6 alkoxy;
• R24, R34, R28 and R38 are identical or different and independently from each other selected from the group consisting of H, C1-10 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 C1-10 alkyl;
• and
• wherein if COMPSUBST is ethene as defined above, FACOMPSUBST is a 1,2-disubstituted ethene.