Direct palladium-catalyzed aromatic fluorination

A palladium complex comprising a ligand of Formula (B) and a ligand of Formula (A′):

• wherein:
• R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• R9, R10, R11, R12, R13, R14, R15, R16, R17, and R18 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• and
• each instance of R is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R attached the same nitrogen atom are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring.

A method of preparing a compound of Formula (I), (II), or (III):

• comprising the steps of:
• contacting a palladium(II) complex of Formula (A) with a phenanthroline ligand of Formula (B) to form a palladium(II) catalyst of Formula (C);
• and
• contacting an aryl or heteroaryl substrate of Formula (D), (E), or (F):
• with a fluorinating agent in the presence of the palladium(II) catalyst of Formula (C) to provide the compound of Formula (I), (II), or (III):
• wherein:
• W1, W2, W3, W4, and W5 is CH, CRA, or N, provided at least one of W1, W2, W3, W4, and W5 is N;
• W6, W7, W8, and W9 is CH, CRA, N, NH, NRA, O, or S, provided at least one of W6, W7, W8, and W9 is N, NH, NRA, O, or S;
• each instance of RA is independently halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —N(RA1)2, —SRA1, —CN, —SCN, —C(═NRA1)RA1, —C(═NRA1)ORA1, —C(═NRA1)N(RA1)2, —C(═O)RA1, —C(═O)ORA1, —C(═O)N(RA1)2, —NO2, —NRA1C(═O)RA1, —NRA1C(═O)ORA1, —NRA1C(═O)N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, or —OC(═O)N(RA1)2, or two vicinal RA groups are joined to form a substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl ring;
• each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of RA1 attached the same nitrogen atom are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• k is 0, 1, 2, 3, 4, or 5;
• Y is an anionic counterion or Y is an alkenyl or alkynyl moiety;
• L is an uncharged, monodentate ligand selected from the group consisting of carbon monoxide, an isonitrile, acetonitrile, an amine, morpholine, phosphines, aliphatic, aromatic or heteroaromatic phosphines, phosphites, arsines (e.g., trifluoroarsine, trimethylarsine, tricyclohexylarsine, tri-tert-butylarsine, triphenylarsine, tris(pentafluorophenyl)-arsine), stibines (e.g., trifluorostibine, trimethylstibine, tricyclohexylstibine, tri-tert-butylstibine, triphenylstibine, tris(pentafluoro-phenyl)stibine, or a nitrogen-containing heterocycle (e.g., pyridine, pyridazine, pyrazine, triazine);
• R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• R9, R10, R11, R12, R13, R14, R15, R16, R17, and R18 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• and
• each instance of R is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R attached the same nitrogen atom are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring.

A method of preparing a compound of Formula (I), (II), or (III):

• comprising contacting a compound of Formula (D), (E), or (F):
• with a fluorinating agent in the presence of a palladium (II) complex of Formula (C):
• to provide a compound of Formula (I), (II), or (III);
• wherein:
• W1, W2, W3, W4, and W5 is CH, CRA, or N, provided at least one of W1, W2, W3, W4, and W5 is N;
• W6, W7, W8, and W9 is CH, CRA, N, NH, NRA, O, or S, provided at least one of W6, W7, W8, and W9 is N, NH, NRA, O, or S;
• each instance of RA is independently halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —ORA1, —N(RA1)2, —SRA1, —CN, —SCN, —C(═NRA1)RA1, —C(═NRA1)ORA1, —C(═NRA1)N(RA1)2, —C(═O)RA1, —C(═O)ORA1, —C(═O)N(RA1)2, —NO2, —NRA1C(═O)RA1, —NRA1C(═O)ORA1, —NRA1C(═O)N(RA1)2, —OC(═O)RA1, —OC(═O)ORA1, or —OC(═O)N(RA1)2, or two vicinal RA groups (groups attached to two adjacent carbon atoms) are joined to form a substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl ring;
• each instance of RA1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of RA1 attached the same nitrogen atom are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
• k is 0, 1, 2, 3, 4, or 5;
• Y is an anionic counterion or Y is an alkenyl or alkynyl moiety;
• R1, R2, R3, R4, R5, R6, R7, and R8 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• R9, R10, R11, R12, R13, R14, R15, R16, R17, and R18 are independently selected from the group consisting of hydrogen, halogen, acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR, —N(R)2, —SR, —CN, —SCN, —C(═NR)R, —C(═NR)OR, —C(═NR)N(R)2, —C(═O)R, —C(═O)OR, —C(═O)N(R)2, —NO2, —NRC(═O)R, —NRC(═O)OR, —NRC(═O)N(R)2, —OC(═O)R, —OC(═O)OR, —OC(═O)N(R)2, —SO3H, and —NR3+Y′ wherein Y′ is an anionic counterion;
• and
• each instance of R is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R attached the same nitrogen atom are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring.