Process for deoxyfluorination of phenols
AssigneesStudiengesellschaft Kohle mbH, President and Fellows of Harvard College
InventorsTobias RITTER, Constanze NEUMANN, Mohammad Hassan BEYZAVI, Martin Georg STREBL-BANTILLO, Debashis MANDAL
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Abstract
The present invention refers to a process for transition-metal-assisted 18F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atmosphere, large substrate scope, and translatability to generate doses appropriate for positron emission tomography (PET) imaging.
Claims14
A method of replacing a hydroxyl group on an aryl or heteroaryl compound with a fluorine atom, the method comprising contacting a compound of Formula (I):
- with a Cp-Ru-(aryl or heteroaryl)-complex in the presence of a fluorine source under conditions sufficient to fluorinate the phenol compound, thereby providing a fluorinated (aryl or heteroaryl) compound, wherein, in Formula (I):
- R1 and R2 are independently selected from the group consisting of C1-30, aliphatic, aromatic, heteroaliphatic or heteroaromatic hydrocarbons, each of which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl, each being optionally further substituted by one or more heteroatoms, or heteroatoms,
- R3 and R4 are independently selected from the group consisting of C1-30, aliphatic, aromatic, heteroaliphatic or heteroaromatic hydrocarbons, each of which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl, each being optionally further substituted by one or more heteroatoms, or heteroatoms, or
- R3 and R4 together form a C4-20 hydrocarbon ring which may be saturated or unsaturated aliphatic, aromatic, heteroaliphatic or heteroaromatic, each of which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl, each being optionally further substituted by one or more heteroatoms, or heteroatoms, and
- X being an anion;
- and
- L being a leaving group,
- wherein the Ru phenol complex is a Ru complex with a C5 to C30, aromatic or heteroaromatic mono- to polycyclic ring system having at least one aromatic or heteroaromatic ring with one hydroxyl group on said ring, said ring system optionally being further substituted with straight chain, branched or cyclic alkyl, alkenyl or alkenyl having 1 to 20 carbon atoms, or heteroatoms being selected from halogen, N, O or S, each being optionally further substituted or each being optionally part of a aliphatic or aromatic ring system, and at least one further ligand optionally being further substituted by one or more heteroatoms or by C1-6 alkyl, optionally being further substituted with halogen.
A method of using a compound of any of the Formula (I), (II) or (III) as defined above for deoxyfluorinating a Ru-phenol-complex in the presence of a fluorine source wherein the Ru phenol complex is a Ru complex with an aryl compound bearing a hydroxyl group (phenol) as a ligand and at least one further ligand preferably optionally being substituted by C1-6 alkyl or halogen.
A complex of the general formula (IV):
- wherein in said formula (IV):
- represents a C5 to C30, aromatic or heteroaromatic mono- to polycyclic ring system having at least one aromatic or heteroaromatic ring and one oxygen OB bound on said aromatic or heteroaromatic ring, said ring system optionally being further substituted with at least one substituent Rp selected from straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaliphatic or heteroaryl each having 1 to 20 carbon atoms, each being optionally further substituted by one or more heteroatoms, or a heteroatom,
- R1 and R2 are independently selected from the group consisting of C1 to C30, aliphatic, aromatic, heteroaliphatic or heteroaromatic hydrocarbons, each of which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl or heteroatoms, each being optionally further substituted by one or more heteroatoms,
- R3 and R4 are independently selected from the group consisting of C1-30, aliphatic, aromatic, heteroaliphatic or heteroaromatic hydrocarbons, each of which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl or heteroatoms, each being optionally further substituted by one or more heteroatoms, or
- R3 and R4 form a C4-20 hydrocarbon ring which may be saturated or unsaturated aliphatic, aromatic, heteoraliphatic or heteroaromatic, which is optionally substituted with at least one substituent selected from C1-20 straight chain, branched or cyclic alkyl, alkenyl, alkenyl, aryl, heteroaryl or heteroatoms, each being optionally further substituted by one or more heteroatoms, and
- X being an anion.
Dependencies are inferred from the claim text.