Methods and systems for selective fluorination of organic molecules

A method for fluorinating an organic molecule, the method comprising

• providing an organic molecule comprising an oxidizable secondary or tertiary carbon atom target site wherein the organic molecule comprises a formula selected from the group consisting of formula I, formula II, formula III, formula IV, formula V and formula VI:
• wherein:
• X is the target site carbon;
• Ar is selected from the group consisting of benzyl, o-chloro-phenyl, p-chloro-phenyl, m-chloro-phenyl, o-fluoro-phenyl, p-fluoro-phenyl, m-fluoro-phenyl, o-methyl-phenyl, p-methyl-phenyl, m-methyl-phenyl, o-methoxy-phenyl, p-methyoxy-phenyl, m-methyoxy-phenyl,
• R1 is selected from the group consisting of hydrogen, carbonyl, a C1-C6 alkyl and a C1-C6 substituted alkyl;
• R2 is selected from the group consisting of hydrogen, a C1-C6 alkyl, a C1-C6 substituted alkyl, and a C4-C7 alkyl linked to R3 to form a ring,
• R3 is selected from the group consisting of a C6-C12 alkyl, a C9-C15 substituted alkyl, a C4-C7 alkyl linked with R2 to form a ring, and a C5-C14 substituted aryl selected from the group consisting of
• R4 is either a C1-C6 alkoxy or a hydroxyl;
• R5 is either a hydrogen or a C1-C6 alkyl;
• R6 is selected from the group consisting of a C12-16 alkyl, a phenyl, and a substituted phenyl selected from the group consisting of benzyl, o-chloro-phenyl, p-chloro-phenyl m-chloro-phenyl, o-fluoro-phenyl, p-fluoro-phenyl, m-fluoro-phenyl, o-methyl-phenyl, p-methyl-phenyl, m-methyl-phenyl, o-methoxy-phenyl, p-methyoxy-phenyl, and m-methyoxy-phenyl;
• R7 is either a hydrogen or a C2-C5 substituted alkenyl;
• R8 is selected from the group consisting of hydrogen, a C1-C6 substituted alkyl linked to R11 to form a substituted ring, a C2-C5 alkenyl linked to R10 to form a ring, and a C1-C6 substituted alkyl linked to R10 to form a substituted ring;
• R9 is selected from the consisting of a C1-C6 alkyl, a C1-C5 substituted alkyl linked to R11 to form a substituted ring, and an alkenyl linked to R11 to form a phenyl;
• R10 is selected from the group consisting of a C1-C6 alkyl, a C2-C5 alkenyl linked with R8 to form a ring, and a C1-C6 substituted alkyl linked to R10 to form a substituted ring;
• R11 is selected from the group consisting of a C1-C6 alkyl, a C1-C5 substituted alkyl linked to R8 to form a substituted ring, an alkenyl linked to R9 to form a phenyl, and a C1-C6 substituted alkyl linked to R9 to form a substituted ring;
• R12 is either a C1-C6 alkyl or a hydrogen;
• R13 is selected from the group consisting of hydrogen, —COOR where R is a C1-C6 alkyl, and a C1-C4 alkyl linked to Ar to form a ring;
• R14 is either a hydrogen cyano;
• R15 is either a hydrogen or 6-dimethylamino-napthyl;
• R16 is selected from the group consisting of hydrogen, 2-methyl-5-phenyl-4,5-dihydrooxazolyl, and 2,3,4,5-tetramethoxy-tetrahydro-2H-pyranyl;
• R17-R18 are hydrogen;
• R19 is either a hydrogen or a C1-C6 alkyl;
• R20 is selected from the group consisting of hydrogen, a C1-C6 alkyl linked to R22 to form a ring, an alkenyl linked to R22 to form a phenyl, a substituted alkenyl linked to R22 by to form a substituted phenyl, and a C2-C12 substituted heteroatom-containing alkenyl linked to R22 to form a substituted heteroatom containing ring;
• R21 is either hydrogen or a C1-C6 alkyl;
• R22 is selected from the group consisting of a C1-C6 alkyl, phenyl, a C2-C10 alkenyl, a C1-C6 alkyl linked to R20 to form a ring, an alkenyl linked to R20 to form a phenyl, a substituted alkenyl linked to R20 to form a substituted phenyl, and a C2-C12 substituted heteroatom-containing alkenyl linked to R20 to form a substituted heteroatom containing ring;
• providing a P450 heme-containing oxygenase having a fold and topology substantially identical to that of a P450 oxygenase comprising the sequence of any of:
• CYP102A1 (SEQ ID NO:2), CYP102A1var4 (SEQ ID NO:46), CYP102A1var8 (SEQ ID NO:50), CYP102A1var1(SEQ ID NO:21), CYP102A1var2(SEQ ID NO:22), CYP102A1var3(SEQ ID NO:23), CYP102A1var3-7(SEQ ID NO:9), CYP102A1var3-5 (SEQ ID NO:27), CYP102A1var3-9(SEQ ID NO:31), CYP102A1var3-14(SEQ ID NO:36), CYP102A1var3-15 (SEQ ID NO:37), CYP102A1var3-17(SEQ ID NO:39), CYP101A1(SEQ ID NO:8), CYP101A1(Y96F), CYP101A1var2-1(SEQ ID NO:67), CYP101A1var1(SEQ ID NO:65), CYP101A1var2-2(SEQ ID NO:68), CYP1A2 (SEQ ID NO:13), CYP2C9 (SEQ ID NO:15), CYP2C19(SEQ ID NO:16), CYP2D6(SEQ ID NO:17), CYP2E1(SEQ ID NO:18), CYP3A4(SEQ ID NO:20), P450BSβ (CYP152A1) (SEQ ID NO:70) that oxidizes the target site by introduction of an oxygen-containing functional group;
• contacting the P450 heme-containing oxygenase with the organic molecule for a time and under condition to allow introduction of the oxygen-containing functional group on the target site thus providing an oxidized organic molecule;
• providing a fluorinating agent;
• and
• contacting the fluorinating agent with the oxidized organic molecule, for a time and under condition to allow replacement of the oxygen-containing functional group with fluorine.