C-halogen bond formation

Abstract

Methods of halogenating a carbon containing compound having an sp3 C—H bond are provided. Methods of fluorinating a carbon containing compound comprising halogenation with Cl or Br followed by nucleophilic substitution with F are provided. Methods of direct oxidative C—H fluorination of a carbon containing compound having an sp3 C—H bond are provided. The halogenated products of the methods are provided.

What is claimed is: 
     
         1 . A composition comprising at least two or more of a carbon containing compound having an sp3 C—H bond hydrogen, a halogenating agent, a halogenating catalyst, or a phase transfer catalyst. 
     
     
         2 . The composition of  claim 1 , wherein the carbon containing compound includes a compound selected from the group consisting of neopentane; toluene; cyclohexane; norcarane; trans-decalin; 5α-cholestane; sclareolide; 1, 3, 5(10)-estratrien-17-one; (1R,4aS, 8aS)-octahydro-5,5,8a-trimethyl-1-(3-oxobutyl)-naphtalenone; (1R, 4S, 6S, 10S)-4, 12, 12-trimethyl-tricyclo[8.2.0.04,6]dodecan-9-one; levomethorphan; lupine; 20-methyl-5alpha(H)-pregnane; isolongifolanone; caryophyllene acetate; N-acetyl-gabapentin methyl ester; acetyl-amantidine; phthalimido-amantadine; methyloctanoate; saturated fatty acid esters; N-acetyl-Lyrica methyl ester; artemisinin, adapalene; finasteride; N-acetyl-methylphenidate; mecamylamine; N-acetyl-mecamylamine; N-acetyl-memantine; phthalimidi-memantine; N-acetyl-enanapril precursor methyl ester; progesterone; artemisinin; adapalene; dopamine derivative; pregabalin; cholestane; finasteride; methylphenidate derivative; mecamylamine; gabapentin; memantine derivative; gabapentin; rimantadine derivative; isoleucine derivative; leucine derivative; valine derivative; pregesterone; tramadol; enalapril precursor; (1R, 4aS, 8aS)-5, 5, 8a-trimethyl-1-(3-oxobutyl)octahydronaphthalen-2(1H)-one; phenylalanine; donepezil precursor; amphetamine; δ-tocopherol form of vitamin E; tyrosine; melatonin; tryptophan; estrone acetate; progesterone; dopamine; homophenylalanine; DOPA; ibuprofen methyl ester; buspirone; eticyclidine; memantine; amantadine; lyrica; lubiprostone; penridopril; fosinopril; N-Phth amantadine; N-Phth Memantine; 2-adamantanone; rimantadine analogue; adapalene precursor; perindopril precursor; protected gabapentin; methyl octanoate; methyl nonanate; methyl hexanoate; cyclohexyl acetate; and cyclohexane carboxylic acid methyl ester; or an analog of any one of the foregoing. 
     
     
         3 . The composition of  claim 1 , wherein the halogenating agent includes a substance selected from the group consisting of a hypohalite, N-chlorosuccinimide (NCS), N-bromosuccinimide, hypochlorous acid, hypobromous acid, hypochlorites, NaOCl, NaOBr, calcium hypochlorite, and cyanuric chloride. 
     
     
         4 . The composition of  claim 3 , wherein the hypohalite is provided by setting conditions to produce a hypohalite in situ with chlorine gas in a water solution of sodium or potassium hydroxide. 
     
     
         5 . The composition of  claim 1 , wherein the halogenating catalyst includes a substance selected from the group consisting of tetraphenylporphyrinatomanganese (III) chloride ([Mn III (TPP)Cl]), 5,10,15,20-tetramesitylporphyrinatomanganese (III) chloride ([Mn III (TMP)Cl]), Mn(III)[tetra-2,6-dichlorophenyl porphyrin, Mn(III) [tetra-2-nitrophenyl porphyrin], Mn(III)[tetra-2-naphthyl porphyrin, Mn(III)[pentachlorophenyl porphyrin, Mn(III)[tetraphenyl-2,3,7,8,12,13,17,18-Octachloroporphyrin], Mn(III)[tetraphenyl-2,3,7,8,12,13,17,18-Octabromoporphyrin], and Mn(III)[tetraphenyl-2,3,7,8,12,13,17,18-Octanitroporphyrin. 
     
     
         6 . The composition of  claim 1 , wherein the halogenating catalyst is selected from the group consisting of M(TPP)Cl, M(TMP)Cl, M[tetra-2,6-dichlorophenyl porphyrin, M[tetra-2-nitrophenyl porphyrin], M[tetra-2-naphthyl porphyrin, M[pentachlorophenyl porphyrin, M[tetraphenyl-2,3,7,8,12,13,17,18-Octachloroporphyrin], M[tetraphenyl-2,3,7,8,12,13,17,18-Octabromoporphyrin], M[tetraphenyl-2,3,7,8,12,13,17,18-Octanitroporphyrin], metal salen complexes having the formula M(salen), metal salophen complexes having the formula M(salophen), metal phthalocyanine complexes having the formula M(phth), and metal porphyrazine complexes having the formula M(Pz), where M is a metal. 
     
     
         7 . The composition of  claim 6 , wherein M is selected from the group consisting of manganese, copper, vanadium, chromium, iron, cobalt and nickel. 
     
     
         8 . The composition of  claim 1 , wherein the phase transfer catalyst includes a substance selected from the group consisting of tetrabutylammonium chloride, tetraalkyl ammonium, mixed alkyl ammonium, aryl ammonium, benzyl-trimethylammonium chloride, benzalkonium chloride, benzyl tributylammonium chloride, benzyl triethylammonium chloride, tetrabutyl phosphonium chloride, tetramethyl phosphonium chloride, and dimethyldiphenyl phosphonium chloride.