Transition metal-catalyzed C—H amination using unactivated amines

A method of amination or amidation, comprising the step of:

• combining a substrate, comprising a reactive C—H bond, and an amine or amide, comprising a reactive N—H bond, in the presence of an oxidizing agent and a metal-containing catalyst, wherein the oxidizing agent is a peroxide represented by:
• R6—O—O—R6
• wherein R6 is independently for each occurrence hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl or heteroaralkyl, and the metal-containing catalyst is a transition metal-containing catalyst, thereby forming a product with a covalent bond between the carbon of the reactive C—H bond and the nitrogen of the reactive N—H bond;
• the substrate is represented by:
• wherein
• the reactive C—H bond is H—C(R3)(R4)(R5);
• R3 is alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
• R4 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
• R5 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, carbocyclyl, heterocyclyl, polycyclyl, carbonyl, ester or ether;
• and
• the substrate is optionally substituted with 1-3 substituents selected from the group consisting of halogens, alkyls, alkenyls, alkynyls, hydroxyls, aminos, nitros, thiols, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, fluoroalkyls, trifluoromethyl, and cyano;
• or
• the substrate is a cyclopropane, cyclobutane, cyclopentane, cyclohexane, indane, 2-oxoindane, thiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxanthene, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine, piperazine, morpholine, lactone, lactam, azetidinone, pyrrolidinone, sultam, or sultone;
• and the substrate is optionally substituted with 1-3 substituents selected from the group consisting of halogens, alkyls, alkenyls, alkynyls, hydroxyls, aminos, nitros, thiols, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, fluoroalkyls, trifluoromethyl, and cyano;
• the amine or amide is represented by:
• wherein
• R1 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
• R2 is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl or heteroaralkyl;
• or R1 and R2 taken together with the atoms to which they are bound, form a five, six or seven membered ring which contains 0-2 heteroatoms and is optionally substituted with 1-3 substituents selected from the group consisting of halogens, alkyls, alkenyls, alkynyls, hydroxyls, aminos, nitros, thiols, amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, fluoroalkyls, trifluoromethyl, and cyano;
• n is 0 or 1;
• the metal-containing catalyst is selected from the group consisting of Formula I and its enantiomer, Formula IIa and its enantiomer, Formula IIb and its enantiomer, Formula III and its enantiomer, and Formula IV and its enantiomer;
• Formula I is represented by:
• wherein
• R11 to R19 are independently selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, halogen, cyano, nitro and trifluoromethyl;
• X1 to X4 are independently selected from the group consisting of hydrogen, halogen and perhaloalkyl;
• L is absent or a Lewis base;
• M is copper;
• Formula IIa is represented by:
• wherein
• R20 is hydrogen, alkyl, aryl or heteroaryl;
• R21 is alkyl, aryl or heteroaryl;
• R22 is hydrogen, alkyl, aryl or heteroaryl;
• R23 is alkyl, aryl or heteroaryl;
• Y is O, S, CH2 or CH2CH2;
• Z is hydrogen or cyano;
• L is absent or a Lewis base;
• M is copper;
• Formula IIb is represented by:
• wherein
• A is aryl or heteroaryl;
• Y is O, S, CH2 or CH2CH2;
• Z is hydrogen or cyano;
• L is absent or a Lewis base;
• M is copper;
• Formula III is represented by:
• wherein
• R20 is hydrogen, alkyl, aryl or heteroaryl;
• R21 is alkyl, aryl or heteroaryl;
• R22 is hydrogen, alkyl, aryl or heteroaryl;
• R23 is alkyl, aryl or heteroaryl;
• R30 is alkyl or both R30 taken together are cycloalkyl;
• Y is O, S, CH2 or CH2CH2;
• L is a Lewis base;
• M is copper;
• Formula IV is represented by:
• wherein
• R24 is aryl or heteroaryl;
• R25 is aryl or heteroaryl;
• L is a Lewis base;
• and
• M is copper.