Reagents and methods for aliphatic carbon-hydrogen bond functionalization

A compound of Formula II:

• wherein,
• RX is an optionally substituted linear or branched C1-10 alkyl or optionally substituted C6-10 aryl;
• R1a, R1b and R1c are each independently selected from the group consisting of hydrogen, C2-C8 alkenyl, C2-C8 alkynyl, —C1-C3 alkyl-C1-C3 alkoxy-, C3-8 cycloalkyl, C6-10 aryl, C3-8 heteroaryl, C2-8 heterocyclyl, —C1-C3 alkyl-C3-8 cycloalkyl, —C1-C3 alkyl-C6-10 aryl, —C1-C3 alkyl-C3-8 heteroaryl, —C1-C3 alkyl-C2-8 heterocyclyl, linear or branched C1-6 alkyl, hydroxy-C1-C6-alkyl, —CN, and —C(═O)-Q-R10a, wherein,
• Q is O or is absent;
• R10a is hydrogen or C1-6 alkyl;
• and
• wherein, the cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl can each be independently optionally substituted;
• only one or two of R1a, R1b and R1c can be hydrogen;
• R2a and R2b are each independently selected from the group consisting of hydrogen, halo, optionally substituted linear or branched C1-10 alkyl, —CN, C1-6 alkoxy, —NO2, —NRaRb, —(C═O)ORc and —(C═O)Rc,
• wherein, Ra, Rb and Rc are each independently selected from the group consisting of hydrogen, methyl, ethyl, propyl and butyl.

A mixture comprising:

• a solvent;
• a compound of Formula I:
• wherein,
• RX is an optionally substituted linear or branched C1-10 alkyl or optionally substituted C6-10 aryl;
• R1a, R1b and R1c are each independently selected from the group consisting of hydrogen, C2-8 alkenyl, C2-8 alkynyl, —C1-C3 alkyl-C1-C3 alkoxy-, C3-8 cycloalkyl, C6-10 aryl, C3-8 heteroaryl, C2-8 heterocyclyl, —C1-C3 alkyl-C3-8 cycloalkyl, —C1-C3 alkyl-C6-10 aryl, —C1-C3 alkyl-C3-8 heteroaryl, —C1-C3 alkyl-C2-8 heterocyclyl, linear or branched C1-6 alkyl, hydroxy-C1-C6-alkyl, —CN, and —C(═O)-Q-R10a,
• wherein, Q is O or is absent;
• R10a is hydrogen or C1-6 alkyl;
• and
• wherein, the cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl can each be independently optionally substituted;
• and,
• R2 is a C6-10 aryl, wherein the aryl can be optionally substituted one to five times with a substituent selected from the group consisting of C1-6 alkyl, halo-C1-6 alkyl, halo, —CN, and —NO2
• and,
• at least one of the following:
• i. a compound of Formula T-A:
• wherein,
• R11 is selected from the group consisting of hydrogen, halo, halo-C1-6 alkyl, —CN, C1-6 alkyl and C1-6 alkoxy;
• f is 0 or 1;
• R10, when f is 1, is selected from the group consisting of halo-C1-6 alkyl, and optionally substituted C6-10 aryl;
• or
• R10, when f is 0, is selected from the group consisting of —CN and —N3;
• or,
• i(a) a compound of Formula T-A1:
• wherein,
• RT is selected from the group consisting of C1-6 alkyl and C6-10 aryl, wherein the C6-10 aryl is optionally substituted with R11;
• R11 is selected from the group consisting of hydrogen, phenyl, halo, —C(O)O—C1-6 alkyl, halo-C1-6 alkyl, —CN, C1-6 alkyl and C1-6 alkoxy;
• f is 0 or 1;
• R10 is a moiety that along with —(S)f— is an X moiety for transferring and binding to a carbon on a substrate;
• or,
• ii. an external trap selected from the group consisting of
• PhO2S—SCF3, PhO2S—SPh, PhO2S—N3, Cl3C—Cl, Cl3C—Br, F13C6—I, F17C8—Br, and F17C8—I.

A method of functionalizing a substrate, comprising:

• i. in the presence of a radical trap comprising a transfer group X and the substrate, wherein the substrate comprises a C—H bond, allowing a compound of Formula I:
• wherein,
• RX is an optionally substituted linear or branched C1-10 alkyl or optionally substituted C6-10 aryl;
• R1a, R1b and R1c are each independently selected from the group consisting of hydrogen, C2-C8 alkenyl, C2-C8 alkynyl, —C1-C3 alkyl-C1-C3 alkoxy-, C3-8 cycloalkyl, C6-10 aryl, C3-8 heteroaryl, C2-8 heterocyclyl, —C1-C3 alkyl-C3-8 cycloalkyl, —C1-C3 alky-C6-10 aryl, —C1-C3 alkyl-C3-8 heteroaryl, —C1-C3 alkyl-C2-8 heterocyclyl, linear or branched C1-6 alkyl, hydroxy-C1-C6-alkyl, —CN, and —C(═O)-Q-R10a,
• wherein, Q is O or is absent;
• R10a is hydrogen or C1-6 alkyl;
• and
• wherein, the cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl can each be independently optionally substituted;
• and,
• R2 is a C6-10 aryl, wherein the aryl can be optionally substituted one to five times with a substituent selected from the group consisting of C1-6 alkyl, halo-C1-6 alkyl, halo, —CN, and —NO2;
• to contact an initiator to form a nitrogen-centered radical;
• ii. allowing the substrate comprising a C—H bond to contact the nitrogen-centered radical to form a substrate radical;
• iii. allowing the substrate radical to contact the radical trap comprising a transfer group X,
• wherein, a C—H bond in the substrate is functionalized to a covalent C—X bond, wherein X is the transfer group;
• and,
• wherein the radical trap comprising a transfer group X is selected from the group consisting of:
• wherein X is selected from the group consisting of —S—C3-8 heteroaryl which can be optionally substituted, —C3-8 heteroaryl which can be optionally substituted, halogen, —S-halo-C1-6 alkyl, —S-Ph, —NO2, —CN, and

A method of functionalizing a substrate, comprising:

• i. in the presence of a radical trap comprising a transfer group X and the substrate, wherein the substrate comprises a C—H bond, allowing a compound of Formula II:
• wherein,
• RX is an optionally substituted linear or branched C1-10 alkyl or optionally substituted C6-10 aryl;
• R1a, R1b and R1c are each independently selected from the group consisting of hydrogen, C2-C8 alkenyl, C2-C8 alkynyl, —C1-C3 alkyl-C1-C3 alkoxy-, C3-8 cycloalkyl, C6-10 aryl, C3-8 heteroaryl, C2-8 heterocyclyl, —C1-C3 alkyl-C3-8 cycloalkyl, —C1-C3 alkyl-C6-10 aryl, —C1-C3 alkyl-C3-8 heteroaryl, —C1-C3 alkyl-C2-8 heterocyclyl, linear or branched C1-6 alkyl, hydroxy-C1-C6-alkyl —CN, and —C(═O)-Q-R10a, wherein,
• Q is O or is absent;
• R10a is hydrogen or C1-6 alkyl;
• and
• wherein, the cycloalkyl, aryl, heteroaryl, heterocyclyl and alkyl can each be independently optionally substituted;
• only one or two of R1a, R1b and R1c can be hydrogen;
• R2a and R2b are each independently selected from the group consisting of hydrogen, halo, optionally substituted linear or branched C1-10 alkyl, —CN, C1-6 alkoxy, —NO2, —NRaRb, —(C═O)ORc and —(C═O)Rc,
• wherein, Ra, Rb and Rc are each independently selected from the group consisting of hydrogen, methyl, ethyl, propyl and butyl
• to contact an initiator to form a nitrogen-centered radical;
• ii. allowing the substrate comprising a C—H bond to contact the nitrogen-centered radical to form a substrate radical;
• iii. allowing the substrate radical to contact the radical trap comprising a transfer group X,
• wherein, a C—H bond in the substrate is functionalized to a covalent C—X bond, wherein X is the transfer group;
• and,
• wherein the radical trap comprising a transfer group X is selected from the group consisting of:
• wherein X is selected from the group consisting of —S—C3-8 heteroaryl which can be optionally substituted, —C3-8 heteroaryl which can be optionally substituted, halogen, —S-halo-C1-6 alkyl, —S-Ph, —NO2, —CN, and