Carbon dioxide as a directing group for C—H functionalization reactions involving Lewis basic amines, alcohols, thiols, and phosphines for the synthesis of compounds
AssigneeThe University of Toledo
InventorsMichael C. Young, Mohit Kapoor
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Abstract
Methods of synthesizing compounds using CO2 as a directing group for C—H functionalization, and compounds made thereby, are described.
Claims19
A method of functionalizing a C—H bond, the method comprising using CO2 as a directing group to convert a C—H bond in a substrate compound into a C—C bond by reacting the substrate compound with an aryl halide in the presence of a transition metal catalyst and CO2 as a gas or a solid, wherein the substrate compound comprises a primary or secondary amine functional group and the C—H bond is in a gamma position relative to the amine functional group.
A method of synthesizing a compound, the method comprising:
- reacting a substrate having a primary or secondary amine functional group with a reactant in the presence of CO2 as a gas or a solid and a transition metal catalyst to produce a compound,
- wherein the substrate is functionalized at a γ-C—H position relative to the primary or secondary amine functional group to produce the compound, and
- wherein the reactant is an aryl halide.
A method of functionalizing a C—H bond, the method comprising using CO2 as a directing group to convert a C—H bond in a substrate compound into a C—C bond in the presence of a transition metal catalyst, wherein the substrate compound comprises a primary or secondary amine functional group, and the substrate compound is functionalized at a gamma C—H position relative to the primary or secondary amine functional group,
- wherein the substrate compound is selected from the group consisting of:
- 1-ethylcyclopentan-1-amine (S-1), 1-ethylcyclohexan-1-amine (S-2), 1-ethylcycloheptan-1-amine (S-3), 4-(tert-butyl)-1-ethylcyclohexan-1-amine (S-4), 9-ethyl-9H-fluoren-9-amine (S-5), 3-methylheptan-3-amine (S-6), 3-methylnon-3-amine (S-7), 3-methylpentan-3-amine (S-8), 3-ethylpentan-3-amine (S-9), heptan-3-amine (S-10), N-(tert-pentyl)propan-1-amine (S-12), N-(tert-pentyl)butan-1-amine (S-13), N-(tert-pentyl)pentan-1-amine (S-14), 2-methyl-N-phenethylbutan-2-amine (S-15), N-benzyl-2-methylbutan-2-amine (S-16), N-(4-methoxybenzyl)-2-methylbutan-2-amine (S-17), N-(3-methoxybenzyl)-2-methylbutan-2-amine (S-18), N-(4-tolyl)-2-methylbutan-2-amine (S-19), N-(3-tolyl)-2-methylbutan-2-amine (S-20), N-propylpentan-2-amine (S-22), and 6-ethyl-3,3,9,9-tetraisopropyl-2,10-dimethyl-4,8-dioxa-3,9-disilaundecan-6-amine (S-11).
A method of synthesizing a compound, the method comprising:
- reacting a substrate having a primary or secondary amine functional group with a reactant in the presence of CO2 and a transition metal catalyst to produce a compound, wherein the substrate is functionalized at a γ-C—H position relative to the amine functional group to produce the compound, and
- wherein the compound is a γ-arylated primary amine or a γ-arylated secondary amine selected from the group consisting of:
- 2-methyl-4-phenylbutan-2-amine (1a), 4-(3-fluorophenyl)-2-methylbutan-2-amine (1b), 4-(4-fluorophenyl)-2-methylbutan-2-amine (1c), 2-methyl-4-[3-(trifluoromethyl)phenyl]butan-2-amine (1d), 2-methyl-4-[4-(trifluoromethyl)phenyl]butan-2-amine (1e), ethyl 2-(3-amino-3-methylbutyl)benzoate (1f), ethyl 3-(3-amino-3-methylbutyl)benzoate (1g), ethyl 4-(3-amino-3-methylbutyl)benzoate (1h), 2-methyl-4-(3-nitrophenyl)butan-2-amine (1i), 2-methyl-4-(4-nitrophenyl)butan-2-amine (1j), 4-[3,5-bis(trifluoromethyl)phenyl]-2-methylbutan-2-amine (1k), dimethyl 5-(3-amino-3-methylbutyl)isophthalate (1l), 4-(3-chloro-4-fluorophenyl)-2-methylbutan-2-amine (1m), 4-(4-bromophenyl)-2-methylbutan-2-amine (1n), 4-(4-iodophenyl)-2-methylbutan-2-amine (1o), 7-(3-amino-3-methylbutyl)-3,4-diphenyl-1H-isochromen-1-one (1p), 2-methyl-4-(N-tosyl-1H-indol-5-yl)butan-2-amine (1q), 4-(3-methoxyphenyl)-2-methylbutan-2-amine (1r), 4-(4-methoxyphenyl)-2-methylbutan-2-amine (1s), 4-(4-ethoxyphenyl)-2-methylbutan-2-amine (1t), 4-(4-benzyloxyphenyl)-2-methylbutan-2-amine (1u), 2-methyl-4-(m-tolyl)butan-2-amine (1v), 2-methyl-4-(p-tolyl)butan-2-amine (1w), 4-(1,1′-biphenyl-4-yl)-2-methylbutan-2-amine (1x), 2-methyl-4-(naphthalen-1-yl)butan-2-amine (1y), 4-(2-fluorophenyl)-2-methylbutan-2-amine (1z), 2-(3-amino-3-methylbutyl)phenol (1aa), 4-(2-methoxyphenyl)-2-methylbutan-2-amine (1ab), 4,4′-(1,4-phenylene)bis(2-methylbutan-2-amine) (1ac), 1-phenethylcyclopentanamine (2a), 1-phenethylcyclohexanamine (2b), 1-phenethylcycloheptanamine (2c), 4-(tert-butyl)-1-phenethylcyclohexanamine (2d), 9-phenethyl-9H-fluoren-9-amine (2e), 3-methyl-1-phenylheptan-3-amine (2f), 3-methyl-1-phenylnonan-3-amine (2g), 2-amino-2-phenethylpropane-1,3-diol (2h), 3-methyl-1-phenylpentan-3-amine (2i-mono), 3-methyl-1,5-diphenylpentan-3-amine (2i-di), 3-ethyl-1-phenylpentan-3-amine (2j-mono), 3-ethyl-1,5-diphenylpentan-3-amine (2j-di), 4-(1,1′-biphenyl-4-yl)butan-2-amine (2k), 1-(1,1′-biphenyl-4-yl)pentan-3-amine (21), 1-(1,1′-biphenyl-4-yl)heptan-3-amine (2m), 4-(1,1′-biphenyl-4-yl)-3,3-dimethylbutan-2-amine (2n), 4-(1,1′-biphenyl-4-yl)-2-methyl-N-propylbutan-2-amine (3a), N-[4-(1,1′-biphenyl-4-yl)-2-methylbutan-2-yl]butan-1-amine (3b), N-[4-(1,1′-biphenyl-4-yl)-2-methylbutan-2-yl]pentan-1-amine (3c), 2-methyl-N-phenethyl-4-phenylbutan-2-amine (3d), N-benzyl-2-methyl-4-phenylbutan-2-amine (3e), N-(4-methoxybenzyl)-2-methyl-4-phenylbutan-2-amine (3f), N-(3-methoxybenzyl)-2-methyl-4-phenylbutan-2-amine (3g), 2-methyl-N-(4-methylbenzyl)-4-phenylbutan-2-amine (3h), 2-methyl-N-(3-methylbenzyl)-4-phenylbutan-2-amine (3i), 2-methyl-N-(naphthalen-2-ylmethyl)-4-phenylbutan-2-amine (3j), ethyl 4-(3-(benzylamino)-3-methylbutyl)benzoate (3k), and 1-(1,1′-biphenyl-4-yl)-N-propylpentan-3-amine (3l).
Dependencies are inferred from the claim text.