10.1002/anie.201901673
Angewandte Chemie International Edition
COMMUNICATION
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further explored in the synthesis of the anticonvulsant and
anesthetic agent MK-801. Starting from undecorated
hydrocarbon 18, intermolecular iodine-catalyzed amination with
either triflamide or tosylamide is directed to one of the methylene
positions providing diastereomeric mixtures for 19a and 19b.
Subsequent cyclization can be carried out under amidyl radical
conditions for the anti-isomer of 19a. Alternatively,
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of 19b providing 20b in an excellent 88% isolated yield. For the
case of tosylamide as nitrogen source, the immediate
conversion of 18 into 20 is realized as a tandem operation, thus
demonstrating the advanced possibilities of the radical-based C-
H amination platform under iodine(I/III) catalysis. MK-801 (21) is
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In summary, we have developed a unique iodine catalysis to
enable the selective intermolecular amination of aliphatic C-H
bonds, including the unexpected preference of secondary
methylene positions over tertiary methine groups and of more
hydridic C-H bonds over acidic ones. This work enables
conceptually new C-N bond formation and compliments
established nitrene chemistry. It streamlines the synthesis of
amines from both conventional feedstock and more elaborated
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9
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Keywords: amidyl radicals • C–H amination • homogeneous
catalysis • iodine catalysis • pharmaceutical synthesis
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