Described herein are studies toward the core modification
of cyclic
aliphatic amines using either a riboflavin/photo-irradiation approach
or Cu(I) and Ag(I) to mediate the process. Structural remodeling of
cyclic amines is explored through oxidative C–N and C–C
bond cleavage using peroxydisulfate (persulfate) as an oxidant. Ring-opening
reactions to access linear aldehydes or carboxylic acids with flavin-derived
photocatalysis or Cu salts, respectively, are demonstrated. A complementary
ring-opening process mediated by Ag(I) facilitates decarboxylative
Csp3–Csp2coupling in Minisci-type reactions
through a key alkyl radical intermediate. Heterocycle interconversion
is demonstrated through the transformation of N-acyl cyclic amines
to oxazines using Cu(II) oxidation of the alkyl radical. These transformations
are investigated by computation to inform the proposed mechanistic
pathways. Computational studies indicate that persulfate mediates
oxidation of cyclic amines with concomitant reduction of riboflavin.
Persulfate is subsequently reduced by formal hydride transfer from
the reduced riboflavin catalyst. Oxidation of the cyclic aliphatic
amines with a Cu(I) salt is proposed to be initiated by homolysis
of the peroxy bond of persulfate followed by α-HAT from the
cyclic amine and radical recombination to form an α-sulfate
adduct, which is hydrolyzed to the hemiaminal. Investigation of the
pathway to form oxazines indicates a kinetic preference for cyclization
over more typical elimination pathways to form olefins through Cu(II)
oxidation of alkyl radicals.