Cyclic secondary amines and 2-hydroxybenzaldehydes
or related ketones
react to furnish benzo[e][1,3]oxazine structures
in generally good yields. This overall redox-neutral amine α-C–H
functionalization features a combined reductive N-alkylation/oxidative
α-functionalization and is catalyzed by acetic acid. In contrast
to previous reports, no external oxidants or metal catalysts are required.
Reactions performed under modified conditions lead to an apparent
reductive amination and the formation of o-hydroxybenzylamines
in a process that involves the oxidation of a second equivalent of
amine. A detailed computational study employing density functional
theory compares different mechanistic pathways and is used to explain
the observed experimental findings. Furthermore, these results also
reveal the origin of the catalytic efficiency of acetic acid in these
transformations.
Caged neurotransmitters, in combination with focused light beams, enable precise interrogation of neuronal function, even at the level of single synapses. However, most caged transmitters are, surprisingly, severe antagonists of ionotropic gamma-aminobutyric acid (GABA) receptors. By conjugation of a large, neutral dendrimer to a caged GABA probe we introduce a “cloaking” technology that effectively reduces such antagonism to very low levels. Such cloaked caged compounds will enable the study of the signaling of the inhibitory neurotransmitter GABA in its natural state using two-photon uncaging microscopy for the first time.
We have performed a combined computational and experimental study to elucidate the mechanism of a metal-free α-amination of secondary amines. Calculations predicted azaquinone methides and azomethine ylides as the reactive intermediates and showed that iminium ions are unlikely to participate in these transformations. These results were confirmed by experimental deuterium labeling studies and the successful trapping of the postulated azomethine ylide and azaquinone methide intermediates. In addition, computed barrier heights for the rate-limiting step correlate qualitatively with experimental findings.
Secondary amines react with thiosalicylaldehydes
in the presence
of catalytic amounts of acetic acid to generate ring-fused N,S-acetals in redox-neutral fashion. A
broad range of amines undergo α-sulfenylation, including challenging
substrates such morpholine, thiomorpholine, and piperazines. Computational
studies employing density functional theory indicate that acetic acid
reduces the energy barriers of two separate steps, both of which involve
proton transfer.
SummaryCopper(II) acetate/acetic acid/O2 and potassium iodide/tert-butylhydroperoxide systems are shown to affect the selective oxidation of ring-fused aminals to dihydroquinazolines and quinazolinones, respectively. These methods enable the facile preparation of a number of quinazoline alkaloid natural products and their analogues.
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