The development of intermolecular alkene aminopyridylation has great potential for quickly increasing molecular complexity with two valuable groups. Here we report a strategy for the photocatalytic aminopyridylation of alkenes using a variety of N-aminopyridinium salts as both aminating and pyridylating reagents. Using Eosin Y as a photocatalyst, amino and pyridyl groups are simultaneously incorporated into alkenes, affording synthetically useful aminoethyl pyridine derivatives under mild reaction conditions. Remarkably, the C4-regioselectivity in radical trapping with N-aminopyridinium salt can be controlled by electrostatic interaction between the pyridinium nitrogen and sulfonyl group of β-amino radical. This transformation is characterized by a broad substrate scope, good functional group compatibility, and the utility of this transformation was further demonstrated by late-stage functionalization of complex biorelevant molecules. Combining experiments and DFT calculations on the mechanism of the reaction is investigated to propose a complete mechanism and regioselectivity.
By
utilizing an underexplored reactivity mode of N-aminopyridinium
ylides, we developed the visible-light-induced ortho-selective aminopyridylation of alkenes via radical-mediated
1,3-dipolar cycloaddition. The photocatalyzed single-electron oxidation
of N-aminopyridinium ylides generates the corresponding
radical cations that enable previously inaccessible 1,3-cycloaddition
with a broader range of alkene substrates. The resulting cycloaddition
adducts rapidly undergo subsequent homolytic cleavage of the N–N
bond, conferring a substantial thermodynamic driving force to yield
various β-aminoethylpyridines. Remarkably, amino and pyridyl
groups can be installed into both activated and unactivated alkenes
with modular control of ortho-selectivity and 1,2-syn-diastereoselectivity under metal-free and mild conditions.
Combined experimental and computational studies are conducted to clarify
the detailed reaction mechanism and the origins of site selectivity
and diastereoselectivity.
A strategy for visible-light-induced
site-selective C–H
acylation of pyridinium salts was developed by employing N-methoxy- or N-aminopyridinium salts, offering a
powerful synthetic tool for accessing highly valuable C2- and C4-acylated
pyridines. The methoxy or amidyl radicals photocatalytically generated
from the pyridinium salts can undergo hydrogen atom abstraction from
readily available aldehydes to form acyl radicals, which can engage
in addition to pyridinium substrates. Remarkably, the use of N-methoxypyridinium salts preferentially gives the C2-acylated
pyridines, and the site selectivity can be switched from C2 to C4
by using N-aminopyridinium salts. The utility of
this transformation was further demonstrated by the late-stage functionalization
of complex biorelevant molecules and by application of acyl radicals
to photocatalytic radical cascades.
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