Herein,
we
reported
an
efficient
and
straightforward
desaturative
β-C(sp3)-H
sulfonylation
phosphonylation
of
cyclic
amines
driven
by
electrochemistry
using
catalytic
amounts
Cp2Fe
as
the
redox
mediator.
This
protocol
which
had
good
functional
group
compatibility,
provided
desired
enaminyl
sulfone
phosphine
oxide
products
with
high
chemo-
regio-selectivity
under
mild
conditions.
Preliminary
mechanistic
study
indicated
that
underwent
multiple
single-electron
oxidation
deprotonation
process,
then
was
captured
sulfonyl
radical
or
phosphonyl
to
deliver
products.
Accounts of Chemical Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
ConspectusAmines
are
frequent
structural
components
in
natural
products,
pharmaceuticals,
ligands,
and
catalysts,
making
their
synthesis
transformation
essential
to
organic
chemistry.
While
C-N
bond
formation
has
become
a
well-established
reliable
synthetic
strategy,
the
selective
cleavage
of
bonds
remains
relatively
underexplored.
This
challenge
arises
from
low
heterolytic
nucleofugality
nitrogen,
property
that
limits
practical
application
cleavage.
gap
underscores
significant
area
methodology
need
further
development.
In
this
context,
N
atom
deletion─defined
as
removal
nitrogen
via
cleavage,
while
preserving
integrity
remaining
framework─has
emerged
promising
approach
for
skeletal
editing.
Since
Levin's
landmark
2021
report,
deletion
gained
attention
its
potential
precisely
modify
molecular
skeletons.
Building
on
editing
concepts
advanced
by
Levin
Sarpong,
particularly
strategies
modifying
cyclic
frameworks,
we
recognized
critical
developing
mild
efficient
methods
enable
manipulation
systems.This
Account
summarizes
our
research
since
2017,
focusing
two
approaches
with
distinct
mechanisms:
rearrangement
sulfamoyl
azides
conversion
triazanium
intermediates.
Initially,
explored
optimized
thermal
derived
secondary
amines,
discovering
viable
strategy
deletion.
2024,
introduced
an
O-diphenylphosphinyl
hydroxylamine
(DPPH)-promoted
deletion,
involving
generation
novel
Both
polar
aliphatic
amines
into
nonpolar
scaffolds
applicable
both
linear
molecules
systems
varying
sizes.
The
DPPH-based
approach,
particular,
demonstrated
exceptional
effectiveness
sterically
hindered
substrates
reaction
conditions
no
anhydrous
or
oxygen-free
environments.
mechanisms
methods─both
isodiazene
radical
intermediates─were
elucidated
through
rigorous
experimental
investigation.
Additionally,
observed
rapid
hydro(deutero)deamination
products
when
primary
were
exposed
DPPH.Beyond
role
typical
crucial
approach.
Though
limitations,
it
transforms
challenging
task
constructing
C-C
more
manageable
sequence:
following
removal.
We
have
applied
hydrocarbon
cages,
pharmaceuticals.
hope
work
will
stimulate
interest
encourage
incorporation
methodologies,
thereby
expanding
utility
across
diverse
areas
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 24, 2024
Abstract
While
selective
defunctionalizations
are
valuable
in
organic
synthesis,
hydrodeamination
of
primary
amines
poses
challenges.
Deuterodeamination,
analogous
to
hydrodeamination,
presents
even
greater
difficulties
due
its
frequently
slower
deuteration
rate,
interference
by
hydrogenation
and
constraints
deuterated
sources.
This
study
introduces
a
reliable,
robust,
scalable
hydro-
deuterodeamination
method
capable
handling
various
amines.
Defined
mild
reaction
conditions,
rapid
completion,
simplified
purification
facilitated
water-soluble
byproducts,
the
leverages
deuterium
oxide
as
source
employs
commercialized
O-diphenylphosphinylhydroxylamine
for
deamination.
Applied
diverse
range
biologically
active
molecules,
it
has
consistently
achieved
high
yields
efficient
incorporation.
By
synergizing
with
site-selective
C–H
functionalization
aliphatic
amines,
our
reveals
synthetic
strategies
utilizing
nitrogen
atom
traceless
directing
group,
encompassing
deaminative
alkylation,
1,1-deuteroalkylation,
1,1-dialkylation,
1,1,1-deuterodialkylation,
arylation,
1,3-deuteroarylation.
Emphasizing
this
innovation,
processes
degree-controlled
have
been
developed.
Asian Journal of Organic Chemistry,
Год журнала:
2022,
Номер
12(2)
Опубликована: Окт. 19, 2022
Abstract
C−H
bond
functionalization
is
one
of
the
most
efficient
strategies
for
rapid
synthesis
cyclic
amines
containing
substituents
in
ring,
which
are
core
structures
many
bioactive
molecules.
However,
it
much
more
challenging
to
perform
this
strategy
on
remote
bonds
than
α
‐C−H
amines.
This
review
provides
a
comprehensive
overview
transition
metal‐free
methods
amines,
complementary
relying
metal
catalysis.
Selected
substrate
scope
and
discussion
reaction
mechanism
given
when
necessary.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(36)
Опубликована: Июль 18, 2023
Unprotected
cis-2,3-diarylpiperidines
are
synthesized
through
an
unprecedented
palladium-catalyzed
cross-coupling
reaction
between
aryl
halides
and
elusive
endocyclic
1-azaallyl
anions.
These
intermediates
generated
in
situ
by
the
deprotonation
of
2-aryl-1-piperideines,
precursors
that
readily
prepared
two
operations
from
simple
piperidines.
An
asymmetric
version
this
with
(2R,
3R)-iPr-BI-DIME
as
ligand
provides
products
moderate
to
good
yields
enantioselectivities.
This
study
significantly
expands
synthetic
utility
Synthesis,
Год журнала:
2023,
Номер
55(15), С. 2343 - 2352
Опубликована: Янв. 30, 2023
Abstract
Secondary
alicyclic
amines
are
converted
into
their
corresponding
ring-fused
imidazoles
in
a
simple
procedure
consisting
of
oxidative
imine
formation
followed
by
van
Leusen
reaction.
Amines
with
an
existing
α-substituent
undergo
regioselective
ring-fusion
at
the
α′-position.
This
method
was
utilized
synthesis
fadrozole.
The Journal of Organic Chemistry,
Год журнала:
2024,
Номер
89(12), С. 8896 - 8905
Опубликована: Июнь 10, 2024
Endocyclic
1-azaallyl
anions
engage
allyl
acetates
in
a
palladium-catalyzed
allylation
followed
by
reduction
to
give
unprotected
2-(hetero)aryl-3-allylpiperidines
and
2-allyl-3-arylmorpholines,
products
not
easily
accessible
other
means.
The
group
is
then
readily
transformed
into
variety
of
functional
groups.
Preliminary
studies
on
the
asymmetric
variant
reaction
using
an
enantiomerically
pure
BI-DIME-type
ligand
provide
product
with
moderate
enantioselectivity.
Computational
suggest
that
energy
barriers
inner-sphere
reductive
elimination
outer-sphere
nucleophilic
substitution
are
almost
same,
which
makes
both
them
possible
pathways.
In
addition,
mechanism
displays
enantiodiscriminating
C–C
bond
forming
step,
while
much
less
selective,
combined
Organic Letters,
Год журнала:
2024,
Номер
26(28), С. 5972 - 5977
Опубликована: Июль 5, 2024
Unprotected
alicyclic
amines
undergo
α-C-H
bond
phosphonylation
via
a
two-stage
one-pot
process
involving
the
oxidation
of
amine-derived
lithium
amides
with
simple
ketone
oxidants,
generating
transient
imines
which
are
then
captured
phosphites
or
phosphine
oxides.
Amines
an
existing
α-substituent
regioselective
α'-phosphonylation.
Amine
α-arylation
and
α'-phosphonylation
can
be
combined,
difunctionalized
product
in
single
operation.
