Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(20), С. 14278 - 14286
Опубликована: Май 10, 2024
The
development
of
catalysts
serves
as
the
cornerstone
innovation
in
synthesis,
exemplified
by
recent
discovery
photoenzymes.
However,
repertoire
naturally
occurring
enzymes
repurposed
direct
light
excitation
to
catalyze
new-to-nature
photobiotransformations
is
currently
limited
flavoproteins
and
keto-reductases.
Herein,
we
shed
on
imine
reductases
(IREDs)
that
remote
C(sp3)–C(sp3)
bond
formation,
providing
a
previously
elusive
radical
hydroalkylation
enamides
for
accessing
chiral
amines
(45
examples
with
up
99%
enantiomeric
excess).
Beyond
their
natural
function
catalyzing
two-electron
reductive
amination
reactions,
upon
visible-light
or
synergy
synthetic
photoredox
catalyst,
IREDs
are
tune
non-natural
photoinduced
single-electron
processes.
By
conducting
wet
mechanistic
experiments
computational
simulations,
unravel
how
engineered
intermediates
toward
productive
enantioselective
pathway.
This
work
represents
promising
paradigm
harnessing
nature's
asymmetric
transformations
remain
challenging
through
traditional
chemocatalytic
methods.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 2, 2025
Regiodivergent
asymmetric
synthesis
represents
a
transformative
strategy
for
the
efficient
generation
of
structurally
diverse
chiral
products
from
single
set
starting
materials,
significantly
enriching
their
enantiomeric
composition.
However,
design
radical-mediated
regiodivergent
and
enantioselective
reactions
that
can
accommodate
wide
range
functional
groups
substrates
has
posed
significant
challenges.
The
obstacles
primarily
lie
in
switching
regioselectivity
achieving
high
enantiodiscrimination,
especially
when
dealing
with
high-energy
intermediates.
To
address
these
issues,
we
have
developed
new
catalytic
system
integrates
photoinduced
hydrogen
atom
transfer
(HAT)
copper
catalysis,
involving
fine-tuning
ligands,
additives,
other
reaction
parameters.
facilitates
cross-couplings
between
N-aryl
glycine
ester/amide
derivatives
abundant
hydrocarbon
feedstocks
through
strong
C(sp3)–H
bond
activation.
This
approach
allows
controlled
stereoselective
formation
C(sp3)–C(sp3)
C(sp3)–N
bonds,
yielding
rich
variety
C-
or
N-alkylated
esters
amides
commendable
yields
(up
to
92%
yield),
exclusive
regioselectivities
(typically
>20:1
rr),
enantioselectivities
96%
ee).
Our
methodology
not
only
provides
promising
avenue
incorporation
alkyl
functionalities
onto
specific
sites
biologically
molecules
but
also
offers
practical
while
simultaneously
induction
within
photochemical
reactions.
Chemical Reviews,
Год журнала:
2023,
Номер
123(20), С. 11817 - 11893
Опубликована: Окт. 4, 2023
Enantioconvergent
catalysis
has
expanded
asymmetric
synthesis
to
new
methodologies
able
convert
racemic
compounds
into
a
single
enantiomer.
This
review
covers
recent
advances
in
transition-metal-catalyzed
transformations,
such
as
radical-based
cross-coupling
of
alkyl
electrophiles
with
nucleophiles
or
alkylmetals
and
reductive
two
mainly
under
Ni/bis(oxazoline)
catalysis.
C–H
functionalization
can
be
performed
an
enantioconvergent
manner.
Hydroalkylation
alkenes,
allenes,
acetylenes
is
alternative
reactions.
Hydrogen
autotransfer
been
applied
amination
alcohols
C–C
bond
forming
reactions
(Guerbet
reaction).
Other
metal-catalyzed
involve
addition
allylic
systems
carbonyl
compounds,
propargylation
phenols,
3-bromooxindoles,
allenylation
allenolates
propargyl
bromides,
hydroxylation
1,3-dicarbonyl
compounds.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 14, 2023
Selective
defluorinative
functionalization
of
trifluoromethyl
group
(-CF3)
is
an
attractive
synthetic
route
to
the
pharmaceutically
privileged
fluorine-containing
moiety.
Herein,
we
report
a
strategy
based
on
photoexcited
copper
catalysis
activate
C-F
bond
di-
or
trifluoromethylated
arenes
for
divergent
radical
C-N
coupling
with
carbazoles
and
aromatic
amines.
The
use
different
ligands
can
tune
reaction
products
diversity.
A
range
substituted,
structurally
diverse
α,α-difluoromethylamines
be
obtained
from
via
carbazoles,
while
interesting
double
ready
difluoromethylated
arenes.
Based
this
success,
carbazole-centered
PNP
ligand
designed
optimal
ligand,
enabling
copper-catalyzed
construction
imidoyl
fluorides
amines
through
functionalization.
Interestingly,
1,2-difluoroalkylamination
styrenes
also
developed,
delivering
γ,γ-difluoroalkylamines,
bioisostere
β-aminoketones,
in
synthetically
useful
yields.
DFT
studies
reveal
inner-sphere
electron
transfer
mechanism
Cu-catalyzed
selective
activation
C(sp3)-F
bonds.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(27), С. 14686 - 14696
Опубликована: Июль 1, 2023
The
enantioconvergent
C(sp3)-N
cross-coupling
of
racemic
alkyl
halides
with
(hetero)aromatic
amines
represents
an
ideal
means
to
afford
enantioenriched
N-alkyl
yet
has
remained
unexplored
due
the
catalyst
poisoning
specifically
for
strong-coordinating
heteroaromatic
amines.
Here,
we
demonstrate
a
copper-catalyzed
radical
activated
under
ambient
conditions.
key
success
is
judicious
selection
appropriate
multidentate
anionic
ligands
through
readily
fine-tuning
both
electronic
and
steric
properties
formation
stable
rigid
chelating
Cu
complex.
Thus,
this
kind
ligand
could
not
only
enhance
reducing
capability
copper
provide
pathway
but
also
avoid
coordination
other
coordinating
heteroatoms,
thereby
overcoming
and/or
chiral
displacement.
This
protocol
covers
wide
range
coupling
partners
(89
examples
secondary/tertiary
bromides/chlorides
amines)
high
functional
group
compatibility.
When
allied
follow-up
transformations,
it
provides
highly
flexible
platform
access
synthetically
useful
amine
building
blocks.
