ACS Catalysis,
Journal Year:
2021,
Volume and Issue:
11(21), P. 13355 - 13362
Published: Oct. 19, 2021
In
this
context,
we
report
the
successful
application
of
a
cross-electrophile
strategy
in
synthesis
multisubstituted
allenes.
Under
catalysis
nickel,
reductive
cross-coupling
between
propargyl
carbonates
and
organoiodides
provides
an
entry
to
prepare
tri-
or
tetrasubstituted
allenes
without
employing
any
pregenerated
organometallics.
Furthermore,
also
prove
be
suitable
allenylating
agents
nickel-catalyzed
asymmetric
aryl-allenylation
aryl-iodide-tethered
unactivated
alkenes,
furnishing
variety
chiral
benzene-fused
cyclic
compounds
bearing
quaternary
allenyl-substituted
stereogenic
center
highly
enantioselective
manner.
Accounts of Chemical Research,
Journal Year:
2023,
Volume and Issue:
56(5), P. 515 - 535
Published: Jan. 23, 2023
ConspectusThe
use
of
quaternary
stereocenters
during
lead
candidate
optimization
continues
to
grow
because
improved
physiochemical
and
pharmacokinetic
profiles
compounds
with
higher
sp3
fraction.
Pd-catalyzed
redox-neutral
alkene
difunctionalization
involving
carbopalladation
alkenes
followed
by
nucleophilic-trapping
σ-alkyl-palladium
intermediates
has
been
developed
as
an
efficient
method
construct
stereocenters.
However,
the
low
chemoselectivity
air
sensitivity
organometallic
nucleophiles,
well
their
availability
accessibility,
limit
scope
application
this
elegant
strategy.
Recently,
Ni-catalyzed
reductive
cross-coupling
evolved
into
a
privileged
strategy
easily
valuable
C(sp3)-C
bonds.
Despite
great
progress,
enantioselective
coupling
C(sp3)
electrophiles
still
relies
on
activated
or
functionalized
alkyl
precursors,
which
are
often
unstable
require
multiple
steps
prepare.
Therefore,
via
selective
cyclization/cross-coupling
was
developed.
This
not
only
offers
robust
practical
alternative
for
traditional
but
also
provides
strategic
complementarity
electrophiles.
In
Account,
we
summarize
latest
results
from
our
laboratory
topic.
These
findings
mainly
include
explorations
in
modulating
enantioselectivity
cyclization
mode
cyclization/cross-couplings.We
will
first
discuss
chiral
heterocycles
focus
effects
ligands,
reductants,
additives
roles
cross-coupling.
A
wide
range
have
explored,
including
aryl
halides,
vinyl
alkynyl
gem-difluoroalkenes,
CO2,
trifluoromethyl
alkenes,
cyano
The
synthetic
potential
approach
demonstrated
synthesis
biologically
active
natural
products
drug
molecules.
Second,
detail
how
tune
steric
nickel
catalysts
modifying
bipyridine
ligands
regiodivergent
cyclization/cross-couplings.
Specifically,
bidentate
favors
exo-selective
cyclization/cross-coupling,
while
carboxylic
acid-modified
ligand
permits
endo-selective
cyclization/cross-coupling.
We
show
activate
amide
substrate
altering
electronic
properties
substituents
nitrogen,
thereby
enabling
nucleophilic
addition
halides
carbonyls.
Further
investigation
led
tunable
cyclization/cross-couplings
(addition
carbonyl
vs
7-endo-cyclization)
divergent
pharmacologically
important
2-benzazepine
frameworks.
Finally,
serendipitously
discover
that
changing
oxidation
state
can
control
migratory
aptitude
different
groups,
thus
providing
switchable
skeletal
rearrangement
transformation
is
high
value
it
represents
conceptually
unprecedented
new
C-C
bond
activation.
Thus,
Account
summarizes
methods
allow
formation
using
variety
insight
relationship
between
structure,
substrate,
selectivity.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Feb. 17, 2024
Abstract
Transition
metal-catalyzed
reductive
difunctionalization
of
alkenes
with
alkyl
halides
is
a
powerful
method
for
upgrading
commodity
chemicals
into
densely
functionalized
molecules.
However,
super
stoichiometric
amounts
metal
reductant
and
the
requirement
installing
directing
group
to
suppress
inherent
β-H
elimination
bring
great
limitations
this
type
reaction.
We
demonstrate
herein
that
two
different
accessible
via
radical-anion
relay
Na
2
S
O
4
as
both
sulfone-source.
The
together
electron-shuttle
catalyst
crucial
divert
mechanistic
pathway
toward
formation
sulfone
anion
instead
previously
reported
alkylmetal
intermediates.
Mechanistic
studies
allow
identification
carbon-centered
radical
sulfur-centered
radical,
which
are
in
equilibrium
capture
or
extrusion
SO
could
be
converted
accelerated
by
iron
catalysis,
leading
observed
high
chemoselectivity.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 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.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(31)
Published: May 25, 2022
Regiodivergent
alkene
functionalization
that
produces
either
regioisomer
starting
from
the
same
raw
materials
is
desirable.
Herein,
we
report
a
nickel-catalyzed
switchable
site-selective
hydroalkylation.
The
selection
of
reaction
temperatures
leads
to
protocols
provide
regiodivergent
hydroalkylated
products
single
substrate.
This
protocol
allows
convenient
synthesis
α-
and
β-branched
protected
amines,
both
which
are
important
fields
pharmaceutical
chemistry
biochemistry.
In
addition,
enantioenriched
alkylamines
can
be
accessed
in
catalytic
asymmetric
variant.
Preliminary
mechanistic
studies
indicate
formation
more
stable
nickelacycle
provides
driving
force
migration.
thermodynamic
kinetic
properties
different
reduction
elimination
intermediates
responsible
for
site-selectivity.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(26), P. 11626 - 11637
Published: May 23, 2022
Skeletal
rearrangement
that
changes
the
connectivity
of
molecule
via
cleavage
and
reorganization
carbon–carbon
bonds
is
a
fundamental
powerful
strategy
in
complex
molecular
assembly.
Because
lack
effective
methods
to
control
migratory
tendency
different
groups,
achieving
switchable
selectivity
skeletal
has
been
long-standing
quest.
Metal-based
dyotropic
provides
unique
opportunity
address
this
challenge.
However,
remains
unexplored.
Herein,
we
show
such
problem
could
be
solved
by
modifying
ligands
on
metal
catalyst
changing
oxidation
states
aptitude
thereby
providing
ligand-controlled,
strategy.
Experimental
density
functional
theory
calculation
studies
prove
rational
design.
The
occurs
only
when
nickel(II)
intermediate
reduced
more
nucleophilic
nickel(I)
species,
sterically
hindered
iPrPDI
ligand
facilitates
1,2-aryl/Ni
rearrangement,
while
terpyridine
promotes
1,2-acyl/Ni
rearrangement.
This
method
allows
site-selective
activation
C–C
applied
for
divergent
synthesis
four
medicinally
relevant
fluorine-containing
scaffolds
from
same
starting
material.
ACS Catalysis,
Journal Year:
2022,
Volume and Issue:
12(11), P. 6495 - 6505
Published: May 17, 2022
Controlling
the
selectivity
of
synthetically
useful
reactions
has
been
a
longstanding
objective
organic
chemistry.
We
report
regiodivergent
synthetic
protocol
allowing
access
to
diverse
fluorinated
1,5-dienes
through
Pd/NHC-catalyzed
ring-opening
allylation
gem-difluorocyclopropanes.
Density
functional
theory
(DFT)
calculations
on
regioselectivity-determining
transition
states
provided
critical
insight
into
design
NHC
ligand
for
switching
regioselectivity.
Consistent
with
DFT
predictions,
N-heterocyclic
carbene
(NHC)
ligands
bulky
ortho
substituents
favored
branched
allylation,
IHept
providing
>
20:1
branched/linear
less
hindered
such
as
IMes
thermodynamically
more
stable
linear
products.
were
able
carry
out
late-stage
modification
various
complex
molecules
using
this
protocol.
Our
ligand-controlled
approach
provides
efficient
regioisomeric
from
same
starting
materials
and
constitutes
valuable
addition
toolbox
diversity-oriented
synthesis.
ACS Catalysis,
Journal Year:
2022,
Volume and Issue:
12(16), P. 10207 - 10221
Published: Aug. 5, 2022
Catalytic
1,4-dicarbofunctionalization
of
1,3-enynes
is
a
powerful
strategy
for
the
synthesis
polysubstituted
allenes.
Despite
impressive
progress,
such
still
restricted
to
use
alkyl-metallic
reagents
or
pre-activated
radical
precursors,
thus
limiting
its
functional
group
compatibility
and
atom
economy.
Herein,
we
report
that
through
combination
decatungstate
photo-hydrogen
transfer
nickel
catalysis,
three-component
2-trifluoromethyl-1,3-enynes
achieved.
This
allows
modular
tetrasubstituted
CF3-allenes
under
exceptionally
mild
conditions.
A
variety
electrophiles
as
aryl
bromides,
alkenyl
acyl
chlorides,
alkynyl
bromides
were
successfully
employed
traps
lead
desired
products.
Another
significant
advantage
most
abundant
hydrocarbons
are
used
feedstocks,
wide
range
synthetically
versatile
groups
complex
drug-like
structures
can
be
easily
incorporated.
Based
on
experimental
density
theories,
possible
catalytic
cycle
involving
1,3-nickel
rearrangement
proposed.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Sept. 21, 2022
Despite
paramount
applications
of
chiral
trifluoromethylated
compounds
in
medicinal
chemistry
and
materials
science,
limited
strategies
have
been
developed
for
catalytic
asymmetric
synthesis
such
valuable
fluorinated
structures.
Here,
we
report
a
nickel
catalyzed
enantioselective
dicarbofunctionalization
inexpensive
industrial
chemical
3,3,3-trifluoropropene
(TFP)
with
readily
available
tertiary
alkyl
aryl
iodides.
The
reaction
overcomes
the
β-F
elimination
side
TFP,
proceeds
efficiently
under
mild
conditions.
protocol
possesses
advantages,
as
synthetic
convenience,
high
enantioselectivity,
excellent
functional
group
tolerance,
providing
rapid
straightforward
access
to
interest.
Journal of the American Chemical Society,
Journal Year:
2022,
Volume and Issue:
144(11), P. 4776 - 4782
Published: March 9, 2022
An
enantioselective
nickel-catalyzed
intramolecular
reductive
cross-coupling
of
C(sp2)
electrophiles
and
cyano
groups
is
reported.
Enantioenriched
CN-containing
all-carbon
quaternary
stereocenters
are
assembled
by
desymmetrizing
cyclization
aryl/alkenyl
halide-tethered
malononitriles.
The
use
an
organic
reductant,
(EtO)2MeSiH,
crucial
to
the
enantioselectivity
reactivity.
Applications
method
demonstrated
through
synthesis
bioactive
molecules
their
cyanated
analogues
total
natural
product
diomuscinone.
This
study
exhibits
potential
coupling
strategies
access
structurally
rigid
synthetically
versatile
from
readily
available
starting
materials.
Angewandte Chemie International Edition,
Journal Year:
2022,
Volume and Issue:
61(46)
Published: Sept. 23, 2022
Abstract
The
introduction
of
fluorine‐containing
groups
into
organic
molecules
can
significantly
affect
their
physical
and
chemical
properties
has
long
been
used
as
an
effective
strategy
for
drug
discovery
development.
Consequently,
the
development
catalytic
asymmetric
methods
synthesis
heterocycles
is
highly
desirable
sought
after.
Herein,
we
describe
a
nickel‐catalyzed
defluorinative
cyclization
fluoroalkyl‐substituted
1,6‐enynes,
providing
expedient
access
to
synthetically
attractive
4‐fluorovinyl‐substituted
2‐pyrrolidones
in
good
yields
with
remarkable
high
levels
chemo‐,
regio‐,
enantioselectivities
(90–99
%
ee,>35
examples).
This
protocol
features
readily
available
starting
materials
excellent
functional
group
compatibility,
exhibits
complementary
regioselectivity.
utility
this
was
demonstrated
enantioselective
antiepileptic
Seletracetam.