Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(28)
Опубликована: Май 1, 2024
Abstract
The
tert
‐butyl
group
is
a
common
aliphatic
motif
extensively
employed
to
implement
steric
congestion
and
conformational
rigidity
in
organic
organometallic
molecules.
Because
of
the
combination
high
bond
dissociation
energy
(~100
kcal
mol
−1
)
limited
accessibility,
absence
directing
groups,
neither
radical
nor
approaches
are
effective
for
chemical
modification
C−H
bonds.
Herein
we
overcome
these
limits
by
employing
highly
electrophilic
manganese
catalyst,
[Mn(
CF3
bpeb)(OTf)
2
],
that
operates
strong
hydrogen
donor
solvent
nonafluoro‐
alcohol
(NFTBA)
catalytically
activates
peroxide
generate
powerful
manganese‐oxo
species
effectively
oxidizes
Leveraging
on
interplay
steric,
electronic,
medium
torsional
effects,
site‐selective
product
chemoselective
hydroxylation
accomplished
with
broad
reaction
scope,
delivering
primary
alcohols
as
largely
dominant
products
preparative
yields.
Late‐stage
at
sites
demonstrated
6
densely
functionalized
molecules
pharmaceutical
interest.
This
work
uncovers
novel
disconnection
approach,
harnessing
potential
functional
strategic
synthetic
planning
complex
molecular
architectures.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(29), С. 15742 - 15753
Опубликована: Июль 11, 2023
Enantioselective
C–H
oxidation
is
a
standing
chemical
challenge
foreseen
as
powerful
tool
to
transform
readily
available
organic
molecules
into
precious
oxygenated
building
blocks.
Here,
we
describe
catalytic
enantioselective
hydroxylation
of
tertiary
bonds
in
cyclohexane
scaffolds
with
H2O2,
an
evolved
manganese
catalyst
that
provides
structural
complementary
the
substrate
similarly
lock-and-key
recognition
operating
enzymatic
active
sites.
Theoretical
calculations
unveil
enantioselectivity
governed
by
precise
fitting
scaffold
site,
through
network
weak
non-covalent
interactions.
Stereoretentive
C(sp3)–H
results
single-step
generation
multiple
stereogenic
centers
(up
4)
can
be
orthogonally
manipulated
conventional
methods
providing
rapid
access,
from
single
precursor
variety
chiral
scaffolds.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(17), С. 11726 - 11739
Опубликована: Апрель 18, 2024
Lysine
dioxygenase
(KDO)
is
an
important
enzyme
in
human
physiology
involved
bioprocesses
that
trigger
collagen
cross-linking
and
blood
pressure
control.
There
are
several
KDOs
nature;
however,
little
known
about
the
factors
govern
regio-
stereoselectivity
of
these
enzymes.
To
understand
how
can
selectively
hydroxylate
their
substrate,
we
did
a
comprehensive
computational
study
into
mechanisms
features
4-lysine
dioxygenase.
In
particular,
selected
snapshot
from
MD
simulation
on
KDO5
created
large
QM
cluster
models
(A,
B,
C)
containing
297,
312,
407
atoms,
respectively.
The
largest
model
predicts
regioselectivity
matches
experimental
observation
with
rate-determining
hydrogen
atom
abstraction
C4–H
position,
followed
by
fast
OH
rebound
to
form
4-hydroxylysine
products.
calculations
show
C,
dipole
moment
positioned
along
bond
substrate
and,
therefore,
electrostatic
electric
field
perturbations
protein
assist
creating
hydroxylation
selectivity.
Furthermore,
active
site
Tyr233
residue
identified
reacts
through
proton-coupled
electron
transfer
akin
axial
Trp
cytochrome
c
peroxidase.
Thus,
upon
formation
iron(IV)-oxo
species
catalytic
cycle,
phenol
loses
proton
nearby
Asp179
residue,
while
at
same
time,
transferred
iron
create
iron(III)-oxo
species.
This
charged
tyrosyl
directs
guides
selectivity
C4-hydroxylation
substrate.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(26)
Опубликована: Апрель 19, 2024
Abstract
Reductive
amination
of
carbonyl
compounds
and
nitro
represents
a
straightforward
way
to
attain
imines
or
secondary
amines,
but
it
is
difficult
control
the
product
selectivity.
Herein,
we
report
selective
formation
C−N
C=N
bond
readily
manipulated
through
solvent‐induced
hydrogen
bridge,
facilitating
swift
photocatalytic
reductive
coupling
process.
The
reductive‐coupling
with
using
formic
acid
sodium
formate
as
donors
over
CdS
nanosheets
selectively
generates
bonds
in
acetonitrile
solvent;
while
taking
methanol
solvent,
are
hydrogenated
via
hydrogen‐bonding
activation.
Experimental
theoretical
study
reveals
that
building
hydrogen‐bond
bridge
between
hydroxyl
groups
N
atoms
motifs
facilitates
transfer
from
surface
upon
illumination,
resulting
rapid
hydrogenation
give
rise
amines
bonds.
Our
method
provides
simple
selectivity
by
altering
solvents
organic
transformations.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 29, 2025
Due
to
their
strong
aromaticity
and
difficulties
in
chemo-,
regio-,
enantioselectivity
control,
asymmetric
hydrogenation
of
naphthol
derivatives
1,2,3,4-tetrahydronaphthols
has
remained
a
long-standing
challenge.
Herein,
we
report
the
first
example
homogeneous
catalyzed
by
tethered
rhodium-diamine
catalysts,
affording
wide
array
optically
pure
high
yields
with
excellent
enantioselectivities
(up
98%
yield
>99%
ee).
Mechanistic
studies
experimental
computational
approaches
reveal
that
fluorinated
solvent
1,1,1,3,3,3-hexafluoroisopropanol
(HFIP)
plays
vital
roles
control
reactivity
selectivity,
1-naphthol
is
reduced
via
cascade
reaction
pathway,
including
dearomative
tautomerization,
1,4-hydride
addition,
1,2-hydride
addition
sequence.
A
novel
synergistic
activation
mode
was
proposed
which
HFIP
assists
both
hydrogen
molecule
presence
base,
situ-generated
fleeting
keto
tautomer
immediately
trapped
Rh(III)-H
species
before
it
escapes
from
cage.
This
protocol
provides
straightforward
practical
pathway
for
synthesis
key
intermediates
several
chiral
drugs.
Particularly,
Nadolol,
drug
treatment
hypertension,
angina
pectoris,
congestive
heart
failure,
certain
arrhythmias,
enantioselectively
synthesized
time.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(13), С. 8904 - 8914
Опубликована: Март 20, 2024
The
C(sp3)–H
bond
oxygenation
of
a
variety
cyclopropane
containing
hydrocarbons
with
hydrogen
peroxide
catalyzed
by
manganese
complexes
aminopyridine
tetradentate
ligands
was
carried
out.
Oxidations
were
performed
in
1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP)
and
2,2,2-trifluoroethanol
(TFE)
using
different
catalysts
carboxylic
acid
co-ligands,
where
steric
electronic
properties
systematically
modified.
Functionalization
selectively
occurs
at
the
most
activated
C–H
bonds
that
are
α-
to
cyclopropane,
providing
access
carboxylate
or
2,2,2-trifluoroethanolate
transfer
products,
no
competition,
favorable
cases,
from
generally
dominant
hydroxylation
reaction.
formation
mixtures
unrearranged
rearranged
esters
(oxidation
HFIP
presence
acid)
ethers
TFE)
full
control
over
diastereoselectivity
observed,
confirming
involvement
delocalized
cationic
intermediates
these
transformations.
Despite
such
complex
mechanistic
scenario,
fine-tuning
catalyst
sterics
electronics
leveraging
on
relative
contribution
pathways
reaction
mechanism,
product
chemoselectivity
could
be
achieved.
Taken
together,
results
reported
herein
provide
powerful
catalytic
tools
rationally
manipulate
ligand
oxidations
hydrocarbons,
delivering
novel
products
good
yields
and,
some
outstanding
selectivities,
expanding
available
toolbox
for
development
synthetically
useful
functionalization
procedures.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(40), С. 22086 - 22096
Опубликована: Сен. 26, 2023
A
detailed
study
on
the
C(sp3)–H
bond
oxygenation
reactions
with
H2O2
catalyzed
by
[Mn(OTf)2(TIPSmcp)]
complex
at
methylenic
sites
of
cycloalkyl
and
1-alkyl
substrates
bearing
19
different
electron-withdrawing
functional
groups
(EW
FGs)
was
carried
out.
Oxidations
in
MeCN
were
compared
to
corresponding
ones
strong
hydrogen
donating
(HBD)
solvents
1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP)
nonafluoro
tert-butyl
alcohol
(NFTBA).
Formation
products
deriving
from
most
remote
observed,
yields,
product
ratios
(PR)
for
over
next
sites,
associated
site-selectivities
that
significantly
increased
going
HFIP
NFTBA.
Unprecedented
obtained
oxidation
cyclohexyl,
cycloheptyl,
cyclooctyl,
1-pentyl,
1-hexyl,
1-heptyl
substrates,
approaching
>99%,
90%,
93%,
88%
(PR
>99,
9.4,
14,
7.5)
cyclohexyl-2-pyridinecarboxylate,
cycloheptyl-2-pyridinecarboxylate,
cyclooctyl-4-nitrobenzenesulfonamide,
1-pentyl-3,5-dinitrobenzoate,
1-hexyl-3,5-dinitrobenzoate,
1-heptyl-3,5-dinitrobenzoate,
respectively.
The
results
are
rationalized
basis
a
polarity
enhancement
effect
via
synergistic
electronic
deactivation
proximal
imparted
EWG
coupled
solvent
HB.
Compared
previous
procedures,
provides
opportunity
tune
site-selectivity
among
multiple
methylenes
substrate
classes,
extending
determined
native
EWGs
two
carbon
atoms.
This
uncovers
simple
procedure
predictable,
high-yielding,
highly
site-selective
occurs
under
mild
conditions,
large
scope,
providing
an
extremely
powerful
tool
be
implemented
synthetically
useful
procedures.
Chemistry - A European Journal,
Год журнала:
2023,
Номер
29(66)
Опубликована: Авг. 29, 2023
Abstract
In
recent
years,
metalloenzymes‐mediated
highly
selective
oxidations
of
organic
substrates
under
mild
conditions
have
been
inspiration
for
developing
synthetic
bioinspired
catalyst
systems,
capable
conducting
such
processes
in
the
laboratory
(and,
future,
industry),
relying
on
easy‐to‐handle
and
environmentally
benign
oxidants
as
H
2
O
.
To
date,
non‐heme
manganese
complexes
with
chiral
bis
‐amino‐
‐pyridylmethyl
structurally
related
ligands
are
considered
possessing
highest
potential,
having
demonstrated
ability
to
mediate
a
variety
chemo‐
stereoselective
oxidative
transformations,
epoxidations,
C(sp
3
)‐H
hydroxylations
ketonizations,
desymmetrizations,
kinetic
resolutions,
etc.
Furthermore,
past
few
years
Mn
based
catalysts
become
major
platform
studies
focused
getting
insight
into
molecular
mechanisms
oxidant
activation
(stereo)selective
oxygen
transfer,
testing
non‐traditional
hydroperoxide
oxidants,
engineering
catalytic
sites
enzyme‐like
substrate
recognition‐based
selectivity,
exploration
regioselectivity
trends
oxidation
biologically
active
natural
origin.
This
contribution
summarizes
progress
catalyzed
C‐H
oxygenative
transformations
substrates,
achieved
essentially
5
(late
2018–2023).