Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 13, 2024
Abstract
Oxetanes
are
valuable
motifs
in
medicinal
chemistry
applications,
with
demonstrated
potential
to
serve
as
bioisosteres
for
an
array
of
functional
groups.
Through
the
visible‐light‐mediated
photoredox
hydrodecarboxylation
2‐aryl
oxetane
2‐carboxylic
acids
this
work
enables
access
products
a
[2+2]‐photocycloaddition
between
alkenes
and
aryl
aldehydes
without
challenges
associated
traditional
UV‐light‐mediated
Paternò‐Büchi
reaction.
Investigation
into
mechanism
reveals
substrate‐dependent
modes
initiation
under
conditions
reported
herein.
Divergence
diastereomeric
outcome
is
observed,
mechanistic
probes
elucidating
key
hydrogen‐bonding
steric
interactions.
Organic & Biomolecular Chemistry,
Journal Year:
2023,
Volume and Issue:
21(27), P. 5553 - 5559
Published: Jan. 1, 2023
Oxetanes
and
azetidines
continue
to
draw
significant
interest
in
medicinal
chemistry,
as
small,
polar
non-planar
motifs.
also
represent
interesting
surrogates
for
carbonyl-containing
functional
groups.
Here
we
report
a
synthesis
of
3,3-disubstituted
oxetane-
azetidine-ethers,
with
comparisons
made
the
ester
group.
The
tertiary
benzylic
alcohols
4-membered
rings
are
selectively
activated
using
Brønsted
acid
catalysis
reacted
simple
form
ethers
maintain
oxetane
ring
intact.
This
approach
avoids
use
strong
bases
halide
alkylating
agents
allows
alcohol
libraries
be
leveraged.
Oxetane
demonstrate
excellent
chemical
stability
across
range
conditions
an
improved
vis-à-vis
analogous
esters
under
basic
reducing
conditions.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(26)
Published: April 23, 2024
Abstract
Alkylamines
form
the
backbone
of
countless
nitrogen‐containing
small
molecules
possessing
desirable
biological
properties.
Despite
advances
in
amine
synthesis
through
transition
metal
catalysis
and
photoredox
chemistry,
multicomponent
reactions
that
leverage
inexpensive
materials
to
transform
abundant
chemical
feedstocks
into
three‐dimensional
α‐substituted
alkylamines
bearing
complex
substitution
patterns
remain
scarce.
Here,
we
report
design
a
catalyst‐free
electroreductive
manifold
merges
amines,
carbonyl
compounds
carbon‐based
radical
acceptors
under
ambient
conditions
without
rigorous
exclusion
air
moisture.
Key
this
aminative
carbofunctionalization
process
is
chemoselective
generation
nucleophilic
α‐amino
intermediates
readily
couple
with
electrophilic
partners,
providing
straightforward
access
architecturally
intricate
drug‐like
scaffolds
which
are
inaccessible
by
conventional
means.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 12, 2024
Four-membered
heterocycles
such
as
oxetanes
and
azetidines
represent
attractive
emergent
design
options
in
medicinal
chemistry
due
to
their
small
polar
nature
potential
significantly
impact
the
physiochemical
properties
of
drug
molecules.
The
challenging
preparation
these
derivatives,
especially
a
divergent
manner,
has
severely
limited
combination
with
other
medicinally
biologically
important
groups.
Consequently,
there
is
substantial
demand
for
mild
effective
synthetic
strategies
access
new
oxetane
azetidine
derivatives
molecular
scaffolds.
Here,
we
report
development
use
sulfonyl
fluorides
(OSFs)
(ASFs),
which
behave
precursors
carbocations
an
unusual
defluorosulfonylation
reaction
pathway
(deFS).
small-ring
are
activated
under
thermal
conditions
(60
°C),
generated
reactive
intermediates
couple
broad
range
nucleophiles.
Oxetane
heterocyclic,
-sulfoximine,
-phosphonate
prepared,
several
do
not
have
comparable
carbonyl
analogs,
providing
chemical
motifs
elements
discovery.
Alternatively,
SuFEx
anionic
accesses
oxetane-sulfur(VI)
derivatives.
We
demonstrate
utility
novel
OSF
ASF
reagents
through
synthesis
11
showcasing
subsequent
diversification
facile
inclusion
into
programs.
Moreover,
propose
application
linker
incorporation
pendant
groups
suitable
common
conjugation
reactions.
Productive
deFS
reactions
E3
ligase
recruiters
pomalidomide
related
provide
degrader
PROTAC
linkers.
European Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
26(33)
Published: June 14, 2023
Abstract
A
strategy
for
anti
‐Markovnikov
hydroalkyl/aryl
thiolation
and
disulfidation
of
2‐azetines
under
continuous
flow
conditions
has
been
developed.
Thiyl
radicals
are
generated
from
thiols
or
disulfides
subsequently
propagate
into
the
azetine
unsaturation
to
forge
C−S
bond
shape
a
secondary
radical
intermediate.
This
carbon‐centered
chain
transfers
another
thiol
via
hydrogen
atom
transfer
(HAT)
disulfide
regenerate
key
thiyl
intermediates.
The
use
technology
ensures
efficient
irradiation
reaction
mixture
leading
extremely
fast,
robust,
scalable
protocols.
Furthermore,
ethyl
acetate
was
adopted
as
an
environmentally
responsible
solvent.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(29), P. 11337 - 11346
Published: Jan. 1, 2024
Naturally
occurring
and
readily
available
α-hydroxy
carboxylic
acids
(AHAs)
are
utilized
as
platforms
for
visible
light-mediated
oxidative
CO
2
-extrusion
furnishing
radicals
proved
to
be
versatile
C1
C
n
hydroxyalkylating
agents.
ChemistryEurope,
Journal Year:
2023,
Volume and Issue:
1(2)
Published: July 19, 2023
Abstract
A
reductive
radical
coupling
reaction
between
non‐activated
aliphatic
alcohols
and
styrenes
has
been
discovered
through
the
use
of
low‐valent
Ti‐mediated
C−O
bond
homolysis.
general
application
styrene
derivatives
in
reactions
remains
a
challenge
organic
synthesis.
The
preliminary
investigation
revealed
that
resulting
benzyl
intermediate
behaves
differently
depending
on
minor
steric
differences
around
spin
center,
which
results
lack
generality.
addition
1,3,5‐trimethyl‐2,5‐cyclohexadiene
uniformly
hydrogenated
radicals
irrespective
environments
attacking
radicals.
Under
optimal
conditions,
all
tertiary,
secondary,
primary
were
applicable.
In
this
study,
successfully
used
directly
as
sources
reacted
with
large
number
styrenes.
The Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
88(17), P. 12451 - 12463
Published: Aug. 15, 2023
Radical
group
transfer
is
a
powerful
tool
for
the
formation
of
C-C
bonds.
These
processes
typically
involve
radical
addition
to
π
bonds,
followed
by
fragmentation
resulting
cyclic
intermediate.
Despite
advantageous
lability
organosilanes
in
this
context,
silicon-tethered
acceptor
groups
have
remained
underexplored
reactions.
We
report
general
photoredox-catalyzed
protocol
vinyl
and
alkynyl
silanes
onto
sp3
carbons,
using
activated
unactivated
iodides
as
precursors.
Our
method
displays
high
diastereoselectivity
excellent
functional
tolerance,
enables
direct
products
situ
ring
opening.
Mechanistic
investigations
revealed
that
reaction
proceeds
via
an
unusual
dual
catalytic
cycle,
overall
redox-neutral
process.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(26)
Published: April 23, 2024
Abstract
Alkylamines
form
the
backbone
of
countless
nitrogen‐containing
small
molecules
possessing
desirable
biological
properties.
Despite
advances
in
amine
synthesis
through
transition
metal
catalysis
and
photoredox
chemistry,
multicomponent
reactions
that
leverage
inexpensive
materials
to
transform
abundant
chemical
feedstocks
into
three‐dimensional
α‐substituted
alkylamines
bearing
complex
substitution
patterns
remain
scarce.
Here,
we
report
design
a
catalyst‐free
electroreductive
manifold
merges
amines,
carbonyl
compounds
carbon‐based
radical
acceptors
under
ambient
conditions
without
rigorous
exclusion
air
moisture.
Key
this
aminative
carbofunctionalization
process
is
chemoselective
generation
nucleophilic
α‐amino
intermediates
readily
couple
with
electrophilic
partners,
providing
straightforward
access
architecturally
intricate
drug‐like
scaffolds
which
are
inaccessible
by
conventional
means.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(29)
Published: April 24, 2024
Abstract
Methods
enabling
the
broad
diversification
of
C(sp
3
)−H
bonds
from
a
common
intermediate
are
especially
valuable
in
chemical
synthesis.
Herein,
we
report
site‐selective
(
N
‐phenyltetrazole)thiolation
aliphatic
and
(hetero)benzylic
using
commercially
available
disulfide
to
access
‐phenyltetrazole
thioethers.
The
thioether
products
readily
elaborated
diverse
fragment
couplings
for
C−C,
C−O,
or
C−N
construction.
C−H
functionalization
proceeds
via
radical‐chain
pathway
involving
hydrogen
atom
transfer
by
electron‐poor
‐phenyltetrazolethiyl
radical.
Hexafluoroisopropanol
was
found
be
essential
reactions
thiolation,
with
computational
analysis
consistent
dual
bonding
radical
imparting
increased
electrophilicity
facilitate
transfer.
Substrate
is
limiting
reagent
all
cases,
reaction
displays
an
exceptional
functional
group
tolerance
well
suited
applications
late‐stage
diversification.