Angewandte Chemie,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
Abstract
Enantioselective
synthesis
of
(spiro)cyclobutane
derivatives
poses
significant
challenges
yet
holds
promising
applications
for
both
synthetic
and
medicinal
chemistry.
We
report
here
a
nickel‐catalyzed
asymmetric
syn
‐hydrometalative
4‐
exo
‐
trig
cyclization
1,4‐alkynones
to
synthesize
alkenyl
cyclobutanols
with
tetrasubstituted
stereocenter.
This
strategy
features
broad
substrate
scope,
delivering
variety
trifluoromethyl‐containing
rigid
(spiro)carbocycle
skeletons
in
good
yields
high
enantioselectivities
(up
84
%
yield
98.5
:
1.5
er).
The
utility
is
demonstrated
through
stereospecific
transformations
into
fused
spiro
molecules.
Experimental
computational
mechanistic
studies
indicate
that
the
reaction
initiated
by
an
active
Ni−H
species,
carbonyl‐directed
hydrometalation
as
key
regioselective
control.
catalytic
method
provides
general
solution
hydrofunctionalization
alkynes
represents
efficient
pattern
assembling
highly
strained
enantioenriched
bioisosteres.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(51)
Опубликована: Ноя. 14, 2023
Rigid
bicycles
are
becoming
more
popular
in
the
pharmaceutical
industry
because
they
allow
for
expansion
to
new
and
unique
chemical
spaces.
This
work
describes
a
strategy
construct
2-azanorbornanes,
which
can
act
as
rigid
piperidine/pyrrolidine
scaffolds
with
well-defined
exit
vectors.
To
achieve
synthesis
of
strain-release
reagent,
azahousane,
is
introduced
along
its
photosensitized
formal
cycloaddition
alkenes.
Furthermore,
reactivity
between
housane
an
imine
disclosed.
Both
strategies
lead
various
substituted
2-azanorbornanes
good
selectivities.
In
this
study,
we
devised
an
innovative
approach
for
the
synthesis
of
pyrazine
derivatives
through
a
photoinduced
formal
cross-[3+3]
cycloaddition
between
vinyldiazo
reagents
and
acceptor-only
diazoalkanes.
This
method
leverages
differential
reactivity
two
distinct
diazo
compounds:
reagents,
which
upon
visible
light
irradiation
form
key
cyclopropane
intermediates,
diazoalkanes,
function
as
1,3-dipoles
to
capture
photogenerated
reactive
species.
The
reactions
proceed
exclusively
under
light,
yielding
1,4-dihydropyridazines
with
broad
substrate
scope
compatibility
various
functional
groups.
Importantly,
synthesized
can
be
readily
converted
other
valuable
products.
mechanism,
elucidated
UV–vis
absorption
studies,
deuterium
labeling
experiments,
control
in
situ
NMR
spectroscopy,
provides
clear
understanding
observed
reactivity.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 24, 2025
Carboxylate
diradical
intermediates,
with
α-carbon
and
carboxylic
oxygen
acting
as
reactive
radical
centers,
represent
a
highly
attractive
long-sought
species
in
reaction
design
synthesis.
However,
capturing
these
intermediates
for
coupling
reactions
poses
formidable
challenge
due
to
their
inherent
instability
spontaneous
decarboxylation.
Here,
we
addressed
this
by
temporarily
masking
the
carboxylate
reactivity
via
photocleavable
dynamic
oxygen–iodine
bond.
This
approach
effectively
prevents
unwanted
decarboxylation
enables
controlled
utilization
of
forming
new
bonds.
Carboxylates
alkenes/heteroarenes,
among
most
readily
available
raw
materials,
can
now
seamlessly
couple
pathways
form
γ-butyrolactones,
which
are
common
motifs
found
numerous
natural
products
bioactive
molecules.
Ionic
traditional
carboxylates
ruled
out
based
on
experimental
studies
density
functional
theory
(DFT)
calculations.
strategy
overcomes
substrate
limitations
methods,
significantly
expanding
range
applicable
alkenes/heteroarenes.
Our
method
allows
transforming
alkenes
modes
diverse
offers
insights
into
developing
di-
multiradical
equivalents
unprecedented
synthetic
designs.
Nature Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 6, 2025
Abstract
The
development
of
[2
+
2]
cyclases
containing
benzophenone
triplet
sensitizers
highlights
the
potential
engineered
enzymes
as
a
platform
for
stereocontrolled
energy
transfer
photocatalysis.
However,
suboptimal
photophysical
features
necessitates
use
ultraviolet
light,
limits
photochemical
efficiency
and
restricts
range
chemistries
accessible.
Here
we
engineer
an
orthogonal
Methanococcus
jannaschii
tyrosyl-tRNA
synthetase/tRNA
pair
encoding
thioxanthone
into
proteins,
which
can
efficiently
harness
visible
light
to
drive
conversions.
Initially,
developed
enantioselective
cyclase
that
is
orders
magnitude
more
efficient
than
our
previously
photoenzymes
(
k
cat
=
13
s
−1
,
>1,300
turnovers).
To
demonstrate
thioxanthone-containing
enable
challenging
conversions,
second
oxygen-tolerant
enzyme
steer
selective
C–H
insertions
excited
quinolone
substrates
afford
spirocyclic
β-lactams
with
high
selectivity
(99%
e.e.,
22:1
d.r.).
This
photoenzyme
also
suppresses
competing
substrate
decomposition
pathway
observed
small-molecule
sensitizers,
underscoring
ability
control
fate
excited-state
intermediates.
The Journal of Organic Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 3, 2025
We
report
an
intermolecular,
cross-selective
[2
+
2]
cycloaddition
between
cyclic
styrenes
and
olefin
acceptors
proceeding
via
visible-light
irradiation,
enabled
by
the
extended
triplet
lifetime
of
styrenes.
A
broad
range
olefins,
including
electron-deficient
simple
alkenes,
(hetero)styrenes,
arylimines,
vinyl
boronate
esters,
among
others,
underwent
efficient
with
constrained
four-,
five-,
rigidified
six-membered
rings,
providing
rapid
access
to
sp3-rich
fused
cyclobutane
scaffolds.
Notably,
two
electronically
similar
styrenes,
which
typically
gives
statistical
mixtures
homo-
heterodimers,
proceeded
excellent
chemoselectivity
yield
acyclic
without
requiring
a
large
excess
one
reactant,
facilitated
significant
difference
in
reacting
partners.
Mechanistic
studies
DFT
calculations
support
Dexter
energy
transfer
mechanism
substrate
activation
underscore
critical
role
extension
enabling
observed
reactivity.
The
utility
this
method
is
demonstrated
total
synthesis
lindleyanin,
only
steps.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 12, 2024
Abstract
Enantioselective
synthesis
of
(spiro)cyclobutane
derivatives
poses
significant
challenges
yet
holds
promising
applications
for
both
synthetic
and
medicinal
chemistry.
We
report
here
a
nickel‐catalyzed
asymmetric
syn
‐hydrometalative
4‐
exo
‐
trig
cyclization
1,4‐alkynones
to
synthesize
alkenyl
cyclobutanols
with
tetrasubstituted
stereocenter.
This
strategy
features
broad
substrate
scope,
delivering
variety
trifluoromethyl‐containing
rigid
(spiro)carbocycle
skeletons
in
good
yields
high
enantioselectivities
(up
84
%
yield
98.5
:
1.5
er).
The
utility
is
demonstrated
through
stereospecific
transformations
into
fused
spiro
molecules.
Experimental
computational
mechanistic
studies
indicate
that
the
reaction
initiated
by
an
active
Ni−H
species,
carbonyl‐directed
hydrometalation
as
key
regioselective
control.
catalytic
method
provides
general
solution
hydrofunctionalization
alkynes
represents
efficient
pattern
assembling
highly
strained
enantioenriched
bioisosteres.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(46), С. 32088 - 32097
Опубликована: Ноя. 8, 2024
Azetidine
units
are
commonly
found
in
natural
products
and
biologically
active
drugs.
The
[2
+
2]
cycloaddition
of
imines
alkenes
has
been
extensively
used
the
synthesis
such
structures,
while
enantioselective
approaches
remain
elusive.
Herein,
an
efficient
B(C
