Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(32), С. 22840 - 22849
Опубликована: Авг. 2, 2024
While
photochemical
deracemization
significantly
enhances
atom
economy
by
eliminating
the
necessity
for
additional
oxidants
or
reductants,
laborious
presynthesis
of
substrates
from
feedstock
chemicals
is
often
required,
thereby
compromising
practicality
this
method.
In
study,
we
propose
a
novel
approach
known
as
de
novo
synthesis,
which
involves
direct
utilization
simple
undergoing
both
transformation
and
reversible
transformation.
The
efficient
enantiocontrol
chiral
catalysts
in
latter
process
establishes
an
effective
platform
deracemization.
This
alternative
practical
to
address
challenges
asymmetric
photocatalysis
has
been
successfully
demonstrated
photosensitized
synthesis
azaarene-functionalized
cyclobutanes
featuring
three
stereocenters,
including
all-carbon
quaternary
center.
By
exclusively
employing
suitable
catalyst
enable
kinetically
controlled
[2
+
2]
photocycloreversion,
pave
creative
path
toward
achieving
more
cost-effective
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(29), С. 19621 - 19628
Опубликована: Май 13, 2024
For
nearly
60
years,
significant
research
efforts
have
been
focused
on
developing
strategies
for
the
cycloaddition
of
bicyclobutanes
(BCBs).
However,
higher-order
and
catalytic
asymmetric
BCBs
long-standing
formidable
challenges.
Here,
we
report
Pd-catalyzed
ligand-controlled,
tunable
cycloadditions
divergent
synthesis
bridged
bicyclic
frameworks.
The
dppb
ligand
facilitates
formal
(5+3)
vinyl
oxiranes,
yielding
valuable
eight-membered
ethers
with
scaffolds
in
100%
regioselectivity.
Cy-DPEphos
promotes
selective
hetero-[2σ+2σ]
to
access
pharmacologically
important
2-oxabicyclo[3.1.1]heptane
(O-BCHeps).
Furthermore,
corresponding
O-BCHeps
94–99%
ee
has
achieved
using
chiral
(S)-DTBM-Segphos,
representing
first
cross-dimerization
two
strained
rings.
obtained
are
promising
bioisosteres
ortho-substituted
benzenes.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(32)
Опубликована: Май 24, 2024
Abstract
Synthesis
of
bicyclic
scaffolds
has
gained
significant
attention
in
drug
discovery
due
to
their
potential
mimic
benzene
bioisosteres.
Here,
we
present
a
mild
and
scalable
Sc(OTf)
3
‐catalyzed
[3+2]
cycloaddition
bicyclo[1.1.0]butanes
(BCBs)
with
ynamides,
yielding
diverse
array
polysubstituted
2‐amino‐bicyclo[2.1.1]hexenes
good
excellent
yields.
These
products
offer
valuable
starting
materials
for
the
construction
novel
functionalized
bicyclo[1.1.0]butanes.
Preliminary
mechanistic
studies
indicate
that
reaction
involves
nucleophilic
addition
ynamides
bicyclo[1.1.0]butanes,
followed
by
an
intramolecular
cyclization
situ
generated
enolate
keteniminium
ion.
We
expect
these
findings
will
encourage
utilization
complex
bioisosteres
foster
further
investigation
into
BCB‐based
chemistry.
Organic Letters,
Год журнала:
2024,
Номер
26(19), С. 4104 - 4110
Опубликована: Май 3, 2024
Herein,
a
B(C6F5)3-catalyzed
formal
(n
+
3)
=
5
and
6)
cycloaddition
of
bicyclo[1.1.0]butanes
(BCBs)
with
imidazolidines/hexahydropyrimidines
is
described.
The
reaction
provides
modular,
atom-economical,
efficient
strategy
to
two
libraries
synthetically
challenging
medium-bridged
rings,
2,5-diazabicyclo[5.1.1]nonanes
2,6-diazabicyclo[6.1.1]decanes,
in
moderate
excellent
yields.
This
also
features
simple
operation,
mild
conditions,
broad
substrate
scope.
A
scale-up
experiment
various
synthetic
transformations
products
further
highlight
the
utility.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(48)
Опубликована: Сен. 2, 2024
Abstract
The
cycloaddition
reaction
involving
bicyclo[1.1.0]butanes
(BCBs)
offers
a
versatile
and
efficient
synthetic
platform
for
producing
C(sp
3
)‐rich
rigid
bridged
ring
scaffolds,
which
act
as
phenyl
bioisosteres.
However,
there
is
scarcity
of
catalytic
asymmetric
cycloadditions
BCBs
to
fulfill
the
need
enantioenriched
saturated
bicycles
in
drug
design
development.
In
this
study,
an
synthesis
valuable
azabicyclo[2.1.1]hexanes
(aza‐BCHs)
by
enantioselective
zinc‐catalyzed
(3+2)
with
imines
reported.
proceeds
effectively
novel
type
BCB
that
incorporates
2‐acyl
imidazole
group
diverse
array
alkynyl‐
aryl‐substituted
imines.
target
aza‐BCHs,
consist
α‐chiral
amine
fragments
two
quaternary
carbon
centers,
are
efficiently
synthesized
up
94
%
96.5:3.5
er
under
mild
conditions.
Experimental
computational
studies
reveal
follows
concerted
nucleophilic
ring‐opening
mechanism
This
distinct
from
previous
on
Lewis
acid‐catalyzed
BCBs.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 25, 2024
The
selective
construction
of
bridged
bicyclic
scaffolds
has
garnered
increasing
attention
because
their
extensive
use
as
saturated
bioisosteres
arene
in
pharmaceutical
industry.
However,
sharp
contrast
to
racemic
counterparts,
assembling
chiral
structures
an
enantioselective
and
regioselective
manner
remains
challenging.
Herein,
we
describe
our
protocol
for
constructing
2-oxa-3-azabicyclo[3.1.1]heptanes
(BCHeps)
by
[4π
+
2σ]
cycloadditions
bicyclo[1.1.0]butanes
(BCBs)
nitrones
taking
advantage
a
copper(II)
complex
Lewis
acid
catalyst.
This
method
features
mild
conditions,
good
functional
group
tolerance,
high
yield
(up
99%),
excellent
enantioselectivity
99%
ee).
Density
theory
(DFT)
calculation
elucidates
the
origin
reaction's
mechanism
BCB
activation
Cu(II)
complex.
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
unknown
Опубликована: Май 31, 2024
Bridged
cyclobutanes
and
sulfur
heterocycles
are
currently
under
intense
investigation
as
building
blocks
for
pharmaceutical
drug
design.
Two
formal
cycloaddition
modes
involving
bicyclobutanes
(BCBs)
pyridinium
1,4-zwitterionic
thiolate
derivatives
were
described
to
rapidly
expand
the
chemical
space
of
sulfur-containing
bridged
cyclobutanes.
By
using
Ni(ClO
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 20, 2024
Abstract
Saturated
three-dimensional
carbocycles
have
gained
increasing
prominence
in
synthetic
and
medicinal
chemistry.
In
particular,
bicyclo[2.1.1]hexanes
(BCHs)
been
identified
as
the
molecular
replacement
for
benzenes.
Here,
we
present
facile
access
to
a
variety
of
BCHs
via
stepwise
two-electron
formal
(3
+
2)
cycloaddition
between
silyl
enol
ethers
bicyclo[1.1.0]butanes
(BCBs)
under
Lewis
acid
catalysis.
The
reaction
features
wide
functional
group
tolerance
ethers,
allowing
efficient
construction
two
vicinal
quaternary
carbon
centers
silyl-protected
tertiary
alcohol
unit
streamlined
fashion.
Interestingly,
with
conjugated
dienol
can
provide
bicyclo[4.1.1]octanes
(BCOs)
equipped
that
facilitate
further
transformation.
utilities
this
methodology
are
demonstrated
by
late-stage
modification
natural
products,
transformations
units
on
bicyclo[2.1.1]hexane
frameworks,
derivatization
bicyclo[4.1.1]octanes,
delivering
functionalized
bicycles
traditionally
inaccessible.
