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.
Chemical Society Reviews,
Год журнала:
2024,
Номер
53(3), С. 1068 - 1089
Опубликована: Янв. 1, 2024
Leveraging
light
energy
to
expose
the
‘dark’
reactive
states
describes
whole
essence
of
triplet–triplet
transfer.
This
offers
an
impressive
opportunity
conduct
a
multitude
diverse
reactions
and
access
sought-after
molecular
motifs.
Communications Chemistry,
Год журнала:
2023,
Номер
6(1)
Опубликована: Янв. 12, 2023
Abstract
Bicyclobutanes
are
among
the
most
highly
strained
isolable
organic
compounds
and
their
associated
low
activation
barriers
to
reactivity
make
them
intriguing
building-blocks
in
chemistry.
In
recent
years,
numerous
creative
synthetic
strategies
exploiting
heightened
have
been
presented
these
discoveries
often
gone
hand-in-hand
with
development
of
more
practical
routes
for
synthesis.
Their
proclivity
as
strain-release
reagents
through
weak
central
C–C
bond
has
harnessed
a
variety
addition,
rearrangement
insertion
reactions,
providing
rapid
access
rich
tapestry
complex
molecular
scaffolds.
This
review
will
provide
an
overview
different
options
available
bicyclobutane
synthesis,
main
classes
that
can
be
prepared
from
bicyclobutanes,
modes
used.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(51), С. 23685 - 23690
Опубликована: Дек. 16, 2022
The
development
of
synthetic
strategies
for
the
preparation
bioisosteric
compounds
is
a
demanding
undertaking
in
medicinal
chemistry.
Numerous
have
been
developed
synthesis
bicyclo[1.1.1]pentanes
(BCPs),
bridge-substituted
BCPs,
and
bicyclo[2.1.1]hexanes.
However,
progress
on
bicyclo[3.1.1]heptanes,
which
serve
as
meta-substituted
arene
bioisosteres,
has
not
previously
explored.
Herein,
we
disclose
first
photoinduced
[3σ
+
2σ]
cycloaddition
trisubstituted
bicyclo[3.1.1]heptanes
using
bicyclo[1.1.0]butanes
cyclopropylamines.
This
transformation
only
uses
mild
operationally
simple
conditions
but
also
provides
unique
bioisosteres.
applicability
this
method
showcased
by
derivatization
reactions.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(38), С. 20716 - 20732
Опубликована: Сен. 15, 2023
The
concept
of
strain
in
organic
compounds
is
as
old
modern
chemistry
and
was
initially
introduced
to
justify
the
synthetic
setbacks
along
synthesis
small
ring
systems
(pars
construens
strain).
In
last
decades,
chemists
have
developed
an
arsenal
strain-release
reactions
destruens
strain)
which
can
generate─with
significant
driving
force─rigid
aliphatic
that
act
three-dimensional
alternatives
(hetero)arenes.
Photocatalysis
added
additional
dimension
processes
by
leveraging
energy
photons
create
chemical
complexity
under
mild
conditions.
This
perspective
presents
latest
advancements
photocatalysis─with
emphases
on
mechanisms,
catalytic
cycles,
current
limitations─the
unique
architectures
be
produced,
possible
future
directions.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(22), С. 12324 - 12332
Опубликована: Май 26, 2023
Dearomative
photocycloadditions
are
valuable
chemical
transformations,
serving
as
an
efficient
platform
to
create
three-dimensional
molecular
complexity.
However,
the
photolability
of
original
addition
product
especially
within
context
ortho
cycloadditions
often
causes
undesired
consecutive
rearrangements,
rendering
these
cycloadducts
elusive.
Herein,
we
report
ortho-selective
intermolecular
photocycloaddition
bicyclic
aza-arenes
including
(iso)quinolines,
quinazolines,
and
quinoxalines
by
utilizing
a
strain-release
approach.
With
bicyclo[1.1.0]butanes
coupling
partners,
this
dearomative
[2π
+
2σ]
cycloaddition
enables
straightforward
construction
C(sp3)-rich
bicyclo[2.1.1]hexanes
directly
connected
N-heteroarenes.
Photophysical
experiments
DFT
calculations
revealed
origin
selectivity
indicate
that,
in
originally
proposed
energy
transfer
or
direct
excitation
pathways,
chain
reaction
mechanism
is
operative
depending
on
conditions.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(34)
Опубликована: Май 11, 2023
Design,
synthesis
and
application
of
benzene
bioisosteres
have
attracted
a
lot
attention
in
the
past
20
years.
Recently,
bicyclo[2.1.1]hexanes
emerged
as
highly
attractive
for
ortho-
meta-substituted
benzenes.
Herein
we
report
mild,
scalable
transition-metal-free
protocol
construction
substituted
bicyclo[2.1.1]hexan-2-ones
through
Lewis
acid
catalyzed
(3+2)-cycloaddition
bicyclo[1.1.0]-butane
ketones
with
disubstituted
ketenes.
The
reaction
shows
high
functional
group
tolerance
documented
by
successful
preparation
various
3-alkyl-3-aryl
well
3,3-bisalkyl
(26
examples,
up
to
89
%
yield).
Postfunctionalization
exocyclic
ketone
moiety
is
also
demonstrated.
ACS Catalysis,
Год журнала:
2023,
Номер
13(7), С. 5096 - 5103
Опубликована: Март 30, 2023
Bicyclo[2.1.1]hexanes
(BCHs)
represent
an
intriguing
class
of
structurally
rigid
hydrocarbons
that
can
serve
as
the
bioisosteres
benzenoids
in
medicinal
chemistry.
Methods
for
synthesis
BCHs
are,
however,
limiting.
Reported
herein
is
a
facile
via
strain-release-driven
[2π
+
2σ]
cycloaddition
bicyclo[1.1.0]butanes
(BCBs)
with
alkenes
facilitated
by
pyridine-boryl
radical
catalyst.
The
mild
reaction
conditions,
broad
substrate
scope,
and
decent
functional
group
tolerance
this
protocol
render
it
appealing
relevant
fields
drug
design
synthesis.
Theoretical
mechanistic
studies
reveal
relay
mechanism
involved.
Synthetic
applications
products
are
performed.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(34)
Опубликована: Июнь 12, 2023
Synthesis
of
bicyclic
scaffolds
has
attracted
tremendous
attention
because
they
are
playing
an
important
role
as
saturated
bioisosteres
benzenoids
in
modern
drug
discovery.
Here,
we
report
a
BF3
-catalyzed
[2π+2σ]
cycloaddition
aldehydes
with
bicyclo[1.1.0]butanes
(BCBs)
to
access
polysubstituted
2-oxabicyclo[2.1.1]hexanes.
A
new
kind
BCB
containing
acyl
pyrazole
group
was
invented,
which
not
only
significantly
facilitates
the
reactions,
but
can
also
serve
handle
for
diverse
downstream
transformations.
Furthermore,
aryl
and
vinyl
epoxides
be
utilized
substrates
undergo
BCBs
after
situ
rearrangement
aldehydes.
We
anticipate
that
our
results
will
promote
challenging
sp3
-rich
frameworks
exploration
BCB-based
chemistry.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(46), С. 25411 - 25421
Опубликована: Ноя. 7, 2023
We
report
the
use
of
photocatalysis
for
homolytic
ring-opening
carbonyl
cyclopropanes.
In
contrast
to
previous
studies,
our
approach
does
not
require
a
metal
cocatalyst
or
strong
reductant.
The
cyclopropanes
can
be
employed
both
[2σ
+
2σ]
and
2π]
annulation
with
either
alkenes/alkynes
bicyclo[1.1.0]butanes,
yielding
cyclopent-anes/-enes
bicyclo[3.1.1]heptanes
(BCHs),
respectively.
BCHs
are
promising
bioisosteres
1,2,4,5
tetra-substituted
aromatic
rings.
Mechanistic
including
density
functional
theory
computation
trapping
experiment
DMPO,
support
1,3-biradical
generated
from
cyclopropane
as
key
intermediate
these
transformations.
Journal of Agricultural and Food Chemistry,
Год журнала:
2023,
Номер
71(47), С. 18087 - 18122
Опубликована: Март 24, 2023
The
design
of
bioisosteres
represents
a
creative
and
productive
approach
to
improve
molecule,
including
by
enhancing
potency,
addressing
pharmacokinetic
challenges,
reducing
off-target
liabilities,
productively
modulating
physicochemical
properties.
Bioisosterism
is
principle
exploited
in
the
bioactive
compounds
interest
both
medicinal
agricultural
chemists,
this
review,
we
provide
synopsis
applications
where
kind
molecular
editing
has
proved
be
advantageous
molecule
optimization.
examples
selected
for
discussion
focus
on
carboxylic
acids,
fluorine
fluorinated
motifs
compound
design,
some
sulfoximine
functionality,
drug-H2O
complexes,
phenyl
ring.