ACS Catalysis,
Год журнала:
2024,
Номер
14(24), С. 18799 - 18809
Опубликована: Дек. 11, 2024
Transition-metal-catalyzed
cycloaddition
reactions
of
strained
small-ring
compounds
are
powerful
methods
for
constructing
carbo-
and
heterocyclic
structures
medicinal
interest.
However,
the
application
this
strategy
to
bicyclo[1.1.0]butanes
(BCBs),
which
among
most
carbocycles
known,
remains
underdeveloped.
Herein,
we
report
vinylbicyclo[1.1.0]butane
(VBCB)
as
a
platform
synthon
palladium-catalyzed
formal
[2σ+2π]
with
various
2π-components,
enabling
synthesis
BCHs,
oxa-BCHs,
aza-BCHs
under
identical
reaction
conditions.
The
zwitterionic
π-allyl-Pd
species
generated
through
activation
VBCBs
is
key
circumventing
potential
carbene
reactivity
serves
common
intermediate
cycloadditions
diverse
2π-systems,
including
alkenes,
aldehydes,
ketones,
imines.
Notably,
by
utilizing
Pd2(dba)3
an
anthracene-derived
Trost
ligand,
wide
array
BCHs
bearing
two
vicinal
chiral
centers
has
been
prepared
in
highly
diastereo-,
enantioselective
manner.
generality
practicality
method
have
demonstrated
broad
substrate
scope,
scale-up
reactions,
versatile
transformation
multiple
functional
groups
into
BCH
scaffolds.
Preliminary
mechanistic
studies
support
formation
species.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 28, 2025
Asymmetric
synthesis
presents
many
challenges,
with
the
selective
formation
of
chiral
bridged
polyheterocycles
being
a
notable
example.
Cycloadditions
using
bicyclo[1.1.0]butanes
(BCB)
offer
promising
solution
along
those
lines,
yet,
despite
significant
advances
in
that
emerging
area,
asymmetric
control
has
remained
limited
thus
far.
Here,
we
describe
an
organocatalytic,
enantioselective
formal
(3
+
3)-cycloaddition
BCBs
1H-indol-3-yl((hetero)aryl)methanol
derivatives.
This
approach
enables
rapid
and
efficient
tetrahydro-1H-1,3-methanocarbazole
derivatives
(34
examples)
from
readily
available
starting
materials,
very
good
stereochemical
(up
to
98:2
er).
Successful
scale-up
experiments
product
modification
demonstrated
potential
this
methodology.
Control
DFT
calculations
provide
insights
into
mechanistic
pathway.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(46), С. 31400 - 31404
Опубликована: Ноя. 7, 2024
Bicyclo[2.1.1]hexanes
have
emerged
as
valuable
scaffolds
for
the
design
of
new
pharmaceutical
and
agrochemical
active
ingredients.
These
structures
can
be
efficiently
synthesized
via
[2π
+
2σ]
photocycloadditions;
however,
control
over
absolute
stereochemistry
these
strain-releasing
reactions
has
remained
challenging.
Herein,
we
demonstrate
that
Brønsted
acid
catalyzed
chromophore
activation
C-acyl
imidazoles
enables
highly
enantioselective
photocycloadditions.
Because
this
approach
is
agnostic
to
identity
coupling
partner,
same
strategy
used
synthesize
several
other
medicinally
relevant
strained
small-ring
structures.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Herein
we
report
a
simple
BF
3
-catalyzed
cycloaddition
of
dihydropyridines
with
bicyclobutanes
for
the
expedient
synthesis
novel
three-dimensional
azacycle-fused
bicyclo[2.1.1]hexane
scaffolds.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
147(9), С. 7950 - 7964
Опубликована: Фев. 19, 2025
Efficiently
constructing
structurally
diverse
and
complex
organic
molecules
through
selective
catalytic
functionalization
is
a
central
goal
in
synthetic
chemistry,
yet
achieving
precise
control
over
multiple
reactive
centers
multisite
substrates
remains
formidable
challenge.
Building
on
foundational
advances
single-
dual-selective
transformations,
we
report
multimodal
strategy
for
the
carbonylation
of
1,3-enynes,
versatile
class
substrates.
Through
meticulous
fine-tuning
conditions,
our
approach
enables
five
distinct
regio-
stereoselective
carbonylative
including
direct
(1,2-
2,1-hydroaminocarbonylation)
tandem
cyclization
pathways
(2,4-,
1,3-,
2,3-carbonylation).
Furthermore,
mechanistic
studies
suggested
that
multidimensional
regulation
seamless
relay
up
to
three
reactions
(hydroaminocarbonylation-hydroamination-transamination)
with
exceptional
accuracy.
This
unified
platform
not
only
establishes
robust
framework
tackling
enduring
challenges
selectivity
but
also
broadens
chemical
space
accessible
1,3-enyne
exemplifying
atom-
step-economic
principles
paving
way
transformative
advancements
drug
discovery,
materials
science,
beyond.
Abstract
Isophorone
is
a
relatively
small
molecule
with
several
neighboring
reacting
sites,
making
it
susceptible
to
various
competing
reactions
aldehydes,
including
aldol,
Baylis‐Hillman
(BH),
aldol
condensation,
and
Michael
addition
reactions.
In
the
present
work,
we
have
designed
switchable
1,8‐diazabicyclo[5.4.0]undec‐7‐ene
(DBU)‐catalyzed
procedure,
where
reaction
of
isophorone
aldehydes
guided
chemoselectively
toward
either
BH,
or
condensation
reactions,
depending
on
use
water
and/or
heat.
This
controllable
divergency
likely
stems
from
ability
tune
dual
nucleophilicity/basicity
characters
DBU/H
2
O
medium.
other
words,
nucleophilicity
DBU
plays
crucial
role
in
directing
process
formation
BH
adducts
absence
water.
At
same
time,
pathway
dominates
when
present.
The
conditions
were
amenable
for
tandem
processes,
as
demonstrated
an
condensation/Diels‐Alder
sequence.
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
The
cycloaddition
reactions
of
bicyclo[1.1.0]butanes
with
alkenes,
imines,
nitrones,
or
aziridines
have
served
as
an
efficient
platform
to
create
conformationally
restricted
saturated
bicyclic
scaffolds.
However,
the
use
readily
available
aromatics
in
such
reactions,
especially
asymmetric
manner,
remains
underexplored.
Herein,
we
report
a
highly
regio-
and
enantioselective
dearomative
[2π
+
2σ]
photocycloaddition
reaction
between
naphthalene
derivatives
bicyclo[1.1.0]butanes,
enabled
by
Gd(III)
catalysis.
Bicyclo[1.1.0]butanes
naphthalenes
adorned
diverse
array
functional
groups
are
well-tolerated
under
mild
conditions,
affording
enantioenriched
pharmaceutically
important
bicyclo[2.1.1]hexanes
30–96%
yields
81–93%
ee
12:1
→
>20:1
rr.
synthetic
versatility
this
is
further
demonstrated
facile
removal
directing
group
derivatizations
dearomatized
product.
UV–vis
absorption
spectroscopy
studies
suggest
involvement
excited
species
process.
