Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(31)
Published: May 20, 2024
Abstract
Neighboring
group
participation,
the
assistance
of
non‐conjugated
electrons
to
a
reaction
center,
is
fundamental
phenomenon
in
chemistry.
In
framework
nucleophilic
substitution
reactions,
neighboring
participation
known
cause
rate
acceleration,
first
order
kinetics
(S
N
1),
and
retention
configuration.
The
latter
result
double
inversion:
one
when
displaces
leaving
group,
second
nucleophile
substitutes
group.
This
powerful
control
stereoretention
has
been
widely
used
organic
synthesis
for
more
than
century.
However,
may
also
lead
inversion
configuration,
which
often
overlooked.
Herein,
we
review
this
unique
mode
stereoinversion,
dividing
relevant
reactions
into
three
classes
with
aim
introduce
fresh
perspective
on
different
modes
stereoinversion
via
as
well
factors
that
stereochemical
outcome.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(32)
Published: May 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.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(13), P. 8904 - 8914
Published: March 20, 2024
The
C(sp3)–H
bond
oxygenation
of
a
variety
cyclopropane
containing
hydrocarbons
with
hydrogen
peroxide
catalyzed
by
manganese
complexes
aminopyridine
tetradentate
ligands
was
carried
out.
Oxidations
were
performed
in
1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP)
and
2,2,2-trifluoroethanol
(TFE)
using
different
catalysts
carboxylic
acid
co-ligands,
where
steric
electronic
properties
systematically
modified.
Functionalization
selectively
occurs
at
the
most
activated
C–H
bonds
that
are
α-
to
cyclopropane,
providing
access
carboxylate
or
2,2,2-trifluoroethanolate
transfer
products,
no
competition,
favorable
cases,
from
generally
dominant
hydroxylation
reaction.
formation
mixtures
unrearranged
rearranged
esters
(oxidation
HFIP
presence
acid)
ethers
TFE)
full
control
over
diastereoselectivity
observed,
confirming
involvement
delocalized
cationic
intermediates
these
transformations.
Despite
such
complex
mechanistic
scenario,
fine-tuning
catalyst
sterics
electronics
leveraging
on
relative
contribution
pathways
reaction
mechanism,
product
chemoselectivity
could
be
achieved.
Taken
together,
results
reported
herein
provide
powerful
catalytic
tools
rationally
manipulate
ligand
oxidations
hydrocarbons,
delivering
novel
products
good
yields
and,
some
outstanding
selectivities,
expanding
available
toolbox
for
development
synthetically
useful
functionalization
procedures.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(20), P. 13748 - 13753
Published: May 9, 2024
We
report
a
highly
diastereoselective
synthesis
of
polysubstituted
bicyclobutanes
possessing
up
to
three
stereodefined
quaternary
centers
and
five
substituents.
Our
strategy
involves
carbometalation
cyclopropenes
followed
by
cyclization
furnish
the
bicyclobutane
ring
system.
This
straightforward
approach
allows
for
incorporation
diverse
range
substituents
functional
groups,
notably
without
need
electron-withdrawing
functionalities.
Organic Letters,
Journal Year:
2023,
Volume and Issue:
25(13), P. 2285 - 2288
Published: March 28, 2023
A
highly
efficient
SnCl4-catalyzed
nucleophilic
isocyanation
of
cyclopropyl
ethers
has
been
developed.
The
reaction
proceeds
at
the
quaternary
carbon
stereocenter
cyclopropane
with
a
complete
inversion
configuration,
providing
new
avenue
for
construction
synthetically
challenging
tertiary
alkyl
isonitriles
high
diastereopurity.
diversity
incorporated
isocyanide
group
demonstrated
by
transformation
into
corresponding
amines,
amides,
and
cyclic
ketoimines.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(31)
Published: May 20, 2024
Abstract
Neighboring
group
participation,
the
assistance
of
non‐conjugated
electrons
to
a
reaction
center,
is
fundamental
phenomenon
in
chemistry.
In
framework
nucleophilic
substitution
reactions,
neighboring
participation
known
cause
rate
acceleration,
first
order
kinetics
(S
N
1),
and
retention
configuration.
The
latter
result
double
inversion:
one
when
displaces
leaving
group,
second
nucleophile
substitutes
group.
This
powerful
control
stereoretention
has
been
widely
used
organic
synthesis
for
more
than
century.
However,
may
also
lead
inversion
configuration,
which
often
overlooked.
Herein,
we
review
this
unique
mode
stereoinversion,
dividing
relevant
reactions
into
three
classes
with
aim
introduce
fresh
perspective
on
different
modes
stereoinversion
via
as
well
factors
that
stereochemical
outcome.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 27, 2025
We
present
a
stereoretentive
nucleophilic
substitution
of
homoallylic
tertiary
alcohols
via
the
formation
nonclassical
cyclopropyl
carbinyl
(CPC)
carbocation
intermediate.
This
strategy
enables
creation
highly
congested
centers
with
preserved
stereocontrol,
addressing
typical
challenges
instability
and
reactivity
in
SN1
mechanisms.
The
stabilization
CPC
intermediate
is
crucial
for
achieving
precise
regio-
stereoselectivity,
significantly
enhancing
utility
SN1-type
mechanisms
complex
molecule
synthesis.
Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(32)
Published: May 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.
