Synthesis,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 4, 2024
Abstract
Recently,
many
saturated
bioisosteres
of
the
benzene
ring
have
been
developed,
and
their
applications
in
drug
development
evaluated.
Most
these
are
caged
hydrocarbons,
which
rigid
skeletons
three-dimensional
spaces.
Recent
efforts
to
synthesize
hydrocarbons
enabled
access
multi-functionalized
congeners
that
expected
be
(bio)isosteres
benzenes.
This
short
review
summarizes
recently
reported
methods
for
obtaining
(typically
more
than
disubstituted)
hydrocarbons.
1
Introduction
2
Proposed
Structures
Caged
Hydrocarbons
as
Saturated
(Bio)isosteres
Benzene
Ring:
A
Brief
Summary
3
Access
Multi-functionalized
Hydrocarbons:
De
Novo
Synthetic
Approaches
3.1
Bicyclo[1.1.1]pentanes
(BCPs)
3.2
Bicyclo[2.1.1]hexanes
(BCHs)
3.3
Bicyclo[3.1.1]heptanes
(BCHeps)
3.4
Others
4
C–H
Functionalization
5
Conclusion
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(8)
Published: Jan. 5, 2024
Abstract
The
introduction
of
trifluoromethyl
groups
into
organic
molecules
is
paramount
importance
in
modern
synthetic
chemistry
and
medicinal
chemistry.
While
methods
for
constructing
C(sp
2
)−CF
3
bonds
have
been
well
established,
the
advancement
practical
comprehensive
approaches
forming
remains
considerably
restricted.
In
this
work,
we
describe
an
efficient
site‐specific
deaminative
trifluoromethylation
reaction
aliphatic
primary
amines
to
afford
corresponding
alkyl
compounds.
proceeds
at
room
temperature
with
readily
accessible
N
‐anomeric
amide
(Levin's
reagent)
bench‐stable
bpyCu(CF
)
(Grushin's
reagent,
bpy=2,2′‐bipyridine)
under
blue
light.
protocol
features
mild
conditions,
good
functional
group
tolerance,
moderate
yields.
Remarkably,
method
can
be
applied
direct,
late‐stage
natural
products
bioactive
molecules.
Experimental
mechanistic
studies
were
conducted,
a
radical
mechanism
proposed,
wherein
dual
roles
Grushin's
reagent
elucidated.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(26), P. 17719 - 17727
Published: June 20, 2024
Selectivity
in
organic
chemistry
is
generally
presumed
to
arise
from
energy
differences
between
competing
selectivity-determining
transition
states.
However,
cases
where
static
density
functional
theory
(DFT)
fails
reproduce
experimental
product
distributions,
dynamic
effects
can
be
examined
understand
the
behavior
of
more
complex
reaction
systems.
Previously,
we
reported
a
method
for
nitrogen
deletion
secondary
amines
which
relies
on
formation
isodiazene
intermediates
that
subsequently
extrude
dinitrogen
with
concomitant
C-C
bond
via
caged
diradical.
Herein,
detailed
mechanistic
analysis
1-aryl-tetrahydroisoquinolines
presented,
suggesting
this
system
previously
determined
diradical
mechanism
undergoes
dynamically
controlled
partitioning
both
normal
1,5-coupling
and
an
unexpected
spirocyclic
dearomatized
intermediate,
converges
expected
indane
by
unusually
facile
1,3-sigmatropic
rearrangement.
This
not
reproduced
DFT
but
supported
quasi-classical
molecular
dynamics
calculations
unifies
several
unusual
observations
system,
including
partial
chirality
transfer,
nonstatistical
isotopic
scrambling
at
ethylene
bridge,
isolation
species
related
heterocyclic
series,
observation
introduction
8-substituent
dramatically
improves
enantiospecificity.
Chinese Journal of Chemistry,
Journal Year:
2024,
Volume and Issue:
42(21), P. 2656 - 2667
Published: July 16, 2024
Comprehensive
Summary
Nitrenes,
as
neutral
monovalent
nitrogen‐centered
molecular
species,
can
insert
into
various
bond
or
remove
nitrogen
atoms
from
amines.
Nitrene
assisted
single‐atom
skeletal
editing,
discovered
decades
ago,
provides
an
efficient
approach
for
the
precise
alteration
of
cyclic
skeletons.
In
this
review,
we
briefly
summarize
early
studies
on
editing
frameworks
involving
nitrene
and
introduce
several
recent
important
advances
systematically.
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 2, 2025
We
recently
reported
a
chiral
phosphoric
acid
(CPA)
catalyzed
enantioselective
photomediated
ring
contraction
of
piperidines
and
other
saturated
heterocycles.
By
extruding
single
heteroatom
from
ring,
this
transformation
builds
desirable
C(sp3)–C(sp3)
bonds
in
the
contracted
products;
however,
origins
enantioselectivity
remain
poorly
understood.
In
work,
has
been
explored
across
an
expanded
structurally
diverse
substrate
scope,
revealing
wide
range
enantioselectivities
(0–99%)
using
two
distinct
CPA
catalysts.
Mechanistic
investigations
support
rate-determining
excitation
that
generates
short-lived
achiral
intermediates
are
intercepted
by
enantiodetermining
closure.
The
effects
competitive
uncatalyzed
reactivity
light-driven
reversibility
closure
on
have
elucidated.
Statistical
models
were
built
regressing
scope
against
key
structural
features
products
for
both
resultant
suggested
factors
influence
response
each
catalyst
enabled
rational
modification
pharmaceutically
relevant
target
molecule
to
improve
enantioselectivity.
Finally,
density
functional
theory
(DFT)-based
transition
state
analysis
identified
noncovalent
interactions
with
correlated
unique
selectivity-relevant
uncovered
through
statistical
modeling.
Our
findings
not
only
offer
comprehensive
insight
into
system
but
should
also
aid
future
development
related
CPA-catalyzed
reactions.
