Angewandte Chemie,
Год журнала:
2023,
Номер
135(13)
Опубликована: Янв. 30, 2023
Abstract
Two
new
ring
expansion
strategies
are
reported
for
the
synthesis
of
medium
sized
and
macrocyclic
sulfonamides.
Both
methods
can
be
performed
without
using
classical
protecting
groups,
with
key
step
initiated
by
nitro
reduction
amine
conjugate
addition
respectively.
Each
method
used
to
make
diversely
functionalised
cyclic
sulfonamides
in
good
excellent
yields,
a
range
sizes.
The
size
dependency
synthetic
reactions
is
agreement
outcomes
modelled
Density
Functional
Theory
calculations.
ACS Central Science,
Год журнала:
2023,
Номер
9(12), С. 2196 - 2204
Опубликована: Дек. 8, 2023
Models
can
codify
our
understanding
of
chemical
reactivity
and
serve
a
useful
purpose
in
the
development
new
synthetic
processes
via,
for
example,
evaluating
hypothetical
reaction
conditions
or
silico
substrate
tolerance.
Perhaps
most
determining
factor
is
composition
training
data
whether
it
sufficient
to
train
model
that
make
accurate
predictions
over
full
domain
interest.
Here,
we
discuss
design
datasets
ways
are
conducive
data-driven
modeling,
emphasizing
idea
set
diversity
generalizability
rely
on
choice
molecular
representation.
We
additionally
experimental
constraints
associated
with
generating
common
types
chemistry
how
these
considerations
should
influence
dataset
building.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(23), С. 12870 - 12883
Опубликована: Июнь 2, 2023
The
development
of
chiral
catalysts
that
can
provide
high
enantioselectivities
across
a
wide
assortment
substrates
or
reaction
range
is
priority
for
many
catalyst
design
efforts.
While
several
approaches
are
available
to
aid
in
the
identification
general
systems,
there
currently
no
simple
procedure
directly
measuring
how
given
could
be.
Herein,
we
present
catalyst-agnostic
workflow
centered
on
unsupervised
machine
learning
enables
rapid
assessment
and
quantification
generality.
uses
curated
literature
data
sets
descriptors
visualize
cluster
chemical
space
coverage.
This
network
then
be
applied
derive
generality
metric
through
designer
equations
interfaced
with
other
regression
techniques
prediction.
As
validating
case
studies,
have
successfully
this
method
identify-through-quantification
most
chemotype
an
organocatalytic
asymmetric
Mannich
predicted
phosphoric
acid
addition
nucleophiles
imines.
mechanistic
basis
gleaned
from
calculated
values
by
deconstructing
contributions
enantiomeric
excess
overall
result.
Finally,
our
permitted
mechanistically
informative
screening
allow
experimentalists
rationally
select
highest
probability
achieving
good
result
first
round
development.
Overall,
findings
represent
framework
interrogating
generality,
strategy
should
relevant
catalytic
systems
widely
synthesis.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(44), С. 24175 - 24183
Опубликована: Окт. 27, 2023
The
arylation
of
2-alkyl
aziridines
by
nucleophilic
ring-opening
or
transition-metal-catalyzed
cross-coupling
enables
facile
access
to
biologically
relevant
β-phenethylamine
derivatives.
However,
both
approaches
largely
favor
C–C
bond
formation
at
the
less-substituted
carbon
aziridine,
thus
enabling
only
linear
products.
Consequently,
despite
attractive
disconnection
that
it
poses,
synthesis
branched
arylated
products
from
has
remained
inaccessible.
Herein,
we
address
this
long-standing
challenge
and
report
first
branched-selective
with
aryl
iodides.
This
unique
selectivity
is
enabled
a
Ti/Ni
dual-catalytic
system.
We
demonstrate
robustness
method
twofold
approach:
an
additive
screening
campaign
probe
functional
group
tolerance
feature-driven
substrate
scope
study
effect
local
steric
electronic
profile
each
coupling
partner
on
reactivity.
Furthermore,
diversity
generation
predictive
reactivity
models
guided
mechanistic
understanding.
Mechanistic
studies
demonstrated
arises
TiIII-induced
radical
aziridine.
ACS Catalysis,
Год журнала:
2023,
Номер
13(13), С. 8845 - 8860
Опубликована: Июнь 20, 2023
Despite
the
unique
position
of
gold
catalysis
in
contemporary
organic
synthesis,
this
area
research
is
notorious
for
requiring
activators
and/or
additives
that
enable
by
generating
cationic
forms
catalysts.
Cycloisomerization
reactions
occupy
a
significant
portion
gold-catalyzed
reaction
space,
while
they
represent
diverse
family
are
frequently
utilized
synthesis.
Herein,
hexafluoroisopropanol
(HFIP)
shown
to
be
uniquely
simple
tool
cycloisomerizations,
rendering
use
external
obsolete
and
leading
highly
active
catalytic
systems
with
ppm
levels
catalyst
loading
certain
cases.
HFIP
assumes
dual
role
as
solvent
an
activator,
operating
via
dynamic
activation
Au–Cl
bond
through
hydrogen
bonding,
which
initiates
cycle.
This
special
mode
can
efficient
scalable
cyclization
propargylamides
ynoic
acids
[AuCl(L)]
complexes.
A
thorough
screening
ancillary
ligands
counter
anions
has
been
performed,
establishing
methodology
alternative
elaborate
ligand/catalyst
design
activators.
Additionally,
concept
applied
C–C
bond-forming
cycloisomerization
2H-chromenes
sequential
or
one-pot
transformations
activated
ketoesters,
functionalized
N-heterocyclic
carbene
(NHC)
precursor
salt,
compound
bearing
bioactive
indole
core,
among
others.
Importantly,
mechanistic
investigations,
including
"snapshot"
species
interest
solid
state,
we
were
able
unambiguously
detect
key
H-bonding
interaction
between
catalyst,
shedding
light
on
intermolecular
enables
catalysis.
In
cases
examined
herein,
not
only
excellent
but
also
potent
activator
valuable
synthetic
handle
when
incorporated
into
functional
groups
products.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(8), С. 5702 - 5711
Опубликована: Фев. 19, 2024
Macrocycles
and
medium-sized
rings
are
important
in
many
scientific
fields
technologies
but
hard
to
make
using
current
methods,
especially
on
a
large
scale.
Outlined
herein
is
strategy
by
which
functionalized
macrocycles
can
be
prepared
cyclization/ring
expansion
(CRE)
cascade
reactions,
without
resorting
high
dilution
conditions.
CRE
reactions
designed
operate
exclusively
via
kinetically
favorable
5–7-membered
ring
cyclization
steps;
this
means
that
the
problems
typically
associated
with
classical
end-to-end
macrocyclization
avoided.
A
modular
synthetic
approach
has
been
developed
facilitate
simple
assembly
of
requisite
linear
precursors,
then
converted
into
an
extremely
broad
range
one
nine
protocols.
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(26)
Опубликована: Март 23, 2023
The
chemistry
community
is
currently
witnessing
a
surge
of
scientific
discoveries
in
organic
supported
by
machine
learning
(ML)
techniques.
Whereas
many
these
techniques
were
developed
for
big
data
applications,
the
nature
experimental
often
confines
practitioners
to
small
datasets.
Herein,
we
touch
upon
limitations
associated
with
ML
and
emphasize
impact
bias
variance
on
constructing
reliable
predictive
models.
We
aim
raise
awareness
possible
pitfalls,
thus,
provide
an
introductory
guideline
good
practice.
Ultimately,
stress
great
value
statistical
analysis
data,
which
can
be
further
boosted
adopting
holistic
data-centric
approach
chemistry.
