ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(13), P. 9150 - 9157
Published: June 26, 2023
Biosynthesis
utilizes
kinetic
strategies
to
regulate
the
chemoselectivity
for
transformations
of
molecules
containing
multiple
active
reaction
sites.
But
it
is
a
grand
challenge
realize
without
protecting
group
manipulations
chemosynthesis.
α-Amino
acid
esters
contain
NH2
and
α-C-H,
two
nucleophilic
Direct
asymmetric
α-C-alkylation
NH2-unprotected
amino
with
alkyl
halides
represents
one
most
straightforward
access
chiral
quaternary
α-amino
acids,
which
are
widely
present
in
many
pharmaceuticals.
However,
transformation
challenging
due
high
reactivity
intrinsic
N-alkylation.
Here,
by
using
pyridoxal
6
having
benzene-pyridine
biaryl
skeleton
as
carbonyl
catalyst,
we
successfully
unlock
C–H
bonds
toward
protection
group,
forming
wide
range
up
99%
yield
ee.
Like
biological
systems,
this
protocol
featured
no
atom
step
efficiencies
enabled
biomimetic
organocatalyst.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 11, 2024
Direct
asymmetric
α-C-H
conjugate
addition
of
propargylamines
to
α,β-unsaturated
ketones
remains
a
great
challenge
due
the
low
α-amino
C-H
acidity
and
nucleophilic
interference
NH
An
approach
utilizing
N-heterocyclic
carbene
for
nitrile
formation
and
desymmetrization
reaction
is
developed.
The
process
involves
kinetic
resolution,
with
the
axially
chiral
aryl
monoaldehydes
obtained
in
moderate
yields
excellent
optical
purities.
These
can
be
conveniently
transformed
into
functionalized
molecules,
showing
great
potential
as
catalysts
organic
chemistry.
The Journal of Organic Chemistry,
Journal Year:
2023,
Volume and Issue:
88(12), P. 7849 - 7857
Published: Jan. 25, 2023
In
the
presence
of
chiral
pyridoxamine
4b
as
catalyst
and
2,2-diphenylglycine
(3)
amine
source,
asymmetric
biomimetic
transamination
trifluoromethyl
ketones
produces
optically
active
α-trifluoromethyl
amines
6
in
81–98%
yields
with
88–95%
ee's
under
mild
conditions.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(34), P. 7161 - 7165
Published: Aug. 19, 2024
Herein
we
present
an
efficient
chiral
phosphoric-acid-catalyzed
atropoenantioselective
asymmetric
reductive
amination
of
biaryl
dialdehydes.
The
process
involves
desymmetrization
and
the
following
kinetic
resolution,
with
a
wide
range
axially
aryl
aldehydes
obtained
high
optical
purities.
Biomimetic
asymmetric
transamination
reactions
have
recently
been
one
of
the
hottest
topics
in
organocatalysis
field,
but
detailed
mechanism
and
origin
stereoselectivity
are
not
clear.
Herein,
these
kinds
between
α-keto
acids
amines
catalyzed
by
axial
pyroxamine
systematically
explored
performing
density
functional
theory
(DFT)
calculations.
The
fundamental
reaction
pathway
can
be
divided
into
two
stages,
i.e.
amino
transfer
stage
to
form
chiral
amine
product
imine
hydration
for
generation
ketone
product.
To
uncover
mystery
center
produced
protonation
stage,
total
five
possible
pathways
were
investigated
compared,
HOAc-assisted
[1,3]-proton
formation
carbon
has
identified
as
stereoselectivity-determining
step
most
energetically
favorable
pathway.
Further
atoms-in-molecules
(AIM)
analyses
carried
out
predict
stereoselectivity,
N–H⋯O
hydrogen
bond
interaction
pyridoxamine
catalyst
acid
substrate
is
responsible
energetical
favorability
S-configurational
These
insights
will
great
value
understanding
rational
design
biomimetic
organocatalysts
reactions.
Catalytic
enantioselective
α-C–H
functionalization
of
achiral
amines
could
provide
an
ideal
synthetic
approach
toward
chiral
amines.
The
alkyl
constitute
the
most
diverse
and
synthetically
important
class
However,
inert
nature
renders
activation
as
carbanionic
nucleophiles
for
catalytic
asymmetric
reactions
yet
unmet
challenge.
We
describe
here
that
N-arylidene
be
activated
carbanions
conjugate
addition
Mannich
reaction.
In
their
own
right,
these
results
represent
a
new
generally
useful
to
synthesis
α,
α-dialkyl
More
importantly,
they
highlight
enormous
potential
readily
available
widely
applicable
synthons
