Abstract
C
‐alkyl
glycosides
play
a
crucial
role
in
various
bioactive
compounds.
However,
the
synthesis
of
poses
significant
challenges,
particularly
through
C(
sp
3
)−H
glycosylation.
Here,
we
report
set
reactions
for
constructing
directing‐group‐mediated
functionalization
unactivated
γ
‐C(
bonds
under
mild
conditions.
These
not
only
achieve
high
regioselectivity
and
stereoselectivity
glycosylation,
but
also
exhibit
wide
substrate
scope.
They
are
compatible
with
both
arene
alkane
substrates,
as
well
natural
unnatural
amino
acid
substrates.
Mechanistic
studies
have
shown
that
directing‐group
8‐aminoquinoline
(AQ)
picolinamide
(PA)
may
affect
chirality
β
‐carbon
L
‐valine
sterically
favorable
trans
‐palladacycle
intermediate,
resulting
(
R
)
or
S
configuration
glycosylated
acid,
respectively.
promising
to
provide
convenient
powerful
tool
carbohydrate‐based
drugs
future.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(22)
Published: March 17, 2023
2-Deoxy-β-C-glycosides
represent
an
important
class
of
carbohydrates
that
are
present
in
many
bioactive
molecules.
However,
owing
to
the
lack
substituents
at
C2
position,
stereoselective
synthesis
2-deoxy-β-C-glycosides
is
highly
challenging.
Herein,
we
report
a
ligand-controlled
C-alkyl
glycosylation
reaction
access
2-deoxy-β-C-alkyl
glycosides
from
readily
available
glycals
and
alkyl
halides.
This
method
exhibits
broad
substrate
scope
excellent
diastereoselectivity
under
very
mild
conditions.
In
addition,
unprecedented
stereodivergent
2-deoxy-C-ribofuranosides
achieved
using
different
chiral
bisoxazoline
ligands.
Mechanistic
studies
suggest
hydrometallation
glycal
with
bisoxazoline-ligated
Co-H
species
may
be
turnover-limiting
stereodetermining
step
this
transformation.
Chemistry - A European Journal,
Journal Year:
2023,
Volume and Issue:
29(32)
Published: March 21, 2023
Abstract
In
recent
years,
the
synthesis
of
C‐aryl
glycosides
hrough
C−H
functionalization
has
attracted
extensive
attention
organic
chemists
due
to
its
steps
and
atomic
economy.
this
concept,
we
systematically
summarizes
with
diverse
regioselectivity
diastereoselectivity
from
perspective
arylation
glycosylation
arenes.
It
can
be
found
that
a
series
recently
developed
reactions
have
higher
site‐selectivity
diastereomeric
selectivity
than
Friedel–Crafts
reaction.
The
reaction
conditions
are
milder,
which
compatible
acid‐sensitive
protective
groups,
such
as
acetals
or
ketals,
deprotection
is
more
convenient.
seen
there
few
reports
on
remote
aromatic
hydrocarbons,
new
field
needs
further
research.
addition,
lot
shortcomings,
need
explored:
a)
precise
regulation
stereoselectivity
in
process
also
optimization;
b)
research
mechanism
almost
limited
DFT
calculation,
no
exact
experimental
evidence.
For
key
parts,
specific
between
cyclo‐metal
intermediates
glycosyl
donors
ortho
‐C
Ar
−H
still
unclear;
c)
fact
aryl
glycoside
compounds
contain
bare
hydroxyl
groups
practical
applications,
it
an
urgent
problem
realize
compatibility
substrates
containing
naked
remove
by
mild
efficient
method
after
reaction;
d)
rapidly
developing
field,
study
greener,
economical
arenes
future,
will
conducive
biological
application
significance.
Molecules,
Journal Year:
2022,
Volume and Issue:
27(21), P. 7439 - 7439
Published: Nov. 1, 2022
Aryl-C-glycosides,
of
both
synthetic
and
natural
origin,
are
great
significance
in
medicinal
chemistry
owing
to
their
unique
structures
stability
towards
enzymatic
chemical
hydrolysis
as
compared
O-glycosides.
They
well-known
antibiotics
potent
enzyme
inhibitors
possess
a
wide
range
biological
activities
such
anticancer,
antioxidant,
antiviral,
hypoglycemic
effects,
so
on.
Currently,
number
aryl-C-glycoside
drugs
on
sale
for
the
treatment
diabetes
related
complications.
This
review
summarizes
findings
scaffolds
over
past
20
years,
concerning
new
(over
200
molecules),
bioactivities—including
anti-inflammatory,
antivirus,
glycation
inhibitory
other
pharmacological
effects—as
well
synthesis.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
11(12)
Published: Jan. 18, 2024
Among
C-glycosides,
C-alkyl
glycosides
are
significant
building
blocks
for
natural
products
and
glycopeptides.
However,
research
on
efficient
construction
methods
remains
relatively
limited.
Compared
with
Michael
acceptors,
non-activated
olefins
more
challenging
substrates
have
rarely
been
employed
in
the
of
C-glycosides.
Here,
a
highly
convenient
approach
synthesis
through
nickel-catalyzed
C(sp
Advanced Synthesis & Catalysis,
Journal Year:
2024,
Volume and Issue:
366(7), P. 1484 - 1508
Published: Feb. 29, 2024
Abstract
Recently,
C
‐glycosidic
bonds
have
emerged
as
pivotal
elementary
units
present
in
many
naturally
occurring
alkaloids
well
pharmaceutically
active
molecules.
Because
of
the
stability
and
great
utility
‐glycosides,
synthetic
approaches
en
route
to
C−C
bond
formation
gradually
become
a
center
attraction
carbohydrate
chemistry.
Towards
these
researches,
‐glycosylation
with
heteroaryl
moieties
like
indole,
tryptophan
can
remarkably
expand
functional
structural
evolution,
which
has
value
for
medicinal
chemists
chemical
biologists.
The
indolyl
tryptophan‐
‐glycosides
unique
structures
biological
activities
that
attracted
number
studies.
Therefore,
motifs
possessed
an
extensive
interest
direction
efficient
synthesis.
Herein,
this
review
systematically
summarizes
classical
‐heteroaryl
glycosides
mainly
focusing
on
indole
Furthermore,
highlighted
recently
developed
metal‐catalyzed
C−H
functionalization
photoinduced
cross‐coupling
strategies
aim
control
regioselectivity
diastereoselectivity
reaction
In
view
type,
mechanism,
status,
will
cover
synthesis
diverse
regio‐
from
four
perspectives
include
a)
conventional
approach,
b)
heterocyclization
sequence,
c)
functionalization,
d)
cross‐coupling.
1.
Introduction
2.
Strategies
2.1.
Conventional
approach
2.2.
Heterocyclization
sequence
2.3.
Metal‐catalyzed
2.4.
Photoinduced
3.
Summary
Outlook
Journal of the American Chemical Society,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 5, 2025
This
study
presents
the
development
and
catalytic
applications
of
tetrafluororesorcin[4]arene
hexameric
capsule
(capsule
II)
as
a
novel
supramolecular
catalyst.
It
demonstrates
unprecedented
activity,
enabling
β-selective
glycosylation
glycals
to
2-deoxy
glycosides─a
transformation
that
has
not
been
achieved
before
in
molecular
catalysis.
Mechanistic
investigations,
including
experimental
computational
studies,
revealed
high
β-selectivity
arises
from
proton
wire
mechanism
along
capsule's
surface,
coupling
glycal
protonation
with
nucleophile
deprotonation.
Control
experiments
confirmed
unique
reactivity
II
compared
its
nonfluorinated
predecessor,
I,
showcasing
potential
expand
boundaries
Organic Letters,
Journal Year:
2023,
Volume and Issue:
25(22), P. 4070 - 4074
Published: May 26, 2023
Conjugation
of
carbohydrates
to
ferrocene
scaffolds
is
great
value
in
drug
design,
given
the
nontoxic
and
lipophilic
nature
ferrocene.
However,
efficient
stereoselective
synthesis
C-ferrocenyl
glycosides
remains
a
challenge.
Herein,
we
developed
Pd-catalyzed
C-H
glycosylation
provide
rapid
access
sole
bis-C-ferrocenyl
good
high
yields
(up
98%
yield)
with
exclusive
stereoselectivity.
A
diverse
range
glycosyl
chlorides
were
well
tolerated,
including
d-mannose,
d-glucose,
l-xylose,
l-rhamnose,
d-mannofuranose,
d-ribofuranose.
Additionally,
mononuclear
PdII
intermediate
was
characterized
by
X-ray
single-crystal
diffraction,
might
participate
palladation
step.
Organic Letters,
Journal Year:
2023,
Volume and Issue:
25(39), P. 7170 - 7175
Published: Sept. 27, 2023
An
efficient
and
general
approach
for
the
synthesis
of
indolyl-C-glycosides
via
aminopalladation
subsequent
Heck-type
glycosylation
easily
available
2-alkynylanilines
glycals
has
been
developed.
This
protocol
features
excellent
stereoselectivity,
a
broad
substrate
scope,
mild
reaction
conditions.
In
addition,
2,3-pseudoglycals
also
successfully
participated
in
this
cascade
reaction,
affording
C2/C3-branched
indolyl
glycosides
with
high
regio-/stereoselectivity.
The
utility
was
demonstrated
by
large-scale
diversified
synthetic
transformations
desired
products.
ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(8), P. 5656 - 5664
Published: April 11, 2023
Mutarotation
of
O-glycans
and
O-glycosides
has
long
been
well-established
exploited
in
the
stereocontrolled
chemical
synthesis
O-glycosides,
while
few
examples
C-glycoside
anomerization
are
known
to
date.
During
development
a
simple
iridium
catalyst-promoted
α-stereoselective
C-glycosylation
2-indoly-pyridine
with
glycal
donors,
we
serendipitously
discovered
occurrence
2-deoxy-C-glycoside
anomerization,
enabling
α-to-β
configuration
conversion.
Control
experiments
density
functional
theory
calculations
were
performed
explore
mechanistic
details
products,
which
could
tolerate
C-aryl
C-alkyl-glycosides.
The
reaction
plausibly
proceeds
through
pathway
involving
activation
C(sp3)–H
bond
mediated
by
catalyst
reversible
hydrogen
transfer,
rather
than
classical
mechanisms
endocyclic
cleavage
C1–O5
or
exocyclic
glycosidic
bond.
