Methods
suitable for the synthesis of both O- and S-glycosylations
are relatively rare because commonly used promoters like halonium
sources or gold catalysts are incompatible with thiols as nucleophiles.
Here, we present (p-MeO)phenylvinylbenzoates (PMPVB)
as easily accessible, stable, and reactive alkene-based glycosyl donors
that can be activated with catalytic amounts of a Brønsted acid.
This activation protocol not only allows us to synthesize O-glycosides but also can successfully provide S- and C-linked
glycosides. The armed and disarmed donors lead to product formation
in 5 min, showcasing the high reactivity of the donors. Competitive
experiments show that the PMPVB donors are much more reactive than
the corresponding PVB donors even under NIS/TMSOTf conditions, whereas
PVB donors are not reactive enough to be efficiently activated under
Brønsted acid conditions. The potential of the catalytic glycosylation
protocol has also been showcased by synthesizing trisaccharides. The
Brønsted acid activation of PMPVB donors also allows access to C-glycosides in a stereoselective fashion. The easy accessibility
of the donor aglycon on a multigram scale in just two steps makes
the PMPVB donors highly attractive alternatives.
2-Deoxy Glycosyl Ortho-[1-(p-MeOPhenyl)Vinyl]Benzoates (PMPVB) donors have been presented as stable, reactive glycosyl donors for the synthesis of 2-deoxy α-glycosides. The donors react under Brønsted acid conditions to provide the 2-deoxy-α-glycosides...
A sterically strained ionic Brønsted pair complex obtained from a sterically bulky base 2,4,6-tri-tert-butylpyridine and hydrochloric acid imbues unusual reactivity to the anionic chloride. The complete shielding of the cationic [N−H] + by the bulky ortho-tert-butyl groups weakens the possible hydrogen-bonding interactions with the chloride anion, and the [N−H] + •••Cl − distance is unusually longer (3.10 Å). This results in strained/frustrated electrostatic interactions between the ion-pair, thus infusing an increased reactivity in both of the ions, which results in the activation of a third molecule like thiol via hydrogen-bonding. This intriguing weak interaction-based reactivity has been utilized to develop an organocatalytic synthesis of 2-deoxy-β-thioglycosides from glycals. While the 1 H NMR studies showcase the diamagnetic activation of thiols in the presence of the catalyst, the electron paramagnetic resonance (EPR) studies reveal the generation of a radical species that suggests a possible frustrated radical pair catalysis. Besides, IR spectroscopic studies explain the intriguing influence of size/charge density of the anion on the solvationinsusceptible, cationic [TTBPyH] + and on the observed reactivity.
We
demonstrate here that the strained and bulky protonated 2,4,6-tri-tert-butylpyridine (TTBPy) triflate salt serves as a mild
and efficient organocatalyst for the diastereoselective C-Ferrier glycosylation of various glycals. The importance of the
role of the 1/2 H2O molecule trapped in the catalyst has
been disclosed. The mechanism of action involves unique anionic triflate
and H2O hydrogen-bond interactions that assist the activation
of allylsilanes, providing unprecedented access to diastereoselective
phenylallyl Ferrier glycosides.
The alkene-based o-[1-(p-MeO-phenyl)vinyl]benzoates
(PMPVB) donors that can be remotely activated under catalytic Brønsted
acidic conditions have been utilized to synthesize the C-linked indolyl glycosides in a regio- and stereoselective manner.
The highly reactive glycosyl donors allow the usage of the poorly
nucleophilic N-Boc and N-acetyl
indole derivatives, leading to the indolyl glycosides in excellent
yields and stereoselectivities. Also, conditions were developed for
recycling the byproduct, which significantly improves the potential
of these donors.
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