9 research outputs found
Asymmetric Synthesis of α‑Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis
Biologically relevant chiral 3,3-disubstituted
oxindole products
containing a β-fluoroamine unit are obtained in high yields
and with excellent stereoselectivity (up to 99% ee, dr >20:1 for <i>syn</i>) through the organocatalytic direct Mannich reaction
of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones
as the bench-stable precursors of sensitive imines by using a chiral
oligoethylene glycol and KF as a cation-binding catalyst and base,
respectively. This protocol can be easily scaled without compromising
the asymmetric induction. Furthermore, this protocol was also successfully
extended to generate tetrasubstituted C–Cl and C–Br
stereogenic centers
Asymmetric Synthesis of α‑Fluoro-β-Amino-oxindoles with Tetrasubstituted C–F Stereogenic Centers via Cooperative Cation-Binding Catalysis
Biologically relevant chiral 3,3-disubstituted
oxindole products
containing a β-fluoroamine unit are obtained in high yields
and with excellent stereoselectivity (up to 99% ee, dr >20:1 for <i>syn</i>) through the organocatalytic direct Mannich reaction
of 3-fluoro-oxindoles as fluoroenolate precursors and α-amidosulfones
as the bench-stable precursors of sensitive imines by using a chiral
oligoethylene glycol and KF as a cation-binding catalyst and base,
respectively. This protocol can be easily scaled without compromising
the asymmetric induction. Furthermore, this protocol was also successfully
extended to generate tetrasubstituted C–Cl and C–Br
stereogenic centers
Organocatalytic Asymmetric Synthesis of Chiral Dioxazinanes and Dioxazepanes with <i>in Situ</i> Generated Nitrones via a Tandem Reaction Pathway Using a Cooperative Cation Binding Catalyst
Heterocyclic
skeletons play major roles in pharmaceuticals and
biological processes. Cycloaddition reactions are most suitable synthetic
tools to efficiently construct chemically diverse sets of heterocycles
with great structural complexity owing to the simultaneous or sequential
formation of two or more bonds, often with a high degree of selectivity.
Herein, we report an unprecedented formal cycloaddition of <i>N</i>-Boc-<i>N</i>-hydroxy amido sulfones as the nitrone
precursors with terminal-hydroxy α,β-unsaturated carbonyls
in the presence of Song’s chiral oligoethylene glycol as a
cation-binding catalyst and KF as a base to afford a wide range of
highly enantio- and diastereo-enriched six-membered dioxazinane and
seven-membered dioxazepane heterocycles. In this process, nitrones
as well as terminal-hydroxy α,β-unsaturated carbonyls
serve as “amphiphilic” building units, and the reaction
proceeds through a tandem pathway sequence of oxa-Mannich reaction/oxa-Michael
reaction/tautomerization/protonation. The cation-binding catalysis
in a densely confined chiral space <i>in situ</i> formed
by the incorporation of potassium salt is the key to this successful
catalysis. This strategy opens a new pathway for the asymmetric synthesis
of diverse heterocyclic skeletons of great complexity
Bioinspired Synthesis of Chiral 3,4-Dihydropyranones via S‑to‑O Acyl-Transfer Reactions
A bioinspired synthesis of chiral
3,4-dihydropyranones via S-to-O
acyl-transfer reactions is described. Asymmetric Michael addition–lactonization
reactions of β,γ-unsaturated α-keto esters with
thioesters are catalyzed by proline-derived urea, providing 3,4-dihydropyranones
and spiro-3,4-dihydrocoumarin-fused 3′,4′-dihydropyranones
in high yield (up to 94%) with excellent stereoselectivities (up to
>20:1 dr, 99% <i>ee</i>) under catalyst loadings as low
as 1 mol %
Fluoride Anions in Self-Assembled Chiral Cage for the Enantioselective Protonation of Silyl Enol Ethers
The potential of Song’s
chiral oligoethylene glycols (oligoEGs) as catalysts was explored
in the enantioselective protonation of trimethylsilyl enol ethers
in combination with alkali metal fluoride (KF and CsF) and in the
presence of a proton source. Highly enantioselective protonations
of various silyl enol ethers of α-substituted tetralones were
achieved, producing chiral α-substituted tetralones in full
conversion and with up to 99% ee. The established protocol was successfully
extended to the synthesis of biologically relevant chiral α-substituted
chromanone and thiochromanone derivatives
Biomimetic Catalytic Retro-Aldol Reaction Using a Cation-Binding Catalyst: A Promising Route to Axially Chiral Biaryl Aldehydes
Here we describe a biomimetic catalytic retro-aldol reaction
of
racemic α-substituted β-hydroxy ketones utilizing a chiral
oligoEG cation-binding catalyst as a type-II aldolase mimic. Our investigation
of various aldol substrates has demonstrated that our biomimetic retro-aldol
protocol enables rapid access to highly enantiomerically enriched
aldols with a selectivity factor (s) of up to 70.
Additionally, we have demonstrated the synthetic strategy’s
feasibility for accessing diverse and valuable axially chiral aldehydes
Enantioselective Synthesis of <i>anti</i>–<i>syn</i>-Trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-Tetrahalides via Asymmetric β‑Elimination
Structural motifs containing contiguous
halide-bearing stereocenters are common in natural products as well
as bioactive molecules. A few successful examples have been reported
in the area of asymmetric vicinal dihalogenation of alkenes for accessing
dihalogenated products; in this report, an alternative generation
method of contiguous halide-bearing stereocenters α,β,γ,δ
relative to carbonyl group in excellent enantioselectivity is proposed
by utilizing a Song’s oligoEG catalyst-catalyzed asymmetric β-elimination.
According to this methodology, a wide range of <i>anti</i>–<i>syn</i>-trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-tetrahalides
with high levels of enantioselectivity were synthesized. The synthetic
utility of the contiguous halide-bearing stereocenters was demonstrated
by several transformations. The results of high-resolution mass spectrometry
indicated that the favorable interaction between catalyst and one
of the enantiomers of racemic contiguously multihalogenated ketone
contributed to the original enantioselectivity of dehydrohalogenation.
A deuterium kinetic isotope effect experiment revealed that this β-elimination
reaction proceeds by the <i>E</i>2 mechanism. This strategy
opens a new pathway for the asymmetric synthesis of contiguous halide-bearing
stereocenters of great complexity
Asymmetric Synthesis of Trisubstituted Tetrahydrothiophenes via in Situ Generated Chiral Fluoride-Catalyzed Cascade Sulfa-Michael/Aldol Reaction of 1,4-Dithiane-2,5-diol and α,β-Unsaturated Ketones
A chiral fluoride-catalyzed
asymmetric cascade sulfa-Michael/aldol
condensation reaction of 1,4-dithiane-2,5-diol and a series of α,β-unsaturated
ketones is described to access chiral trisubstituted tetrahydrothiophene
derivatives. The target products, including the spiro tetrahydrothiophene
derivatives bearing a five-, six-, and seven-membered ring, were highly
functionalized and showed high ee value. This established protocol
realized a highly enantioselective reaction with a catalytic amount
of KF and Song’s chiral oligoEG via in situ generated chiral
fluoride to construct useful heterocyclic skeletons with great complexity
Enantioselective Synthesis of <i>anti</i>–<i>syn</i>-Trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-Tetrahalides via Asymmetric β‑Elimination
Structural motifs containing contiguous
halide-bearing stereocenters are common in natural products as well
as bioactive molecules. A few successful examples have been reported
in the area of asymmetric vicinal dihalogenation of alkenes for accessing
dihalogenated products; in this report, an alternative generation
method of contiguous halide-bearing stereocenters α,β,γ,δ
relative to carbonyl group in excellent enantioselectivity is proposed
by utilizing a Song’s oligoEG catalyst-catalyzed asymmetric β-elimination.
According to this methodology, a wide range of <i>anti</i>–<i>syn</i>-trihalides and <i>anti</i>–<i>syn</i>–<i>anti</i>-tetrahalides
with high levels of enantioselectivity were synthesized. The synthetic
utility of the contiguous halide-bearing stereocenters was demonstrated
by several transformations. The results of high-resolution mass spectrometry
indicated that the favorable interaction between catalyst and one
of the enantiomers of racemic contiguously multihalogenated ketone
contributed to the original enantioselectivity of dehydrohalogenation.
A deuterium kinetic isotope effect experiment revealed that this β-elimination
reaction proceeds by the <i>E</i>2 mechanism. This strategy
opens a new pathway for the asymmetric synthesis of contiguous halide-bearing
stereocenters of great complexity