15 research outputs found
Direct Catalytic Enantioselective Vinylogous Aldol Reaction of α‑Branched Enals with Isatins
The direct vinylogous aldol reaction of α-substituted α,β-unsaturated aldehydes with isatins is described. The chemistry provides easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol and perfect γ-site selectivity. Preliminary mechanistic studies suggest that, depending on the nature of the α-branched enal substituents, two divergent reaction mechanisms can be operating, leading to different products and stereochemical outcomes
Mechanism of the Stereoselective α‑Alkylation of Aldehydes Driven by the Photochemical Activity of Enamines
Herein
we describe our efforts to elucidate the key mechanistic
aspects of the previously reported enantioselective photochemical
α-alkylation of aldehydes with electron-poor organic halides.
The chemistry exploits the potential of chiral enamines, key organocatalytic
intermediates in thermal asymmetric processes, to directly participate
in the photoexcitation of substrates either by forming a photoactive
electron donor–acceptor complex or by directly reaching an
electronically excited state upon light absorption. These photochemical
mechanisms generate radicals from closed-shell precursors under mild
conditions. At the same time, the ground-state chiral enamines provide
effective stereochemical control over the enantioselective radical-trapping
process. We use a combination of conventional photophysical investigations,
nuclear magnetic resonance spectroscopy, and kinetic studies to gain
a better understanding of the factors governing these enantioselective
photochemical catalytic processes. Measurements of the quantum yield
reveal that a radical chain mechanism is operative, while reaction-profile
analysis and rate-order assessment indicate the trapping of the carbon-centered
radical by the enamine, to form the carbon–carbon bond, as
rate-determining. Our kinetic studies unveil the existence of a delicate
interplay between the light-triggered initiation step and the radical
chain propagation manifold, both mediated by the chiral enamines
Direct Catalytic Enantioselective Vinylogous Aldol Reaction of α‑Branched Enals with Isatins
The direct vinylogous aldol reaction of α-substituted α,β-unsaturated aldehydes with isatins is described. The chemistry provides easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol and perfect γ-site selectivity. Preliminary mechanistic studies suggest that, depending on the nature of the α-branched enal substituents, two divergent reaction mechanisms can be operating, leading to different products and stereochemical outcomes
Direct Catalytic Enantioselective Vinylogous Aldol Reaction of α‑Branched Enals with Isatins
The direct vinylogous aldol reaction of α-substituted α,β-unsaturated aldehydes with isatins is described. The chemistry provides easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol and perfect γ-site selectivity. Preliminary mechanistic studies suggest that, depending on the nature of the α-branched enal substituents, two divergent reaction mechanisms can be operating, leading to different products and stereochemical outcomes
Direct Catalytic Enantioselective Vinylogous Aldol Reaction of α‑Branched Enals with Isatins
The direct vinylogous aldol reaction of α-substituted α,β-unsaturated aldehydes with isatins is described. The chemistry provides easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol and perfect γ-site selectivity. Preliminary mechanistic studies suggest that, depending on the nature of the α-branched enal substituents, two divergent reaction mechanisms can be operating, leading to different products and stereochemical outcomes
Direct Catalytic Enantioselective Vinylogous Aldol Reaction of α‑Branched Enals with Isatins
The direct vinylogous aldol reaction of α-substituted α,β-unsaturated aldehydes with isatins is described. The chemistry provides easy access to valuable 3-substituted 3-hydroxyoxindole derivatives with high stereocontrol and perfect γ-site selectivity. Preliminary mechanistic studies suggest that, depending on the nature of the α-branched enal substituents, two divergent reaction mechanisms can be operating, leading to different products and stereochemical outcomes
Asymmetric Photocatalytic C–H Functionalization of Toluene and Derivatives
Reported herein is a visible-light-mediated
organocatalytic direct
C–H functionalization of toluene derivatives to afford enantioenriched
β-benzylated aldehydes from the corresponding enals. The process
combines the oxidative power of a chiral excited-state iminium ion
and the basic nature of its counteranion to trigger the generation
of benzylic radicals by means of a sequential multisite proton-coupled
electron transfer mechanism. This study shows that feedstock chemicals
generally used as solvents, such as toluene and xylene derivatives,
can be used as substrates for making chiral molecules with high enantioselectivity
A Mechanistic Rationale for the 9‑Amino(9-deoxy)<i>epi</i> Cinchona Alkaloids Catalyzed Asymmetric Reactions via Iminium Ion Activation of Enones
The 9-amino(9-deoxy)<i>epi</i> cinchona alkaloids have
expanded the synthetic potential of asymmetric aminocatalysis, enabling
the highly stereoselective functionalization of a variety of sterically
hindered carbonyl compounds. However, there is a lack of basic understanding
of the mechanisms of cinchona-based primary aminocatalysis. Herein,
we describe how a combination of experimental and theoretical mechanistic
studies has revealed the origin of the stereoselectivity of the Friedel–Crafts
alkylation of indoles with α,β-unsaturated ketones catalyzed
by 9-amino(9-deoxy)<i>epi</i> quinine. An essential role
for the achiral acid cocatalyst is uncovered: upon condensation of
the cinchona catalyst with the enone, the resulting covalent imine
intermediate and the acid interact to build-up a well-structured ion-pair
supramolecular catalytic assembly, which is stabilized by multiple
attractive noncovalent interactions. All the components of the assembly
cooperatively participate in the stereocontrolling event, with the
anion of the achiral acid being the structural element responsible
for the π-facial discrimination of the iminium ion intermediate
Multicatalytic Asymmetric Synthesis of Complex Tetrahydrocarbazoles via a Diels–Alder/Benzoin Reaction Sequence
Expanding upon the recently developed aminocatalytic asymmetric indole-2,3-quinodimethane strategy, a straightforward synthesis of structurally and stereochemically complex tetrahydrocarbazoles has been devised. The chemistry’s complexity-generating power was further harnessed by designing a multicatalytic, one-pot Diels–Alder/benzoin reaction sequence to stereoselectively access <i>trans</i>-fused tetracyclic indole-based compounds having four stereogenic centers with very high fidelity
Computational Study with DFT and Kinetic Models on the Mechanism of Photoinitiated Aromatic Perfluoroalkylations
A combination of DFT calculations
and kinetic models is applied
to fully elucidate the seemingly complex reactivity of α-cyano
arylacetates toward metal-free photoinitiated aromatic perfluoroalkylation.
The resulting mechanistic framework rationalizes the observed quantum
yield as well as the differences in reactivity and/or selectivity
of seemingly similar substrates. The use of a kinetic model for the
chemical interpretation of the DFT-computed reaction constants is
shown to be critical