71 research outputs found
The interplay of thermodynamics and kinetics in dictating organocatalytic reactivity and selectivity
Recent reports of the real-time identification of intermediates in organocatalytic reactions by NMR spectroscopy coupled with detailed kinetic studies highlight a potential role for stable intermediates reversibly formed downstream from what is generally considered to be the enantioselectivity-determining step. In this work, we employ kinetic modeling to explore these concepts further. We demonstrate that when an intermediate is common to multiple reaction pathways, the relative reactivity of these pathways dictates the ultimate outcome, regardless of the relative stability of other intermediates connected to these pathways. Kinetic modeling also illustrates important implications for enantioselectivity depending on whether such intermediates lie on or off the catalytic cycle.</jats:p
Rational Ligand Design for the Arylation of Hindered Primary Amines Guided by Reaction Progress Kinetic Analysis
We report the Pd-catalyzed arylation of very hindered α,α,α-trisubstituted primary amines. Kinetics-based mechanistic analysis and rational design have led to the development of two biarylphosphine ligands that allow the transformation to proceed with excellent efficiency. The process was effective in coupling a wide range of functionalized aryl and heteroaryl halides under mild conditions.National Institutes of Health (U.S.) (GM5816)Fundación Obra Social de La Caixa (Predoctorate Fellowship
Insights into the Role of Transient Chiral Mediators and Pyridone Ligands in Asymmetric Pd-Catalyzed C–H Functionalization
Mechanistic investigations uncover a novel role for 2-pyridone ligands and interrogate the origin of enantioselectivity in the (+)-norbornene-mediated Pd-catalyzed meta-C(aryl)–H functionalization of diarylmethylamines. Observations from kinetic analysis in concert with in situ ¹⁹F NMR monitoring allow us to propose that the pyridone ligand plays a role in enhancing the rate- and enantio-determining insertion of an arylpalladium species into a chiral norbornene derivative. The unprecedented features of 2-pyridone ligands in asymmetric 1,2 migratory insertion, and norbornene as a transient chiral mediator in relay chemistry, provide new insights into this ligand scaffold for future developments in stereoselective transition-metal-catalyzed C–H functionalization
Insights into the Role of Transient Chiral Mediators and Pyridone Ligands in Asymmetric Pd-Catalyzed C–H Functionalization
Mechanistic investigations uncover a novel role for 2-pyridone ligands and interrogate the origin of enantioselectivity in the (+)-norbornene-mediated Pd-catalyzed meta-C(aryl)–H functionalization of diarylmethylamines. Observations from kinetic analysis in concert with in situ ¹⁹F NMR monitoring allow us to propose that the pyridone ligand plays a role in enhancing the rate- and enantio-determining insertion of an arylpalladium species into a chiral norbornene derivative. The unprecedented features of 2-pyridone ligands in asymmetric 1,2 migratory insertion, and norbornene as a transient chiral mediator in relay chemistry, provide new insights into this ligand scaffold for future developments in stereoselective transition-metal-catalyzed C–H functionalization
Necessary conditions for the emergence of homochirality via autocatalytic self-replication
We analyze a recent proposal for spontaneous mirror symmetry breaking based on the coupling of first-order enantioselective autocatalysis and direct production of the enantiomers that invokes a critical role for intrinsic reaction noise. For isolated systems, the racemic state is the unique stable outcome for both stochastic and deterministic dynamics when the system is in compliance with the constraints dictated by the thermodynamics of chemical reaction processes. In open systems, the racemic outcome also results for both stochastic and deterministic dynamics when driving the auto-catalysis unidirectionally by external reagents. Nonracemic states can result in the latter only if the reverse reactions are strictly zero: these are kinetically controlled outcomes for small populations and volumes, and can be simulated by stochastic dynamics. However, the stability of the thermodynamic limit proves that the racemic outcome is the unique stable state for strictly irreversible externally driven autocatalysis. These findings contradict the suggestion that the inhibition requirement of the Frank autocatalytic model for the emergence of homochirality may be relaxed in a noise-induced mechanism
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Chiral Sugars Drive Enantioenrichment in Prebiotic Amino Acid Synthesis
Chiral pentose sugars mediate the enantioselective synthesis of amino acid precursors, with the magnitude of the chiral induction dictated by a subtle cooperativity between sugar hydroxyl groups. Ribose and lyxose give opposite chiral preferences, and theoretical calculations reveal the pseudoenantiomeric nature of transition state structures from the two sugars. Prebiotically plausible mixtures of natural d-sugars lead to enantioenrichment of natural l-amino acid precursors. Temporal monitoring and kinetic modeling of the reaction reveal an unusual dynamic kinetic resolution that shifts toward an enantioselective pathway over time, providing an amplification mechanism for the transfer of chiral information. This work adds to growing evidence for synergy in the etiology of the single chirality of the two most important classes of biological molecules, the sugars that make up DNA and RNA and the amino acids that form proteins
Solution-phase racemization in the presence of an enantiopure solid phase.
Solution-phase racemization
drives the evolution of single chirality
in the solid phase by the "chiral amnesia"
process first described by Viedma.
The current investigations lay the basis
for a better understanding of the mechanism
of the solid-phase deracemization
by uncoupling the chemical rate
processes associated with the interconversion
of enantiomers in the solution
phase from the physical processes associated
with solution-solid phase transfer
via dissolution and reaccretion of
molecules onto crystals. In addition,
the enantiomer concentration profiles
presented in this work, together with
an analytical treatment of the racemization
process in the presence of excess
enantiopure solid, unequivocally reconfirm
the validity of the Meyerhoffer
double solubility rule for systems
under solution racemization conditions
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