Christophe Coudret

Nonlinear Effects in Asymmetric Synthesis: A Practical Tool for the Discrimination between Monomer and Dimer Catalysis

Nonlinear effects in asymmetric synthesis are identified by a nonlinear relationship between the enantiomeric excess of the product versus that of the chiral catalyst. Such information is not always sufficient to reveal if the active catalyst acts in its monomeric or dimeric form. Numerical simulations of two kinetic models including monomer and dimer catalysis with a Michaelis–Menten‐type reaction mechanism suggest that the nonlinear effects are mainly sensitive to an analogue of the Michaelis–Menten constant as well as to the diastereomeric energy difference between homochiral and heterochiral catalyst dimers. A practical monomer–dimer discrimination table is presented showing that the influence of the initial catalyst enantiomeric excess and the catalytic charge on the product enantiomeric excess and on the reaction half‐time together with the assessment of the kinetic order of the prochiral substrate are sufficient to assess whether the active catalyst acts in its monomeric or dimeric form.

Proton Catalysis in the Redox Responsivity of a Mini‐Sized Photochromic Diarylethene

A thermally irreversible dithienylethene (DTE) photochrom can be turned into a thermally reversible one in presence of Cu(II) triflate. A ring opening (DTEC closed→DTEO open) occurs through the formation of a copper-containing fast transient intermediate. Stopped-flow experiments monitored at 410 and 780 nm have allowed to show that the stoichiometry of this intermediate is DTE/Cu=1:1. At longer monitoring times (i.e., several seconds after mixing), the intermediate undergoes a slow decay while the residual DTEC closed form opens. A joint detailed kinetic and electrochemical analysis has unveiled a proton catalysis scenario in which electron transfer between DTEC and Cu(II), ligand exchange, protonation-deprotonation equilibria of the cation radicals and ring opening are embedded into two main reaction cycles. At the beginning of the reaction, Cu(II) is reduced into Cu(I) and DTE is degraded without ring opening. Then, as the reaction progresses, the triflic acid released from the Cu(II) reduction switches-on a propagation cycle during which ring opens without any more Cu(II) consumption. Cyclic voltammetry, spectro-electrochemical measurements, delayed photocoloration experiments in presence of Cu(II) and acid-base additions have confirmed the main features of the proton catalysis.

Kinetic and Structural Aspects of Mirror-Image Symmetry Breaking in the Soai Reaction

Abstract The mechanism of the Soai reaction remains a challenge for experimentalists and theorists. It appears to be much more complex than simple models describing asymmetric autocatalyis in generalized terms. Numerous oligomer species obeying the principles of chiral combinatorics are likely involved. A number of these intermediates have been either isolated or recognized by nuclear magnetic resonance (NMR) studies. A combination of kinetic analyses and density functional theory (DFT) calculations could shed some light on the deeper understanding of this asymmetric autocatalysis. A recent breakthrough was provided by the identification of X-ray structures of various oligomers. To rationalize its mechanism, kinetic modeling of the Soai reaction has been developed in two complementary directions: a structural approach validated by DFT calculations and a functional approach by numerical studies and the reproduction of experimental features. Recently, we introduced a new mechanistic feature related to the concept of kinetic proofreading. We showed that whatever the values of the kinetics parameters, an increase in the catalytic oligomer size from one to three lead to a higher tolerance to poorer chiral recognition between the diastereoisomers, which is a key element for asymmetric amplification and spontaneous symmetry breaking. In the present contribution, we also show that numerical simulation is useful to understand the ee amplification during the stepwise addition of aldehyde and organozinc in a typical Soai reaction experimental procedure. Also, we present a first modeling approach in respect to the observed high sensitivity of the Soai reaction towards chiral additives. Our model predicts that the aldehyde concentration plays the role of a bifurcation parameter inducing a transition from a racemic state to an optically active one. Our results also confirm that in such complex systems, kinetic orders must be handled with care.