ABSTRACT
In the Comment on our paper on the description of the Gibbs Free energy profile of Claisen-Schmidt condensation, it is claimed that our calculations are flawed due to inconsistencies with experimental isotope effects in aqueous acetonitrile. In this Reply, we presented rigorous arguments, ambiguities in the Comment and new calculations confirming the consistency of our results: (i) small differences in the relative energetic barriers in both experimental and theoretical curves make the assignment of the rate-limiting step debatable, making the concept of RCS questionable; (ii) it is shown how the misinterpretation of the elementary steps and of the overall processes rate constants led the Comment to incorrect conclusions about the behavior of the inverse isotopic effect; (iii) neglect in the Comment of the inverse kinetic isotope effect in step R2 due to the hybridization conversion, and of the inverse equilibrium isotopic effect for step R1 to describe an overall iKIE > 1, (iv) an erroneous suggestion in the Comment that the disagreement between experimental kinetic parameters is due to the fact that acetonitrile is not used in previous experimental works, when contradictorily the literature recommends it as being indispensable to allow kinetic accuracy; and (v) new calculations improved by explicit-implicit hybrid treatment again ensure that step R4, and not step R5, can assume the role of RCS in protic solvents. Recognizing that questioning is an excellent path for promoting understanding, we hope that the answers provided here will help to clarify and expand the pertinent topics under discussion.
ABSTRACT
Recent studies have found that hydroxide elimination and the C[double bond, length as m-dash]C bond formation step in base-promoted aldol condensation have a strong influence on the overall rate of the reaction, in contrast to the well-accepted first enolization or C-C bond formation step. Here, applying theoretical models to the prototypical reaction of chalcone formation, the complete free energy profile of Claisen-Schmidt condensation is assessed, revealing how a protic solvent and a slight increase in temperature can induce the second enolization as the rate-controlling step (RCS). It is also observed: i) the nonexistence of a step with a much higher energetic barrier than the others, making the concept of RCS debatable; and ii) that the overall inverse kinetic isotopic effect does not exclude second enolization as a RCS in protic continuum medium. We expect that these results can expand the understanding of the decisive role of physicochemical factors on the choose of the RCS in the aldol condensation.
ABSTRACT
Herein we report the first systematic investigation of the tandem mercury(ii) catalysed transvinylation/Hurd-Claisen rearrangement of MBH adducts derived from alkyl acrylates. This is the first report of E-selectivity for MBH adducts with alkyl side chains and is complementary to the previously reported Johnson-Claisen and Eschenmoser-Claisen rearrangements. The rearrangement products were obtained in good yields and could be readily converted to 2-alkenyl δ-valerolactones. Combined DFT and F-SAPT studies demonstrate that reaction rates are primarily governed by non-covalent interactions dictating the relative stability of the transition states. Our F-SAPT calculations revealed that the hyperconjugative effects are not so significant, but that electrostatic interactions, instead, are the driving forces for the relative E : Z stereoselectivity.
