Insight into the Mechanism of the Michael Reaction

Abstract

The mechanism for the nucleophilic addition step of the Michael reaction between methanethiol as a model Michael donor and several α-substituted methyl acrylates (X=F, Cl, Me, H, CN, NO2 ) as model Michael acceptors is described in detail. We suggest a novel way to condense electrophilic Fukui functions at specific atoms in terms of the contributions from the atomic orbitals to the LUMO or, more generally, to the orbital controlling the reaction. This procedure correctly associates activation energies to local electrophilic Fukui indices for the cases treated in this work. The calculated reaction barriers strongly depend on the nature of the substituent. As a general rule, activation energies are governed by structural changes, although electronic factors are significant for electron-withdrawing groups. Nucleophilic addition to Michael receptors is best described as a highly nonsynchronous process, in which the geometry of the transition state comprises a nonplanar six-membered ring. Formation of the S⋅⋅⋅C bond, which defines the interaction between the reactants, progresses ahead of all other primitive processes in the early stages of the transformation. In view of our results, we postulate that highly complex chemical reactions, as is the case for the nucleophilic addition step studied herein, that involve cleavage/formation of a total of six bonds, lower their activation energies by favoring nonsynchronicity, that is, for these types of systems, primitive changes should advance at different rates.

Revisiting the Rearrangement of Dewar Thiophenes

“…As expected, larger retarding forces lead to larger activation energies. This is not just a simple trend, the work involved in going from reactants to activated reactants (W1) is correlated ( Figure 2) with the activation energies, as has been reported for other reactions [28].…”

“…Note that from the perspective of primitive changes, our results indicate that Dewar rearrangements are chemical processes that occur with a high degree of synchronicity: bonds sharing a common atom evolve at the same rate, thus, on the one hand, the single C1-C2 bond is converted to a double bond at the same rate as the C1-C4 double bond is transformed into a single bond; while on the other hand, the C2-S9 bond disappears at the same rate as the C4-S9 bond is being formed. This simultaneous evolution of chemical bonding may be better appreciated by a criteria for synchronicity developed elsewhere [28] and plotted at the bottom panel of Figure 5: If the C1-C2 bond is taken as reference, the other bonds involved in the chemical transformation depart from the initial bond order at approximately the same rate as this bond, while the bonds not taking part in the rearrangement do not change. While all the primitive changes are occurring, the pivotal C3-S9 bond changes only slightly, however, the evolution of this bond is quite important because changes in this bond are directly related to the activation energy in the fluxional case (vide supra).…”

How Dihalogens Catalyze Michael Addition Reactions

“…As mentioned above,t he catalytic effect of dihalogen molecules has been typically attributed to the enhancement of the HOMO(nucleophile)-LUMO(Michael acceptor) interaction, where LUMO refers to the empty p*o rbital of the Michael acceptor. [8] Figure 1c onfirms that the computed electronic activation energies (DE°)c orrelate (R 2 = 0.97) with the De(HOMO py j LUMO 1a-5 a )w hich, at first sight, seems to be in line with this traditional view on the origin of the computed reactivity trend.…”

“…[6] It is widely accepted that the origin of the catalytic effect of these species,i nn ot only this but also in related transformations, [7] can be attributed to an attractive halogen bonding resulting from the interaction of the X 2 molecules and the substrate.This mode of activation strongly resembles that found in typical Lewis acid catalyzed processes,w here the catalysis is mostly governed by af avorable interaction involving the corresponding frontier molecular orbitals (FMOs), namely HOMO(nucleophile)-LUMO(Michael acceptor). [8] Nevertheless,a nd despite recent studies on the mechanism of I 2 -catalyzed Michael addition reactions, [9] very little is known about the ultimate factors behind the catalytic activity of X 2 molecules.F or this reason, we decided to use state-of-the-art computational methods [10] to quantitatively unravel the nature of the catalytic power of these species.…”

Automating the IRC‐Analysis within Eyringpy

“…has been amply used to understand several chemical reactions such as intra/intermolecular single and double proton transfers [15][16][17][18][19][20][21], conformational changes [22][23], bond-dissociation and bond-formation [24][25][26][27][28], S N 2 substitution [29][30], solvent effects [31][32], and catalysts [33][34][35].…”