Understanding the Mechanism of the Intramolecular Stetter Reaction. A DFT Study

Abstract

The mechanism of the N-heterocyclic carbene (NHC)-catalyzed intramolecular Stetter reaction of salicylaldehyde 1 to yield chromanone 3 has been theoretically studied at the B3LYP/6-31G** level. This NHC-catalyzed reaction takes place through six elementary steps, which involve: (i) formation of the Breslow intermediate IN2; (ii) an intramolecular Michael-Type addition in IN2 to form the new C-C σ bond; and (iii) extrusion of the NHC catalyst from the Michael adduct to yield chromanone 3. Analysis of the relative free energies in toluene indicates that while formation of Breslow intermediate IN2 involves the rate-determining step of the catalytic process, the intramolecular Michael-type addition is the stereoselectivity determining step responsible for the configuration of the stereogenic carbon α to the carbonyl of chromanone 3. An ELF analysis at TSs and intermediates involved in the Michael-type addition allows for the characterization of the electronic changes along the C-C bond-formation.

Understanding the participation of 3-nitropyridine in polar Diels–Alder reactions. A DFT study

“…This finding makes it possible to establish that at very advanced and asynchronous TSs, such as TS-2-pn, while the formation of the C2-C6 bond is very advanced, the formation of the C1-C3 one has not started yet. This behavior, which is also characterized at some points of the IRC of P-DA reactions taking place along a two-stage one-step mechanism, allows establishing that the bonding changes in these reactions are non-concerted [4].…”

“…These lengths indicate that the TSs associated with the most favorable regioisomeric para channels are more advanced and more asynchronous than the meta ones. The high asynchronicity found at the para TSs, Dl = 0.78 (TS-2-pn), indicates that this P-DA reaction takes place through a two-stage one-step mechanism [4].…”

“…According to the mechanism, it can be considered that these polar Diels-Alder (P-DA) reactions [3] involving electrophilic aromatic heterocyclic compounds and nucleophilic dienes usually take place through a two-stage one-step mechanism [4], via highly asynchronous transition state structures (TSs) with high polar character [5], although a twostep mechanism via the formation of a zwitterionic intermediate cannot be completely discarded. In this way, we have been working with P-DA reactions using aromatic carbo-and heterocyclic nitro-substituted dienophiles and different electron-rich dienes [6].…”

A theoretical study on the hydrogen adducts of diamidocarbenes and diaminocarbenes

“…Various quantum chemical calculations were performed to examine not only the peculiar stability of NHCs but also their reactivity [13][14][15][16][17][18][19][20]. In 2006, Dixon and coworkers [20] discovered that NHCs may be suitable candidates for use as hydrogen storage materials by using a sophisticated theoretical level.…”

Impact of Global and Local Reactivity Descriptors on the Hetero-Diels-Alder Reaction of Enaminothione With Various Electrophiles

“…[21][22][23][24][25][26][27][28] Moreover, recent literature study reveals that global and local descriptors are very useful and reliable tools for the predication of reaction mechanisms. [29][30][31][32][33] Thus exploration of global and local reactivity descriptors to understand the mechanistic aspects for a cycloaddition reaction is worth important.…”