Insights into the Diels–Alder Reaction between 3-Vinylindoles and Methyleneindolinone without and with the Assistance of Hydrogen-Bonding Catalyst Bisthiourea: Mechanism, Origin of Stereoselectivity, and Role of Catalyst

Abstract

The Diels-Alder reaction between 3-vinylindoles and methyleneindolinone can proceed both under catalyst-free conditions and with bisthiourea as the catalyst. The reaction with bisthiourea is much faster and results in higher stereoselectivity of the product. The reaction mechanism, origin of stereoselectivity, and role of the catalyst were elaborated based on quantum mechanical calculations and theoretical methods of reactivity indices, NCI, QTAIM, and distortion/interaction models. In the uncatalyzed reaction, the two C-C bonds that are formed undergo conversion from noncovalent to covalent bonding via a concerted asynchronous mechanism. The weak intermolecular interactions formed in the transition state play important roles. The difference between the interaction and distortion energies is responsible for the stereoselectivity. In the catalyzed reaction, bisthiourea induces both the diene and dienophile to approach it via weak intermolecular interactions, which greatly lowers the energy barrier of the reaction and leads to the product with excellent stereoselectivity. The possible pathways of this reaction were explored, which suggested that the formation of the two C-C bonds goes through either a stepwise or concerted asynchronous mechanism. These results detail the reaction mechanism and shed light on both the significant role of the bisthiourea catalyst and the origin of stereoselectivity for this type of Diels-Alder reaction and related ones.

TfOH-Catalyzed One-Pot Domino Reaction for Diastereoselective Synthesis of Polysubstituted Tetrahydrospiro[carbazole-1,3′-indoline]s

“…On the basis of the above results and the previously reported reactions, ,− a plausible domino reaction mechanism is relationally proposed in Scheme by using 3-phenacylideneoxindoline as the substrate. At first, a 3-alkenylindole ( A ) was generated by the Friedel–Crafts reaction of indole and acetophenone with dehydration in the presence of triflic acid.…”

Unveiling Mechanism of a Quinine-Squaramide Catalyzed Enantioselective Aza-Friedel–Crafts Reaction between Cyclic Trifluoromethyl Ketimine and Naphthol: A DFT Study

“…Accordingly, the global electrophilicity index ω is measured by ω = (μ 2 /2η). The empirical (relative) nucleophilicity index , N taking the HOMO energy of tetracyanoethylene (TCE) as a reference was defined as N = E HOMO(R) – E HOMO(TCE) by Domingo and co-workers, which was calculated basing on the HOMO energies of reactants. The HOMO and LUMO orbital energy, electronic chemical potential (μ), chemical hardness (η), electrophilicity (ω), and nucleophilicity ( N ) indices for reactants ( R1 , R2 ) are listed in Table , respectively.…”

Hydrogen-Bond-Assisted Diels–Alder Kinetics or Self-Healing in Reversible Polymer Networks? A Combined Experimental and Theoretical Study

“…Materials), which might influence the kinetics of the model systems by hydrogen bonding (HB) interactions. Several studies have demonstrated that strong or bifunctional hydrogen bonds are capable of catalyzing the Diels–Alder cycloaddition reaction and may even alter the preference for endo versus exo [ 19 , 20 , 21 , 22 , 23 ].…”