Understanding the Mechanism of the Lewis Acid Promoted [3 + 2] Cycloaddition of Propargylic Alcohol and α-Oxo Ketene Dithioacetals

Abstract

The mechanism and origin of selectivities in BF3·Et2O-catalyzed intermolecular [3 + 2] cycloadditions of propargylic alcohol and α-oxo ketene dithioacetals have been studied using density functional theory. Several possible reaction pathways were evaluated on the basis of two possible binding modes between the carbonyl or hydroxyl oxygen of substrates and catalyst. The preferred mechanism initiates dehydroxylation of propargylic alcohol by Lewis acid BF3 and generates active allenic carbocation species to provide the favorable electrophile. It then proceeds via four processes involving nucleophilic addition of C(α) on α-oxo ketene dithioacetals to the C1 of active allenic carbocation intermediate, [1,4]-alkylthio shift, H(α)-elimination, and intramolecular cyclization. This reaction sequence is in contrast to the mechanism by a previously published study, that is, [1,4]-alkylthio migration occurs prior to the cyclization. Our calculated results suggested that electrostatic attraction and hydrogen-bonding interactions between substrates and catalyst play a vital role in the [3 + 2] cycloaddition.

Selective 5‐Exo‐Dig versus 6‐Endo‐Dig Cyclization of Benzoimidazole Thiols with Propargyl Alcohols

“…Our study was based on the knowledge that propargyl alcohols, in presence of Lewis acid, are excellent substrates for obtaining cationic intermediates, [43] and thus can suffer a nucleophilic attack, which could undergo an intermolecular cyclization via 5‐ exo ‐dig or 6‐ endo ‐dig modes. We began by studying the different reaction parameters to determine the best reaction conditions.…”

Transition-metal-free C–S bond cleavage and transformation of organosulfur compounds

“…Furthermore, the theoretical calculation by the Zhang group disclosed that both hydrogen bonding and electrostatic attraction interactions between BF 3 ·Et 2 O and reaction substrates play a vital role in this novel cycloaddition process. 62…”

“…Furthermore, the theoretical calculation by the Zhang group disclosed that both hydrogen bonding and electrostatic attraction interactions between BF 3 ÁEt 2 O and reaction substrates play a vital role in this novel cycloaddition process. 62 In addition, Luo and co-workers reported an unprecedented [3+2] cycloaddition strategy for the synthesis of multisubstituted furan-3-carbothioates in the presence of HOTf (Scheme 25b). 63 This was the first example in which a-oxo ketene dithioacetals 135 were used as 1,3-bis-nucleophiles in this regioselective annulation process.…”

Exploring the Effects of Water on the Mechanism of the Catalyst-Free Reaction between Isatin and 3-Methyl-2-pyrazolin-5-one from the Mixed Implicit/Explicit Multiple Types of Water Clusters

“…The DFT M06-2X functional accompanied with the D3 Grimme dispersion correction , and 6-31+G­(d,p) basis set were used to optimize geometries of reaction systems without the involvement of auxiliary water molecules and with the assistance of different water cluster models in the gas phase. The M06-2X method provided better thermodynamics, kinetics, and noncovalent interactions compared to B3LYP-D, , and some reports pointed out that M06-2X could deal well with the C–H···O noncovalent interactions and hydrogen transfer systems, which was generally considered to be more accurate for energetics. ,− The harmonic vibrational frequency calculations were conducted at the same level to characterize all stationary points including the transition states with only one imaginary frequency and the minima without imaginary frequency and to obtain the Gibbs free energy correction at 298.15 K and 101.325 kPa. Intrinsic reaction coordinate calculations were performed to ensure that the stationary points were smoothly connected to each other after structural optimization.…”