Theoretical investigations of the reaction between 1,4-dithiane-2,5-diol and azomethine imines: mechanisms and diastereoselectivity

Abstract

In the present study, mechanistic insights into the domino reaction between 1,4-dithiane-2,5-diol and azomethine imines were derived from the computational study with B3LYP and M06-2X functionals. On the whole, the domino process comprises two consecutive reactions: cleavage of 1,4-dithiane-2,5-diol leading to mercaptoacetaldehyde and [3 + 3] cycloaddition of mercaptoacetaldehyde with azomethine imines. The cleavage of 1,4-dithiane-2,5-diol can take place via multiple possible pathways (1A-1E), and pathway 1E in which double-methanol molecules mediate the proton transfer process is the most energetically favorable, with an energy barrier of 19.9 kcal mol(-1). For the [3 + 3] cycloaddition, three possible pathways (2F-2H) were explored. The calculated energy profiles reveal that pathway 2H with activation energies ranging from 6.9 to 10.2 kcal mol(-1) is more energetically favorable than pathways 2F and 2G. Specifically, pathway 2H comprises three reaction steps: deprotonation of mercaptoacetaldehyde by DABCO allows for the formation of the thiol anion, which subsequently launches a nucleophilic attack on azomethine imines followed by intramolecular cyclization resulting in the final products. The calculated results are in agreement with the experimental observations that the reaction can proceed most efficiently in the presence of both DABCO and methanol. Furthermore, the hydrogen bonding interaction is identified to be the main factor determining the observed diastereoselectivity The current systematic theoretical study gives a full scenario of the reaction between 1,4-dithiane-2,5-diol and azomethine imines catalyzed by DABCO, and thus provides some valuable clues for further investigation and development of this kind of important reaction.

Mechanisms and regioselectivities of DABCO/DMAP‐catalyzed [2+4] annulation reactions of allenoate with α,β‐unsaturated cyclic ketimine: A DFT study

“…In the past decades, density functional theory (DFT) has been extensively used as a powerful method to explore the detailed reaction mechanisms, and predict the regioselectivity as well as chemoselectivities in organocatalytic and biological reactions . It is worth mentioning that the DABCO‐catalyzed [2+4] cycloaddition of ethyl allenoate with arylidenoxindole has been theoretically investigated, but the observed regioselectivity is remarkably different from the reaction in this paper.…”

1,4‐Dithiane‐2,5‐diol: An Attractive Platform for the Synthesis of Sulfur‐Containing Functionalized Heterocycles

“…captoacetaldehyde generated from 1 under equilibrium conditions. [94] Later, the kinetic resolution of the azomethine imines was successfully achieved with high selectivity factors (S factor up to 67). The base-catalyzed [3+3] annulation of the resolved enantioenriched azomethine imine (R)-149 (R = Ph, 91 % ee) with 1 in the presence of 1 mol-% of DABCO proceeded smoothly in 20 min to produce the highly functionalized sulfur-containing heterocycle 150 in 92 % yield with exclusive diastereoselectivity and maintained enantioselectivity (Scheme 52).…”

“…[94] Later, the kinetic resolution of the azomethine imines was successfully achieved with high selectivity factors (S factor up to 67). Diastereoselective [3+3] cycloaddition between 1 and azomethine imines 147 for the synthesis of highly functionalized six-membered dinitrogen-fused heterocycles.…”

Mechanisms of DABCO‐ and DMAP‐catalyzed [2 + 4] cycloaddition reactions of methylallenoate with methyleneindolonone: A DFT study

“…Allene and its derivatives, which possess cumulative double bond, are important building blocks in synthesis organic chemistry . Under the catalysis of Lewis bases (phosphanes and amines), allenoates can act as one, two, three, and four carbon synthons to construct the rings in cyclic compounds, for reviews see Refs. [ ].…”

“…K E Y W O R D S (2 1 4) cycloaddition, density functional calculations, reaction mechanisms, stereoselectivity 1 | I N T R O D U C T I O NAllene and its derivatives, which possess cumulative double bond, are important building blocks in synthesis organic chemistry. [1] Under the catalysis of Lewis bases (phosphanes and amines), allenoates can act as one, two, three, and four carbon synthons to construct the rings in cyclic compounds, [2][3][4][5][6][7][8][9][10][11][12][13][14][15] for reviews see Refs. [16][17][18][19].…”