Total Facial Discrimination of 1,3-Dipolar Cycloadditions in a d-Erythrose 1,3-Dioxane Template: Computational Studies of a Concerted Mechanism

Abstract

A new d-erythrose 1,3-dioxane derivative was synthesized from d-glucose and found to be a highly stereoselective template as a dipolarophile. Different 1,3-dipoles of allenyl-type were employed, giving different regioselectivities, depending on its nature; the regioselectivity is complete with alkyl azides and phenyldiazomethane, but is inexistence with nitrile oxides. Computational studies were performed to understand the mechanisms of cycloadditions. All the studied cycloadditions were found to be concerted involving small free activation energies and are all exoenergonic. The stereoselectivity is due to a combined result of the steric effect H-8a and the hyperconjugative effect of the *C-O to the incoming 1,3-dipole. The regioselectivity observed in alkyl azides and phenyldiazomethane is mostly dependent on the distortion effect during the cycloaddition process. This distortion effect is however higher in the alkyl azide compounds than in phenyldiazomethane.

Total Stereoselective Michael Addition of N- and S- Nucleophiles to a d-Erythrosyl 1,5-Lactone Derivative. Experimental and Theoretical Studies Devoted to the Synthesis of 2,6-Dideoxy-4-functionalized-d-ribono-hexono-1,4-lactone

“…The origin of the stereoselectivity observed in these reactions (1,4-nucleophilic additions) is similar to what was found in 1,3-dipolar cycloadditions to α,β-unsaturated lactone 1 and can be justified by the position occupied by hydrogen H -4a from the lactone that precludes the nucleophile molecule to attack the lactone at the bottom face. The regioselectivity is an outcome of the reactants that are used.…”

“…All reagents were purchased from Sigma-Aldrich, Acros, TCI, or Alfa Aesar and used without further purification, except for p -toluenesulfonic acid monohydrate, which was dried under a vacuum pistol at 120 °C; acetonitrile was dried by reflux under CaH 2 and NEt 3 by distillation. Aldehyde and lactone 1 were synthesized following the procedures described in the literature. Flash chromatography was performed using silica 60 Å 230–400 mesh as stationary phase.…”

“…7 Recently a new derivative of 2,4-O-alkylidene-D-erythrose, enclosing a CC moiety into a 1,5-lactone ring, was found to induce on its ground a complete facial selectivity as dipolarophile in 1,3-dipolar cycloadditions. 8 This D-erythrosyl 1,5-lactone was now studied as a Michael acceptor with sulfur and nitrogen active nucleophiles. Complete facial selectivity was demonstrated for all cases, giving optically pure adducts.…”

molUP: A VMD plugin to handle QM and ONIOM calculations using the gaussian software

“…Despite the methodological developments of the QM/MM methods, and the good results obtained through their application, they are still very challenging . The two major bottlenecks of these methods are i) the computational cost of the QM method that is employed, which turns the full process very time and resource demanding and ii) the way through which the coupling between the QM and MM parts is accomplished.…”

A Short Synthesis of (2S,3S,4R)-Dihydroxyhomoprolines from d-Erythrose-Derived 5,6-Dihydro-2H-pyran-2-one

“…7 In contrast, very few investigations have focused on the -amino acid congeners; only two papers have appeared recently, published by the Davis group. 8,9 In this work a 1,5-lactone 1, obtained from D-erythrose, 10 is used as a remote chiral synthon for the syntheses of the title (2S,3S,4R)-dihydroxyhomoprolines 2. In previous work, primary amines and sulfides were added to 1, and the mechanism of the addition reaction was studied computationally.…”