Diels–Alder reaction of vinylene carbonate and 2,5-dimethylfuran: kinetic vs. thermodynamic control

Abstract

The Diels-Alder reaction between 2,5-dimethylfuran and vinylene carbonate was studied, both from an experimental and a theoretical point of view. The system was shown to slowly reach a thermodynamic equilibrium, characterized by the almost exclusive formation of the exo isomer. We rationalized these results by a comparison with classical systems involving maleic anhydride, and highlighted the different reactivity of vinylene carbonate as a dienophile. Finally, a preparative scale synthesis of pure exo isomer 4, a potentially useful synthon, ensued from this work.

A highly diastereoselective “super silyl” governed aldol reaction: synthesis of α,β-dioxyaldehydes and 1,2,3-triols

“…A quick optimization of the asymmetric dihydroxylation step (see ESI † ) showed that cis -osmilation using osmium tetroxide in presence of excess of N -methylmorpholine N -oxide provided the desired hexose-like structure. 13 Thus, compound 40 , containing six adjacent stereocenters, was obtained in 68% yield and with an exclusive 4,5- anti stereochemistry. The determination of the stereochemistry of the latter compound was based on the optimization reactions where we obtained the same single isomer using both chiral AD-mix-α or β with comparable selectivity but with a slower reaction rate (50% conversion after 4 days), which can be explained by the preferred attack of osmium from the opposite side of the free hydroxy group present in 39 .…”

Crystal structure and Hirshfeld surface analysis of dimethyl (1R*,3aS*,3a1 R*,6aS*,9R*,9aS*)-3a1,5,6,9a-tetrahydro-1H,4H,9H-1,3a:6a,9-diepoxyphenalene-2,3-dicarboxylate

“…The first example of kinetic/thermodynamic control in the course of the Diels-Alder reaction was reported in 1948 (Woodward & Baer, 1948). Since then, the reversibility of the [4 + 2] cycloaddition was observed many times for examples of a broad range of dienes and dienophiles, including alkynes and furans (Boutelle & Northrop, 2011;Taffin et al, 2010;White et al, 2000;Marchand et al, 1998;Manoharan & Venuvanalingam, 1997;Bott et al, 1996;Bartlett & Wu, 1985). From this diversity of diene/dienophile combinations, tandem and domino reactions of the [4 + 2] cycloaddition based on acetylenic dienophiles are more interesting for the total synthesis of natural or bioactive products (Sears & Boger, 2016;Parvatkar et al, 2014;Winkler, 1996).…”

Synthetic Studies towards New Nucleoside Analogues: Preparation of (±)‐1′,4′‐Dimethyladenosine

“…dropwise; a white precipitate appeared. The resulting mixture was stirred at room temperature for 3 h. After dilution with AcOEt (50 mL), the mixture was quenched with a saturated aqueous NH 4 Cl solution (40 mL), and the layers were separated. The organic layer was washed successively with water (40 mL), 1 n HCl (2 ϫ 40 mL), water (40 mL), and brine (40 mL).…”

“…[3] During our studies on the Diels-Alder reaction between 1 and 2, we evidenced that prolonged heating leads to clean conversion of the endo/exo mixture into exo adduct 3 only, enabling large-scale production of the latter on a preparative scale after direct crystallization. [4] Therefore, we decided to exploit this result to design another route to 1Ј,4Ј-dimethyl nucleoside analogues, which is both shorter and suitable for purine synthesis (Scheme 1). It is the purpose of this communication to report our first results regarding this approach.…”

“…dropwise. A white precipitate formed, and the resulting mixture was stirred at room temperature for 2 h. The reaction medium was diluted with AcOEt (50 mL) and quenched with MeOH (2 mL), then with a saturated aqueous NH4 Cl solution (15 mL). The layers were separated, the organic layer was washed with water (2 ϫ 15 mL) and brine(15 mL), dried with Na 2 SO 4 , and concentrated in vacuo.…”