Exploration of a Novel, Enamine-Solid-Base Catalyzed Aldol Condensation with C-Glycosidic Pyranoses and Furanoses

Abstract

A variety of unprotected C-glycosidic ketones were employed in a novel enamine-solid-base catalyzed (ESBC) aldol condensation to expand the scope and scalability of a previously reported reaction. The starting ketones were obtained from unprotected pyranoses and furanoses following Lubineau's method via a Knoevenagel condensation. The aldol condensation reaction of the C-glycosidic ketones was performed with a nontoxic and abundant amino acid, L-proline, along with magnesium oxide (MgO) as a recyclable and sustainable catalyst. The enamine-solid-base catalyzed aldol condensations provided the corresponding (E)-α,β-unsaturated ketones in excellent isolated yields (91−100%).

Sustainable Straightforward Synthesis and Evaluation of the Antioxidant and Antimicrobial Activity of Sinapine and Analogues

“…After concentration in vacuo, the crude reaction mixture (Table , entry 7) was directly submitted to a proline-mediated Knoevenagel–Doebner condensation with syringaldehyde in ethanol to afford sinapine. , The mechanism of this reaction, previously described by Peyrot et al , involves the activation of the aldehyde moiety through the formation of iminium 12, which will then react with the monoester 9 . The intermediary 13 thus formed will undergo decarboxylation to yield 14 that rearranges to regenerate proline and provide sinapine (Scheme ).…”

Proline-Mediated Knoevenagel–Doebner Condensation in Ethanol: A Sustainable Access to p-Hydroxycinnamic Acids

“…In their work dedicated to the preparation of α,βunsaturated ketones through aldol condensation, 31 de Winter et al determined the following optimized conditions: 1 equiv of ketone, 1.2 equiv of aldehyde, 10 wt % MgO, 1 equiv of Lproline in methanol (0.45 M) at 50 °C. These conditions were thus directly applied on malonic acid and syringaldehyde and, after 4 h, resulted in a mixture of sinapic acid (10%), diacid (27%), and unreacted syringaldehyde (63%) as measured by 1 H NMR.…”

“…More recently, De Winter et al performed an aldol condensation in presence of L-proline and magnesium oxide, nontoxic and naturally occurring compounds. This method allowed the synthesis of α,β-unsaturated ketone in excellent yields 13 . In the present work, this approach has been implemented and optimized to synthesize natural phydroxycinnamic acids from the corresponding p-hydroxybenzaldehydes.…”

“…28−30 More recently, de Winter et al described the synthesis of α,β-unsaturated ketones in excellent yields through an aldol condensation in the presence of Lproline and magnesium oxide, two nontoxic and naturally occurring chemicals. 31 In the present work, we aimed to determine whether this sustainable approach could be applied to Knoevenagel−Doebner condensation for the synthesis of naturally occurring p-hydroxycinnamic acids from the corresponding p-hydroxybenzaldehydes.…”

“…Another alternative consists of performing a solvent-free Knoevenagel–Doebner reaction that permits decrease of the amount of catalyst needed and reduction of the reaction time . Other catalysts such as Lewis acids (NbCl 5 , ZnCl 2 ), heterogeneous solid bases, or amino acids have also been investigated. − Combinations of these approaches have been also reported such as the use of amino acids as catalysts in the presence of ionic liquid or PEG. − More recently, de Winter et al described the synthesis of α,β-unsaturated ketones in excellent yields through an aldol condensation in the presence of l -proline and magnesium oxide, two nontoxic and naturally occurring chemicals . In the present work, we aimed to determine whether this sustainable approach could be applied to Knoevenagel–Doebner condensation for the synthesis of naturally occurring p -hydroxycinnamic acids from the corresponding p -hydroxybenzaldehydes.…”