Dimethyl Acetylenedicarboxylate: A Versatile Tool in Organic Synthesis

Abstract

This review presents the recent progress in the chemistry of dimethyl acetylenedicarboxylate (DMAD). The interest in and applications of this powerful reagent with more than 135 years of history have greatly increased in the last 10 years, further proving its versatility. Undoubtedly, DMAD can be a multi-tool in the quest of molecular complexity and diversity. The extreme structural diversity of the products described in this review illustrates the powerful potential of DMAD as a building block in organic synthesis.

Computational study on the mechanism of the three-component reaction of dimethylacetylene dicarboxylate and triphenylphosphine with 2-acetylbutyrolactone

“…Then a ring-closure reaction gives the cyclobutene intermediates 7 or 8via elimination of triphenyl phosphinoxide. The following process is a ring-opening electrocyclic reaction of 8 or 7 to give the final products (9)(10)(11)(12). Moreover, the PES analysis show that the phosphorus ylide was more stable than the corresponding 1,3-butadiene, demonstrating that the intramolecular Wittig reaction could not easily occur at room temperature to produce the isomeric 1,3-butadiene derivative, which is in good agreement with the experimental results.…”

“…Based on the experiment, 9 we suggest that the reaction process of triphenylphosphine As shown in Scheme 2, the processes (ii) and (iii) can take place along two possible competitive reaction routes (pathways I and II) to form the intermediates 7 and 8. For personal use only.…”

“…Also, Schemes 3 and 4 show that 1,3-butadiene stereoisomers (9)(10)(11)(12) can be converted to their enantiomers (9 ‫׳‬ -12 ‫׳‬ ) via the two different transition states s-trans (TS6sand TS9s) and scis (TS7sand TS10s). Based on the PES (Table 1), while the s-trans transition states are more stable than s-cis ones, the TS10-a has the highest energy barrier (93.34 kJmol -1 ).…”

“…8 In order to investigate the mechanism of these reactions, the previously synthesized stable phosphorus ylide and the corresponding functionalized 1,3-diene was adopted as a case study. 9 The synthetic route leading to these products is depicted in Scheme 1. were carried out to confirm that the obtained transition states were connected both with the reactants and the products. 14 The electronic structures of stationary points were analyzed by the natural bond orbital (NBO) method.…”

Synthesis with Perfect Atom Economy: Generation of Furan Derivatives by 1,3-Dipolar Cycloaddition of Acetylenedicarboxylates at Cyclooctynes

“…Esters of acetylene dicarboxylic acid and especially dimethyl acetylenedicarboxylate (DMAD, 1a ) are highly versatile tools for organic chemists [1,2,3,4,5,6,7]. These compounds are successfully utilized as dienophiles in Diels–Alder reactions, as dipolarophiles in 1,3-dipolar cycloadditions and also as components in [2 + 2] or other cycloaddition reactions.…”