Dimethyl Acetylene Dicarboxylate

Biographical Sketches

Manoj Kumar Sahoo obtained his B.Sc. (Govt. College, Angul, Orissa) and M.Sc. (Utkal University Chemistry Department, India). After qualifying via the CSIR-National eligibility test (NET) for a research fellowship, he joined the research group of Dr. N. P. ­Argade for a Ph.D. at National Chemical Laboratory, Pune. In 2004, he passed the DRDO-Scientist Eligibility Test (SET) and moved to Defence ­Research and Development Establishment, Gwalior where he is currently working under the supervision of Dr. R. C. Malhotra. His research interests include total synthesis of bioactive natural products, ­development of new methodologies, decontamination of chemical warfare agents and medicinal chemistry.

Introduction

Dimethyl acetylene dicarboxylate (DMAD) is an electron-deficient alkyne diester widely used as dienophile and dipolarophile in cycloaddition reactions. It is used as a standard in Diels-Alder reactions to check the efficiency of various dienes. It can undergo [2+2] cycloaddition ­reactions, [1] 1,3-dipolar cycloaddition with 1,3-dipoles, for example azides, [2] diazoalkanes, nitrile oxide, carbonyl ylides, [3] and azomethine ylides. Besides it is also a powerful Michael acceptor and can accept various nucleophiles, for example nitrogen, oxygen, carbon, sulfur, and phosphorus.

DMAD is inexpensively available, and it can be prepared from maleic acid via a bromination-dehydrohalogenation sequence to furnish acetylene dicarboxylic acid, [4] which, upon esterification with methanol using sulfuric acid, gives dimethyl acetylene dicarboxylate. [5]

Scheme 1

Abstracts

(A) N-Heterocyclic carbenes undergo multicomponent reactions with DMAD and different types of aldehydes (aromatic, α,β-unsaturated) to produce substituted furans. [6] The nature of the product depends on the nature of the N-heterocyclic carbene used and on the type of aldehyde.
(B) An inverse Wittig-reaction-type protocol was demonstrated where cyclic 2,4,6-trialkylphenyl phosphineoxides undergo [2+2] cycloaddition with DMAD to furnish spirocyclic oxaphosphate i­ntermediates which afford a stabilized phosphonium ylide. [7]
(C) Diisopropylamino isocyanide reacts with DMAD to generate zwitter ions which react with a variety of dicarbonyl and vicinal tricarbonyl compounds affording substituted 1-aminopyrrolin-2-ones and tetrasubstituted furans under mild conditions. [8]
(D) Diastereoselective synthesis of 2H-pyrimido[2,1-a]isoquinolines is reported through a novel three-component reaction in­volving DMAD, isoquinoline, and N-tosyl imines. [9] 1,4-Dipoles are generated by reaction of isoquinoline with DMAD and react readily with N-tosylimine to produce pyrimidoisoquinoline.
(E) Alkoxy maleimides/maleic anhydrides can be synthesized from DMAD through base-induced oxa-Michael addition of alcohols to DMAD and hydrolysis followed by cyclization. [10] This is a very simple and straightforward method for the synthesis of alkoxy maleic anhydrides as well as maleimides which are important ­intermediates in organic synthesis.
(F) When pyridine reacts with DMAD, zwitterions are generated. Those have been engaged in a novel strategy with cyclobutene ­diones for the selective synthesis of highly substituted benzene and cyclopentene dione derivatives. [11] The selectivity is merely dependent on the concentration of pyridine.
(G) Couplings of dienyl furans with DMAD proceed via [8+2] ­cycloaddition to afford furan-bridged 10-membered ring systems as single diastereomers. [12] These [8+2] cycloadducts undergo ­electrophilic reactions selectively at the enol ether alkene to give substituted 10-membered rings.
(H) Various 2-aminothiazoles undergo [2+2] cycloaddition reactions with DMAD at the C-C double bond of the thiazole ring to generate fused cyclobutene intermediates. [13] Thermal disrotatory ring opening of the cyclobutene intermediates furnished tetrasubstituted pyridines in good yield.

References

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