Synlett 2007(13): 2142-2143  
DOI: 10.1055/s-2007-984894
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

Dimethyl Acetylene Dicarboxylate

Manoj Kumar Sahoo*
Process Technology Development Division, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474002 (MP) India
e-Mail: mks9@rediffmail.com;

Dedicated to Dr. N. P. Argade, OCS Division, NCL, Pune


Further Information

Publication History

Publication Date:
12 July 2007 (online)

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

  • 1 Cook AG. Enamines: Synthesis, Structure, and Reactions   2nd ed.:  Cook AG. Dekker; New York: 1988.  p.384 
  • 2 Prabhakar JK. Shanmugasundaram P. Ananthnarayanan C. Ramakrishnan VT. Indian J. Heterocycl. Chem.  1992,  1:  157 
  • 3 Paquette LA. Shen CC. J. Am. Chem. Soc.  1990,  112:  1159 
  • 4 Abbot TW. Arnold RT. Thompson RB. Org. Synth., Coll. Vol. II  1943,  10 
  • 5 Huntress EH. Lesslie TE. Bornstein J. Org. Synth., Coll. Vol. IV  1963,  329 
  • 6 Ma C. Ding H. Wu G. Yang Y. J. Org. Chem.  2005,  70:  8919 
  • 7 Keglevich G. Kortvelyesi T. Forintos H. Vasko AG. Vladiszlav I. Toke L. Tetrahedron  2002,  58:  3721 
  • 8a Nair V. Mathen JS. Viji S. Srinivas R. Nandakumar MV. Varma L. Tetrahedron  2002,  58:  8113 
  • 8b Nair V. Deepthi A. Tetrahedron Lett.  2006,  47:  2037 
  • 9 Nair V. Sreekanth AR. Abhilash N. Bhadbhade MM. Gonnade RC. Org. Lett.  2002,  4:  3575 
  • 10 Sahoo MK. Mhaske SB. Argade NP. Synthesis  2003,  346 
  • 11 Nair V. Pillai AN. Beneesh PB. Suresh E. Org. Lett.  2005,  7:  4625 
  • 12 Zhang L. Wang Y. Buckingham C. Herndon JW. Org. Lett.  2005,  7:  1665 
  • 13 Mateo A. Jose C. Pastor A. Sanchez-Andrada P. Bautista D. J. Org. Chem.  2006,  71:  5328 

    References

  • 1 Cook AG. Enamines: Synthesis, Structure, and Reactions   2nd ed.:  Cook AG. Dekker; New York: 1988.  p.384 
  • 2 Prabhakar JK. Shanmugasundaram P. Ananthnarayanan C. Ramakrishnan VT. Indian J. Heterocycl. Chem.  1992,  1:  157 
  • 3 Paquette LA. Shen CC. J. Am. Chem. Soc.  1990,  112:  1159 
  • 4 Abbot TW. Arnold RT. Thompson RB. Org. Synth., Coll. Vol. II  1943,  10 
  • 5 Huntress EH. Lesslie TE. Bornstein J. Org. Synth., Coll. Vol. IV  1963,  329 
  • 6 Ma C. Ding H. Wu G. Yang Y. J. Org. Chem.  2005,  70:  8919 
  • 7 Keglevich G. Kortvelyesi T. Forintos H. Vasko AG. Vladiszlav I. Toke L. Tetrahedron  2002,  58:  3721 
  • 8a Nair V. Mathen JS. Viji S. Srinivas R. Nandakumar MV. Varma L. Tetrahedron  2002,  58:  8113 
  • 8b Nair V. Deepthi A. Tetrahedron Lett.  2006,  47:  2037 
  • 9 Nair V. Sreekanth AR. Abhilash N. Bhadbhade MM. Gonnade RC. Org. Lett.  2002,  4:  3575 
  • 10 Sahoo MK. Mhaske SB. Argade NP. Synthesis  2003,  346 
  • 11 Nair V. Pillai AN. Beneesh PB. Suresh E. Org. Lett.  2005,  7:  4625 
  • 12 Zhang L. Wang Y. Buckingham C. Herndon JW. Org. Lett.  2005,  7:  1665 
  • 13 Mateo A. Jose C. Pastor A. Sanchez-Andrada P. Bautista D. J. Org. Chem.  2006,  71:  5328 

Scheme 1