Meldrum’s Acid

Introduction

Meldrum"s acid (1, isopropylidene malonate or 2,2-di­methyl-4,6-dioxo-1,3-dioxane), was first synthesized by Meldrum in 1908 [1] and the structure was incorrectly assigned as the b-lactone of b-hydroxyisopropylmalonic acid (b,b-dimethyl-b-propiolactone-a-carboxylic acid). [2] It was only 40 years later that Davidson and Bernhard assigned the correct structure. [2] Meldrum’s acid has attracted considerable attention due to its high acidity (pK _a = 4.97) [3] and rigid cyclic structure. Acylated derivatives (synthetic equivalents of mixed ketenes) readily undergo alcoholysis to give b-keto esters. [4] Alkylidene derivatives are strong electrophiles and can undergo Diels-Alder reactions with high diasteroselectivity. [5] This versatile tool is a key intermediate for a large number of important building blocks and there remains much to discover.

References

• 1 Meldrum AN. J. Chem. Soc.  1908,  93:  598 
• 2 Davidson D. Bernhard SA. J. Am. Chem. Soc.  1948,  70:  3426 
• 3 Pihlaja K. Seilo M. Acta Chem. Scand.  1969,  23:  3003 
• 4 Oikawa Y. Sugano K. Yonemitsu O. J. Org. Chem.  1978,  43:  2087 
• 5 Endo T. Kihara N. Mizukami S. Tetrahedron Lett.  1993,  34:  7437 
• 6 Zawacki FJ. Crimmins MT. Tetrahedron Lett.  1996,  37:  6499 
• 7 Hemtenäs H. Soto G. Hultgren SJ. Marshall GR. Almqvist F. Org. Lett.  2000,  14:  2065 
• 8a Huang X. Chen B.-C. Synthesis  1986,  967 
• 8b Chen B.-C. Huang X. Wang J. Synthesis  1989,  317 
• 9 Arcadi A. Attanasi OA. Liao Z. Serra-Zanetti F. Synthesis  1994,  605 
• 10 Shing TK. Li L.-H. Narkunan K. J. Org. Chem.  1997,  62:  1617 
• 11 Sørensen US. Falch E. Krogsgaard-Laesen P. J. Org. Chem.  2000,  65:  1003 
• 12 Gaber AE.-A. McNab H. Synthesis  2001,  2059