[5617-70-9]  · C8H10O4  · 6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione  · (MW 170.18)

(reagent for electrophilic four-carbon homologation by homo-Michael reactions and for preparation of five- and six-membered heterocycles)

Physical Data: mp 58-60 °C;1 for MS and NMR spectral data, see Maquestiau and Helferty.2

Solubility: sol ether, THF, DME, DMF; insol H2O.

Preparative Method: the preparation of this compound has been described (eq 1).1

Handling, Storage, and Precautions: use in a fume hood.

Nucleophilic Ring Opening Reactions.

This derivative of Meldrum's acid (2,2-Dimethyl-1,3-dioxane-4,6-dione) exhibits enhanced reactivity in nucleophilic ring opening reactions compared to the corresponding diester of 1,1-cyclopropanedicarboxylate. For example, (1) undergoes ring opening with piperidine to give the zwitterion (2) (eq 2).3 The facility of these homo-Michael reactions is attributable to the enhanced overlap of the carbonyl group double bonds with the adjacent cyclopropane ring bonds and to the stability of the 1,3-dioxane-4,6-dione anion leaving group.

Similarly a number of carbon, sulfur, nitrogen, and oxygen nucleophiles react with this substrate under very mild conditions (eq 3).3,4

The norcarane analog of (1) has been prepared from bicyclo[4.1.0]heptane-7,7-dicarboxylic acid (eq 4). Hydrolytic ring cleavage occurs in refluxing aqueous acetone with inversion of stereochemistry to give, after fragmentation of the dioxane ring and lactonization, the trans-fused g-butyrolactone-a-carboxylic acid. Conversion to the a-methylene lactone is accomplished by a Mannich reaction.5

Reaction of (1) with aniline at rt results in opening of the cyclopropane ring and cyclization to give 2-oxo-1-phenyl-3-pyrrolidine carboxylic acid (eq 5).3

A number of amino esters,6 pyrroles,7 and other heterocyclic derivatives8 have been used to effect nucleophilic ring opening of (1). However, due to the poor nucleophilicity of pyrrole, the reaction is carried out using Sodium Hydride as base (eq 6).

Reaction of (1) with alkyl- and arylhydrazines gives 1-substituted 1,4,5,6-tetrahydro-3(2H)-pyridazinones (eq 7).9

Lewis acid-catalyzed ring opening of (1) using Ethylaluminum Dichloride and Allyltrimethylsilane has also been reported (eq 8).10

The spiro-activated vinylcyclopropane 6,6-dimethyl-1-vinyl-5,7-dioxaspiro[2.5]octane-4,8-dione reacts with nucleophiles exclusively on the cyclopropane ring position bearing the vinyl group (eq 9).11

Ketene Formation.

Pyrolysis of (1) at 500 °C/0.5 mmHg gives carbonylcyclopropane which dimerizes at rt or which can be trapped using aniline to give a cyclopropanecarboxamide (eq 10).12

Related Reagents.

Cyclopropanone; Cyclopropenone 1,3-Propanediyl Acetal; Diethyl Malonate; Diethyl Methylenemalonate; 2,2-Dimethyl-1,3-dioxane-4,6-dione; [1-(Ethoxycarbonyl)cyclopropyl]triphenylphosphonium Tetrafluoroborate; 1-Ethoxycyclopropanol.

1. Singh, R. K.; Danishefsky, S. OSC 1990, 7, 411.
2. (a) Maquestiau, A.; Pauwels, P; Flammang, R.; Lorencak, P., Wentrup, C. OMR 1986, 21, 259. (b) Helferty, P. H.; Yates, P. Org. Mass. Spectrom. 1983, 21, 352.
3. (a) Danishefsky, S.; Singh, R. K. JACS 1975, 97, 3239. (b) Danishefsky, S. ACR 1979, 12, 66.
4. Horton, M.; Pattenden, G. JCS(P1) 1984, 811.
5. Singh, R. K.; Danishefsky, S. JOC 1976, 41, 1668.
6. Freidinger, R. M. JOC 1985, 50, 3631.
7. (a) Franco, F.; Greenhouse, R.; Muchowski, J. M. JOC 1982, 47, 1682. (b) Oritz, C.; Greenhouse, R. TL 1985, 26, 2831. (c) Muchowski, J. M.; Cho, I. S. U.S. Patent 5 082 951, 1992 (CA 1992, 116, 214 338d) and references therein.
8. (a) Tsuji, M. et. al. Eur. Patent 307 034, 1989 (CA 1989, 111, 115 117r). (b) Grinter, T. J.; Geen, G. R.; Parratt, M. J. Eur. Patent 302 644, 1989 (CA 1990, 112, 7269j). (c) Grinter, T. J.; Kincey, P. M. Eur. Patent 352 953 1990 (CA 1990, 113, 40 345z). (d) Geen, G. R.; Hanson, J. C. Eur. Patent 369 583, 1990 (CA 1990, 113, 191 061e).
9. Hwang, K. J.; Park, K. H. H 1993, 36, 219.
10. Bambal, R.; Kemmitt, R. D. W. CC 1988, 734.
11. Danishefsky, S.; Singh, R. K. JOC 1975, 40, 3807.
12. Baxter, G. J.; Brown, R. F. C.; Eastwood, F. W.; Harrington, K. J. TL 1975, 4283.

Rajendra K. Singh

Monsanto Company, St. Louis, MO, USA

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