[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)
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.
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
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
Rajendra K. Singh
Monsanto Company, St. Louis, MO, USA