Cyclopentenone ketals

This reaction can be used to effect a [3 + 2] or a [3 + 2 + 2] annelation to a cyclopentenone ketal or a cycloheptadienone ketal, respectively. Thus the adduct of a vinylcuprate with 1 rearranges thermally (240-290°) to 3-cyclopentenone ketals (3) in 50-80% yield (equation I). [3 + 2 + 2]Annelation involves preparation of... 

The same protocol shown in Scheme 63 was also applied to the cyclopentenone ketal 182, which gave the expected compounds 183 after final deprotection under acidic conditions (2 M HCl) in 33-40% yield. This acidic deprotection applied to products 181 gave... 

Photosolvolysis of 3-alkoxypyridinium tetrafluoroborates 16 under basic aqueous conditions generates the substituted cyclopentenone ketals 17 <99SL93,99T6183>. 

Penkett, C.S. and Simpson, I.D., New methods of preparing cyclopentenone ketals. The photosolvolysis of 3-alkoxypyridinium tetrafluoroborates, Synlett., 93, 1999 Penkett, C.S., and Simpson, I.D., Photosolvolysis reactions of 3-alkoxypyridinium tetrafluoroborate salts. Tetrahedron, 55,6183, 1999. 

In an analogous approach explored by Dixneuf et al., a conjugated enynyl carbonate is converted into an oxolenone or a bicyclic lactone in significant yields via double carbonylation in the presence of methanol (Scheme 22) [128]. When a neighboring carbonyl group is present in the substrate, it can also participate in palladium-catalyzed cyclization-carbonylation. Indeed, 4-yn-l-ones lead to cyclic ketals that can be easily converted into 2-cyclopentenone carboxylates in an acidic medium (Scheme 22) [129]. 

Bromo-2-cyclopentenone ethylene ketal was prepared according to a published procedure. The compound is quite unstable and should be purified b distillation before use to remove impurities. The submitters stored the... 

The preparation of (S)-(-)-menthyl p-toluenesulfinate described in Part A is based upon the procedure reported by Solladie. 2-Bromo-2-cyclopentenone ethylene ketal is available from 2-cyclopentenone by the procedure of Smith and co-workers. The present procedure has been used by the submitters to prepared analogous chiral ci-sulf1nyl a,B-enones (Table I).11 The utility of these chiral synthons is enhanced by their stability, the facility of their... 

S)-(+)-2-(p-Toluenesulflnyl)-2-cyclopentenone ethylene ketal l,4-Dioxaspiro[4.4]non-6-ene, 6-[(4-methyl phenyl)sulfinyl]-,... 

B. 2-Bromocyclopentenone ethylene ketal. A solution of 22.00 g (136.7 mmol) of freshly distilled 2-bromo-2-cyclopentenone, 21.80 g (351.2 mmol) of ethylene glycol, 1.5 L of benzene (Note 4), and 60 mg of p-toluenesulfonic acid monohydrate is refluxed for 64 hr (Note 5), with azeotropic removal of water, in a 3-L, round-bottomed flask, equipped with a Dean-Stark trap, condenser, and Drierite drying tube. The solution is cooled to room temperature, dried with potassium carbonate, and filtered by vacuum through 15 g of Celite. The filter cake is washed with 150 mL of benzene. Removal of the solvent under reduced pressure yields a mobile yellow oil. Distillation (65-67°C, 0.7 mm) affords 22.4 g (109.0 mmol, 80%) (Note 6) of the ketal (Note 7). 

Without purification, 8.1 g of the above crude ketal is added to a solution consisting of 1.0 g of oxalic acid, 5 mL of water, and 40 mL of methylene chloride. The resultant mixture is stirred for 5 hr at room temperature. At the end of this period the solution is filtered through 50 g of magnesium sulfate impregnated with 1.0 g of potassium carbonate (Note 14). Evaporation of the solvent from the filtrate affords a solid which, after purification by short-path distillation (70-80°C, 0.1 mm) (Note 15), gives 4.9 g (46%, based on bromoketal) (Note 16) of pure 2-hydroxymethyl-2-cyclopentenone, mp 68-69°C (off-white crystals) (Notes 17 and 18). 

Pure 2-bromo-2-cyclopentenone ethylene ketal displayed the following spectroscopic properties IR (CC14) cm 2975 (s), 2950 (s), 2880... 

A more versatile, as well as a more direct approach for the conversion of 1 to 2 employs the ethylene ketal of a-bromo-ot,p-enones (e.g., 5) as a latent equivalent of a-ketovinyl anion 4.7 Indeed, independent studies by Ficini and Depezay,8 House and McDaniel,9 and Manning et al.10 as well as our own" suggested that such a general strategy would be viable. To illustrate this approach, we record here the preparation of the very useful synthon a-hydroxymethyl-2-cyclopentenone ... 

Ketals have also been used as an alternative to link the chiral inductor to the starting reagents. An important asymmetric induction was observed during the cycloaddition of ketals 94 having a C2 axis of symmetry, and a cyclopentenone or cyclohexenone derivative 95. Unfortunately, the observed chemical yields of 96 remain low (Scheme 22) [68]. With ketals of aliphatic enones, the selectivity decreases, and complex mixtures of isomers were observed [69]. 

Friedel-Crafts acylation. Posner el al. have developed a remarkably efficient route to the methyl ether of the steroid 11-oxoequilenin (5) from 2-methyl-2-cyclopentenone (1). jS-Addition of the organocoppermagnesium reagent 2 to 1 followed by a-alkylation with ethyl iodoacetate proceeds stereospecifically to give the secosteroid 3 in 94% yield. The final step requires an intramolecular Friedel-Crafts acylation, a reaction that has proved troublesome in previous syntheses of steroids via 9,11-secosteroids. And indeed attempts to cyclize the free acid corresponding to 3 with HF proceeded in yields of 10%. However, cyclization of the ketal acid 4 gives stereochemically pure 5 in 75% yield based on recovered secosteroid. The overall yield from 2-bromo-6-methoxynaphthalene is 52%. 

The last example illustrates one advantage of this method the enol ether function of 1 can be hydrolyzed without effect on a ketal grouping. Another advantage is that the intramolecular Wittig-Homer reaction proceeds without isomerization of the initially formed cyclopentenone. 

Previous preparations, of 2-cyclopentenone have involved the elimination of HCl from 2-clrlorocyclopentanone or its ketal. The oxidation of 3-chloro- or 3-hydroxycyclopentene has been... 

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