3- Hydroxymethyl-4- -cyclopentanones

Alai/r[(Z)-CF=C]-Pro containing N, 0-diacylhydroxamic acid type protease inhibitors have been prepared as shown in Scheme 18 [63,64], The synthesis is based upon the use of fert-butyl-a-fluoro-trimethylsilylacetate in a variation of the Peterson olefination procedure to construct the necessary functionalized fluoroolefin. Treatment of 51 with 4 equiv. of lithium diisopropylamide (LDA) and 6equiv. of chlorotri-methylsilane at 78°C formed 52 in 71% yield. The key step is the Peterson olefination reaction of the TBDMS-protected 2-(hydroxymethyl)cyclopentanone (53) with tert-butyl-a-fluoro-a-trimethylsilylacetate (52). The fluoroolefin product was obtained as a mixture of (Z) (E) isomers (54). Separation of the double-bond isomers by column chromatography provided (Z) isomer (54) in 43% yield. Further... 

A variation of this route was applied to the preparation of a-methylenecyclo-pentane 179, an intermediate that was employed for the synthesis of prostaglandin PGF2o, (180) (Scheme 6.82). The acetonide-protected oxime-diol 175 [derived from propanal (174)] was treated with sodium hypochlorite without the addition of base. This led to the tricyclic adduct 176 with high stereoselectivity. One of the side chains was subsequently elaborated and the fully protected cyclopentano-isoxazo-line (177), when exposed to Raney Ni/boron trichloride, gave the 2-hydroxymethyl-cyclopentanone (178). This compound was dehydrated using mesyl chloride/ pyridine to furnish enone (179) (324). In another related synthesis of PGF2q, the p-side-chain (3-hydroxyoctenyl) was introduced prior to the cycloaddition (325). 

Eschenmoser, A., Frey, A. Cleavage of methanesulfonyl esters of 2-methyl-2-(hydroxymethyl)cyclopentanone with bases. Helv. Chim. Acta 1952, 35, 1660-1666. 

Starling material was the silylprotected hydroxymethyl-cyclopentanone 8, readily available by a Lewis-acid promoted reaction (22) of 1-trimethylsilyloxyclyclopentene with formaldehyde-dibenzylacetal followed by hydrogenolytic debenzylation and protection (see scheme 3). 

Polyspiroketal from 2,2,5,5-Tetrakis(hydroxymethyl)cyclo-pentanone and 1,4-Cyclohexanedione. A mixture consisting of 1.12 g (0.01 mol) of 1,4-cyclohexanedione, 2.04 g (0.01 mol) of 2,2,5,5-tetrakis-(hydroxymethyl)cyclopentanone, 0.1 g of -toluenesulfonic acid, and 300 ml of benzene were heated under reflux with stirring until no more water was collected in a Dean-Stark trap. The time required was approximately 12 hr. The hot mixture was filtered through a Buchner funnel and the polymeric residue was washed with 300-ml portions of boiling benzene, methanol and carbon tetrachloride. The residue was then vacuum desiccated for several hours to yield 2.07 g (74%) of polymer, mp 370-395°C. 

Figure 5.2.10. Cellulose pyrolysate obtained at 59CP C by Py-GC/MS. The separation was done on a Carbowax type column. 1 CO2, 2 acetaldehyde, 3 acetone, 4 2-butanone, 5 2,3-butandione, 6 toluene, 7 water, 8 cyclopentanone, 9 methylfuran, 10 3-hydroxy-2-butanone, 11 hydroxypropanone, 12 cyclopent-1-en-2-one, 13 2-methylcyclopentenone, 14 acetic acid, 15 acetic acid anhydride, 16 furancarboxaldehyde, 17 methylcyclopentenone, 18 dimethylcyclopentenone, 19 5-methylfurancarboxaldehyde, 20 2,3-dihydro-2-furanone, 21 furan-2-methanol, 22 3-methylfuran-2-one, 23 2(5H)-furanone, 24 hydroxycyclopentenone, 25 3,5-dimethylcyclopentan-1,2-dione, 26 2-hydroxy-3-methyl-2-cyclopenten-1-one, 27 2-hydroxy-3-ethyl-2-cyclopenten-1-one, 28 2,3-dimethyl-2-cyclopenten-1-one, 29 phenol, 30 dimethylphenol, 31 3 thyl-2,4(3H,5H)-furandione, 32 3-butenoic acid, 33 1,4 3,6-dianhydro-a-D-glucopyranose, 34 5-(hydroxymethyl)-furfural.

The condensation of cyclohexanone (13) and cyclopentanone (14) with formaldehyde produced the corresponding tetrakis-(hydroxymethyl) -ketones in 37 and 90% yields, respectively. When the tetramethylolcyclohexanone was treated with cyclohexanone, a 77% yield of the model keto spiro ketal was formed. In this compound the carbonyl group located between the two quaternary carbon atoms is so hindered that no ketal formation apparently takes place. 

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