CYCLOBUTANONE, 2-HYDROXY

Cyclobutanediol, 1,2-dimethyl- synthesis, 53 Cyclobutanone, 2-hydroxy- synthesis, 54 Cyclobutanones synthesis, 77, 79, 335-336 Cyclobutene synthesis, 142... 

Gyciobutanones s. Amino-cyclobutanones, Hydroxy-Gyclodehydration 17, 836 —, stereochemical effect of ring activity 17, 941... 

If a bromomethyl- or vinyl-substituted cyclopropane carbon atom bears a hydroxy group, the homoallyiic rearrangement leads preferentially to cyclobutanone derivatives (J. Sa-laun, 1974). Addition of amines to cydopropanone (N. J. Turro, 1966) yields S-lactams after successive treatment with tert-butyl hypochlorite and silver(I) salts (H.H. Wasserman, 1975). For intramolecular cyclopropane formation see section 1.16. 

Diethyl A-(4-hydroxy-4-phenylpiperidin-1 -yl)methylenemalonate did not react with ketene in acetone to give a cyclobutanone derivative (64JMC68). 

One of the most reactive, with respect to phosphine, ketones, hexafluoro-cyclobutanone, produces with phosphine primary and secondary 1 hydroxy-fluorocyclobutylphosphines instead of phosphine oxides ... 

Tabic 5. Enantioselective Synthesis of 2-Alkyl- and 2-Aryl-2-(hydroxy-methyl)cyclobutanones by Asymmetric Epoxidation and 1,2-Rearrangement of Cyclopropylidene Alcohols55... 

Formation of CK-configurated cyclobutanones has also been observed with 2-methylcyclopen-tanone and 2-methylcyclohexanone/8 However, stereoreversed eyclobutanone formation can be achieved by opening the intermediate oxaspiropentane with sodium phenyl selenide, oxidation of the resulting / -hydroxy selenide with 3-chloroperoxybenzoic acid and subsequent rearrangement in the presence of pyridine/18 Thus, from one oxaspiropentane 8, either stereoisomeric eyclobutanone cis- or lrans-9 was produced. The stereoreversed eyclobutanone formation proceeds from a stereohomogenous / -hydroxy selenoxide and is thought to be conformationally controlled. 

Hydroxymelhyl)cyc opropan-l-ol (11), readily obtained by hydrogen peroxide oxidation of methylenecyclopropane, was rearranged to cyclobutanone (12) either directly, or via an intermediate l-(tosyloxymethyl)cyclopropan-l-ol.114 115 Competitive ring opening to 1-hydroxy-butan-2-one (13) was observed in the boron trifluoridc catalyzed process. 

Analogs ofl-lithiocyclopropyl phenyl sulfide bearing a methylsulfanyl instead of a phenyl-sulfanyl group were obtained from dibromocyclopropanes by sequential treatment with butyl-lithium, dimethyl sulfide and butyllithium. Addition to aldehydes occurred readily and rearrangement of the resulting /7-hydroxy sulfides 10 with trifluoroacetic acid yielded cyclobutanones II.172... 

Moreover, reaction of racemic 15 with two equivalents of iron(III) chloride afforded pure 2-(l-hydroxy-2,2-dirncthylpropyl)cyclobutanone 16 in 70% yield. Carrying out this reaction on enantiomerically pure ( —)-15 gave optically pure cyclobutanone 16.138... 

The hydrolysis of acetals are reported to go smoothly.292 However, some precautions should occasionally be taken since it has been reported that treatment of cAO-2-hydroxymethyl-7,7-dimcthoxybicyclo[3.2.0]heptan-m7o-2-ol with a mixture of 3% hydrochloric acid/acetone/wa-ter (1 9 1) gave a mixture of ertafo-2-hydroxy-< .xo-2-hydroxymethylbicyclo[3.2.0]heptan-7-one (5) and 8-hydroxymethyl-2-oxabicyclo[3.3.0]oct-7-en-3-one (6) in 2 1 ratio.323 The reaction is explained by a rearrangement of an intermediate cyclobutanone hydrate, but since other acetals do hydrolyze without similar byproduct formation it seems likely that the neighboring tertiary alcohol must be involved in the rearrangement. 

A similar example is the ring expansion of cyclobutanone via l-tris(methylsulfanyl)methyl-cyclobutanol (6) to 2,2-bis(methylsulfanyl)cyclopentanone (7).43 The use of Af,A-diisopropyl-ethylamine is unneccessary in this reaction as the hydroxy group has already been deprotonated with butyllithium. Further examples of this type of reaction can be found in refs 43 and 44. 

Linkers that enable the preparation of y-lactones by cleavage of hydroxy esters from insoluble supports are discussed in Section 3.5.2. Resin-bound y-lactones have been prepared by Baeyer-Villiger oxidation of cyclobutanones [39], by intramolecular addition of alkyl radicals to oximes [48], by electrophilic addition of resin-bound sele-nenyl cyanide or bromide to 3,y-unsaturated acids (Figure 9.2 [100]), and by palladium-mediated coupling of resin-bound aryl iodides with allenyl carboxylic acids (Entry 10, Table 5.7 [101]). 

A considerable number of electrophiles were used, and the dithiane route found great utility for the syntheses of simple monofunctional compounds as well as for polyfunctional molecules, for which the dithiane moiety affords an invaluable temporary protection of a future carbonyl group. Some experimental procedures published in Organic Syntheses — cyclobutanone [277] and 3-hydroxy-l-cyclohexene-l-carboxaldehyde [278] — are illustrative. A similar route to aldehydes [279] makes use of sym-trithiane as a formyl anion equivalent. 

Hsiao, C.-N. et al. Efficient Syntheses of Protected (2S,3S)-2,3-Bis(hydroxy-methyl)cyclobutanone, Key Intermediates for the Synthesis of Chiral Carbocyclic Analogues of Oxetanocin. 4.1 1990 [127]... 

Gas-liquid chromatography [1/8 in. x 6 ft, 10% diethylene glycol succinate (LAC-728) column, 70°C] of cyclobutanone (99.2% pure) revealed the presence of small amounts of methylene chloride (0.6%) and cyclobutanol (0.2%). No cleavage product, 4-hydroxy butyraldehyde, was found. The traces of water, detected by NMR spectroscopy using CD3COCD3 as a solvent, can be removed by drying over molecular sieves. 

The cathodic reduction of 2,2,4,4-tetramethylcyclobutanedione leads to the formation of the l-hydroxy-3-cyclobutanone derivative. It was proposed that this product is formed via the intermediacy of a bicyclobutane derivative (82). 

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