Cyclobutanones, oxidation

Cycloaddition of vinylketenes, produced in situ from the dehydrohalogenation of appropriately substituted unsaturated acid chlorides, with alkenes provides a convenient source of 2-vinyl-cyclobutanones. Oxidation with ruthenium(III) chloride trihydrate gave the corresponding P-oxo acid, which by treatment with oxalyl chloride and diazomethane, successively, led to the desired 2-(2-diazoacetyl)cyclobutanones. These diazo ketones are thermally labile and rearrange upon brief heating in refluxing xylene to give the spiro[cyclopropane-l,5 -furan-2 (5 i/)-ones] 2 (Table 2). ... 

V-F-1.2. Summary of the Mechanism and End Products of Cyclobutanone Oxidation, and Summary of Its Atmospheric Fate... 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

The oxidation by chromic acid alone leads to a mixture of cyclobutanone and 4-hydroxybutyraldehyde the existence of an isotope effect for the oxidation of I-deuteriocyclohexanol suggests that Cr(VI) produces the ketone and lower oxidation states of chromium produce the cleavage product. 

This chapter begins by classifying the combinations of oxidation/reduction processes with subsequent cationic transformations, though to date the details of only two examples have been published. The first example comprises an asymmetric epoxidation/ring expansion domino process of aryl-substituted cyclopropyl-idenes (e. g., 7-1) to provide chiral cyclobutanones 7-3 via 7-2, which was first described by Fukumoto and coworkers (Scheme 7.1) [2]. 

The same epoxide 335 was easily obtained in mild conditions (0°C, 5 min) by m-ehloroperbenzoic acid oxidation [13b]. Epoxidation of alkylidenecyclo-propanes by m-chloroperbenzoie acid has been greatly exploited as a route to the synthesis of cyclobutanones 638 via the well known ring expansion of oxaspiropentanes 637 (Scheme 98) [176,177,8]. 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

A nickel(O) complex catalyzes insertion of alkynes into cyclobutanones (Equation (79)).437 Formation of metalla-cycle 194 via oxidative cyclization of an alkyne with the carbonyl group of a cyclobutanone followed by /3-carbon elimination (formation of metallacycle 195) and reductive elimination are postulated for the mechanism (Scheme 92). 

Cyclobutanone annulation onto a carbonyl group translates into y-butyrolactone annulation because of the facility of the Baeyer-Villiger reaction (Eq. 68 a)8). Indeed, the reaction proceeds sufficiently rapidly that even basic hydrogen peroxide effects the oxidation whereas, with less reactive carbonyl partners, peracids must be used. 

The fragmentation is stereospecifically anti as shown by complementary geometry obtained in the cleavage of the epimeric pair of epoxycyclobutanones 91 and 92 (Eq. 110). The fragmentation product 93 of cyclobutanone 91 is transformable into the dimethyl ester of the pheromone of the Monarch butterfly. Considering the availability of the starting epoxy ketones from enones, the oxasecoalkylation serves to reorient the oxidation pattern with chain extension as summarized in Eq. 111. 

In Grieco s total synthesis of the antileukemic secoeudesmanolides ivangulin (194)67) and eriolanin (197)68), the Baeyer-Villiger oxidation was again found to be indispensable in the conversion of the cyclobutanones (192) and (195) to the y-lactones (193) and (196)respectively 67,68). 

The key step in Smith s paniculides synthesis was the oxidation of the cyclobutanone (198) to the epoxylactones (199) and (200), which were separated by flash chromatography 69). 

The cyclobutanone (201) also underwent smooth oxidation to afford the y-lactone (202), which was not isolated and was allowed to react further to yield the cytotoxic germacranolide eucannabinolide (203) in a number of steps 70 (... 

A systematic study of the Baeyer-Villiger oxidation of cyclobutanones was recently reported by Jeffs71). The cycloalkenes (206) reacted readily with dichloro-ketene to give the gem-dichlorocyclobutanone (205), which were reduced by Zn to the cyclobutanone (204). Baeyer-Villiger oxidation of (204) yielded the y-lactone (207) in fair yields. (Table 11)71). 

The benzene ring containing cyclobutanones (208), (210) and (212) were also oxidized to their y-lactones (209), (211) and (213) respectively71 These examples demonstrate convincingly the order of alkyl migration. 

Cyclobutanones were found to be much more reactive under these conditions, presumably due to relief of ring strain (131). Racemic cyclobutanone (192) is oxidized under the conditions described above to provide lactones 193 and 194 in a ratio of 55 45, Eq. 111. The expected lactone product 193 is formed in 67% ee while the abnormal product 194 is formed in 92% ee. The major enantiomers of the two products are complementary, resulting from enantiomeric ketones. 

The stereoselective [2+2] cycloaddition between ketenes and enolethers can be used as a key step in the construction of y-butyrolactones (Scheme 14) [45], if the resulting cyclobutanones can subsequently undergo ring enlargement by a regioselective Baeyer-Villiger oxidation. 

In the past few years, new approaches for the enantioselective synthesis of / -benzyl-y-butyrolactones appeared in the literature. Some of these approaches involve the asymmetric hydrogenation of 2-benzyl-2-butenediols (j [34]), the radical mediated rearrangement of chiral cyclopropanes (r [35]), the transition metal catalyzed asymmetric Bayer-Villiger oxidation of cyclobutanones n [36]), or the enzymatic resolution of racemic succinates (g [37]). 

In the same year, chiral phosphoric acids were found to catalyze the enantioselective Baeyer-ViUiger (BY) oxidation of 3-substituted cyclobutanones 140 with aqueous... 

Scheme 56 Baeyer-Villiger oxidation of 3-substituted cyclobutanones...

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