Ring expansion of cyclohexanone

Ring expansion of cyclohexanone to cycloeheptanone may be effected by reaction with diazomethane (Expt 7.17). The ring-expanded ketone is obtained in about 60 per cent yield and is accompanied by some epoxide and some cyclo-octanone which results from further ring expansion of the cycloheptanone. Mechanistically the reaction may be represented in the following manner. 

Cyclic ketones. Diazomethane ring expansion of cyclohexanone gives cyclo-heptanone in yields as high as 63% and smaller amounts of cyclooctanone and methylenecyclohexane oxide. The cycloheptanone is easily separated from the... 

Ring expansion. In early work3 the ring expansion of cyclohexanone to 2-methylcycloheptanone by reaction with ethereal diazoethane was found to proceed slowly and in poor yield. The results were confirmed by Marshall and Partridge.4 These chemists noted, however, that Mosettig5 had observed that methanol accelerates the reaction of cyclohexanone with diazomethane. They then carried out the ring expansion of cyclohexanone (1) with diazoethane in 20% ethanol in diethyl ether as solvent. The reaction was complete within 2 hours and gave a 9 1 mixture of 2-methylcycloheptanone (2) and the oxide (3) in over 90% yield. They also carried out the reaction on a number of 4-substituted cyclohexanones. 

Radical ring expansion of cyclohexanones. This reaction is a useful route to medium-size ring systems. Thus the precursor 1, prepared in two steps from cyclohexenone, on treatment with Bu3SnH and A1BN furnishes the cyclodeccnone 2 in 78% yield. 

An industrially important application is the ring expansion of cyclohexanone oxime to 6-hexanolactam 133... 

Similarly, ring expansions of cyclohexanones have been achieved with a-diazoacetates via Lewis acid catalysis (Scheme 11). ° Using AlMc3 and (78) in a 2 1 ratio allowed high to excellent yields and enantioselectivities to be achieved. This method has been successfully applied to the desymmetrization of 4-substituted cyclohexanones (79) yielding seven-membered carbocycles (80). 

A chiral aluminium Lewis acid catalyst composed of Me3Al and 3,3 -bis-(trimethylsilyl)-BINOL has been reported to promote catalytic asymmetric ring expansion of cyclohexanone with a-substituted a-diazoacetates to give seven-membered rings with an all-carbon quaternary centre (Scheme 70). ... 

Hashimoto T, Naganawa Y, Mamoka K (2011) Desymmetrizing asymmetric ring expansion of cyclohexanones with a-diazoacetates catalyzed by chiral aluminum lewis acid. J Am Chem Soc 133 8834-8837... 

This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous tt,/3-unsaturated ketones. The key step in the sequence is the iron(III) chloride-induced cleavage of the central bond of trimethyl-silyloxycyclopropanes which me obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene from cyclohexanone described in Part A is that of House, Czuba, Gall, and Olmstead. ... 

Alkoxy radical fragmentation is also involved in ring expansion of 3- and 4-haloalkyl cyclohexanones. The radical formed by halogen atom abstraction adds to the carbonyl group, after which fragmentation to the carboethoxy-stabilized radical... 

The trimethylsilyl ethers 212 of four-membered 1-alkenyl-1-cyclobutanols rearrange to the ring-expanded 0-mercuriocyclopentanones 213. These can be converted into the a-methylenecyclopentanones 214 through elimination or further expanded by one-carbon atom into cyclohexanones 215 via the Bu3SnH-mediated free radical chain reactions [116]. A similar radical intermediate is suggested to be involved in the ring expansion of a-bromomethyl-fi-keto esters [117]. (Scheme 84)... 

Ring expansion (7, 153-154). Details are available for expansion of cyclohexanone to 2-cycloheptenone via cyclopropanation of enol silyl ethers (equation 1). The report includes six other examples of this method yields range from 80 to 98%. In all cases the more highly substituted C C bond of the cyclopropane ring is cleaved by FeCI,.1... 

An asymmetric Schmidt ring expansion of the 4-substituted cyclohexanones 312 using chiral azido alcohols 313 gave the azepan-2-ones 314 in high yields and good diastereomeric ratios depending on the nature and position of R1 (Scheme 40) <2003JA7914>. 

Photolytic ring expansion of a spirooxaziridine intermediate was central to the ring expansion of the cyclohexanone 324 to 326 (e.g., R = Bn) after initial imine formation from reaction of 324 with 325 the oxaziridine was then generated by oxidation of the imine with w-chloroperoxybenzoic acid (Scheme 41) <1997JOG654>. 

The Baeyer-Villiger enzyme, cyclohexanone monooxygenase (CHMO), has been applied to the oxidative ring expansion of m-2,6-dialkylperhydropyrans to afford 28 with very high yields and ee s, when R = methyl or ethyl (Scheme 11) <2001JM0349, 2003SL1973>. 

Fig. 14.23. Ring expansion of a cyclohexanone via addition of diazoacetic acid ethyl ester and subsequent [l,2]-rear-rangement.

Scheme VII /19. A free radical mediated ring expansion of ds and trans a-alkylated /i-stanny-lated cyclohexanones [49] [50].

The most general methods for preparing seven- or eight-membered rings from enamines are by ring expansion of the cyclobutene, cyclobutanone or chlorocyclopro-pane adducts formed by cycloaddition of acetylene carboxylates, ketenes or chlor-ocarbenes, respectively, to enamines of cyclopentanone or cyclohexanone. These are two-carbon or one-carbon ring expansions. Three-carbon ring expansions can also be carried out by cycloaddition of activated cyclopropenes or cyclopropenones. 

Intramolecular cyclizations. Cyclizations of a>azido-/3-ketoesters, such as 138 (obtained by a multistep reaction starting from cyclohexanone), produced eight-membered enamines 139 (Scheme 57 <2004JOC997>). Preparations of 138 are based on a method developed from the formal ring expansion of cyclic ketones via retro-Reformatsky fragmentation <2004JOC997>. 

There is an abundance of literature dealing with the diazomethane, diazomethane derivatives and Tif-feneau-Demjanov expansions of six-membered and larger ring ketones, with most of the simpler examples reported in the older literature. For example, e diazomethane expansion of cyclohexanone... 

The one-carbon expansion of cyclohexanones with introduction of a carbonyl group, trifluromethyl, cyano, phosphonate or benzenesulfonate has also been reported to proceed in the presence of Lewis acids (Scheme 14). The analogous reactions of larger ring ketones [expressed as ring size (yield)] with ethyl diazoacetate [7 (81%), 8 (85%)] and phenylsulfonyldiazomethane [7 (86%), 8 (27%), 12 (43%), 14 (48%), 15 (54%) and 16 (58%)] have also been reported. In the reaction of ethyl diazoacetate and... 

Table 6. Formation of 3-Substituted Cycloheptanones by Ring Expansion of 2-Substituted Cyclohexanones and Analogs...

Ring expansion (1, 369-370). Ring expansion of unsymmetrical a-mono-and a,a-disubstituted cyclopentanones and cyclohexanones (1) with ethyl diazoacetate in the presence of boron trifluoride etherate gives mixtures of (2) and... 

In the case of 9, the approach involved reaction of a trifluoroalkane-2,3-dione-3-oxime with cyclohexanone, while synthesis of 41 was achieved via ring expansion of A -methyloxadiazolium salts. The scope and limitations of the 2,3-dione-3-oxime route to 9 is difficult to evaluate since only a single example was reported, though a trifluoromethyl group may be required for activation of this system and thus would limit possible substitution patterns on the resulting oxadiazine ring. However, the reaction would presumably tolerate a number of different ketone partners, thereby increasing its scope. 

Reactions of this type (Scheme 3.44) are especially useful for the preparation of cyclic p,p-dihaloenones by ring expansions of alkynyl cyclopentanols or alkynyl cyclohexanols. 1-Bromoethynylcyclopentanols 111 react with equimolar amounts of iodine and PhI(OH)OTs under mild conditions to produce cyclohexanone derivatives 112 with a high degree of stereoselectivity (Scheme 3.45) [129]. 

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