Ring expansion cyclohexanone

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

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>. 

Cyclohexanone and pulegone provide useful examples to illustrate ring expansion and ring contraction procedures. 

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. 

Related to simple chain extension is ring expansion and contraction useful because some ring sizes are easier to make than others. So available cyclohexanone can be expanded into cycloheptanones such as the useful keto-ester 20 with an activated position for enolate reactions. The reagent is ethyl diazoacetate 18 readily available from glycine esters. Addition to the ketone 18 automatically... 

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

Reaction of cc(n-butylthiomethylene) cyclohexanone 307 with 1-phenylthiocyclo-propyllithium 116a did afford the desired adduct 308a efficiently, but, the expected C3 -> C4 ring expansion into cyclobutanone 310 could not be effected cleanly, probably because the intermediate cation 309a was more stable than its analogue without the... 

Lastly, in a very similar ring expansion process, bicyclic compounds, formed by reaction of mono- or dihalocarbenes with cyclohexanone enols, undergo ring expansion to give cyclohexenones (equation 194)1015-1017. 

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

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

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>. 

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