Ketones, bicyclic rearrangement

Application of the same type mechanistic sequence rationalizes the second step of the aqueous dioxane photolytic rearrangement, in which the bicyclic ketone IX rearranges to 2,3-diphenylphenol (X), 6,6-diphenyl-3,5-hexadienoic acid (XI) and minor amounts of 3,4-diphenyl-... 

The metabolism of 7-endo-fenchol to ci-fenchone in fennel has been studied in quite some detail by Croteau and co-workers (Croteau and Felton, 1980). Croteau et al. (1980a) later reported a soluble enzyme preparation from the leaves of fennel which catalysed the cation-dependent cyclization of both geranyl pyrophosphate and neryl pyrophosphate to the bicyclic rearranged monoterpene 1-enc/o-fenchol. Croteau et al. (1980b) found that (+)-(lS)-fenchone, an irregular bicyclic monoterpene ketone thought to be derived... 

High quantum and chemical yields of ODPM rearrangements are obtained with substrates in which the ly-enone chromophore is part of a conformationally rigid molecular assembly which at the same time guarantees adequate orbital overlap of the C=C and rr-bonds. Whereas in bicyclic and bridged 3, y-unsaturated ketones these prerequisites are widely met, acyclic p,7-unsaturated ketones usually rearrange inefficiently since other channels of energy dissipation from the triplet state predominate. Exceptions to this rule are substrates in which the C= ir-bond is part of a styrene or an a, -enone moiety (Section 2.6.3.1). In this context it should also be noted that p,7-unsaturated aldehydes, except for one case, are ODPM unreactive (Section 2.6.3.2). 

On irradiation the diazepinone 7 rearranges to the bicyclic ketone 8 by a symmetry allowed disrotatory 4rc-electrocyclization.9 5... 

Bicyclic ketone (33) was needed for a chrysanthemic acid synthesis. tarbene disconnection next to the ketone group (Chapter T30) reveals y. (5-unsaturated acid (35) as an intermediate, available by a Claisen-Cope rearrangement. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

The use of trifluoroethanol as solvent or absorption of the dienone on silica gel promotes the photoconversion of dienones into bicyclic ketenes.<47) For the photolysis<48 60) of (63) it has been shown by low-temperature infrared and ultraviolet spectroscopy that the initial photolysis gives a ketene which can be efficiently trapped by cyclohexylamine or, in the absence of a good nucleophile, thermally rearranges by a OA, + 20) allowed process to a bicyclic ketone (64) ... 

The impulse to the study of these cycloadditions came from the discovery that 5-spirocyclopropane isoxazolidines (or isoxazolines) undergo a thermal rearrangement resulting in the production of selectively substituted tetrahydro-(or dihydro) pyrid-4-ones (Scheme 42) [64], In particular, cyclic nitrones gave ultimately N-bridgehead bicyclic ketones, molecular skeleton of many alkaloid families [65]. 

Direct interception of the initially formed bicyclic oxyallyl zwitterion derived from cyclohexadienones is difficult, due to its facile rearrangement to cyclopropyl ketone. One notable exception is the observation that 4-trichloromethyl-substituted dienone 94 gave solvent adduct 97 when irradiated in methanol, and both 97 and 98 upon irradiation in acidic methanol (Scheme 24)48. It was proposed that 97 arises either from a facile... 

The bicyclic ketone (555) was treated with cyclopentenyllithium (354) at —78 °C to form the intermediate (555), which underwent a rapid Cope rearrangement to the intermediate (356). By treatment of (356) with methyl iodide, compound (357) was obtained. The ketone (357) would serve as an intermediate in the synthesis of ophiobolin A (358) 124). 

Cyclopentadienones produce 6,6-dihaIobicyclo[3,l,0]hex-3-en-2-ones in high yield (>90 % from chloroform, 50-60% from bromoform). Subsequent reduction of the bicyclic products with lithium aluminium hydride produces 3-chlorophenols [84] (Scheme 7.14). In a somewhat analogous manner, phenolic ketones and sulphones have been synthesized via a base-catalysed rearrangement of the initially formed cyclopropane derivatives [174]. 

The enantioselective formation of bicyclic ketones through enantioselective deprotonation of the bicyclooxiranes 147,148 and 149 (Scheme 64) by homochiral lithium amides (such as 50) and subsequent rearrangement have also been reported with moderate enantiomeric excesses and yields . 

Capnellane is the generic name applied to a group of sesquiterpene alcohols and the hydrocarbon isolated from the soft coral Capnella imbricata A < >-Capnellene (667), the presumed biosynthetic precursor of the capnellenols, was first synthesized in 1981 by Stevens and Paquette Their synthetic plan called for the construction of bicyclic ketone 668 and its appropriate annulation. The latter event was achieved by application of the Rupe rearrangement to 668, conjugate addition of a vinyl group to 669, ozonolysis, and cyclization (Scheme LXVIII). Hydrogenation and olefination completed the sequence. 

Of equal importance to the Beckmann rearrangement for the preparation of azepines and azepinones is the Schmidt reaction of ketones. Again, however, with unsymmetrically substituted cyclohexanones or with bicyclic ketones such as a-tetralone, two azepines are possible, a -Substituted cyclohexanones invariably yield the product of attack by azide ion at the least hindered side of the protonated ketone as exemplified in Scheme 19 (B-67MI51600). 

Oxaspiropentanes have been generated and rearranged in a large variety of different environments. A series of alkylidene- and allylidenecyclopropanes, present in the structures of bicy-clo[3.1.0]hexanes or bicyclo[4.1.0]heptanes, were epoxidized and rearranged in situ to bicyclic ketones with the alkyl or allyl group preferentially to exclusively in the exo position (Table 4).51 This corresponds to a preferential to exclusive epoxidation of the corresponding alkenes from the sterically less demanding exo face. 

Donor-substituted 1-aminomethylcyclopropanes 108 110 and tosylhydrazones of 1-donor-substituted cyclopropyl ketones 111 can undergo ring enlargement to cyclobutanones through deamination. To this purpose, aminomethylcyclopropanes were diazotized with sodium nitrite 108-110 or isopentyl nitrite 109 in acidic medium and tosylhydrazones were decomposed in basic medium.111 The rearrangements proceed via diazonium ions and are especially useful for the construction of bicyclic systems. For examples of these rearrangements see 1,108 2,109 3,109 4,110 5,111 6 and 7.1 1... 

A second and more recent example, the photochemical rearrangement of 4,4-diphenylcyclohexadienone (VIII), was provided by the present author and co-workers (4, 5,14). This compound (VIII) when photolyzed in aqueous dioxane with light of wavelength above 310 mp. was found (4, 5) to afford the bicyclic ketone IX, 2,3-diphenylphenol (X) and an acid whose structure was shown (14) to correspond to XI. Additionally, 3,4-diphenylphenol (XII) was shown (14) to be a minor by-product. Strikingly and reminiscent of the dependence of product distribution on solvent in santonin photolysis, it was found (14) that approximately equal quantities of 3,4-diphenylphenol and 2,3-diphenylphenol (X) were formed when the photolysis was run in 50% aqueous acetic acid. [Control experiments (14) demonstrated that neither 4,4-diphenylcyclohexadienone nor bicyclic ketone IX were reactive in the dark under the aqueous dioxane or aqueous acetic acid reaction conditions, in the presence or absence of acid XI.] Furthermore, the bicyclic ketone IX has been demonstrated to afford 2,3-diphenylphenol (X) and the photoacid XI on photolysis in aqueous dioxane, and consequently this ketone may be formulated as a reaction intermediate in the formation of X and XI from 4,4-diphenylcyclohexadienone (VIII) (4, 5, 14). 

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