Ketone bicyclo octan-3-ones

When formation of either the five- or six-membered ring was possible for N-chloroamine 37, only the five-membered ring was conducive under the Hofmann-Ldffler-Freytag reaction conditions, forming exclusively 6-ethyl-6-aza-bicyclo[3.2.1]-octane (38). No 2-ethyl-2-aza-bicyclo[2.2.2]-octane (39) was observed. On the other hand, 2-methyl-2-aza-bicyclo[2,2.2]octan-6-one (41) was installed by UV irradiation of a solution of A -chloroamine 40 in TFA. Ironically, when the ketone functionality on 40 was protected as its ethylene ketal group, the resultant steric interactions completely prohibited the classic Hofmann-Loffler-Freytag reaction. 

Exclusive exo (equatorial) attack is also observed with bicyclo[3.2.1]octan-3-one (5), whereas addition of methylmagnesium iodide to bicyclo[3.2.1]octan-2-one (7) affords the diastereomeric products in almost equal amounts5i. The cyclohexanone moiety of both bicyclic ketones 5 and 7 adopts a chair conformation and therefore the 3,5-diaxialethano bridge in... 

Interestingly, Lewis acid catalyzed rearrangement of 6-methyltricyclo[8.2.0.0, 6]dodecan-9-one gave the spiroannulated triquinane ketone (l/ , 5/ )-l-methylspiro[bicyclo[3.3.0]octane-2,lf-cyclopentane]-6-one as the major product (70%).85... 

Fluoro ketones based on the tropinone skeleton and other bicyclo[3.2.1]octan-3-ones were studied by Denmark et al. (eg. 23) [34, 35] and Armstrong et al. (eg. 24) [36, 37]. Ketone 24 proved particularly efficient for asymmetric epoxidation of unfunctionalized olefins (Table 10.3). 

Properly alkylated bicyclo[4.2.0]-octan-2-ones formed by 2+2 photocycloaddition of alkenes to cyclohexenones cleave to 5, -unsaturated ketones, one example leading to a sesquiterpene synthesis [73]. 

Bicyclic ketones are prepared by cycloadditions of methylenecyclopropanes with cyclic a,P-unsatu-rated carbonyl compounds. c J-Bicyclo[3.3.0]octan-2-ones (50), (51) and (52) are obtained in good yields by phosphine-nickel(0)-catalyzed cross coupling reactions of 2-cyclopentenone with methylenecyclopropanes in the presence of 0.1-1 equiv. of triethylborane as a Lewis acid (equations 18 and 19 and... 

Molecules containing a bicyclo[2.2.2]octen-2-one subunit fused or bridged to an additional ring have been investigated in detail, as their oxa-7c-methane rearrangements afford tetracyclic ketones, usually in very good yields. The commonest examples are 7,8-fused substrates 33 which afford 6,7-exo-fused tricyclo[3.3.0.0 ]octan-3-ones 34. 

Scheme 3.6 Selected examples of bicyclo[3.2.1]octan-3-ones and related ketones.

The conversion of norbornene into bicyclo[3,2,l]octan-3-one, achieved by standard procedures, has been used to effect a synthesis of the uracil derivative (462). Baeyer-V illiger oxidation of the above ketone followed by treatment of the product lactone with... 

Bicyclo[2.2.2]octanes can be obtained by a simple method The synthesis of the griseofulvin system has been accomplished in essentially one operation by a double Michael addition to an ethynyl vinyl ketone The sesquiterpenes longifolene with its highly intricate skeleton, and caryophyllene have yielded to ingenious synthetic endeavors. Cyclobutene ring closures by photoisomerization of conjugated dienes are used for the construction of various isocyclic and heterocyclic systems... 

The energy-minimization technique has been used to study bicyclo[3,2,11-octane, bicyclo[3,2,l]octan-3-one, and the corresponding a-bromo-ketones. The calculated results are in satisfactory agreement with the observed molecular geometry, but are less reliable in estimating strain energies. The concept of the anti-reflex effect is supported by these results. 

Solvolytk ring-expansion to give a bicyclo[4,l,l]octan-3-one (Scheme 18) and ring-expansion with diazomethane to give ketones in the bicyclo[4,2,l]-nonane and bicyclo[5,2,l]decane series are reported. 

In 1998, Armstrong et al. reported fluoro ketone catalysts 370 based on the tropinone skeleton [252, 253], Ketone 370a epoxidized a variety of olefins quickly and in good yield with up to 83% ee for phenylstilbene. Other bicyclo[3.2.1]octan-3-ones 371-373 bearing electronegative substituents at the a-position are equally suitable (Table 7.26) [254],... 

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