Bicyclo 4.1.0 ketones

Yamamoto et al reported nitroso Diels-Alder type reaction of diene with nitrosobenzene by a binaphthol derivative (39). Bicyclo ketones were obtained with excellent diastereo- and enantioselectivity (Scheme 2.82) [151]. The cyclization reaction involved the sequential N-nitroso aldol reaction followed by the Michael reaction. Optically active l-amino-3,4-diols are synthesized. 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Bicyclo[3.3.1]nonan-9-one is another ketone that exhibits interesting stereoselectivity. Reduction by hydride donors is preferentially syn to electron-attracting substituents at C-5 (X = EWG in the structure shown below) and anti to electron-releasing substituents (X = ERG below). These effects are observed even for differentially substituted phenyl... 

Photochemical cyclohex-2-enone bicyclo (3.1.0)hexan-2-one rearrangement, 320 Photochemical a-cyclopropyl ketone isomerization, 313... 

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. 

Acetic acid, reaction with bicyclo[2.2,1]-hepta-2,5-diene, 45, 74 reaction with dibenzyl ketone, 47, 54... 

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... 

When a ketone is relatively hindered, as, for example, in the bicyclo[2.2. l]heptan-2-one system, steric approach control governs stereoselectivity even for small hydride donors. 

The elimination of carbon monoxide can occur by a concerted process in some cyclic ketones. The elimination of carbon monoxide from bicyclo[2.2.1]heptadien-7-ones is very facile. In fact, generation of bicyclo[2.2.1]heptadien-7-ones is usually accompanied by spontaneous decarbonylation. 

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 ambivalent aptitude of sulfur [19] to stabilize adjacent anionic as well as cationic centers is a remarkable fact that has shown to be a reliable feature for the assembly of four-membered ring scaffolds utilizing cyclopropyl phenyl sulfides [20]. Witulski and coworkers treated the sulfide 1-69 with TsOH in wet benzene (Scheme 1.19) [21]. However, in addition to the expected cyclobutanone derivative 1-70, the bicyclo[3.2.0]heptane 1-70 was also obtained as a single diastereoisomer, but in moderate yield. Much better yields of 1-71 were obtained using ketone 1-72... 

Twofold Michael additions have been utilized by the groups of Spitzner [2] and Hagiwara [3] to construct substituted bicyclo[2.2.2]octane frameworks. In Hagiwara s approach towards valeriananoid A (2-6) [4], treatment of trimethylsily-enol ether 2-2, prepared from the corresponding oxophorone 2-1, and methyl acrylate (2-3) with diethylaluminum chloride at room temperature (r.t.) afforded the bicyclic compound 2-4 (Scheme 2.2). Its subsequent acetalization allowed the selective protection of the less-hindered ketone moiety to provide 2-5, which could be further transformed into valeriananoid A (2-6). 

Direct irradiation of (3,y-unsaturated ketones affords rearranged 3,y-unsaturated ketones via a 1,3 shift of the acyl group 214a> b). This is exemplified in the preparation of a bicyclo[3,3,l]nonanone (2.10)215),... 

Another example of suprafacial migration with inversion is the rearrangement of bicyclo octenone to give again a ketone and reported by J.A. Berson (1972). 

Intraactions between elections in three-membered rings and unsaturated groups in the same molecule have been detected via 13C chemical-shift variations in a number of instances. Thus, introduction of the carbonyl function in tricy-clo[3.2.1,02,7]decane (e.g., 274) leads to significant downfield shifts of the signals of C(l) (+8.0), C(2) (+15.5), and C(7) (+7.7) (385), whereas corresponding effects in bicyclo[3.1.0]hexan-2-one (275) are smaller (385,386). A corresponding dependence was reported for 276 and 277 and related to more effective electron withdrawal in 276 (387). An even more pronounced deshielding effect was observed by Murata and co-workers (388,389) in the ketone 278 when they compared it with 279. 

Neuerdings wurden durch WoLFF-KiSHNER-Reduktion cc./J-unge-sattigter Ketone die Cyclopropankohlenwasserstoffe 2-Phenyl-dicyclo-propyl (III) (228), l.l-Pentamethylen-bicyclo(0.1.4)heptan (IV) (114) some einige l-Phenyl-2-alkylcyclopropane (88) dargestellt. Versuche Cyclopropylvinylketon auf diesem Wege in Dicyclopropyl zu verwandeln fiihrten nicht zum Ziel (235). 

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