Bicyclo nonan-3-ones, 7-substituted

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... 

Decarbonylation is observed, however, in substituted 9,10-epoxycholestan-6-ones,104 and Norrish Type II photocyclization, leading to the formation of cyclobutanols, is preferred in other y-epoxy ketones.105 A photoreaction of a different type has been observed in the bicyclo[3.3.1]nonane (126) and affords the diol (127).106... 

For studies of the conformations of other 3- and 7-substituted bicyclo[3.3.1]nonan-9-ones, see references 24,42, and 59. 

An interesting example of a reaction involving conformational equilibria in 3,7,9-substituted bicyclo[3.3.1]nonane systems is the base-induced rearrangement of endo-7,7-dimethylbicyclo[3.3.1]nonan-3-ol-9-one (80) into 81. The rearrangement is rationalized by a reversible intramolecular transfer of hydride from the carbinol methine to the carbonyl carbon (60). The reacting centers at C-3 and C-9 are only placed in proximity when the cyclohexanol ring adopts a boat conformation. The resulting ketol 81 is 2.7 kcal mol 1 more stable than its isomer 80 (60). 

In recent years, a number of complexation agents have been developed that incorporate the bicyclo[3.3.1]nonane skeleton. In a series of publications, selective model receptors consisting of two substituted 3-azabicyclo [3.3.1]-nonane fragments interconnected with various aromatic bridges were described (231 -242 and references therein). The X-ray study of one of them (compound 277) revealed a chair-envelope conformation for the bicyclo[3.3.1]nonane fragments (231) a similar conformation was found in the monomeric compound 278 (231) and in the salts of compounds analogous to 277 (237,238). 

The free radical addition of a thiol to carbon-carbon double or triple bonds is a well-established reaction. It represents one of the most useful methods of synthesizing sulfides under mild conditions. Since its discovery [5] and its much later formulation as a free-radical chain reaction (Scheme 1) [6], the anti-Markovnikov addition of thiols to unsaturated compounds has been the subject of many reviews [8, 9]. These reactions were originally initiated by thermal decomposition of peroxides or azocompounds, by UV irradiation or by radiolysis [10]. (An example of addition of 1-thiosugar to alkenes initiated by 2,2 -azobisisobutyronitrile (AIBN) [11] is reported in equation (1)). More recently, organoboranes have been used as initiators and two examples (Et3B and 9-bora-bicyclo [3.3.1.] nonane) are reported in equations (2) and (3) [12,13]. Troyansky and co-workers [14a] achieved the synthesis of macrocycles like 12- and 13-membered sulfur-containing lactones by the double addition of thiyl radical to alkynes. An example is depicted in equation (4). The same approach has also been applied to the construction of 9- and 18-membered crown thioethers [14b]. The radical chain addition of thiyl radicals to differently substituted allenes has been considered in detail by Paste and co-workers [15], who found that preferential attack occurs at the central allenic carbon and gives rise to a resonance-stabilized ally radical. The addition of benzenethiol to allenic esters has been reported and the product formation has been similarly inferred (equation (5)) [16]. 

Snatzke has extended the useful analysis of the effect of 3-substituents upon the circular dichroism of adamantanones and substituted bicyclo[3,3,l]-nonan-9-ones. With earlier studies the effect of a wide range of substituents is now established, and the failure of the octant rule to account for the observed results is clear, but a satisfactory general analysis of substituent effects is still awaited. 

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