Nonan-9-one

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... 

To a solution of 11.8 g of 2-A-pyrrolidylbicyclo[3.3.1]nonan-9-one in 25 ml of dry ether is added 25 g of methyl iodide in one portion. The solution is allowed to stand at room temperature for 2 hours, then filtered to remove the product. To the filtrate is added 5 g of methyl iodide and after 5 hours at room temperature, solid is again collected. A third crop is similarly obtained. The combined solids (approx. 17 g) are recrystallized from acetone-ethanol to give about 16 g of the methiodide, mp 220-222°. 

The final step to 46 is cyclocondensation of 3,7-diazabicyclo[3.3.1]nonane (51), bispidine70, with formaldehyde. There are two different approaches to 51 (i) a pyridine is converted to a piperidine and (ii) the double Mannich or Robinson-Schopf condensation of ketone 52 with formaldehyde and primary amines affords 1,5-disubstituted 3,7-dazabicyclo[3.3.1]nonan-9-one (53), bispidone, from which 5,7-disubstituted l,3-diazaadamantan-6-one (61) is derived. Route (i) is adopted by Galinovsky and Langer,71 Stetter and... 

Moderately sterically hindered adamantanone and bicyclo[3.3.1]nonan-9-one give the corresponding cycloadducts. 

Enehydroxylamines (102) are invoked as intermediates in the rearrangement of O-vinyl, acyl or aryl oximes (101) (equation 31). Varlamov and coworkers demonstrated that the heterocyclization of ketoximes (103) with acetylene in snper basic medium and in the presence of metal hydroxides proceeds by a [3,3]-sigmatropic rearrangement of the enehydroxylamine 105 of the corresponding oxime vinyl ethers 104 (equation 32). The unreactivity of 3-methyl-2-azabicyclo[3.3.1]nonan-9-one oxime (106) in the same reaction conditions was explained by its inability to isomerize to the corresponding enehydroxylamine. 

A similar vinylogous Mannich reaction has been used by Martin in the total syntheses of the heteroyohimboid alkaloids (—)-ajmalicine and (—)-tetrahydroalstonine <1995JOC3236>. An attempted synthesis of an opioid analgesic 2,4-dibenzyl-3,7-diazabicyclo[3.3.1]nonan-9-one-l,5-dicarboxylate (piperidone) by a double Mannich reaction of oxoglutarate, 2 equiv of phenylacetaldehyde, and methylamine did not give the expected product but instead gave rise to an unexpected [l,6]naphthyridine derivative (Scheme 57) <1998PHA442>. 

In contrast to the synthesis of bicyclic azetidinones containing a carboxyl group on the atom adjacent to the lactam nitrogen (see Section 5.12.3.4), few examples are reported in which bicyclic azetidinones without this carboxyl group are prepared from azetidinone precursors. One unique approach, however, utilized a free radical ring closure to obtain 6-oxa-l-azabicyclo[5.2.0]nonan-9-one (116) in modest yield (81TL2689). 

This transformation was first explored by treatment of l-bromo-4-(cyanomethyl)pentacyclo-[4.3.0.02 5.03-8.04-7]nonan-9-one ethylene acetal (61) with lithium diisopropylamide in tetrahy-drofuran at 0 °C, which resulted in almost quantitative yield of an inseparable mixture of two alkenes to which the structures l-bromo-4-cyanomethyltricyclo[4.2.1.02,5]nona-3,7-dien-9-one ethylene acetal (66) and l-bromo-4-(cyanomethylene)tricyclo[4.2.1.02,5]non-7-en-9-one ethylene acetal (67) were assigned.170,171 As illustrated below, the overall cage-degradation reaction can be mechanistically represented by the stepwise C —C bond fission reactions, whose driving force can be attributed to the apparently substantial reduction in cage constraint. 

BORANES IN FUNCTIONALIZATION OF DIENES TO CYCLIC KETONES BICYCLO[3.3.1]NONAN-9-ONE... 

Bicyclo[3.3 l]nonan-9-one, (2,4-dinitrophenyl)hydrazone (8,9) (—) Monochloroborane diethyletherate Borane, chloro-, compound with ethyl ether (8), Borane, chloro-, compound with 1,1 -oxybis[ethane] (1 1) (9) (36594-41-9). 

Heteroatoni groups such as boron or silicon can activate or direct synthetic reactions. Use of such activation has become of major importance in organic syntheses. Examples in this volume are BORANES IN FUNCTIONALIZATION OF DIENES TO CYCLIC KETONES BICYCLO[3.3.1]NONAN-9-ONE and BORANES IN FUNCTIONALIZATION OF OLEFINS TO AMINES 3-PINANAMINE. Use of trimethylsilyl or trimethyl-silyloxy groups to activate a 2-butenone or a butadiene are illustrated by the preparations 3-TRIMETHYLSILYL-3-BUTEN-... 

Palladium-catalyzed reaction of allylic 1,1-diol diacetate 136 with the pyrrolidino enamine of cyclohexanone (137) yields 2-acetoxybicyclo[3.3.1]nonan-9-one (138)68 (equation 25). 

Examples are known of photoextrusion reactions which occur with ring contraction and provide bicyclo[3.3.0]octane derivatives. 1,2-Quinone diazides (e. g., 225)189 190) and bicyclo[3.3.1]nonan-9-ones (e. g., 126)191,192) are particularly... 

Synthesis of l-aza-5-silabicyclo[5.2.0]nonan-9-one, a silylated bicyclic lactam 329 (Figure 20) which shows antimicrobial activity against Gram positive bacteria was also achieved <1995JOC8403>. 

Selenium 3,7-diazabicyclo-[3.3.1]nonan-9-one derivatives have also been prepared by the author (2) as illustrated in Eq. 2 ... 

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