Norborneols

D. ej o-NoRBORNEOL FROM Norbornene External Generation of Diborane (i)... 

The procedure given above is applied to norbornene. However, the formation of the alcohol is accompanied by formation of moderate amounts of the acetate. Therefore, the dried tetrahydrofuran solution of the alcohol-acetate mixture is treated with 0.4 g (O.OI mole) of lithium aluminum hydride dissolved in 10 ml ofTHF. The excess hydride is decomposed by careful addition of water, followed by filtration, drying of the organic solution, and evaporation of the solvent. The residue is almost pure (>99.8%) exo-1-norborneol. It may be purified by direct distillation, bp 178-17971 atm, crystallizing slowly on cooling, mp 127-128°. 

The interest in catalyst recyclability has led to the development of biphasic catalysts for hydro-boration.22 Derivitization of Wilkinson s catalyst with fluorocarbon ponytails affords [Rh(P (CH2)2(CF2)5CF3 3)3Cl] which catalyzes FIBcat addition to norbornene in a mixture of C6FnCF3 and tetrahydrofuran (TF1F) or toluene (alternatively a nonsolvent system can be used with just the fluorocarbon and norbornene) to give exo-norborneol in 76% yield with a turnover number up to 8,500 (Scheme 4). Mono-, di- and trisubstituted alkenes can all be reacted under these conditions. The catalyst can be readily recycled over three runs with no loss of activity.23... 

Minor product (less than 1%) cyclopentanecarboxyaldehyde. d Minor product (less than 1%) norborneol. 

Early studies with a purified and reconstituted rabbit P450, CYP2B4 (earlier name P450 LM2) on the hydroxylation of the hydrocarbon, norbomane, found that the reaction proceeded to yield a 3.4 1 mixture of exo-endo norborneols (4). Further, hydroxylation of exo-2,3,5,6-tetradeuteronorbornane was found to proceed with a large deuterium isotope effect (11.5 0.5) and a significant amount of epimerization in forming the endo and exo metabolites (Fig. 4.3). 

The effect of steric hindrance can be nicely demonstrated in the reduction of two bicyclic ketones, norcamphor and camphor. The relatively accessible norcamphor yielded on reduction with complex hydrides predominantly (the less stable) endo norborneol while sterically crowded camphor was reduced by the same reagents predominantly to the less stable exo compound, isobor-neol [837], From the numerous examples shown it can be deduced that the stereoselectivity increases with increasing bulkiness (with some exceptions), and that it is affected by the nucleophilicity of the reagent and by the solvent. 

Similar stereoselectivity was noticed in reductions of ketones by alkali metals in liquid ammonia and alcohols. 4-rerr-Butylcyclohexanone gave almost exclusively the more stable equatorial alcohol, norcamphor 68-91% of the less stable e cfo-norborneol, and camphor a mixture of bomeol and isoborneol [860],... 

Norbornyl systems were used to study the /i-effect in the synperiplanar geometry42. The solvolyses of the mesylates (X = MeSOaO) of ewrfo-3-(trimethylsilyl)-ewrfo-2-norbomeol 12 and ewrfo-2-norborneol 13 were shown to take place via carbocationic mechanisms, and the trimethylsilyl-substituted system showed a rate acceleration of 105. 

Analysis of the crystal structure of the p-nitrobenzoate and 2,4-dinitrobenzoate derivatives of ewrfo-3-(trimethylsilyl)-ewrfo-2-norborneol 47, in which the Si—C and C—O bonds are in the synperiplanar geometry, showed that there was no significant lengthening of the C—O bond in these cases64. By comparison, the cyclohexyl ester 48, in which the Si—C and C—O bonds are in the antiperiplanar conformation, did show a significant lengthening of the C—O bond compared to model compounds64. 

Nafion-H has also been shown to be active in the Ritter reaction. Treatment of alcohols, such as benzyl alcohols, 1-adamantanol [Eq. (5.346)], and 2-norborneols with acetonitrile or benzonitrile in the presence of Nafion-H under forcing conditions (140-145°C, 18—48h), affords the corresponding carboxamides in moderate to excellent yields (40-99%).652 Nafion-H can be reused after a simple activation (washing with deionized water and acetone followed by drying at 105°C). 

Alkali metal counterion has been found to control the enolate protonation stereoselectivity.12 This remarkable phenomenon has been reported for lithium and potassium enolates of a norborneol derivative. 

Despeyroux, D. Cole, R. B. Tabet, J. C. Ion-molecule reactions in the gas phase. XVIII. Nucleophilic substitution of diastereomeric norborneols, norbornyl acetates and benzoates under ammonia chemical ionization, Org. Mass Spectrom. 1992, 27, 300-308. 

Application of this procedure to 1,3-cyclohexadienc (5) yields only the anti-1-norborneol 6. 

Quite pure 2-eA <7-norborneol, m.p. 127-128°, can be prepared by saponification of 2-eoM-norbornyl formate in an aqueous ethanolic solution of potassium hydroxide. The product can be isolated in about 85% yield by distillation and boils at 178-179°. 

Spontaneous resolution has also been achieved by sublimation. In the case of the norborneol derivative 60, when the racemic solid is subjected to sublimation, the (+) molecules condense into one crystal and the (—)... 

Catalytic dehydrogenation of volatile alcohols is carried out by passing their vapors over copper at 300 °C [344] or over copper chromite at 275-325 °C for 1.7-4 h, with yields ranging from 20 to 80% [554]. Dehydrogenation in the liquid phase is accomplished by refluxing the alcohol with copper chromite in xylene for 4 h [556] or by heating the alcohol in paraffin oil with Raney nickel and a catalytic amount of potassium hydroxide at 150-180 °C for 6 h. Thus endo-norborneol is transformed into norcamphor in 95% yield [928]. 

Steric effects are evident in the oxidation of sterically hindered alcohols exo-isoborneol is oxidized 2 times faster than endo-homeo], and endo-norborneol is oxidized 2.5 times faster than exo-norborneol (equation 248) [1145]. 

Vanadium(V) alkoxides have been known since 1913,69 and in Table 2 we show some of the known alkoxides, the parent alcohol, and the nature of the complex in organic solvents and in aqueous solution. Alkoxides have been prepared from methanol, ethanol, isopropanol, t-butanol, silsequioxanes, cyclopentanol, cyclohexanol, norborneol, adamantanol, phenol, and other alcohols (see Table 2).70- 0 The simple complexes associate in organic solvents and dimerization in the presence of alkoxide is observed with the isopropanol complex.70 The more sterically hindred alcohols are less reactive and do not hydrolyze completely in the presence of small amounts of water.73 The first simple alkoxide to be structurally characterized was the methoxide complex (14) and the vanadium was found to be a six-coordinate dinuclear species however, the structure of this compound did not refine very well.91 This was the first report of the diamond core V—O—V—0 unit, albeit associated with two six-coordinate vanadium atoms. The diamond core V—O—V—O (11), which has since then been found to be a typical structural unit for these complexes, was distinctly asymmetric revealing a difference in the interactions between the two mononuclear parts of the molecule. The first monodentate alkoxide found to contain... 

A further advantage is that the reaction appears to be free from rearrangements involving carbonium ion intermediates.41 Thus norbomene (9) is converted in close to quantitative yield into exo-norborneol (10) of > 99.8% purity. 

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