Norcamphor reduction

Similarly to 8-lactone 260, y-lactone 263, prepared also from ( )-norcamphor (228), proved to be another useful intermediate for the synthesis of all four corynantheidol stereoisomers as well as of the corresponding 18,19-didehydro derivatives. Cleavage of the a-diketone monothioketal moiety in 263 and the formation of amide 265 by its reaction with tryptamine, followed by Bischler-Napieralski cyclization and sodium borohydride reduction, resulted in a mixture... 

Atkins, W.M. and Sligar, S.G. (1988) Deuterium isotope effects in norcamphor metabolism by cytochrome P-450cam kinetic evidence for the two-electron reduction of a high-valent iron-oxo intermediate. Biochemistry, 27 (5), 1610-1616. 

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],... 

Electrochemical reductions of camphor oxime (R = Me) and norcamphor oxime (R = H) at a mercury cathode proceed with a high degree of diastereoselectivity (equation 3) . The products are in fact of opposite stereochemistry to those formed in dissolving metal (sodium-ethanol) reductions of the oximes. 

Reduction of cyclic and bicyclic ketones. This hydride reduces 4-r-butyl- and 3-methylcyclohexanone with some bias favoring formation of the more stable isomer. In contrast, 2-methylcyclohexanone is reduced preferentially to the less stable cis-isomer (72%). Essentially, only the ra-isomer is formed on reduction of 2-f-butylcyclohexanone (98% stereoselectivity). Norcamphor is reduced to the endo-alcohol in > 99% stereoselectivity, whereas the more hindered camphor is reduced to the exo-alcohol with 98% stereoselectivity. 

Secologanin has been converted (by stages) into the hydrazone (110), which, on Bischler-Napieralsky ring-closure, reduction, and hydrolysis, yields protoemetine this was converted into cephaeline and deoxytubulosine by its reaction with (3-hydroxy-4- methoxyphenyl)ethylamine and with tryptamine respectively.138 The dithioacetal (111), prepared from norcamphor (see Volume... 

Cathodic reduction of camphor and norcamphor oxime 144a appears to be cases where the stereochemistry is controlled by attack by the electrode from the least hindered side of the molecule ... 

Norcamphor isobutylene ketal appears (NMR) to be a nearly equal mixture of the isomers (21) and (22) (Scheme 6), but it is reduced as though it were only (21), reacting via a retention mechanism. The reduction is very slow (168 h) and it is this author s view that one cannot exclude the possibility that (22) is not reduced at all but is isomerized to replace (21) as it is consumed (a few such isomerizations have been observed). 

Selective reductions. Brown et al.2 conducted an extensive study of reductions with diborane in THF. Most aldehydes and ketones are readily reduced unusually high stereoselectivity was realized in the case of norcamphor, which was reduced to 98% endo-norbornanol and 2% exo-norbornanol. p-Benzoquinone is reduced to hydroquinone at a moderate rate, but reduction of anthraquinone is sluggish. Carboxylic acids are reduced very rapidly indeed this group can be reduced selectively in the presence of many other substituents. Acid chlorides react much more slowly than carboxylic acids. Esters and ketones are reduced relatively slowly. Reactions with epoxides are relatively slow and complex. 

Other synthetic work in this area includes a new synthesis of ( )-iV-benzoyl-meroquinene aldehyde (302), in eighteen steps, from ( )-norcamphor. The lack of stereospecificity in an intermediate reduction stage afforded also a synthesis of the diastereoisomer of (302). 

With ketones that are locked due to a bridged ring system, then it is normally straightforward to predict which is the less-hindered side of the carbonyl group. Reduction of camphor with lithium aluminium hydride, for example, leads mainly to the exo alcohol (isobomeol), whereas norcamphor (which lacks the gem-dimethyl group on the bridging carbon atom), in which approach of the hydride anion is now easier from the side of the methylene bridge, leads mainly to the endo alcohol. 

Cyclic and bicyclic ketones such as cyclohexanone, 2-methylcyclohexanone, 4-tert-butylcyclohexanone, and norcamphor undergo complete reduction in 30-60 min. Hindered ketones, like diisopropyl ketone and camphor, need 6-12... 

The reduction of monocyclic ketones with disiamylborane and di-3-pinanyl-borane takes place from the less hindered side to yield predominantly the less stable of the two possible isomers. In contrast, 9-BBN exerts little influence on the direction taken by the reduction. With 3-methyl- and 4-tert-butylcyclohex-anones, the products are predominantly the more stable of the two possible isomers. Reduction of bicyclic ketones such as norcamphor and camphor proceeds with preferential attack of the 9-BBN from the less hindered side, yielding the less stable of the two possible isomers (Eq. 25.1). 

Aldehydes and ketones of wide variety such as caproaldehyde, benzaldehyde, 2-heptanone, and norcamphor utilize 1 equiv of hydride in THF and are reduced rapidly and quantitatively to the corresponding alcohols at 15 2 °C. The hindered ketone, 2,2,4,4-tetramethyl-3-pentanone, which is inert to 9-BBN [5], however, is rapidly reduced with Li9-BBNH. Reduction of camphor gives 91% isoborneol and 9% borneol (Eq. 25.13). 

P-hydride elimination takes place to afford complex 71, which then undergoes intramolecular hydrometalation to form bicyclic rhodacycUc complex 72. Reductive elimination in 72 affords hexahydropentalenone ketiniine 73, which is hydrolyzed to form 68. It is interesting that C-C bond activation in 65 takes place to cleave the cyclohexanone moiety, a likely consequence of the inherent ring strain in the norcamphor skeleton. 

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