Camphor-isoborneol, reduction

The lithium 9-boratabicyclo[3.3.1]nonane (Li 9-BBNH) is prepared [1] by refluxing 1 equiv of 9-BBN with excess of finely divided lithium hydride. The reagent reduces [2] cyclic ketones, and the hydride adds from the less hindered side. For example, camphor on reduction with Li 9-BBNH affords the less stable exo isomer isoborneol in 91% yield (Eq. 26.36). 

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],... 

In a thermodynamically controlled reaction, 3-oxo-e.vo-tricyclo[4.2.1.02 s]nonane is converted to e. vo-3-hydroxy-e.vo-tricyclo[4.2.1.02,5]nonane (85-95%). With sodium borohydride the ewfo-alcohol is obtained185. For example, the Meerwein-Ponndorf-Verley reduction of camphor yields a 70 30167 (75 2525, 69 31 186) mixture of the exo- and endol,7,7-trimethylbi-cyclo[2.2.1]heptan-2-ols (isoborncol and borneol). The equilibrium has been established to give a 29 71 mixture of isoborneol and borneol183, giving another example where the Meerwein-Ponndorf-Verley reduction leads predominantly to the less stable product. 

Brit. pat. 803,178 (1958), Prepn of the /-form by reduction of d-camphor with lithium aluminum hydride Trevoy, Brown, J. Am. Chem. Soc. 71, 1675 (1949). Separation of isoborneol from its ewfo-isomer, borneol, via the p-nitro-benxoare deriv Truett, Moulton, foe. cit. Resolution of the d/-form Pickard, Litflebury, foe, cit. Kenyon, Priston, ibid. 127, 1472 (1925). Configuration (isoborneol = c o-form borneol = eflrfo-form) Toivonen et al, Acta Chem. Scand. 3, 991 (1949), Review J. L. Simonsen, The Terpenes vol. 11 (University Press, Cambridge, 2nd ed., 1949) pp 365-367 A. R, Pinder, The Chemistry of the Terpenes (Chapman Hall, London, I960) pp 22-24, Id, 103, 105-107, 111-... 

A vast array of chiral auxiliaries have been derived from naturally occurring compounds containing the bicyclo[2.2.1]heptane unit (for review articles, see refs 1 -3). In all cases, the ultimate sources of these auxiliaries are the ketones camphor and fenchone, and the alcohols borneol and fenchol, as at least one enantiomer of each compound is provided in enantiomericaUy pure form by nature. Thus. ( + )-camphor [( + )-2], (-)-borneol [(-)- ], and (+)-fenchonc [( + )-5] are enan-tiomerically pure, convenient and inexpensive starting materials for organic synthesis and deriva-tization to give chiral auxiliaries. Most other compounds of this series are also commercially available, but can be prepared by oxidation or reduction of inexpensive precursors by standard methods. The evo-alcohols, such as the enantiomeric isoborneols, are accessible by standard complex hydride reductions of the ketones. The interconnection between these compounds is shown diagrammatically. 

The stereochemistry of epiborneol and epi-isoborneol has been established chemically. The two were prepared by reduction of the thioketal of each of the two acetoxycamphors (329a and b). The latter were then converted into the corresponding 4-hydroxy-c7s-camphoric acids (330), only one of which had an intramolecular hydrogen bond and formed a lactone, and must therefore correspond to epiborneol (331), having an em/o-hydroxy-group. ° ... 

Carbonyl Reactivity—The reagent lithium dimesitylborohydride bis(dimethoxy-ethane), which has been isolated and whose crystal structure has been reported, may be employed as a stereoselective reducing agent Thus after 3 h at 0°C in di-methoxyethane 2-, 3-, and 4-methylcyclohexanones were reduced respectively to the cis- (99 %), trans- (99 %), and cis- (94 %) alcohols. However, 3 days, at 25°C, were required for complete reduction of camphor to give 99.8 % isoborneol. 

Steric Effects.—The consequences upon chemical reaction of non-bonded interactions between enantiomeric pairs of molecules have been discussed an antipodal interaction effect was observed in a reductive camphor dimerization and in a camphor reduction. The full paper on the correlation of the rates of chromic acid oxidation of secondary alcohols to ketones with the strain change in going from the alcohol to the carbonyl product has now appeared. It is concluded that the properties of the product are reflected in the transition state for the oxidation. High yields of hindered carbonyls are available from the corresponding alcohols by reaction with DMSO and trifluoroacetic anhydride (TFAA) indeed, the more hindered the alcohol, the higher the yield of carbonyl compound reported Since the DMSO-TFAA reaction occurs instantaneously at low temperatures (<—50°C), it is possible to oxidize alcohols that form stable sulphonium salts only at low temperature. Thus, ( )-isoborneol reacts at room temperature to give camphene, the product of solvolysis of the sulphonium salt the oxidation product, ( + )-camphor, was obtained by the addition of base at low temperature. 

Determine the infrared spectium of fhe sublimed camphor and compare it to the spectrum provided in the experiment (use the dry film method in Technique 25, Section 25.4 or other method recommended by your instructor). The spectrum should demonstrate complete oxidation to camphor (absence of OH peak and presence of C=0 peak). There should be sufficienf material for the reduction of camphor to isoborneol. Part B. At the option of fhe instructor, determine the H and NMR spectra of your camphor. Also, at the option of the instructor, determine the melting point (literature mp about 177°C, but it is often lower than this value). Store the camphor in a tightly sealed vial. 

Camphor, a bicyclic monoterpene, is extracted from the woods of Cinnamomum camphora, a tree located in Southeast Asia and North America. Furthermore, it is also one of the major constituents of the essential oil of common sage (Salvia officinalis). Solid camphor forms white, fatty crystals with intensive camphoraceous odor and is used commercially as a moth repellent and preservative in pharmaceuticals and cosmetics (Wichtel, 2002). In dogs, rabbits, and rats, camphor is extensively metabolized whereas the major hydroxylation products of d- and L-camphor were 5-endo-md 5-ex -hydroxycamphor. A small amount was also identified as 3-e do-hydroxycamphor (Figure 8.2). Both 3- and 5-bornane groups can be further reduced to 2,5-bornanedione. Minor biotransformation steps also involve the reduction of camphor to borneol and isoborneol. Interestingly, all hydroxy-lated camphor metabolites are further conjugated in a Phase II reaction with glucuronic acid... 

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). 

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