Bicyclo heptanone reduction

It must be emphasized that reduction of carbonyl compounds by dissolving metals, either in the presence or absence of an added proton donor is a kinetically controlled process. This was tacitly stated in 1972," and has been repeated or implied in more recent reviews of this topic. A recent study of the reduction of several bicyclo[2.2.1]heptanones using alkali metal-NH3-NH4Cl systems emphasizes that these reductions are kinetically controlled. ... 

The dissolving metal reductions of bicyclo[2.2. l]heptanones have been studied extensively, and it has been established that both metal-alcohol and metal-NH -proton donor systems provide the cndr>-alcohol regardless of its stability relative to the exo isomer. " - In the case of camphor (1) which has been studied in the most detail, the ratio of endo-alcohol (bomeol 2) to CAo-alcohoI (isobomeol 3) is very close to 90 10 for all metal-NH3 conditions employed. The variables include temperature (-33 and -78 °C), cosolvent (ether and THF), metal (Li, Na, K, Rb) and proton donor (NH4CI and ethanol). - The same results are obtained with both (+)- and (+)-camphor. These results are, coincidentally, almost identical to the equilibrium ratio for alcohols (2) and (3). ... 

Table 1 Metal-Ammonia Reductions of Bicyclo[2.2.1]heptanones and Equilibrium Ratios of the Corresponding...

Metal-ammonia reduction of bicyclo[2,2,l]heptanones has been examined by Coulombeau and Rassat, who point out that the conformationally more stable forms of substituted alcohols are the exo-isomers in the case of norbornan-2-ol and the 1-methyl homologue, but the endo-isomers in the case of borneol (1,7,7-trimethyl) and fenchol (1,3,3-trimethyl). The same authors have also examined the reduction of camphorquinone [2,3-dioxo-bornane, (249)] with... 

In contrast to bicyclo[2.2.1]heptanones, which produce mainly the cwfo-alcohols, it has been found that related aminobornanones5 behave differently upon metal alcohol reductions, giving mainly the exo-con figurated alcohols (sec Table 2, p 3972). 

Oxymercuration followed by borohydride reduction of 6-methylenebicyclo-[3,l,l]heptane (166) gave the alcohols shown in Scheme 8. Similar reaction with 5-methylenebicyclo[2,l,l]hexane gave entirely monocyclic products. Stereochemical aspects are discussed for the formation and reduction of epoxides of 2-methylene- and 3-methylene-bicyclo[3,l,l]heptanes, the hydrobora-tion-oxidation of 3-methylenebicyclo[3,l,l]heptanes, and reduction by lithium aluminium hydride and diborane of bicyclo[3,l,l]heptanones. ... 

Chiral bicyclo[3.2.0]heptanone has been recognized as a chiral precursor for (+)-prostaglandin A2 136 and (+)-prostaglandin-F2a 137 synthesis. The reduction of racemic bicyclo[3.2.0]hept-2-en-6-one 139 in high optical purity by cells of Mortierella ramanni-ana has been demonstrated (Fig. 49). The same organism has also been used for the stereoselective reduction of 7,7-dimethylbicyclo[3.2.0]hept-2-ene-6-one 139 to prepare the chiml synthon for (+)-leukotiiene B4 synthesis [247]. 

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