Octalone, hydrogenation

Table 1. Influence of pH of the Medium, of the Solvent, of the C-10 Substituent on Ring Fusion, during /3-Octalones Hydrogenation...

The differences noted in Table I in the hydrogenation of cholestenone and testosterone are probably due to differences in solvent acidity used in each case. This is difficult to check since the acid concentrations used were not always reported. It is further possible that with substrates such as A4-3-ketosteroids the acid concentrations corresponding to the two product distribution breakpoints shown in Fig. 6 are different from those found for octalone hydrogenation. Thus, the change in acidity between alcoholic HC1 and alcoholic HBr could correspond to a change analogous to that found between the two breakpoints in Fig. 6. 

The ease and the stereochemical course of hydrogenation of a,p-unsaturated ketones are particularly influenced by the nature of the solvent and the acidity or basicity of the reaction mixture. Some efforts have been made to rationalize the effect of the various parameters on the relative proportions of 1,2- to 1,4-addition, as well as on the stereochemistry of reduction. For example, the product distribution in -octalone hydrogenation in neutral media is related to the polarity of the solvent if the solvents are divided into aprotic and protic groups. The relative amount of cis- -decalone decreases steadily with decreasing dielectric constant in aprotic solvents, and increases with dielectric constant in protic solvents, as exemplified in Scheme 21 (dielectric constants of the solvents are indicated in parentheses). Similar results were observed in the hydrogenation of cholestenone and of testosterone. In polar aprotic solvents 1,4-addition predominates, whereas in a nonpolar aprotic solvent hydrogenation occurs mainly in the 1,2-addition mode. 

Table 3-1 illustrates the influence of solvent polarity on the amount of 6W-product e.g. 10) formed from hydrogenation of octalone (9), testo-sterone and cholestenone. The product composition is determined by the amount of 1,2 and 1,4 adsorption of the substrate. 

In this experiment, advantage is made of the fact that lithium-ammonia reduction usually proceeds to give trans-fused Decalins 4). Thus, hydrogenation of A -octal one-2 over palladium catalyst gives essentially cw-2-decalone as the product, whereas the lithium-ammonia reduction of the octalone gives the trans ring fusion. 

III. Effect of Variables on the Hydrogenation of j3-Octalone and Related Compounds... 

The hydrogenation of j3-octalone (XII) in a number of neutral solvents over a palladium catalyst gave mixtures of the cis- and tra s-j3-decalones. Initial examination of these product ratios showed no correlation between the dielectric constant of the solvent and the amount of cis-j3-decalone (XIIII) obtained. When the solvents were separated into protic and aprotic categories, however, a direct relationship between product stereochemistry and solvent polarity in each series became apparent, as shown by the data given in Tables II and III (24). 

Product Stereochemistry Obtained on Hydrogenation of 0-Octalone in Neutral Aprotic Solventsa... 

FIG. 2. 1,2-Diadsorbed and 1,4-diadsorbed octalone under low hydrogen availability conditions [Augustine et al. (24). ... 

To examine more fully this effect of acid strength on product stereochemistry, (3-octalone was hydrogenated in a variety of ethanolic HC1 solutions (21,24). The product distribution curve shown in Fig. 6 is comprised of three straight lines. 

The presence of base in the hydrogenation of A4-3-ketosteroids has long been known to lead to the almost exclusive formation of the 5)3 product (9,10), but, when base is added to the reaction medium in the hydrogenation of j3-octalone... 

XII), there is only a slight increase in the amount of cis product formed (13). The effect of varying base concentrations on product stereochemistry in the hydrogenation of octalone is shown in Fig. 7. As in the acid-promoted reaction (Fig. 6), the product distribution in base is composed of three straight line segments one in very dilute base, a second at intermediate concentrations, and a third in more concentrated basic media. The position of the first breakpoint is dependent on the quantity of catalyst used, whereas the position of the second breakpoint depends on the amount of substrate present (20,24). 

Replacement of one of the carbon atoms of the octalone ring system, as in compounds XXX, XXXI, and XXXII, by a nitrogen results in different hydrogenation stereochemistry, as shown in Table IV. It is possible that in the... 

The stereoselectivity in the hydrogenation of bicyclic and polycyclic a,P-unsaturated ketones with the double bond at the ring juncture has been the subject of extensive investigations.252 Formation of cA-2-decalone in the hydrogenation of A1,9-2-octalone (115) with palladium catalysts increases with increasing polarity of aprotic solvents and also in the presence of acid, especially in nonhydroxylic solvents.253,254 Hydro-bromic acid has been found to be more effective than hydrochloric acid for cA-2-de-calone, especially in tetrahydrofuran (eq. 3.72).255 Formation of alcoholic products was also completely depressed in the presence of hydrobromic acid, although the rate of hydrogenation became considerably lower than in the presence of hydrochloric acid.256... 

Three independent syntheses of fukinone (335) have been published. In the first of these, Piers and Smillie ° converted the octalone (336), which they had previously used in connection with their synthesis of aristolone, into (337) by treatment with ethyl formate followed by catalytic reduction. Dehydrogenation of (337) with 2,3-dichloro-5,6-dicyanobenzoquinone and subsequent oxidation and esterification yielded (338). This keto-ester was converted into fukinone (335) by hydrogenation followed by methylation of the enolate ester and dehydration of the resultant keto-alcohol (339). Torrence and Finder have also completed the synthesis of fukinone using the octalone (336) as the key intermediate. 

The catalytic reactions of polar groups is influenced by the polarity of the solvent. The hydrogenation of A >9-octalone-2 (13) produces both the cis (14) and trans (15) p decalones (Eqn. 5.3). As shown by the data in Table 5.1, in aprotic... 

Table 5.1 Relationship between solvent dielectric constant and product stereochemistry in the hydrogenation of 5-octalone (13) over Pd catalysts.2.8 ...

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