Cis-Decalones

In fact, a similar intramolecular cyclisation was studied by Reusch [11] and he found a remarkable methyl substituent effect on the aldol equilibrium. Starting from the cis-decalones 25 (easily prepared from the Wieland-Miescher ketone), in which the angular methyl group prevents isomerisation to the more stable trans-decalone, it was found that other methyl groups may exert profound but less... 

Intramolecular reactions between donor and acceptor centres in fused ring systems provide a general route to bridged polycyclic systems. The cis-decalone mesylate given below contains two d2-centres adjacent to the carbonyl function and one a -centre. Treatment of this compound with base leads to reversible enolate formation, and the C-3 carbanion substitutes the mesylate on C-7 (J. Gauthier, 1967 A. Belanger, 1968). 

Using methylene-triphenylphosphorane 205, in many cases carbonyl functions have been converted into exomethylene groups in cyclic terpene chemistry. This technique was used, among others in the preparation of (+)-steviol methyl ether 244), dihydro-5,6-norcaryophyllene 245), ( )-nootkatone 246 (-)-phyllodadene 247), and (+)-e-cadinene 248). In the synthesis of the latter the trans-decalin derivative 462 was formed from the cis-decalone 461 the epimerization of which proceeded via the enol form during the methylenation 248 (Scheme 80). 

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. 

Structurally rigid substrate surrogates were added to the cubic section model before more flexible molecules as the following order signifies pentacyclic, tetracyclic, tricyclic, bicyclic ketones, trans/cis-decalones, methyl cyclohexanones and alkyl cyclohexanones. The hydroxyls of cyclohexanols were oriented axially with respect to cyclohexyl rings consistent with the Jones protocol and with the obsen/ation that... 

Activation of the catalyst by solvent or an acidic additive may be also satisfactory. " Hydrogenation of dienone, 6, over Pd-on-carbon in ethanol or acetic acid leads to a cis-decalone ... 

In other cases, the decisive factor is usually attack on the less crowded side of the molecule. Hydrogenation of an alkene is a good example because one side of the flat alkene must be in contact with the catalyst and selectivity in favour of the less crowded side is usually high. Hydrogenation of (47) givesa large proportion of the less stable cis decalone (48). 

Cis-decalone (20) has four adjacent chiral centres. One (C6) needs no control as it is to be oxidised to a ketone in the transformation to (16). The other three must be as shown in (20) if the cyciisation of (19) to (IT) is to occur because the S s[2 displacement goes with inversion. Disconnection (17a) also... 

However, the relation between stereoselectivity of hydrogenation and solvents polarity is not always so clear as shown by the hydrogenation of P-octalone 9 to trans decalone-3 iO and cis-decalone-3 U. (6). 

The reduction of 212 (R=H) gives a mixture of trans and cis decalones 219 and 220 (R=H) in a 99 1 ratio (63). An analysis of non-bonded interactions in the corresponding enolates 216 and 217 (R=H) indicates that the former should be favored only by about 1.0 kcal/mol, which should correspond to an approximately 80/20 trans/cis ratio. This result indicates that there is a significantly greater preference for the trans species 216 than would be predicted by analysis of non-bonded interactions. 

Lithium dimethyl copper reacted with (186) to introduce a methyl group stereo-selectively trans to the 5-isopropyl group. The enolate anion (187) so formed underwent intramolecular alkylation to give the cis-decalone(188), which was reduced to d/-valerane (189). Conjugate addition of lithium methyl vinyl cuprate to cyclopent-2-... 

In a redetermination of the 5a- and 5P-cholestan-4-one equilibrium it was found that 87 + 1% of the 5a-species is present at 25°C in ethanol. For 9-methyl-l-decalone the cis-isomer is favoured at equilibrium, and for 10-methyl-1-decalone the trans-isomer is favoured. These results are supported by molecular mechanics calculations. The amount of cis-isomer contained in equilibrium,mixtures of 1-decalones is larger than in the steroidal counterparts, and this was rationalized in terms of the two low-energy a s-conformers which are available in the cis-decalones. 

A review of the thermal cyclization of unsaturated carbonyl compounds includes the formation of cycloalkanones and cis-decalones nia 5-ethylenic ketones. 

An additional advantage of the use of cis-decalones is that axial attack on the more readily accessible "convex of-side of the folded molecule of cis-decalone leads exclusively to products with the natural /3-configuration of the methyl group at Ciq. Consequently, intermediates with a cis- B/C linkage have been used in the total synthesis of cortisone (Scheme 62) and of other nonaromatic steroids (Schemes 75, 77), in spite of the necessity for subsequent inversion at C3, which is effected only with great difficulty in many cases. 

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