2- Decalone 3-substituted enolates

The addition of large enolate synthons to cyclohexenone derivatives via Michael addition leads to equatorial substitution. If the cyclohexenone conformation is fixed, e.g. as in decalones or steroids, the addition is highly stereoselective. This is also the case with the S-addition to conjugated dienones (Y. Abe, 1956). Large substituents at C-4 of cyclic a -synthons direct incoming carbanions to the /rans-position at C-3 (A.R. Battersby, 1960). The thermodynamically most stable products are formed in these cases, because the addition of 1,3-dioxo compounds to activated double bonds is essentially reversible. 

Intramolecular reactions between donor and acceptor centres in fused ring systems provide a general route to bridged polycyclic systems. The cts-decalone mesylate given below contains two d -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 3-substituted cyclohexanones the /rans-diastereoselective synthesis of decalones and octahydro-1 //-indenones may be achieved 164 169. This method has been applied, for instance, in the synthesis of 19-norsteroids. In a related Michael addition the lithium enolate of (R)-5-trimethylsilyl-2-cyclohexenone reacts with methyl 2-propenoate selectively tram to the trimethylsilyl substituent. Subsequent intramolecular ring closure provides a single enantiomer of the bicyclo[2.2.2]octane170 (see also Section 1.5.2.4.4.). 

Alkylations of tran.v-2-decalone enolates 30 have been performed with high degrees of diastereose-lectivity. 1,3-Interactions are clearly very important steric-control elements in the angularly substituted compounds. The examples shown also demonstrate that reductive alkylations of a,/ -unsaturated ketones are a useful diastereoseleclive step in the syntheses of polycyclic compounds19 11 7S-80. 

Studies pertaining to diastereoselectivity in Lewis acid catalyzed alkylations of enol derivatives have been limited. Reetz has reported that r-butylation of l-trimethylsiloxy-4-f-butylcyclohex-l-ene gave an 8S 1S mixture of cis- and frafu-2,4-di-f-butylcyclohexanone, which could result from kinetic equatorial and axial alkylation, respectively. However, equilibration of the products, which would favor formation of the former isomer, was not ruled out. Titanium tetrachloride promoted phenylthiomethylation of the more-substituted TMS enol ether of 1-decalone gave a 4 1 mixture of cis- and rranj-fused 1-deca-lones. In this case, where equilibration of the product could not occur, the diastereoselectivity was similar to that of methylation of the corresponding lithium enolate (49). ... 

Lithium etiolates of imsymmetriealketones. House et a .2 find that the less highly substituted lithium enolates of unsymmetrical ketones are best obtained by kinetically controlled deprotonation of the ketone with the hindered base lithium diisopropyl-amide. Thus treatment of 1-decalone (1) with 1.03 eq. of the base in 1,2-dimethoxyethane for 10 min. gives predominantly the lithium enolate (2) alkylation of the mixture with a... 

The trimethylsilyl enol ethers of 1-acetylcyclohexenes 1 undergo a Lewis acid assisted two fold Michael reactions with Michael acceptors 2 to produce 5-substituted 2-decalones 3. The application of these reactions have enabled syntheses of ( )-8-cadinene 4, ( )-khusitone 5, and ( )-khusilal 6. By employing 8- phenylmenthyl acrylate, optically active 2-decalone 3 (ca. 

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