2-Decalones lithium 2-enolate

A comparison of the data for alkylation of the lO-methyl-2-decalone lithium enolate (44) with those for enolate (43a) clearly shows that if axial alkylation involves development of a 1,3-interaction with an... 

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.). 

Angular alkylations of fused-ring ketones are an important step in syntheses of terpenoids, steroids and related natural products. The steric course of these alkylations has therefore been the subject of several systematic investigations and has been reviewedl 3 71. Alkylation of the lithium enolate 38 (R = H) derived from octahydro-1 (2//)-naphthalenone (1 -decalone) primarily yields the civ-fused octahydro-8a-methyl-l(2F/)-naphthalenone (39, R = H)35,62,79. Due to steric reasons, the lithium enolate 38 (R = CH3), with an angular methyl group, provides the irans-fused product 39 (R = CH3). 

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 above stereoelectronic arguments were proposed by Stork and Darling (61) to explain why the more stable isomer is not necessarily always obtained (62). For example, reduction of the octal one 221 with lithium-ammonia-ethanol followed by oxidation afforded the trans-2-decalone 222 even though the isomeric cis-2-decalone 223 is about 2 kcal/mol more stable than 222. Conformation 226 of the enolate dianion is the most favored sterically but it is electronically disfavored. Conformations 224 and 225 are both electronically favored but 225 is less favored sterically than 224. Therefore,... 

Stork deduced that the octalone (1) should be convertible into the less stable of iwo possible enolates by reaction with lithium in liquid ammonia, and experimentation showed this prediction to be correct. Reduction of the unsaturated ketone (1) afforded only the fru/ij-jS-decalone (3) as the initial product. The reaction is considered to involve addition of an electron from lithium to ketone (1) to produce a hybrid intermediate (2) with carbanion character at the j3-carbon, and this intermediate abstracts a proton from ammonia to form the product (3). These observations suggested a new method of alkylation." Alkylation of the t .v-2-decalone (4) in the presence of base proceeds through the mure stable enolaie and gives (.5). However, the leas stable enulate (2) can be generated by l.i-NH,i reduction of the unseturated ketone (I) and alkylated to give the liomarlu methylated product (A). 

Reductive alkylation and carbomethoxylation. Stork1 has now published details of his method of generating the less stable enol of an a,/3-unsaturated ketone and trapping this intermediate by alkylation or carboxylation before equilibration can occur (1, 601-602). For example, reduction of A1<9>-2-octalone (1) with lithium-ammonia followed by addition of methyl iodide instead of the usual proton source gives in about 50% yield a mixture of l-methyl-fra/is-2-decalone (2, 83%) and the product of reduction, fron.r-2-decalone (3,17%). Direct alkylation of trans-2-... 

Regiosp>ecific synthesis of enol silyl ethers can also be achieved from enones either by reductive silylation or by 1,4-addition of the conjugated system. Thus, Li/NH reduction of the decalone (27) and silylation give the enol silyl ether (28). Similarly, addition of lithium dimethylcuprate to cyclohexenone followed by silylation gives the enol silyl ether (29). Trimethylsilyl cyanide (30) normally adds 1,2 to conjugated ketones (e.g. carvone, 31). However, in the presence of trialkylaluminum, 1,4-addition bdces place to give the enol silyl ether (32 Scheme 9). The same overall transformation can be accomplished by diethylaluminum cyanide and trimethylchlorosilane. ... 

Similarly, specific enolates of unsymmetrical ketones can be obtained by reduction of a,p-unsaturated ketones with lithium in liquid ammonia. Alkylation of the intermediate enolate gives an a-alkyl derivative of the corresponding saturated ketone which may not be the same as that obtained by base-mediated alkylation of the saturated ketone itself. For example, base-mediated alkylation of 2-decalone generally leads to 3-alkyl derivatives whereas, by proceeding from the enone 11, the 1-alkyl derivative is obtained (1.26). The success of this procedure depends on... 

Whatever the exact mechanism of the conjugate-addition reaction, it seems clear that enolate anions are formed as intermediates and they can be trapped as the silyl enol ether or alkylated with various electrophiles. For example, addition of lithium methylvinyl cuprate (a mixed-cuprate reagent) to cyclopentenone generates the intermediate enolate 166, that can be alkylated with allyl bromide to give the product 167 (1.161). The trans product often predominates, although the transxis ratio depends on the nature of the substrate, the alkyl groups and the conditions and it is possible to obtain the cis isomer as the major product. Examples of intramolecular trapping of the enolate are known, as illustrated in the formation of the ds-decalone 168, an intermediate in the synthesis of the sesquiterpene valerane (1.162). 

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-... 

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