1-Decalones angular alkylation

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). 

Angular alkylations of 1-decalone enolates provide important models for angular alkylations of 18-nor-D-homo steroids. The manner in which structural modifications influence cisUrans product ratios in alkylations of various enolates of 1-decalones containing blocking groups at C-2 has been thoroughly investigated and reviewed. ... 

The most widely used method for the introduction of angular subsituents is the direct alkylation of cyclic ketones with keto groups at C5 (Scheme 74), Ci7 (Scheme 27), and (Schemes 85, 97-99, and 102), The features of these reactions are conveniently discussed in the case of a bicyclic model compound, 1-decalone (51), which represents the CD moiety of the steroid molecule. While in the alkylation of monocyclic ketones the attack of the alkylating group takes place mainly at a tertiary carbon atom, in the case of decalone (51), instead of the expected angularly-alkylated 9-methyl derivative (50) the 2-methyl derivative (52) is formed as the product of attack on a secondary carbon atom [38, 39], This makes it necessary to protect position 2 and thereby to direct the attack of the alkylating agent to position 9. 

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. 

The stereochemistry of alkylations of extended dienolates of enones such as (70) has been extensively investigated (Scheme 33).In general, the results are similar to those found for the related decalone enolates (43a) and (44), i.e. steric factors within the anion play a dominant role. Thus, axial attack is preferred with (70 R = H), but equatorial attack is strongly favored when an angular methyl group is present (70 R = Me). There is a modest preference for axial alkylation when an angular ethoxycarbonyl... 

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