Cycloalkylation enolates

Ketone enolate cycloalkylations may be used to form small to medium and even larger rings under appropriate conditions. Space limitations permit only a few examples of these reactions to be covered here. The literature prior to 1978 has been reviewed. ... 

The requisite 1,3-diketones have been prepared by the condensation of acid chlorides with lithium enolates at -70 °C. The technique has proved of value in the synthesis of cycloalkyl fused chromones (456) (78JCS(P1)726). 

Partial rate constants for H-D exchange at the methyl and methine sites of cycloalkyl methyl ketones have been measured chiefly in order to examine the ring-size effect on exocyclic enol and enolate formation. Under base-catalysed... 

Exo cycloalkylations have been used to synthesize ct5-1-decalones. For example, treatment of 2-methyl-3(4-tosyloxybutyl)cyclohexanone with sodium t-pentylate in benzene gave c/j-9-methyl-l-deca-lone (50) in 60% yield. Also, as shown in Scheme 28, conjugate addition-cycloalkylation was employed to synthesize a cw-fused decalone related to the sesquiterpene, ( )-valerane. Apparently, in these cases, the enolate intermediate adopts a conformation having the 4-bromobutyl side chain quasi-axial, and C—C bond formation occurs via equatorial attack to give initially a twist-boat conformation of the product. 

In addition to ( )-valerane, a wide variety of other sesquiterpenes, including ( )-ishwarane, ( )-ish-warone, ° copaene, ylangene, ( )-seychellene ( )-sativene, ( )-longifoline, " ( )-copa-camphene," ( )-damsin," ( )-A < >-capnellene, ( )-pentalenene, (-)-P-vetivone" and ( )-P-eudesmol have been synthesized by pathways involving cycloalkylation of saturated ketone enolates. 

The enol acetate (122) provided a model system for investigating some of the problems associated with the synthesis of alnusenone. Saponification and introduction of a methylene group gave the olefin (124). The latter and the two related epimeric tertiary alcohols provided useful substrates for examining the stereochemistry of the Friedel-Crafts cycloalkylation reaction. Polyphosphoric acid yielded the same mixture in each case, the major product being the compound (125) with the desired stereochemistry. The mechanistic details of this reaction are considered at length. 

An interesting example of how a change in the base can influence the course of a cycloalkylation reaction is shown in eq 8. Since the reaction with f-BuOK involves equilibrating conditions, exo-cycloalkylation occurs via the more-substituted eno-late, which is more thermodynamically stable. On the other hand, when LDA is used as the base, endo-cycloalkylation occurs via the kinetically formed terminal enolate. 

Iodobenzenesulfonamide 43 undergoes photostimulated Sj j. 1 reactions in liquid ammonia with alkyl and cycloalkyl enolate ions and gives fair to good yields of 3-alkyl 277-1,2-benzothi-azine-1,1-dioxides 44 and fused 277-1,2-benzothiazine-1,1-dioxides 45 (Scheme 10.9) [38]. 

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