2.5- Hexanedione, intramolecular aldol reaction

Figure 23.4 Intramolecular aldol reaction of 2,5-hexanedione yields 3-methyl-2-cyclopentenone rather than the alternative cyclopropene.

The selectivity observed in the intramolecular aldol reaction of 2,5-hexanedione is due to the fact that all steps in the mechanism are reversible, so an... 

The mechanism of intramolecular aldol reactions is similar to that of inter-molecular reactions. The only difference is that both the nucleophilic carbonyl anion donor and the electrophilic carbonyl acceptor are now in the same molecule. One complication, however, is that intramolecular aldol reactions might lead to a mixture of products, depending on which eiiolate ion is formed. For example, 2,5-hexanedione might yield either the five-membered-ring product 3-methyl-2-cyclopentenone or the three-membered-ring product (2-methyl-cyclopropenyl)ethanone (Figure 23.4). In practice, though, only the cycio-pentenone is formed. 

Finally, the organocatalytic KR of 6-aryl-2,6-hexanediones was achieved very recently by Cheng et al. [306] via intramolecular aldol reactions. These reactions catalysed by chiral secondary amines cleanly afforded chiral cyclohexenones together with enantioenriched starting hexanediones with moderate-to-high enantioselectivities. 

Compounds that possess two carbonyl groups can undergo intramolecular aldol reactions. Consider the reaction that occurs when 2,5-hexanedione is heated in the presence of aqueous sodium hydroxide. 

The aldol reactions we ve seen thus far have all been intermolecular, meaning that they have taken place between two different molecules. When certain dzcarbonyl compounds are treated with base, however, an intramolecular aldol reaction can occur, leading to the formation of a cyclic product. For example, base treatment of a 1,4-diketone such as 2,5-hexanedione yields a... 

Antibodies 38C2 and 33F12 also catalyzed intramolecular aldol reactions and Robinson annulation (Scheme 6.4) 1,5-diketones 28 and 30 were converted into 29 and 31, respectively [15]. To explore the scope of Baldwin s rules in antibody-catalyzed intramolecular aldol reactions, 38C2 was incubated with three different aliphatic diketones - 2,4-hexanedione, 2,5-heptanedione and 2,6-octanedione. No catalysis was observed in the... 

The aldol reaction can be applied to dicarbonyl compounds in which the two groups are favorably disposed for intramolecular reaction. Kinetic studies on cyclization of 5-oxohexanal, 2,5-hexanedione, and 2,6-heptanedione indicate that formation of five-membered rings is thermodynamically somewhat more favorable than formation of six-membered rings, but that the latter is several thousand times faster.170 A catalytic amount of acid or base is frequently satisfactory for formation of five- and six-membered rings, but with more complex structures, the techniques required for directed aldol condensations are used. 

A.ii. Intramolecular Reactions. The intramolecular aldol condensation is one of the most important synthetic methods known, illustrated by the simple reaction of 2,5-hexanedione with LDA to first give kinetic enolate 146. This enolate could condense with a second molecule of dione to give an aldol product, but... 

The entropic advantages of intramolecularity are particularly noticeable in intramolecular ketone condensations, transformations that provide a ready source of cyclic and bicyclic a,jS-unsaturated ketones. Since ketones can have two enolizable a-carbons, several aldol products may be possible. However, the reversibility of the reaction ensures that usually the least strained ring is generated, typically one that is five or six membered. Thus, reaction of 2,5-hexanedione results in condensation of the terminal methyl (Cl functioning as the enolate carbon) and the C5 carbonyl group to furnish 3-methyl-2-cyclopentenone. 

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