Large ring synthesis

Includes bibliographical references (pages 35-36)Synthesis of 1,3-diketone compounds was explored via condensations of various lithium enolates of methyl ketones with acid chlorides in THF at -78 ??C. Salient features of this method are good yields and steric control of products. The simplest 1,3-diketone product was 1,3-diphenyl-1,3-propanedione (enol) prepared in 75% yield from the condensation of benzoyl chloride with the lithium enolate of acetophenone and subsequent hydrolysis. The more complex tetraketone product, 1,6-diphenyl-1,3,4,6-hexanetetraone (enol), was prepared successfully by two approaches. Condensation of oxalyl dichloride with the lithium enolate of acetophenone, followed by hydrolysis, yielded 66% of the tetraketone. Alternatively, condensation of benzoyl chloride with the lithium enolate of biacetyl produced the tetraketone in 49% yield.\ud Steric control over multi-ketone syntheses is attributable to tight chelation of 1,3-diketone enolate products to lithium. One application of this synthetic strategy is to prevent small ring closure. Alternatively, the limited conformational freedom of lithium 1,3-diketone enolates increases the likelihood of large ring formation relative to polymerization. This hypothesis was tested by the condensations of isophthaloyl dichloride with the lithium enolate of biacetyl and oxalyl dichloride with the lithium enolate of m-diacetylbenzene