1.4- Diketones, cyclization

Diketones cyclize much more efficiently than simple ketones. Photochemical cyclobutanol formation is the key step in a novel route14 to 1,3-cyclopentanediones, as exemplified by the conversion of l-bromo-5-phenyl-2,3-pentanedione to 4-phenyl-l,3-cyclopentanedione. 

The Michael addition of deoxybenzoin to several ethyl a-acetylcinnamates, obtained from ethyl acetoacetate and an aromatic aldehyde in the presence of piperidine, resulted in the formation of 1,5-diketones. Cyclization to 4/f-pyrans occurred in acetic acid and p-toluenesulfonic acid (76DC(B)739). 

The Kostanecki-Robinson reaction proceeds through O-acylation followed by a Baker-Venkataraman rearrangement to the 1,3-diketone. Cyclization then yields the chromone. Early evidence was based on the observation that both of the 1,3-diketones (448) and (449) yielded the same chromone on reaction with the appropriate acid anhydride (33JCS1381). Thus, the reactions were considered to proceed through the common intermediate (450 Scheme 159). 

A 2,2-disubstituted chromanone results from the condensation of o-hydroxyacetophenone with diethyl oxalate. The initially formed 1,3-diketone cyclizes spontaneously to ethyl 2-hydroxy-4-oxochroman-2-carboxylate (77LA1707). The enolate also reacts with aliphatic ketones to give 2,2-disubstituted chroman-4-ones via the diol (79TL3685). 

Danishefsky examined the regiochemistry of 1,5-diketone cyclization in the context of a steroid syn-thesis. Diketone (71) cyclizes in aqueous ethanolic base to give a mixture of isomeric cyclohexenones (72) and (73) (equation 123). If the reaction is carried out at room temperature, the (72) (73) ratio is 77 23 after refluxing for 50 h, the ratio is 21 79. Furthermore, pure (72) is converted into (73) under the latter reaction conditions. With diketone (74), cyclohexenone (75) is the only product seen under either conditions (equation 124). 

McCurry has investigated the regiochemistry of unsymmetrical 1,4-diketone cyclizations.139 2,5-Non-anedione undergoes cyclization under weakly basic conditions to give cyclopentenones (59) and (60) in a ratio of 94 6 (equation 117). Under the reaction conditions, independently synthesized (60) was not converted into (59). However, it was found that such trisubstituted alkenes are rearranged to the more stable tetrasubstituted isomers under more drastic conditions (equation 118). 

Base-catalyzed reactions were reviewed in general by Hattori [208,222], and from the reactions described butene isomerization, alcohol conversion, toluene alkylation, acetone condensation/diacetone alcohol decomposition, Knoevenagel condensations, diketone cyclization, ring transformation reactions, and dimerization of aldehydes to the corresponding esters were used to evaluate the acid-base properties in molecular sieves. 

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