Studies on Ring Forming Reactions: Geminal Acylation, Nazarov Cyclization and Cyclohexyne Reactions

Abstract

Geminal acylation is a powerful tool for converting ketones into 1,3- diketones. An ambitious synthesis of a propellane was envisaged by three geminal acylation reactions. Geminal acylations were done on the ethylene glycol ketal of ethyl levulinate with four- and five-membered acyloins, generating, following a ring- opening process, a series of ketodiesters. A methyl substituent appeared to sterically inhibit the subsequent geminal acylation under many different reaction conditions and with different ester moieties. Thus, an unmethylated analog was prepared, but, unfortunately, the geminal acylation of that substrate was also unsuccessful. Nazarov reactions of allenyl vinyl ketones (AVKs) can be interrupted by the addition of a nucleophile to the reaction mixture. The oxyallyl cations of AVKs were intercepted with a wide variety of oxygen-substituted dienes by (4+3) cycloaddition with a high degree of regioselectivity and with very high facial selectivity. Dienes with a substituent on the terminus of the oxygenated double bond formed (4+3) products in greater than 95% yield, but with modest diastereoselectivities, whereas dienes with a substituent on the terminus of the other double bond formed (4+3) products in modest yield but with high diastereoselectivity. The results were most consistent with a mechanism for the cycloaddition that is concerted but asynchronous. Cyclohexyne is so strained that it cannot be isolated, but it can be generated and reacted in situ with nucleophiles. Cyclohexyne has been studied very little and not much is known about its ability to undergo Diels-Alder reactions. Diels-Alder products were produced from the reactions of cyclohexyne with furan, an oxygenated acyclic diene, and a carbocyclic diene. 3-Methylcyclohexyne was prepared, and it reacted with furan forming diastereomeric adducts in a 2:1 ratio. Attempts were made to generate 3,3-dimethylcyclohexyne, but difficulties in methylation prevented its formation. The Diels-Alder reactions were generally low yielding. Tetramerization of cyclohexyne was a dominant reaction pathway, and the tetramer was obtained as a single diastereomer in 80% yield by a novel method.