Alpha- and beta-prodine type compounds.

The relative configurations of alphaand beta-prodine have been discussed in a number of papers. Recently, ZIERISG, MOTCHANE and LEE^ have published an interpretation of the infra-red absorption spectra of the derived alcohols which they consider supports their original assignments, viz., cis methyl/ phenyl for alphaand trans methyl/phenyl for beta-prodine. BECKETT, CASY and WALKER,^,^ on the other hand, were led to advance the reverse configurations on the basis of conformational analysis and hydrolysis rates. Further evidence in favour of the assignments of Beckett and co-workers has been provided by the determination of the isomeric compositions of tertiary alcohols obtained by the addition of lithium aryls to 1,3-dimethyl-4p iper id~ne .~ It has been shown, from considerations of the stereochemistry of addition to ketones, that this information is of value in assigning configurations to the various stereoisomers. This present work reports the extension of addition studies to a series of N-jSf-phenylethyl-4-piperidones with the object of providing further evidence for the assignment of configurations to alphaand beta-prodine type compounds. It has the further object of producing compounds of known configuration for analgesic tests to provide information about the stereochemical requirements of analgesics and the analgesic receptor site. The key intermediates in the synthesis of the tertiary alcohols and esters reported in this present work were 4-piperidones of general formula (I, R = H or alkyl). Reaction of the ketone (I) with a lithium aryl and subsequent acylation of the resultant tertiary alcohol (11) gave the ‘reversed ester’ (111, R l = lower alkyl). The synthesis of the 4-piperidones (I, R = H , CH, and