Synthetic Studies of Laurencin and Related Compounds. I. The Synthesis of t-3-Bromo-r-2,c-8-diethyl-3,4,7,8-tetrahydro-2H-oxocin

The synthesis of the titled bromohydrooxocin (2), one of model compounds for synthetic approaches to laurencin (1), is described, trans- and cis-2,5-Diethyl-2,5-dihydrofurans (25), prepared by treatment of furan with bromine and then with ethyl magnesium bromide, was submitted, after oxidation with ozone, to the Robinson-Schöpf condensation with methylamine to give trans- and cis-2,4-diethylbicyclononanones (19a and 19b), whose configurations were discussed on the NMR spectra. These compounds were converted into trans- and cis-diethylhydrooxocinones (38a and 38b), respectively, according to a six-step process analogous to the Paguette procedure. It is to be noted that (i) thermally induced, intramolecular dienyl 1,5-hydrogen transfer (36 to 37), one of the key reactions in the process, took place without difficulty with cis-aminodiene (36b), while the rearrangement did not proceed smoothly with trans-aminodiene (36a), and (ii) trans-ketone (38a) was isomerized readily into cis-ketone (38b). Further hydride reduction of cis-ketone (38b) followed by bromination with carbon tetrabromide and triphenylphosphine yielded the aimed bromohydrooxocin (2) as a major product, which possessed the same relative configuration concerning the ring substituents as laurencin (1).