Avermectin–milbemycin synthetic studies. Part 7. An approach to the southern hemisphere of milbemycin α1
An asymmetric approach to oxahydrindene 5, the southern hemisphere of the anthelmintic macrolide milbemycin α1, 2, is described. [2 + 2]-Photocycloaddition of the dihydrofuran chiral template (+)-11 with cyclobutenoate 12 furnished the requisite cis-anti-cis, head-to-tail photoadduct (+)-17 in 54% yield. de Mayo-type fragmentation then smoothly furnished hydrindane 21α,β; further elaboration afforded the 3,4-dihydro-4-normethyl southern fragment 39. Efforts to install the C(4) methyl group and C(3,4) unsaturation in several advanced intermediates related to 39 gave unsatisfactory results.