A NEW APPROACH TO THE SYNTHESIS OF LONG-CHAIN POLYPROPIONATES BASED ON THE DIELS-ALDER MONOADDITIONS OF 2,2'-ETHYLIDENEBIS[3,5-DIMETHYLFURAN]

Acidic condensation of 2,4-dimethylfuran with acetaldehyde provided 2, 2'-ethylidenebis[3,5-dimethylfuran] (7) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8. Regio- and stereoselective hydroboration of the latter 7-oxanorbornadiene derivative followed by alcohol protection and methanolysis of its beta-bromoacrylate moiety g ave (1RS,2RS,4RS,5SR,6SR,1'RS)-methyl 4-[1'-(3 '',5 ''-dimethylfuran-2 thyl-7-oxabicyclo[2.2.1]heptane-2-endo-carboxylate (24) (Schemes 2 an d 3). Reduction of 24 with LiAlH4, followed by H2O and MeOH eliminatio n gave the 3-methylidene-7-oxanorbornan-2-one derivative 26 which unde rwent 7-oxa ring opening through a S(N)2' type of reaction with Me(2)C uLi (Scheme 4). Stereoselective hydrogenation and ketone reduction pro vided (1RS,2SR,3RS,4RS, SSR,6RS,1'SR)-1-[1'-(3 '',5 ''-dimethylfuran-2 )methoxy]-t-4,t-6-dimethylcyclohexane-r-1,c-2-diol (32), the oxidativ e cleavage of which with Pb(OAc)(4) generated a 6-oxo-aldehyde 33 (Sch emes 4 and 5). Chemoselective protection of 33 and chemo- and stereose lective reductions generated l)-2-ethyl-6-hydroxy-4-[(2-methoxyethoxy) methoxy]- 3,5-dimethyloct-1-yl pivaloate (36) and its 4-hydroxy 6-epim er 40 (12 and 13 steps, resp., from adduct 8; Scheme 5). Oxidation of the furan ring of 36 led to a )-7-ethyl-3,5,8-trihydroxy-2,4,6-trimeth yloctanoic acid derivative 44, a polypropionate fragment with six cont iguous stereogenic centres (Scheme 6).