TOTAL SYNTHESIS OF THE TOLYPOTHRIX PENTAETHER FROM ENANTIOMERICALLY PURE HOMOALLYL ALCOHOLS BY A BUTYROLACTONE-]1,3-DIOL STRATEGY

Following the retrosynthetic plan of Scheme 1 the permethyl ether 1 fr om Tolypothrix conglutinata was synthesized from aldehyde 2 and the hy droxylated butyrolactone 3b. Each of these building blocks was obtaine d from a homoallyl alcohol, i. e, aldehyde 2 from homoallyl alcohol 5 (Scheme 3; 98.1% eel and lactone 3b from homoallyl alcohol 30 (Schemes 10, 11; 97.7% eel. These alcohols, in turn, stemmed from the Ti(OEt)( 4)/S-BINOL-mediated enantioselective addition of the beta-substituted stannane 7 to hexanal (Scheme 3) and the Ti(OEt)(4)/R-BINOL-mediated e nantioselective addition of the beta-substituted stannane 31 to aldehy de 32 (Scheme 10), respectively. After O-methylation of hydroxy lacton e 3b (Scheme 11), the resulting methoxy lactone 38 was condensed with aldehyde 2 by Larson's modification of the Peterson olefination to pro vide the gamma-alkylidene lactone 39 as a 65:35 mixture of Z/E isomers (Scheme 12), Hydrogenation of this mixture gave the cis-configured ga mma-alkyl lactone 40 (Scheme 12). It was accompanied by no more than 5 mol-% of its trans isomer; this observation seems to imply the occurr ence of butenolide 41 as an intermediate of this reaction, An oxidativ e degradation of lactone 40 via the Criegee rearrangement of a derived peroxonosylate provided the syn-diol 42 from where another three step s led to the target ether 1 (Scheme 13).