Total Synthesis of the Tolypothrix Pentaether from Enantiomerically Pure Homoallyl Alcohols by A Butyrolactone → 1,3‐Diol Strategy

Abstract

AbstractFollowing the retrosynthetic plan of Scheme 1 the permethyl ether 1 from Tolypothrix conglutinata was synthesized from aldehyde 2 and the hydroxylated butyrolactone 3b. Each of these building blocks was obtained from a homoallyl alcohol, i. e. aldehyde 2 from homoallyl alcohol 5 (Scheme 3; 98.1% ee) and lactone 3b from homoallyl alcohol 30 (Schemes 10, 11; 97.7% ee). These alcohols, in turn, stemmed from the Ti(OEt)4/S‐BINOL‐mediated enantioselective addition of the β‐substituted stannane 7 to hexanal (Scheme 3) and the Ti(OEt)4/R‐BINOL‐mediated enantioselective addition of the β‐substituted stannane 31 to aldehyde 32 (Scheme 10), respectively. After O‐methylation of hydroxy lactone 3b (Scheme 11), the resulting methoxy lactone 38 was condensed with aldehyde 2 by Larson's modification of the Peterson olefination to provide the γ‐alkylidene lactone 39 as a 65:35 mixture of Z/E isomers (Scheme 12). Hydrogenation of this mixture gave the cis‐configured γ‐alkyl lactone 40 (Scheme 12). It was accompanied by no more than 5 mol‐% of its trans isomer; this observation seems to imply the occurrence of butenolide 41 as an intermediate of this reaction. An oxidative degradation of lactone 40 via the Criegee rearrangement of a derived peroxonosylate provided the syn‐diol 42 from where another three steps led to the target ether 1 (Scheme 13).