Enantioselective total synthesis and correction of the absolute configuration of megislactone

The title compound, one of the constituents from Iryanthera megistophylla, has been synthesized in enantiopure forms. The stereogenic centers at C-2 and C-3 were constructed by using a chiral auxiliary induced asymmetric aldolization and the C-4 was derived from the corresponding optically active lactates. The carbon–carbon double bond in the side chain was derived from a pure cis vinyl iodide using a Suzuki coupling with an alkyl borane formed in situ from the corresponding terminal alkene. A previously unknown (partial) cis to trans transformation of an isolated C–C double bond in a long alkyl chain was observed during the deprotection of TBS group with CAN. Somewhat unexpectedly, the otherwise undetectable co-presence of the trans isomer of the remote double bond in a long alkyl chain was clearly revealed in 1H and 13C NMR in the presence of a lactone ring. The present work unambiguously shows that the absolute configuration of the natural compound is the antipode of the one originally reported. Some errors in the previous 1H and 13C NMR signal assignments are also corrected.