Synthesis of (±) Wine Lactone and Its Analogues by a Diels-Alder Approach

A novel route to (+/-)-wine lactone (1) by a cis-selective kinetically controlled intramolecular Diels-Alder (IMDA) cycloaddition of the linear triene 2 is reported. The triene precursor was synthesised by TBAF-catalysed coupling of an acyl fluoride with an silyl enol ether. Four butadienyl but-3-enoates were prepared and cyclised under mild conditions to give a series of wine lactone analogues. The diastereoselectivity of the IMDA cycloadditions was determined by NMR spectroscopy and GC-MS, whereby the formation of the natural cis-configured wine lactone (1) was established. The diastereomeric IMDA transition states were optimised by using density functional theory at the B3LYP/6-31+G(d) level, and the Boltzmann populations of the electronic energies were found to correlate well with the experimentally observed diastereoselectivity. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)