Synthesis of talaromycins A, B, C, and E

The synthesis of 2,2-diethyl-5-ethynyl-1,3-dioxane (9) is reported in an overall yield of 27% from diethyl malonate. Addition of 5-ethyl tetrahydropyran-2-one to the lithium anion of (9) gave the hydroxy ketoacetylene (10) which was converted in four steps to the olefinic spiroacetals (19) and (20), which were obtained in a ratio of 2 : 1. The individual olefinic spiroacetals (19) and (20) gave access to the (±)-talaromycins A and C, and B and E via a chlorohydration, reductive dechlorination, and deprotection sequence.