Reaction of methylmagnesium iodide and diethyl 1,2-cyclohexanedicarboxylates

Total Synthesis of Dumsin. 1. Retrosynthetic Strategy and the Elaboration of Key Intermediates from (−)-Bornyl Acetate

“…Stirring was continued for 15 min, and the temperature was lowered to -78 °C, and then 2 mL of HMPA was added. This reaction mixture was added dropwise to a solution of lactone 16 24 (1.01 g, 6.0 mmol) in a mixed solvent system consisting of THF (10 mL) and HMPA (2 mL). The resulting yellow solution was stirred at -78 °C for 1 h followed by the addition of 2-(2-bromoethyl)-1,3-dioxolane (1.187 g, 6.6 mmol) in THF (10 mL).…”

“…By judicious selection of this terpenoid ester, one introduces absolute configuration directly relatable to that resident in dumsin ( 2 the nucleophilic addition of a protected cyanohydrin to a ketone 22 or aldehyde group have been documented in the context of natural products synthesis, 23 no reports of analogous cyclization onto a lactone carbonyl had been reported. To ensure the feasibility of this step and hence our entire tactical design, the previously described lactone 16 24 was deprotonated with LDA and alkylated with 2-(2-bromoethyl)-1,3-dioxolane. The angular side chain was thereby introduced to give 17 in 77% yield (Scheme 3), but only when standard conditions 25 were avoided and use was made of HMPA as cosolvent.…”