Studies On Synthesis Of 4-Ethoxy-5, 6-Dihydro-6, 6-Disubstituted Pyran-2-One Using A Combinational Lewis Acid-Base System

The unequivocal chemical synthesis of δ-lactones, which were important intermediates in the synthesis of a variety of structures with biological and medical significance, such as antifungal and antitumor, has attracted wide attention in organic chemistry. There are several synthetic methodologies to afford 8-lactones, such as the annulation of open-chained precursors, the derivatization from a 2, 3-dihydropyran-4-one, and the two-step addition reaction of ene to dicarbonyl compounds. In this paper, the author developed an efficient approach to 5, 6-dihydro-6, 6-disubstituted pyran-2-one, which was successfully carried out from the reaction between commercially available ethyl 3-ethoxybut-2-enoate and ketones by a combinational Lewis acid-base system.Considering the reactivity of the substrates, the dual activation strategy was used. Ethyl 3-ethoxybut-2-enoate was employed instead of Brassard's diene. Lewis acid and LDA were also employed to activate ketone and ethyl 3-ethoxybut-2-enoate, respectively. Extensive screening showed that the optimized catalytic reaction conditions were 0.25mmol of ketones, 3 equiv of 1b, 50 mol% BF₃Et₂O, 20 mol% InBr₃ and 3 equiv of LDA in 2.0 mL CH₂Cl₂ at room...