Copper-catalyzed Conjugate Alkylative Aldol Addition-lactonization Reactions Of α,β-Unsaturated Diesters

Paraconic acid and its analogues, β-carboxylic acid-γ- lactone, are widely found in natural products. They can be obtained via selective hydrolysis of β-ester-γ-butyrolactone, and have potential antitumor and antimicrobial activities.In this thesis, β-ester-γ-butyrolactones with a variety of multi-substituents were synthesized from the reaction among diethylzinc, α,β- unsaturated dicarboxylic diester, carbonyl compounds under CuF(PPh3)3·2MeOH catalysis via Michael addition-aldolizationlactonization domino mode. The intermolecular Michael reaction is carried out using diethyl zinc as a nucleophilic reagent and α,β-unsaturated dicarboxylate as a Michael receptor, and the Michael addition product spontaneously reacted with a carbonyl via a intermolecular aldol reaction, and a followed Latinization reaction.β-Ester-γ-butyrolactones were yielded from dimethyl itaconate and fifteen ketones and five aromatic and aliphatic aldehydes. The carbonyls contain electron-donating/withdrawing groups. Structures of the lactones were characterized by 1H NMR, 13 CNMR and HRMS. The carbonyl compounds included electron-donating group and electron-withdrawing aromatic ketones, aromatic aldehydes and aliphatic ketones, etc. The reaction can be finished in 1 to 5 h, giving most lactones in 90% yield and up to 6.5:1 dr value.Dimethyl fumarate, a Michael receptor, reacted with ethylzinc and carbonyls, yielding α-ethyl-β-ester-butyrolactones. In this kind of reaction, diethyl zinc provides H-, which is different to the case where ethylzinc acts as an Et- reagent. The interesting and somewhat puzzling results were discussed.