A Simple Zinc-Mediated Method for Selenium Addition to Michael Acceptors

• Main Authors: Francesca Giulia Nacca, Bonifacio Monti, Eder João Lenardão, Paul Evans, Claudio Santi
• Format: Article
• Language: English
• Published: MDPI AG 2020-04-01
• Series: Molecules
• Subjects: zinc; selenium; nucleophilic addition; seleno-Michael reaction; conjugate addition; reduction
• Online Access: https://www.mdpi.com/1420-3049/25/9/2018

In this work, we focused our attention on seleno-Michael type reactions. These were performed using zinc-selenolates generated in situ from diphenyl diselenide <b>1</b>, 1,2-bis(3-phenylpropyl)diselenide <b>30</b>, and protected selenocystine <b>31</b> via an efficient biphasic Zn/HCl-based reducing system. Alkenes with a variety of electron-withdrawing groups were investigated in order to gauge the scope and limitations of the process. Results demonstrated that the addition to acyclic α,β-unsaturated ketones, aldehydes, esters amides, and acids was effectively achieved and that alkyl substituents at the reactive β-centre can be accommodated. Similarly, cyclic enones undergo efficient Se-addition and the corresponding adducts were isolated in moderate to good yield. Vinyl sulfones, α,β-unsaturated nitriles, and chalcones are not compatible with these reaction conditions. A recycling experiment demonstrated that the unreacted Zn/HCl reducing system can be effectively reused for seven reaction cycles (91% conversion yield at the 7° recycling rounds).