Synthesis of 5-Substituted 2-Pyrrolidinones by Coupling of Organozinc Reagents with Cyclic N-Acyliminium Ions

Abstract

A coupling reaction between cyclic N-acyliminium ions with organozinc reagents is described. The cyclic N-acyliminium ions, generated in situ from N-substituted-5-hydroxy-2-pyrrolidinones by treatment with boron trifluoride–diethyl ether complex or titanium tetrachloride, are trapped by the organozinc reagent, which is formed from an alkyl bromide in the presence of zinc in the same reaction medium. The N-substituted-5-allyl-2-pyrrolidinones generated using this method serve as versatile intermediates for the synthesis of azabicyclic systems with indolizidine and pyrroloazepinolizidine cores.

N-Acyliminium Ion Chemistry: Improving the Access to Unsaturated γ-Lactams and Their N-α-Methoxylated Derivatives: Application to an Expeditive Synthesis of (±)-Crispine A

“…N-Acyliminium ions precursors 9 or 10 were mostly synthesized via reduction of succinimides. 15 Typical reducing reagents such as NaBH 4 , 16 DIBAL-H, 17 LiBH 4 , 18 LiEt 3 BH 19 required careful control of temperature and pH to avoid undesired side products. Hydrogenation with Co or Ru catalysis 20 and Zn catalysis with hydroxysilane 21 were used more recently.…”