Synthesis of Pyrrolidinones via α,β-Unsaturated Acylammonium Ions

Key words

acylammonium salts - heterocycles - pyrrolidinones

Significance

An asymmetric enantioselective ­Michael addition–proton transfer–lactamization or lactonization organocascade reaction is reported. The cinchona alkaloid derived catalysts 1 can generate chiral α,β-unsaturated acylammonium salts with crotonyl chlorides 2, giving pyrrolidinones, ­piperid-2-ones, and dihydropyridinones in good yields and high enantioselectivities.

Comment

In the first step, the lithiated enolate is formed to participate in a conjugate addition to the acylammonium species, which derives from reaction of the chiral tertiary amine (R³ ₃N) with the acid chloride. After an intra- or intermolecular proton transfer, the acylammonium species undergoes intramolecular lactamization to regenerate the tertiary amine catalyst R³ ₃N. The products could be transformed into known precursors of various biologically active compounds.