Vellalath S, Van KN, Romo D * Texas A&M University, College Station, USA
Direct Catalytic Asymmetric Synthesis of N-Heterocycles from Commodity Acid Chlorides by Employing α,β-Unsaturated Acylammonium Salts.
Angew. Chem. Int. Ed. 2013;
DOI:
10.1002/anie.201306050
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.
