Thiourea Catalysis via Anion Binding

Significance

Asymmetric Pictet-Spengler-type cyclizations of β-indolyl ethyl hydroxylactams 1 have been achieved in the presence of thiourea derivative 2 as chiral catalyst. Both indolizidinones (3, n = 1) and quinolizidinones (3, n = 2) are obtained in good to excellent yields and optical purities. TMSCl is required for the generation of chlorolactams 4. Plausibly thiourea catalyst 2 abstracts the chloride from 4 generating a chiral N-acyl iminium chloride-thiourea complex 5 as reactive intermediate. Subsequent cyclization in the chiral environment provided by the chiral thiourea-chloride anion complex (2×Cl^-) leads to enantiomerically enriched products.