Carmen Simal

Organocatalytic Functionalization of Carboxylic Acids: Isothiourea-Catalyzed Asymmetric Intra- and Intermolecular Michael Addition−Lactonizations

Tetramisole promotes the catalytic asymmetric intramolecular Michael addition-lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition-lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).

Anhydrides as α,β-unsaturated acyl ammonium precursors: isothiourea-promoted catalytic asymmetric annulation processes

The asymmetric annulation of a range of α,β-unsaturated acyl ammonium intermediates, formed from isothiourea HBTM 2.1 and anhydrides with either 1,3-dicarbonyls, β-ketoesters or azaaryl ketones gives either functionalised esters (upon ring opening), dihydropyranones or dihydropyridones in good yields (up to 93%) and high enantioselectivity (up to 97% ee).

Sequential synthesis of (E)-alpha,beta-unsaturated primary amides with complete stereoselectivity.

A novel, efficient, and totally stereoselective synthesis of (E)-alpha,beta-unsaturated primary amides is reported. This process is consistent with a SmI(2)-mediated sequential reaction of an unmasked samarium chloroacetamide enolate with an aldehyde, followed by a beta-elimination to produce (E)-alpha,beta-unsaturated primary amides in good yields.

Asymmetric Michael Addition-Lactonization of Carboxylic Acids

A highly efficient asymmetric intra- and intermolecular Michael addition-lactonization of a variety of enone acids, arylacetic acids, and α-keto-β,γ-unsaturated esters using chiral isothioureas as catalysts was reported. The combination of an activating agent and the catalyst was crucial to generate an efficient catalytic cycle. To further demonstrate the utility of this process, the authors performed a simple derivatization of the products to obtain indene carboxylates in good yields and high enantioselectivities.