Search

Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate-catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.

We describe a biomimetic organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to imines. This simple protocol makes use of readily available Cinchona-derived organocatalysts and nucleophiles at the carboxylate oxidation state. The resulting β-amino thioesters, being attractive precursors for the preparation of optically active β-amino acids, are formed in good yields and in up to 79 % ee. As suggested by several mechanistic insights the desired products are formed via initial formation of a thioester acetate enolate via decarboxylation of the malonic acid half thioester, followed by addition to the imine.

The highly enantioselective reaction between in situ generated, Cbz-protected azomethines and malonates in the presence of 150 mol % of potassium carbonate (50 % w/w) and 1 mol % of quinine-derived quaternary ammonium bromides as phase-transfer organocatalysts has been developed. This study reports a novel approach for the asymmetric Mannich-type reaction and a wide range of azomethines, including those derived from enolizable aldehydes, is tolerated by the present system. The adducts, obtained in excellent yields with ee up to 98 %, are suitable precursors of optically pure β-amino acids.

A general approach to the catalytic asymmetric aza‐Henry reaction has been developed. The combination of a commercially available phase‐transfer catalyst (PTC) with a base is able to promote the in situ formation of N‐carbamoyl imines from α‐amido sulfones and activate nitromethane towards the asymmetric addition reaction, thus furnishing N‐carbamoyl‐protected β‐nitroamines in good yields and with up to 98 % ee (see scheme; PG=protecting group).