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Organocatalytic Asymmetric Mannich Reactions with N ‐Boc and N ‐Cbz Protected α‐Amido Sulfones (Boc: tert ‐Butoxycarbonyl, Cbz: Benzyloxycarbonyl)
Author(s) -
Marianacci Olindo,
Micheletti Gabriele,
Bernardi Luca,
Fini Francesco,
Fochi Mariafrancesca,
Pettersen Daniel,
Sgarzani Valentina,
Ricci Alfredo
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700908
Subject(s) - chemistry , mannich reaction , catalysis , adduct , organocatalysis , amino acid , enantioselective synthesis , combinatorial chemistry , organic chemistry , biochemistry
Different malonates and β‐ketoesters can react with N ‐ tert ‐butoxycarbonyl‐ ( N ‐Boc) and N ‐benzyloxycarbonyl‐ ( N ‐Cbz) protected α‐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 α‐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 β 3 ‐amino acids in one easy step. Enantioenriched N ‐Boc and N ‐Cbz protected β‐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.