Hydrogen-Borrowing Alkylation of 1,2-Amino Alcohols in the Synthesis of Enantioenriched γ-Aminobutyric Acids.

Autor: Hall CJJ; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK., Goundry WRF; Early Chemical Development, Pharmaceutical Sciences, R&D, AstraZeneca, Macclesfield, SK10 2NA, UK., Donohoe TJ; Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 Mar 22; Vol. 60 (13), pp. 6981-6985. Date of Electronic Publication: 2021 Feb 24.
DOI: 10.1002/anie.202100922
Abstrakt: For the first time we have been able to employ enantiopure 1,2-amino alcohols derived from abundant amino acids in C-C bond-forming hydrogen-borrowing alkylation reactions. These reactions are facilitated by the use of the aryl ketone Ph*COMe. Racemisation of the amine stereocentre during alkylation can be prevented by the use of sub-stoichiometric base and protection of the nitrogen with a sterically hindered triphenylmethane (trityl) or benzyl group. The Ph* and trityl groups are readily cleaved in one pot to give γ-aminobutyric acid (GABA) products as their HCl salts without further purification. Both steps may be performed in sequence without isolation of the hydrogen-borrowing intermediate, removing the need for column chromatography.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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