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

Abstract

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.