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

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. The scope of carbon–carbon bond‐forming hydrogen‐borrowing reactions has been expanded to include 1,2‐amino alcohols derived from both natural and unnatural amino acids. The vulnerable amine stereocentre is preserved in the reaction by the use of a bulky nitrogen protecting group (trityl or benzyl), with the products being readily cleaved under acidic conditions to the corresponding γ‐aminobutyric acids without further purification.