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Hydrogen‐Borrowing Alkylation of 1,2‐Amino Alcohols in the Synthesis of Enantioenriched γ‐Aminobutyric Acids
Author(s) -
Hall Christopher J. J.,
Goundry William R. F.,
Donohoe Timothy J.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202100922
Subject(s) - chemistry , alkylation , enantiopure drug , amine gas treating , organic chemistry , steric effects , aryl , amino acid , catalysis , enantioselective synthesis , alkyl , biochemistry
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.