Enantioselective Intramolecular α-Arylation of Benzylamine Derivatives: Synthesis of a Precursor to Levocetirizine.

Autor: Saunthwal RK; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Schwarz M; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Mallick RK; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Terry-Wright W; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK., Clayden J; School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2023 Mar 27; Vol. 62 (14), pp. e202216758. Date of Electronic Publication: 2023 Feb 23.
DOI: 10.1002/anie.202216758
Abstrakt: A practical, transition metal-free method allows the enantioselective synthesis of α,α-diarylmethylamines by asymmetric α-arylation of benzylamines. Enantioselective lithiation of N'-aryl-N-benzyl-N-isopropyl ureas using a chiral lithium amide base generates a benzyllithium that undergoes an unactivated stereospecific intramolecular nucleophilic aromatic substitution to generate an α,α-diarylmethylamine in the form of its urea derivative, in up to >99 % ee. Treatment with acid induces an "azatropic shift" with retention of configuration, the product of which may be hydrolysed to the target amine.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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