Abstract
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.
Original language | English |
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Article number | e202216758 |
Journal | Angewandte Chemie - International Edition |
Volume | 62 |
Issue number | 14 |
Early online date | 25 Jan 2023 |
DOIs | |
Publication status | Published - 27 Mar 2023 |
Bibliographical note
Funding Information:Financial support was provided by the EU through Marie Sklodowska Curie fellowships 839739 (COOPCAT) and 101023251 (PHOTOLITH), the ERC through Advanced Grant 883786 (DOGMATRON), and the Royal Society of Chemistry for an Undergraduate Research Bursary (to WTW).
Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
Keywords
- Arylation
- Benzylamine
- Chiral Lithium Amide
- Enantioselective
- Levocetirizine