Access to Unprotected β-Fluoroalkyl β-Amino Acids and Their α-Hydroxy Derivatives

Publication

https://doi.org/10.1021/acs.orglett.9b00622

Domain

Fellow

Org. Lett. 2019, 21, 7, 2340–2345

Volodymyr Sukach^1,2, Serhii Melnykov^3,4, Sylvain Bertho², Iryna Diachenko², Pascal Retailleau⁵, Mykhailo Vovk³, and Isabelle Gillaizeau²

¹Le Studium Loire Valley Institute for Advanced Studies, 1, rue Dupanloup, Orléans 45000, France

²Institute of Organic and Analytical Chemistry, ICOA UMR 7311 CNRS, Universitéd’Orléans, rue de Chartres, Orléans 45100,France

³Institute of Organic Chemistry of NAS of Ukraine, 5, Murmanska Str., Kyiv 02660, Ukraine

⁴Enamine LTD, 78 Chervonotkats’ka Str., Kyiv 02094, Ukraine

⁵Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Avenue de laTerrasse, Gif-sur-Yvette 91198, France

Abstract

Unprotected β-(het)aryl-β-fluoroalkyl β-amino acids and their α-hydroxy derivatives can be readily obtained using a decarboxylative Mannich-type reaction without protection/deprotection steps. This protocol utilizes lithium hexamethyldisilazide and (het)arylfluoroalkyl ketones to generate NH-ketimine intermediates. The mild reaction conditions allow the preparation of original fluorinated β-amino acids as useful building blocks in a practical and scalable manner.

Keywords

β‑Fluoroalkyl

β-Amino Acids

α-Hydroxy Derivatives

Proteins

Peptides

lithium hexamethyldisilazide

NH-ketimine intermediates

Published by

American Chemical Society