Chiral imines on the wave: reactivity of tert-butyl acrylate and stereoselectivity determination using NMR in liquid crystals

¹ BioCIS, UMR CNRS 8076, Université Paris Saclay, School of Pharmacy, Université Paris-Sud, 5, rue J.-B. Clément, F-92296 Châtenay-Malabry, France
² LRSSS, UMR CNRS 8615, Université Paris Saclay, UFR de Sciences, Université Paris-Sud, ICMMO, Bât. 410, F-91405 Orsay, France
³ LCSO, UMR CNRS 8182, Université Paris Saclay, UFR de Sciences, Université Paris-Sud, ICMMO, Bât. 410, F-91405 Orsay, France
⁴ ICSN, UPR CNRS 2301,1 avenue de la Terrasse, F-91190 Gif sur Yvette, France
⁵ GCAPS, EA 3343, Université Paris Saclay, School of Pharmacy, Université Paris-Sud, 5, rue J.-B. Clément, F-92296 Châtenay-Malabry, France

Published: 04 December 2015 by MDPI in MOL2NET'15, Conference on Molecular, Biomed., Comput. & Network Science and Engineering, 1st ed. congress CHEMBIO.MOL-01: Org. Chem., Med. Chem., Pharm. Industry, & Mol. Biol., Congress, Paris, France-Galveston, USA, 2023., Rostock, Germany-Bilbao, Spain-Galveston, Texas, USA, 2015

https://doi.org/10.3390/MOL2NET-1-a003

Abstract:

In connection with synthetic applications, we have foreseen to study the reactivity of the poorly reactive tert-butyl acrylate electrophile with chiral imines of unsymmetrical ketones, using conventional or microwave flash heating under carefully controlled reaction conditions in order to develop a very quick and efficient access to the corresponding Michael adducts in which a created stereogenic quaternary carbon center was fully stereocontrolled. Depending on the conditions, either a keto ester or a lactam were obtained. A good correlation was obtained between experiment and theoretical calculations. . The stereoselectivity of the process (e>95%) was determined using natural abundance ¹³C-{¹H} NMR in a chiral polypeptide liquid crystal.

Keywords: Aza-ene process, Asymmetric Michael reaction, Enamine activation, Unsymmetrical ketones, tert-butyl acrylate, Quaternary carbon center

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