Unprecedented copper-catalyzed asymmetric conjugate addition of organometallic reagents to α,β-unsaturated lactams

Abstract

For the first time, an excellent enantioselectivity has been obtained in the conjugate addition of hard organometallic reagents to alpha,beta-unsaturated lactams bearing appropriate protecting-activating groups on the nitrogen.

Phosphoramidite: privilegierte Liganden in der asymmetrischen Katalyse

“…[178,179] Weiterhin wurden konjugierte Additionen von Dialkylzinkreagentien an cyclische stickstoffhaltige Michael-Akzeptoren wie die Lactame 72 und die Piperidone 74 beschrieben (Schema 21 a und b). [180,181] [183] Die Addition von weniger reaktivem Dimethylzink an die von Chalkon abgeleiteten, a,b-ungesättigten (Pyridyl)sulfonylimine 81 wurde ebenfalls untersucht (Schema 24 a). [184] In Gegenwart eines Katalysators mit dem PhosphoramiditLiganden ent-L2b (siehe Abbildung 4) wurden die Enamide 82 in guten Ausbeuten (bis 91 %), ee-Werten bis 80 % und Z/E-Verhältnissen > 83:17 erhalten.…”

Cu‐ and Ni‐Catalyzed Conjugated Additions of Organozincs and Organoaluminums to α,β‐Unsaturated Carbonyl Compounds

“…The copper-catalyzed enantioselective conjugated addition of organoaluminums has also been recently studied and, once again, the use of chiral phosphoramidite ligands proved to be the essential factor to achieve high enantioselectivity. One of the first reported examples was the enantioselective addition of trialkylaluminums to α,β-unsaturated lactams by Pineschi et al (Scheme 2.16) [73]. However, the reaction proceeded with a mediocre enantioselectivity of 68%.…”

Chiral amides via copper-catalysed enantioselective conjugate addition

“…The desired chiral β-alkyl substituted amide can be obtained from the corresponding oxazolidinones in one additional step. Furthermore, the copper-catalysed enantioselective CA to α,β-unsaturated lactams has been described with alkylzinc reagents 17 and alkyl-and alkenylalananes 17,18 giving rise to β-substituted lactams in good yields and selectivities. There is also one example of the asymmetric CA of Me 3 Al to an N-acylpyrrole derivative in which the corresponding methylated product is obtained in 54% yield and 96% ee.…”