Cooperative Chiral Lewis Base/Palladium-Catalyzed Asymmetric Syntheses of Methylene-Containing δ-Lactams

Paul Zebrowski; Uwe Monkowius; Mario Waser

doi:10.1002/ejoc.202300982

Cooperative Chiral Lewis Base/Palladium-Catalyzed Asymmetric Syntheses of Methylene-Containing δ-Lactams

European J Org Chem. 2023 Dec 1;26(45):e202300982. doi: 10.1002/ejoc.202300982. Epub 2023 Nov 9.

Authors

Paul Zebrowski¹, Uwe Monkowius², Mario Waser¹

Affiliations

¹ Institute of Organic Chemistry Johannes Kepler University Linz Altenbergerstrasse 69 4040 Linz Austria.
² School of Education Chemistry Johannes Kepler University Linz Altenbergerstrasse 69 4040 Linz Austria.

Abstract

We herein report a two-step approach for the enantioselective synthesis of novel chiral δ-lactams. By using a cooperative chiral ITU/achiral Pd-catalyst system, this protocol proceeds via an asymmetric α-allylation of activated aryl esters first, followed by an acid-mediated lactam formation. A variety of differently substituted products could be obtained with usually high levels of enantioselectivities and in reasonable yields (16 examples, up to 98 : 2 er and 73 % yield over two steps). In addition, further utilizations of the products via transformations of the exocyclic double bond were successfully carried out as well.

Keywords: Lewis base catalysis; Pd-catalysis; asymmetric organocatalysis; cyclizations; lactams.